CHAPTER 14 ORGANOMETALLIC COMPOUNDS O rganometallic compounds are compounds that have a carbon–metal bond; they lie at the place where organic and inorganic chemistry meet. You are already familiar with at least one organometallic compound, sodium acetylide (NaCPCH), which has an ionic bond between carbon and sodium. But just because a compound contains both a metal and carbon isn’t enough to classify it as organometal- lic. Like sodium acetylide, sodium methoxide (NaOCH 3 ) is an ionic compound. Unlike sodium acetylide, however, the negative charge in sodium methoxide resides on oxygen, not carbon. The properties of organometallic compounds are much different from those of the other classes we have studied to this point. Most important, many organometallic com- pounds are powerful sources of nucleophilic carbon, something that makes them espe- cially valuable to the synthetic organic chemist. For example, the preparation of alkynes by the reaction of sodium acetylide with alkyl halides (Section 9.6) depends on the pres- ence of a negatively charged, nucleophilic carbon in acetylide ion. Synthetic procedures that use organometallic reagents are among the most impor- tant methods for carbon–carbon bond formation in organic chemistry. In this chapter you will learn how to prepare organic derivatives of lithium, magnesium, copper, and zinc and see how their novel properties can be used in organic synthesis. We will also finish the story of polyethylene and polypropylene begun in Chapter 6 and continued in Chapter 7 to see the unique way that organometallic compounds catalyze alkene polymerization. Sodium acetylide (has a carbon-to-metal bond) Na H11001 CPCH H11002 Sodium methoxide (does not have a carbon-to-metal bond) Na H11001 OCH 3 H11002 546 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 14.1 ORGANOMETALLIC NOMENCLATURE Organometallic compounds are named as substituted derivatives of metals. The metal is the base name, and the attached alkyl groups are identified by the appropriate prefix. When the metal bears a substituent other than carbon, the substituent is treated as if it were an anion and named separately. PROBLEM 14.1 Both of the following organometallic reagents will be encoun- tered later in this chapter. Suggest a suitable name for each. (a) (CH 3 ) 3 CLi (b) SAMPLE SOLUTION (a) The metal lithium provides the base name for (CH 3 ) 3 CLi. The alkyl group to which lithium is bonded is tert-butyl, and so the name of this organometallic compound is tert-butylithium. An alternative, equally correct name is 1,1-dimethylethyllithium. An exception to this type of nomenclature is NaCPCH, which is normally referred to as sodium acetylide. Both sodium acetylide and ethynylsodium are acceptable IUPAC names. 14.2 CARBON–METAL BONDS IN ORGANOMETALLIC COMPOUNDS With an electronegativity of 2.5 (Table 14.1), carbon is neither strongly electropositive nor strongly electronegative. When carbon is bonded to an element more electronegative than itself, such as oxygen or chlorine, the electron distribution in the bond is polarized H MgCl CH 3 MgI Methylmagnesium iodide (CH 3 CH 2 ) 2 AlCl Diethylaluminum chloride Li H Cyclopropyllithium CH 2 CHNa Vinylsodium (CH 3 CH 2 ) 2 Mg Diethylmagnesium 14.2 Carbon–Metal Bonds in Organometallic Compounds 547 TABLE 14.1 Electronegativities of Some Representative Elements Element F O Cl N C H Cu Zn Al Mg Li Na K 4.0 3.5 3.0 3.0 2.5 2.1 1.9 1.6 1.5 1.2 1.0 0.9 0.8 Electronegativity Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website so that carbon is slightly positive and the more electronegative atom is slightly negative. Conversely, when carbon is bonded to a less electronegative element, such as a metal, the electrons in the bond are more strongly attracted toward carbon. Figure 14.1 uses electrostatic potential maps to show how different the electron distri- bution is between methyl fluoride (CH 3 F) and methyllithium (CH 3 Li). An anion that contains a negatively charged carbon is referred to as a carbanion. Covalently bonded organometallic compounds are said to have carbanionic character. As the metal becomes more electropositive, the ionic character of the carbon–metal bond becomes more pronounced. Organosodium and organopotassium compounds have ionic carbon–metal bonds; organolithium and organomagnesium compounds tend to have covalent, but rather polar, carbon–metal bonds with significant carbanionic character. It is the carbanionic character of such compounds that is responsible for their usefulness as synthetic reagents. C M H9254H11002 H9254H11001 M is less electronegative than carbon C X H9254H11001 H9254H11002 X is more electronegative than carbon 548 CHAPTER FOURTEEN Organometallic Compounds (a) Methyl fluoride (b) Methyllithium FIGURE 14.1 Electro- static potential maps of (a) methyl fluoride and of (b) methyllithium. The elec- tron distribution is reversed in the two compounds. Car- bon is electron-poor (blue) in methyl fluoride, but electron- rich (red) in methyllithium. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 14.3 PREPARATION OF ORGANOLITHIUM COMPOUNDS Before we describe the applications of organometallic reagents to organic synthesis, let us examine their preparation. Organolithium compounds and other Group I organometal- lic compounds are prepared by the reaction of an alkyl halide with the appropriate metal. The alkyl halide can be primary, secondary, or tertiary. Alkyl iodides are the most reac- tive, followed by bromides, then chlorides. Fluorides are relatively unreactive. Unlike elimination and nucleophilic substitution reactions, formation of organo- lithium compounds does not require that the halogen be bonded to sp 3 -hybridized carbon. Compounds such as vinyl halides and aryl halides, in which the halogen is bonded to sp 2 - hybridized carbon, react in the same way as alkyl halides, but at somewhat slower rates. Organolithium compounds are sometimes prepared in hydrocarbon solvents such as pentane and hexane, but normally diethyl ether is used. It is especially important that the solvent be anhydrous. Even trace amounts of water or alcohols react with lithium to form insoluble lithium hydroxide or lithium alkoxides that coat the surface of the metal and prevent it from reacting with the alkyl halide. Furthermore, organolithium reagents are strong bases and react rapidly with even weak proton sources to form hydrocarbons. We shall discuss this property of organolithium reagents in Section 14.5. PROBLEM 14.2 Write an equation showing the formation of each of the fol- lowing from the appropriate bromide: (a) Isopropenyllithium (b) sec-Butyllithium SAMPLE SOLUTION (a) In the preparation of organolithium compounds from organic halides, lithium becomes bonded to the carbon that bore the halogen. Therefore, isopropenyllithium must arise from isopropenyl bromide. Reaction with an alkyl halide takes place at the metal surface. In the first step, an electron is transferred from the metal to the alkyl halide. H11001H11001Li H11001 Lithium cationLithium Li Alkyl halide RX Anion radical [R ] H11002 X H11001CH 2 ?CCH 3 W Br Isopropenyl bromide 2Li Lithium H11001 W Li CH 2 ?CCH 3 Isopropenyllithium LiBr Lithium bromide diethyl ether diethyl ether 35°C Br Bromobenzene H11001 2Li Lithium Li Phenyllithium (95–99%) H11001 LiBr Lithium bromide H11001H11001RX Alkyl halide 2M Group I metal M H11001 X H11002 Metal halide RM Group I organometallic compound H11001H11001(CH 3 ) 3 CCl tert-Butyl chloride 2Li Lithium LiCl Lithium chloride (CH 3 ) 3 CLi tert-Butyllithium (75%) diethyl ether H1100230°C 14.3 Preparation of Organolithium Compounds 549 The reaction of an alkyl halide with lithium was cited earlier (Section 2.16) as an example of an oxidation– reduction. Group I metals are powerful reducing agents. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Having gained one electron, the alkyl halide is now negatively charged and has an odd number of electrons. It is an anion radical. The extra electron occupies an antibonding orbital. This anion radical fragments to an alkyl radical and a halide anion. Following fragmentation, the alkyl radical rapidly combines with a lithium atom to form the organometallic compound. 14.4 PREPARATION OF ORGANOMAGNESIUM COMPOUNDS: GRIGNARD REAGENTS The most important organometallic reagents in organic chemistry are organomagnesium compounds. They are called Grignard reagents after the French chemist Victor Grignard. Grignard developed efficient methods for the preparation of organic deriva- tives of magnesium and demonstrated their application in the synthesis of alcohols. For these achievements he was a corecipient of the 1912 Nobel Prize in chemistry. Grignard reagents are prepared from organic halides by reaction with magnesium, a Group II metal. (R may be methyl or primary, secondary, or tertiary alkyl; it may also be a cycloalkyl, alkenyl, or aryl group.) Anhydrous diethyl ether is the customary solvent used when preparing organo- magnesium compounds. Sometimes the reaction does not begin readily, but once started, it is exothermic and maintains the temperature of the reaction mixture at the boiling point of diethyl ether (35°C). The order of halide reactivity is I H11022 Br H11022 Cl H11022 F, and alkyl halides are more reac- tive than aryl and vinyl halides. Indeed, aryl and vinyl chlorides do not form Grignard reagents in diethyl ether. When more vigorous reaction conditions are required, tetrahy- drofuran (THF) is used as the solvent. Mg THF, 60°C Vinyl chloride CH 2 CHCl Vinylmagnesium chloride (92%) CH 2 CHMgCl diethyl ether 35°C Cl H Cyclohexyl chloride H11001 Mg Magnesium H MgCl Cyclohexylmagnesium chloride (96%) diethyl ether 35°C Br Bromobenzene H11001 Mg Magnesium MgBr Phenylmagnesium bromide (95%) H11001 Organic halide RX Magnesium Mg Organomagnesium halide RMgX H11001 Alkyl radical R Lithium Li Alkyllithium RLi H11001 Alkyl radical R Halide anion X H11002 Anion radical [R ] H11002 X 550 CHAPTER FOURTEEN Organometallic Compounds Grignard shared the prize with Paul Sabatier, who, as was mentioned in Chapter 6, showed that finely divided nickel could be used to cat- alyze the hydrogenation of alkenes. Recall the structure of tetrahydrofuran from Sec- tion 3.15: O Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website PROBLEM 14.3 Write the structure of the Grignard reagent formed from each of the following compounds on reaction with magnesium in diethyl ether: (a) p-Bromofluorobenzene (c) Iodocyclobutane (b) Allyl chloride (d) 1-Bromocyclohexene SAMPLE SOLUTION (a) Of the two halogen substituents on the aromatic ring, bromine reacts much faster than fluorine with magnesium. Therefore, fluorine is left intact on the ring, while the carbon–bromine bond is converted to a car- bon–magnesium bond. The formation of a Grignard reagent is analogous to that of organolithium reagents except that each magnesium atom can participate in two separate one-electron transfer steps: Organolithium and organomagnesium compounds find their chief use in the prepara- tion of alcohols by reaction with aldehydes and ketones. Before discussing these reactions, let us first examine the reactions of these organometallic compounds with proton donors. 14.5 ORGANOLITHIUM AND ORGANOMAGNESIUM COMPOUNDS AS BR?NSTED BASES Organolithium and organomagnesium compounds are stable species when prepared in suitable solvents such as diethyl ether. They are strongly basic, however, and react instantly with proton donors even as weakly acidic as water and alcohols. A proton is transferred from the hydroxyl group to the negatively polarized carbon of the organometallic compound to form a hydrocarbon. H H9254H11001 H9254H11002 ORH11032 H9254H11001 M H9254H11002 R RHH11001 RH11032OM H11001 H11002 CH 3 CH 2 CH 2 CH 2 Li Butyllithium H11001 H 2 O Water CH 3 CH 2 CH 2 CH 3 Butane (100%) H11001 LiOH Lithium hydroxide MgBr Phenylmagnesium bromide H11001 CH 3 OH Methanol Benzene (100%) H11001 CH 3 OMgBr Methoxymagnesium bromide H11001H11001 Magnesium Mg Mg H11001 Alkyl halide RX Anion radical [R ] H11002 X H11001 Alkyl radical R Halide ion X H11002 Anion radical [R ] H11002 X Alkylmagnesium halide Mg H11001 XR H11002Mg H11001 H11001BrF p-Bromofluorobenzene Mg Magnesium diethyl ether MgBrF p-Fluorophenylmagnesium bromide 14.5 Organolithium and Organomagnesium Compounds as Br?nsted Bases 551 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Because of their basicity organolithium compounds and Grignard reagents can- not be prepared or used in the presence of any material that bears a hydroxyl group. Nor are these reagents compatible with ±NH or ±SH groups, which can also con- vert an organolithium or organomagnesium compound to a hydrocarbon by proton transfer. The carbon–metal bonds of organolithium and organomagnesium compounds have appreciable carbanionic character. Carbanions rank among the strongest bases that we’ll see in this text. Their conjugate acids are hydrocarbons—very weak acids indeed. The equilibrium constants K a for ionization of hydrocarbons are much smaller than the K a ’s for water and alcohols. Table 14.2 presents some approximate data for the acid strengths of representative hydro- carbons. Acidity increases in progressing from the top of Table 14.2 to the bottom. An acid will transfer a proton to the conjugate base of any acid above it in the table. Organo- lithium compounds and Grignard reagents act like carbanions and will abstract a proton from any substance more acidic than a hydrocarbon. Thus, N±H groups and terminal alkynes (RCPC±H) are converted to their conjugate bases by proton transfer to organolithium and organomagnesium compounds. H11001C H Hydrocarbon (very weak acid) Proton H H11001 H11002 C Carbanion (very strong base) 552 CHAPTER FOURTEEN Organometallic Compounds TABLE 14.2 Approximate Acidities of Some Hydrocarbons and Reference Materials Compound 2-Methylpropane Ethane Methane Ethylene Benzene Ammonia Acetylene Ethanol Water 10 H1100271 10 H1100262 10 H1100260 10 H1100245 10 H1100243 10 H1100236 10 H1100226 10 H1100216 1.8 H11003 10 H1100216 K a 71 62 60 45 43 36 26 16 15.7 pK a Formula* (CH 3 ) 3 C±H CH 3 CH 2 ±H CH 3 ±H CH 2 ?CH±H H 2 N±H HCPC±H CH 3 CH 2 O±H HO±H H H H H H H Conjugate base H11002 H H H H H (CH 3 ) 3 C H11002 H 3 C H11002 HCPC H11002 H 2 N H11002 CH 3 CH 2 O H11002 HO H11002 CH 3 CH 2 H11002 CH 2 ?CH H11002 *The acidic proton in each compound is shaded in red. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website PROBLEM 14.4 Butyllithium is commercially available and is frequently used by organic chemists as a strong base. Show how you could use butyllithium to pre- pare solutions containing (a) Lithium diethylamide, (CH 3 CH 2 ) 2 NLi (b) Lithium 1-hexanolate, CH 3 (CH 2 ) 4 CH 2 OLi (c) Lithium benzenethiolate, C 6 H 5 SLi SAMPLE SOLUTION When butyllithium is used as a base, it abstracts a proton, in this case a proton attached to nitrogen. The source of lithium diethylamide must be diethylamine. Although diethylamine is not specifically listed in Table 14.2, its strength as an acid (K a H11015 10 H1100236 ) is, as might be expected, similar to that of ammonia. It is sometimes necessary in a synthesis to reduce an alkyl halide to a hydrocar- bon. In such cases converting the halide to a Grignard reagent and then adding water or an alcohol as a proton source is a satisfactory procedure. Adding D 2 O to a Grignard reagent is a commonly used method for introducing deuterium into a molecule at a spe- cific location. 14.6 SYNTHESIS OF ALCOHOLS USING GRIGNARD REAGENTS The main synthetic application of Grignard reagents is their reaction with certain car- bonyl-containing compounds to produce alcohols. Carbon–carbon bond formation is rapid and exothermic when a Grignard reagent reacts with an aldehyde or ketone. A carbonyl group is quite polar, and its carbon atom is electrophilic. Grignard reagents are nucleophilic and add to carbonyl groups, forming a new carbon–carbon bond. This normally written as COMgX R C R H11001 MgX O H11002 MgXR C O H9254H11001 H9254H11001H9254H11002 H9254H11002 Mg THF D 2 O 1-Bromopropene CH 3 CH CHBr Propenylmagnesium bromide CH 3 CH CHMgBr 1-Deuteriopropene (70%) CH 3 CH CHD H11001(CH 3 CH 2 ) 2 NH Diethylamine (stronger acid) CH 3 CH 2 CH 2 CH 2 Li Butyllithium (stronger base) H11001(CH 3 CH 2 ) 2 NLi Lithium diethylamide (weaker base) CH 3 CH 2 CH 2 CH 3 Butane (weaker acid) CH 3 Li Methyllithium (stronger base) H11001 NH 3 Ammonia (stronger acid: K a H11005 10 H1100236 ) CH 4 Methane (weaker acid: K a H33360 10 H1100260 ) H11001 LiNH 2 Lithium amide (weaker base) CH 3 CH 2 MgBr Ethylmagnesium bromide (stronger base) H11001 HCPCH Acetylene (stronger acid: K a H33360 10 H1100226 ) CH 3 CH 3 Ethane (weaker acid: K a H33360 10 H1100262 ) H11001 HCPCMgBr Ethynylmagnesium bromide (weaker base) 14.6 Synthesis of Alcohols Using Grignard Reagents 553 Deuterium is the mass 2 iso- tope of hydrogen. Deute- rium oxide (D 2 O) is some- times called “heavy water.” Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website addition step leads to an alkoxymagnesium halide, which in the second stage of the syn- thesis is converted to an alcohol by adding aqueous acid. The type of alcohol produced depends on the carbonyl compound. Substituents pres- ent on the carbonyl group of an aldehyde or ketone stay there—they become substituents on the carbon that bears the hydroxyl group in the product. Thus as shown in Table 14.3, formaldehyde reacts with Grignard reagents to yield primary alcohols, aldehydes yield secondary alcohols, and ketones yield tertiary alcohols. PROBLEM 14.5 Write the structure of the product of the reaction of propyl- magnesium bromide with each of the following. Assume that the reactions are worked up by the addition of dilute aqueous acid. (a) (c) (b) (d) SAMPLE SOLUTION (a) Grignard reagents react with formaldehyde to give pri- mary alcohols having one more carbon atom than the alkyl halide from which the Grignard reagent was prepared. The product is 1-butanol. An ability to form carbon–carbon bonds is fundamental to organic synthesis. The addition of Grignard reagents to aldehydes and ketones is one of the most frequently used reactions in synthetic organic chemistry. Not only does it permit the extension of carbon chains, but since the product is an alcohol, a wide variety of subsequent func- tional group transformations is possible. 14.7 SYNTHESIS OF ALCOHOLS USING ORGANOLITHIUM REAGENTS Organolithium reagents react with carbonyl groups in the same way that Grignard reagents do. In their reactions with aldehydes and ketones, organolithium reagents are somewhat more reactive than Grignard reagents. diethyl ether H 3 O H11001 CH 3 CH 2 CH 2 MgBr C H H O Propylmagnesium bromide H11001 formaldehyde CH 3 CH 2 CH 2 H H C OMgBr CH 3 CH 2 CH 2 CH 2 OH 1-Butanol 2-Butanone, CH 3 CCH 2 CH 3 O Benzaldehyde, C 6 H 5 CH O Cyclohexanone, O Formaldehyde, HCH O H11001H11001H11001H11001H 3 O H11001 Hydronium ion H 2 O Water Mg 2H11001 Magnesium ion X H11002 Halide ion Alkoxymagnesium halide COMgXR Alcohol COHR 554 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 14.7 Synthesis of Alcohols Using Organolithium Reagents 555 TABLE 14.3 Reactions of Grignard Reagents with Aldehydes and Ketones Reaction Reaction with formaldehyde Grignard reagents react with formal- dehyde (CH 2 ?O) to give primary alcohols having one more carbon than the Grignard reagent. Reaction with aldehydes Grignard reagents react with aldehydes (RCH?O) to give secondary alcohols. Reaction with ketones Grignard reagents react with ketones (RCRH11032) to give tertiary alcohols. O X General equation and specific example RMgX Grignard reagent H11001 Formaldehyde HCH O diethyl ether H 3 O H11001 OMgX H RC H Primary alkoxymagnesium halide OH H RC H Primary alcohol RMgX Grignard reagent H11001 Aldehyde RH11032CH O diethyl ether H 3 O H11001 OMgX H RC RH11032 Secondary alkoxymagnesium halide OH H RC RH11032 Secondary alcohol RMgX Grignard reagent H11001 Ketone RH11032CRH11033 O diethyl ether H 3 O H11001 OMgXRC RH11032 RH11033 Tertiary alkoxymagnesium halide OHRC RH11032 RH11033 Tertiary alcohol MgCl Cyclohexylmagnesium chloride CH 2 OH Cyclohexylmethanol (64–69%) H11001 Formaldehyde HCH O 1. diethyl ether 2. H 3 O H11001 H11001CH 3 (CH 2 ) 4 CH 2 MgBr Hexylmagnesium bromide Ethanal (acetaldehyde) CH 3 CH O 2-Octanol (84%) CH 3 (CH 2 ) 4 CH 2 CHCH 3 OH 1. diethyl ether 2. H 3 O H11001 CH 3 MgCl Methylmagnesium chloride O Cyclopentanone H11001 1-Methylcyclopentanol (62%) H 3 COH 1. diethyl ether 2. H 3 O H11001 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 14.8 SYNTHESIS OF ACETYLENIC ALCOHOLS The first organometallic compounds we encountered were compounds of the type RCPCNa obtained by treatment of terminal alkynes with sodium amide in liquid ammonia (Section 9.6): These compounds are sources of the nucleophilic anion RCPC : H11002 , and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9.6). The nucleophilicity of acetylide anions is also evident in their reactions with aldehydes and ketones, which are entirely analogous to those of Grignard and organolithium reagents. Acetylenic Grignard reagents of the type RCPCMgBr are prepared, not from an acetylenic halide, but by an acid–base reaction in which a Grignard reagent abstracts a proton from a terminal alkyne. H11001 CH 3 CH 2 MgBr Ethylmagnesium bromide H11001 CH 3 CH 3 Ethane diethyl ether CH 3 (CH 2 ) 3 CCH 1-Hexyne CH 3 (CH 2 ) 3 C CMgBr 1-Hexynylmagnesium bromide HC CNa Sodium acetylide H11001 O Cyclohexanone 1. NH 3 2. H 3 O H11001 1-Ethynylcyclohexanol (65–75%) CHO CH H11001 RH11032CRH11033 O Aldehyde or ketone H 3 O H11001 NH 3 RC CNa Sodium alkynide Sodium salt of an alkynyl alcohol C ONa RH11033 RH11032 RC C Alkynyl alcohol CCOH RH11033 RH11032 RC NaNH 2 Sodium amide H11001RCPCH Terminal alkyne NH 3 Ammonia H11001RCPCNa Sodium alkynide NH 3 H1100233°C RLi Alkyllithium compound H11001 C O Aldehyde or ketone R C OLi Lithium alkoxide H 3 O H11001 R C OH Alcohol CH 2 CHLi Vinyllithium H11001 CH O Benzaldehyde CHCH OH CH 2 1-Phenyl-2-propen-1-ol (76%) 1. diethyl ether 2. H 3 O H11001 556 CHAPTER FOURTEEN Organometallic Compounds In this particular example, the product can be variously described as a secondary al- cohol, a benzylic alcohol, and an allylic alcohol. Can you identify the structural reason for each classifica- tion? These reactions are normally carried out in liquid ammo- nia because that is the sol- vent in which the sodium salt of the alkyne is prepared. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website PROBLEM 14.6 Write the equation for the reaction of 1-hexyne with ethyl- magnesium bromide as if it involved ethyl anion instead of CH 3 CH 2 MgBr and use curved arrows to represent the flow of electrons. 14.9 RETROSYNTHETIC ANALYSIS In our earlier discussions of synthesis, we stressed the value of reasoning backward from the target molecule to suitable starting materials. A name for this process is retrosyn- thetic analysis. Organic chemists have employed this approach for many years, but the term was invented and a formal statement of its principles was set forth only relatively recently by E. J. Corey at Harvard University. Beginning in the 1960s, Corey began stud- ies aimed at making the strategy of organic synthesis sufficiently systematic so that the power of electronic computers could be applied to assist synthetic planning. A symbol used to indicate a retrosynthetic step is an open arrow written from prod- uct to suitable precursors or fragments of those precursors. Often the precursor is not defined completely, but rather its chemical nature is empha- sized by writing it as a species to which it is equivalent for synthetic purposes. Thus, a Grignard reagent or an organolithium reagent might be considered synthetically equiva- lent to a carbanion: Figure 14.2 illustrates how retrosynthetic analysis can guide you in planning the synthesis of alcohols by identifying suitable Grignard reagent and carbonyl-containing precursors. In the first step, locate the carbon of the target alcohol that bears the hydroxyl group, remembering that this carbon originated in the C?O group. Next, as shown in Figure 14.2, step 2, mentally disconnect a bond between that carbon and one of its attached groups (other than hydrogen). The attached group is the group that is to be trans- ferred from the Grignard reagent. Once you recognize these two structural fragments, the carbonyl partner and the carbanion that attacks it (Figure 14.2, step 3), you can read- ily determine the synthetic mode wherein a Grignard reagent is used as the synthetic equivalent of a carbanion (Figure 14.2, step 4). Primary alcohols, by this analysis, are seen to be the products of Grignard addi- tion to formaldehyde: Disconnect this bond RC H H OH R H11002 O H H C RMgX or RLi is synthetically equivalent to R H11002 Target molecule precursors (CH 3 CH 2 H11002 ) CH 3 (CH 2 ) 3 C CMgBr 1-Hexynylmagnesium bromide CH 3 (CH 2 ) 3 C CCH 2 OH 2-Heptyn-1-ol (82%) H11001 HCH O Formaldehyde 1. diethyl ether 2. H 3 O H11001 14.9 Retrosynthetic Analysis 557 Corey was honored with the 1990 Nobel Prize for his achievements in synthetic or- ganic chemistry. Problem 14.6 at the end of the preceding section intro- duced this idea with the sug- gestion that ethylmagnesium bromide be represented as ethyl anion. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Secondary alcohols may be prepared by two different combinations of Grignard reagent and aldehyde: R H11002 H RH11032 OC R C H RH11032 OH RH11032 H11002 H R OC Disconnect R±C Disconnect RH11032±C 558 CHAPTER FOURTEEN Organometallic Compounds Step 1: Locate the hydroxyl-bearing carbon. Step 2: Disconnect one of the organic substituents attached to the carbon that bears the hydroxyl group. Step 3: Steps 1 and 2 reveal the carbonyl-containing substrate and the carbanionic fragment. Step 4: Since a Grignard reagent may be considered as synthetically equivalent to a carbanion, this suggests the synthesis shown. RMgBr This carbon must have been part of the C?O group in the starting material X C Y O R H11002 H11001 C O X Y 1. diethyl ether 2. H 3 O H11001 R X C Y OH R XYC OH Disconnect this bondR XYC OH R XYC OH FIGURE 14.2 A retrosynthetic analysis of alcohol preparation by way of the addition of a Grignard reagent to an aldehyde or ketone. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Three combinations of Grignard reagent and ketone give rise to tertiary alcohols: Usually, there is little to choose among the various routes leading to a particular target alcohol. For example, all three of the following combinations have been used to prepare the tertiary alcohol 2-phenyl-2-butanol: PROBLEM 14.7 Suggest two ways in which each of the following alcohols might be prepared by using a Grignard reagent: (a) (b) SAMPLE SOLUTION (a) Since 2-hexanol is a secondary alcohol, we consider the reaction of a Grignard reagent with an aldehyde. Disconnection of bonds to the hydroxyl-bearing carbon generates two pairs of structural fragments: 2-Phenyl-2-propanol, C 6 H 5 C(CH 3 ) 2 OH 2-Hexanol, CH 3 CHCH 2 CH 2 CH 2 CH 3 OH CH 3 MgI Methylmagnesium iodide H11001 CCH 2 CH 3 O 1-Phenyl-1-propanone CH 3 CCH 2 CH 3 OH 2-Phenyl-2-butanol 1. diethyl ether 2. H 3 O H11001 CH 3 CH 2 MgBr Ethylmagnesium bromide H11001 CCH 3 O Acetophenone CH 3 CCH 2 CH 3 OH 2-Phenyl-2-butanol 1. diethyl ether 2. H 3 O H11001 MgBr Phenylmagnesium bromide H11001 CH 3 CCH 2 CH 3 O 2-Butanone CH 3 CCH 2 CH 3 OH 2-Phenyl-2-butanol 1. diethyl ether 2. H 3 O H11001 R H11002 RH11033 RH11032 OC RC RH11032 RH11033 OH RH11032 H11002 RH11033 R OC Disconnect R±C Disconnect RH11032±C Disconnect RH11033±C RH11033 H11002 RH11032 R OC 14.9 Retrosynthetic Analysis 559 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Therefore, one route involves the addition of a methyl Grignard reagent to a five- carbon aldehyde: The other requires addition of a butylmagnesium halide to a two-carbon alde- hyde: All that has been said in this section applies with equal force to the use of organo- lithium reagents in the synthesis of alcohols. Grignard reagents are one source of nucleo- philic carbon; organolithium reagents are another. Both have substantial carbanionic character in their carbon–metal bonds and undergo the same kind of reaction with alde- hydes and ketones. 14.10 PREPARATION OF TERTIARY ALCOHOLS FROM ESTERS AND GRIGNARD REAGENTS Tertiary alcohols can be prepared by a variation of the Grignard synthesis that employs an ester as the carbonyl component. Methyl and ethyl esters are readily available and are the types most often used. Two moles of a Grignard reagent are required per mole of ester; the first mole reacts with the ester, converting it to a ketone. The ketone is not isolated, but reacts rapidly with the Grignard reagent to give, after adding aqueous acid, a tertiary alcohol. Ketones are more reactive than esters toward Grignard reagents, and so it is not normally possible to interrupt the reaction at the ketone stage even if only one equivalent of the Grignard reagent is used. RMgX Grignard reagent H11001 RH11032COCH 3 O Methyl ester diethyl ether RH11032C OCH 3 O R MgX RH11032CR O Ketone H11001 CH 3 OMgX Methoxymagnesium halide CH 3 CH 2 CH 2 CH 2 MgBr Butylmagnesium bromide H11001 Acetaldehyde CH 3 CH O 1. diethyl ether 2. H 3 O H11001 CH 3 CH 2 CH 2 CH 2 CHCH 3 OH 2-Hexanol CH 3 MgI Methylmagnesium iodide H11001 Pentanal CH 3 CH 2 CH 2 CH 2 CH O 1. diethyl ether 2. H 3 O H11001 CH 3 CH 2 CH 2 CH 2 CHCH 3 OH 2-Hexanol and CH 3 CHCH 2 CH 2 CH 2 CH 3 OH CH 3 CHCH 2 CH 2 CH 2 CH 3 OH H11002 CH 2 CH 2 CH 2 CH 3 HCCH 2 CH 2 CH 2 CH 3 O H11002 CH 3 CH 3 CH O 560 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Two of the groups bonded to the hydroxyl-bearing carbon of the alcohol are the same because they are derived from the Grignard reagent. For example, PROBLEM 14.8 What combination of ester and Grignard reagent could you use to prepare each of the following tertiary alcohols? (a) (b) SAMPLE SOLUTION (a) To apply the principles of retrosynthetic analysis to this case, we disconnect both ethyl groups from the tertiary carbon and identify them as arising from the Grignard reagent. The phenyl group originates in an ester of the type C 6 H 5 CO 2 R (a benzoate ester). An appropriate synthesis would be 14.11 ALKANE SYNTHESIS USING ORGANOCOPPER REAGENTS Organometallic compounds of copper have been known for a long time, but their ver- satility as reagents in synthetic organic chemistry has only recently been recognized. The most useful organocopper reagents are the lithium dialkylcuprates, which result when a copper(I) halide reacts with two equivalents of an alkyllithium in diethyl ether or tetrahy- drofuran. H11001H110012RLi Alkyllithium CuX Cu(I) halide (X H11005 Cl, Br, I) LiX Lithium halide R 2 CuLi Lithium dialkylcuprate diethyl ether or THF 2CH 3 CH 2 MgBr Ethylmagnesium bromide H11001 Methyl benzoate C 6 H 5 COCH 3 O 1. diethyl ether 2. H 3 O H11001 C 6 H 5 C(CH 2 CH 3 ) 2 OH 3-Phenyl-3-pentanol C 6 H 5 C(CH 2 CH 3 ) 2 OH C 6 H 5 COR O H11001 2CH 3 CH 2 MgX (C 6 H 5 ) 2 C OH C 6 H 5 C(CH 2 CH 3 ) 2 OH 2CH 3 MgBr Methylmagnesium bromide CH 3 OH Methanol H11001H11001(CH 3 ) 2 CHCCH 3 OH CH 3 2,3-Dimethyl- 2-butanol (73%) (CH 3 ) 2 CHCOCH 3 O Methyl 2-methylpropanoate 1. diethyl ether 2. H 3 O H11001 RMgX Grignard reagent H11001 RH11032CR OH R Tertiary alcohol RH11032CR O Ketone 1. diethyl ether 2. H 3 O H11001 14.11 Alkane Synthesis Using Organocopper Reagents 561 Copper(I) salts are also known as cuprous salts. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website In the first stage of the preparation, one molar equivalent of alkyllithium displaces halide from copper to give an alkylcopper(I) species: The second molar equivalent of the alkyllithium adds to the alkylcopper to give a neg- atively charged dialkyl-substituted derivative of copper(I) called a dialkylcuprate anion. It is formed as its lithium salt, a lithium dialkylcuprate. Lithium dialkylcuprates react with alkyl halides to produce alkanes by carbon–car- bon bond formation between the alkyl group of the alkyl halide and the alkyl group of the dialkylcuprate: Primary alkyl halides, especially iodides, are the best substrates. Elimination becomes a problem with secondary and tertiary alkyl halides: Lithium diarylcuprates are prepared in the same way as lithium dialkylcuprates and undergo comparable reactions with primary alkyl halides: The most frequently used organocuprates are those in which the alkyl group is pri- mary. Steric hindrance makes organocuprates that bear secondary and tertiary alkyl groups less reactive, and they tend to decompose before they react with the alkyl halide. The reaction of cuprate reagents with alkyl halides follows the usual S N 2 order: CH 3 H11022 primary H11022 secondary H11022 tertiary, and I H11022 Br H11022 Cl H11022 F. p-Toluenesulfonate esters are suitable substrates and are somewhat more reactive than halides. Because the alkyl halide and dialkylcuprate reagent should both be primary in order to produce satisfactory yields of coupled products, the reaction is limited to the formation of RCH 2 ±CH 2 RH11032 and RCH 2 ±CH 3 bonds in alkanes. A key step in the reaction mechanism appears to be nucleophilic attack on the alkyl halide by the negatively charged copper atom, but the details of the mechanism are not well understood. Indeed, there is probably more than one mechanism by which H11001(C 6 H 5 ) 2 CuLi Lithium diphenylcuprate ICH 2 (CH 2 ) 6 CH 3 1-Iodooctane C 6 H 5 CH 2 (CH 2 ) 6 CH 3 1-Phenyloctane (99%) diethyl ether H11001(CH 3 ) 2 CuLi Lithium dimethylcuprate CH 3 (CH 2 ) 8 CH 2 I 1-Iododecane CH 3 (CH 2 ) 8 CH 2 CH 3 Undecane (90%) ether 0°C R 2 CuLi Lithium dialkylcuprate RRH11032 Alkane RH11032X Alkyl halide RCu Alkylcopper LiX Lithium halide H11001 H11001H11001 Li R Alkyllithium [R Cu R]Li H11001 H11002 Lithium dialkylcuprate (soluble in ether and in THF) Cu R Alkylcopper H11001 RLi Cu I LiI Lithium iodide H11001RCu Alkylcopper 562 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website cuprates react with organic halogen compounds. Vinyl halides and aryl halides are known to be very unreactive toward nucleophilic attack, yet react with lithium dialkylcuprates: PROBLEM 14.9 Suggest a combination of organic halide and cuprate reagent appropriate for the preparation of each of the following compounds: (a) 2-Methylbutane (b) 1,3,3-Trimethylcyclopentene SAMPLE SOLUTION (a) First inspect the target molecule to see which bonds are capable of being formed by reaction of an alkyl halide and a cuprate, bearing in mind that neither the alkyl halide nor the alkyl group of the lithium dialkylcuprate should be secondary or tertiary. There are two combinations, both acceptable, that give the CH 3 ±CH 2 bond: 14.12 AN ORGANOZINC REAGENT FOR CYCLOPROPANE SYNTHESIS Zinc reacts with alkyl halides in a manner similar to that of magnesium. Organozinc reagents are not nearly as reactive toward aldehydes and ketones as Grignard reagents and organolithium compounds but are intermediates in certain reactions of alkyl halides. An organozinc compound that occupies a special niche in organic synthesis is iodomethylzinc iodide (ICH 2 ZnI), prepared by the reaction of zinc–copper couple [Zn(Cu), zinc that has had its surface activated with a little copper] with diiodomethane in ether. H11001RX Alkyl halide Zn Zinc Alkylzinc halide RZnX ether (CH 3 ) 2 CuLi Lithium dimethylcuprate H11001 1-Bromo- 2-methylpropane BrCH 2 CH(CH 3 ) 2 CH 3 CH 2 CH(CH 3 ) 2 2-Methylbutane CH 3 I Iodomethane H11001 Lithium diisobutylcuprate LiCu[CH 2 CH(CH 3 ) 2 ] 2 CH 3 CH 2 CH(CH 3 ) 2 2-Methylbutane A bond between a methyl group and a methylene group can be formed. None of the bonds to the methine group can be formed efficiently. CH 3 CH 2 CH 3 CH CH 3 14.12 An Organozinc Reagent for Cyclopropane Synthesis 563 diethyl ether (CH 3 CH 2 CH 2 CH 2 ) 2 CuLi Lithium dibutylcuprate H11001 Br 1-Bromocyclohexene CH 2 CH 2 CH 2 CH 3 1-Butylcyclohexene (80%) diethyl ether (CH 3 CH 2 CH 2 CH 2 ) 2 CuLi Lithium dibutylcuprate I Iodobenzene CH 2 CH 2 CH 2 CH 3 Butylbenzene (75%) H11001 Victor Grignard was led to study organomagnesium compounds because of ear- lier work he performed with organic derivatives of zinc. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website What makes iodomethylzinc iodide such a useful reagent is that it reacts with alkenes to give cyclopropanes. This reaction is called the Simmons–Smith reaction and is one of the few methods avail- able for the synthesis of cyclopropanes. Mechanistically, the Simmons–Smith reaction seems to proceed by a single-step cycloaddition of a methylene (CH 2 ) unit from iodomethylzinc iodide to the alkene: PROBLEM 14.10 What alkenes would you choose as starting materials in order to prepare each of the following cyclopropane derivatives by reaction with iodomethylzinc iodide? (a) (b) SAMPLE SOLUTION (a) In a cyclopropane synthesis using the Simmons–Smith reagent, you should remember that a CH 2 unit is transferred. Therefore, retro- synthetically disconnect the bonds to a CH 2 group of a three-membered ring to identify the starting alkene. The complete synthesis is: Methylene transfer from iodomethylzinc iodide is stereospecific. Substituents that were cis in the alkene remain cis in the cyclopropane. CH 3 1-Methylcycloheptene CH 3 1-Methylbicyclo[5.1.0]octane (55%) CH 2 I 2 , Zn(Cu) diethyl ether [CH 2 ] CH 2 CH 3 CH 3 H11001 CH 3 ZnI 2 ICH 2 ZnI C C C CH 2 C I ZnI Transition state for methylene transfer C CH 2 C H11001 CH 2 CH 3 CH 2 CH 3 C 2-Methyl-1-butene CH 2 CH 3 CH 3 1-Ethyl-1-methylcyclopropane (79%) CH 2 I 2 , Zn(Cu) diethyl ether H11001ICH 2 I Diiodomethane Zn Zinc Iodomethylzinc iodide ICH 2 ZnI diethyl ether Cu 564 CHAPTER FOURTEEN Organometallic Compounds Iodomethylzinc iodide is known as the Simmons– Smith reagent, after Howard E. Simmons and Ronald D. Smith of Du Pont, who first described its use in the preparation of cyclo- propanes. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Yields in Simmons–Smith reactions are sometimes low. Nevertheless, since it often provides the only feasible route to a particular cyclopropane derivative, it is a valuable addition to the organic chemist’s store of synthetic methods. 14.13 CARBENES AND CARBENOIDS Iodomethylzinc iodide is often referred to as a carbenoid, meaning that it resembles a carbene in its chemical reactions. Carbenes are neutral molecules in which one of the carbon atoms has six valence electrons. Such carbons are divalent; they are directly bonded to only two other atoms and have no multiple bonds. Iodomethylzinc iodide reacts as if it were a source of the carbene . It is clear that free : CH 2 is not involved in the Simmons–Smith reaction, but there is substantial evidence to indicate that carbenes are formed as intermediates in certain other reactions that convert alkenes to cyclopropanes. The most studied examples of these reactions involve dichlorocarbene and dibromocarbene. Carbenes are too reactive to be isolated and stored, but have been trapped in frozen argon for spectroscopic study at very low temperatures. Dihalocarbenes are formed when trihalomethanes are treated with a strong base, such as potassium tert-butoxide. The trihalomethyl anion produced on proton abstraction dissociates to a dihalocarbene and a halide anion: When generated in the presence of an alkene, dihalocarbenes undergo cycloaddition to the double bond to give dihalocyclopropanes: Br 3 CH Tribromomethane H11001 OC(CH 3 ) 3 H11002 tert-Butoxide ion Br 3 C H11002 Tribromomethide ion H11001 H OC(CH 3 ) 3 tert-Butyl alcohol C Br Br Br H11002 Tribromomethide ion Br Br C Dibromocarbene H11001 Br H11002 Bromide ion C Cl Cl Dichlorocarbene C Br Br Dibromocarbene H±C±H CH 2 I 2 Zn(Cu) ether CH 2 CH 3 HH CH 3 CH 2 CC (Z)-3-Hexene CH 3 CH 2 H CH 2 CH 3 H cis-1,2-Diethylcyclopropane (34%) CH 2 I 2 Zn(Cu) ether CH 2 CH 3 H H CH 3 CH 2 CC (E)-3-Hexene CH 3 CH 2 HCH 2 CH 3 H trans-1,2-Diethylcyclopropane (15%) 14.13 Carbenes and Carbenoids 565 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website The reaction of dihalocarbenes with alkenes is stereospecific, and syn addition is observed. PROBLEM 14.11 The syn stereochemistry of dibromocarbene cycloaddition was demonstrated in experiments using cis- and trans-2-butene. Give the structure of the product obtained from addition of dibromocarbene to each alkene. The process in which a dihalocarbene is formed from a trihalomethane corresponds to an elimination in which a proton and a halide are lost from the same carbon. It is an H9251-elimination proceeding via the organometallic intermediate K H11001 [ : CX 3 ] H11002 . 14.14 TRANSITION-METAL ORGANOMETALLIC COMPOUNDS A large number of organometallic compounds are based on transition metals. Examples include organic derivatives of iron, nickel, chromium, platinum, and rhodium. Many important industrial processes are catalyzed by transition metals or their complexes. Before we look at these processes, a few words about the structures of transition-metal complexes are in order. A transition-metal complex consists of a transition-metal atom or ion bearing attached groups called ligands. Essentially, anything attached to a metal is a ligand. A ligand can be an element (O 2 , N 2 ), a compound (NO), or an ion (CN H11002 ); it can be inor- ganic as in the examples just cited or it can be an organic ligand. Ligands differ in the number of electrons that they share with the transition metal to which they are attached. Carbon monoxide is a frequently encountered ligand in transition-metal complexes and contributes two electrons; it is best thought of in terms of the Lewis structure in which carbon is the reactive site. An example of a carbonyl complex of a transition metal is nickel carbonyl, a very toxic substance, which was first prepared over a hun- dred years ago and is an intermediate in the purification of nickel. It forms spontaneously when carbon monoxide is passed over elemental nickel. Many transition-metal complexes, including Ni(CO) 4 , obey what is called the 18- electron rule, which is to transition-metal complexes as the octet rule is to main-group elements. It states that for transition-metal complexes, the number of ligands that can be attached to a metal will be such that the sum of the electrons brought by the ligands plus the valence electrons of the metal equals 18. With an atomic number of 28, nickel has the electron configuration [Ar]4s 2 3d 8 (10 valence electrons). The 18-electron rule is satisfied by adding to these 10 the 8 electrons from four carbon monoxide ligands. A useful point to remember about the 18-electron rule when we discuss some reactions of transition-metal complexes is that if the number is less than 18, the metal is considered coordinatively unsaturated and can accept additional ligands. PROBLEM 14.12 Like nickel, iron reacts with carbon monoxide to form a com- pound having the formula M(CO) n that obeys the 18-electron rule. What is the value of n in the formula Fe(CO) n ? H11001Ni Nickel 4CO Carbon monoxide Ni(CO) 4 Nickel carbonyl CPO H11002H11001 Cyclohexene H11001 CHBr 3 Tribromomethane KOC(CH 3 ) 3 (CH 3 ) 3 COH Br Br 7,7-Dibromobicyclo[4.1.0]heptane (75%) 566 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 14.15 Ziegler–Natta Catalysis of Alkene Polymerization 567 Not all ligands use just two electrons to bond to transition metals. Chromium has the electron configuration [Ar]4s 2 3d 4 (6 valence electrons) and needs 12 more to satisfy the 18-electron rule. In the compound (benzene)tricarbonylchromium, 6 of these 12 are the H9266 electrons of the benzene ring; the remaining 6 are from the three carbonyl ligands. Ferrocene has an even more interesting structure. A central iron is H9266-bonded to two cyclopentadienyl ligands in what is aptly described as a sandwich. It, too, obeys the 18- electron rule. Each cyclopentadienyl ligand contributes 5 electrons for a total of 10 and iron, with an electron configuration of [Ar]4s 2 3d 6 contributes 8. Alternatively, ferrocene can be viewed as being derived from Fe 2H11001 (6 valence electrons) and two aromatic cyclopentadienide rings (6 electrons each). Indeed, ferrocene was first prepared by adding iron(II) chloride to cyclopentadienylsodium. Instead of the expected H9268-bonded species shown in the equation, ferrocene was formed. After ferrocene, a large number of related molecules have been prepared—even some in which uranium is the metal. There is now an entire subset of transition-metal organometallic complexes known as metallocenes based on cyclopentadienide ligands. These compounds are not only structurally interesting, but many of them have useful applications as catalysts for industrial processes. Naturally occurring compounds with carbon–metal bonds are very rare. The best example of such an organometallic compound is coenzyme B 12 , which has a carbon–cobalt H9268 bond (Figure 14.3). Pernicious anemia results from a coenzyme B 12 deficiency and can be treated by adding sources of cobalt to the diet. One source of cobalt is vitamin B 12 , a compound structurally related to, but not identical with, coen- zyme B 12 . 14.15 ZIEGLER–NATTA CATALYSIS OF ALKENE POLYMERIZATION In Section 6.21 we listed three main methods for polymerizing alkenes: cationic, free- radical, and coordination polymerization. In Section 7.15 we extended our knowledge of polymers to their stereochemical aspects by noting that although free-radical polymer- ization of propene gives atactic polypropylene, coordination polymerization produces a stereoregular polymer with superior physical properties. Because the catalysts responsi- ble for coordination polymerization are organometallic compounds, we are now in a posi- tion to examine coordination polymerization in more detail, especially with respect to how the catalyst works. 2 H11002 Na H11001 Cyclopentadienylsodium H11001 FeCl 2 Iron(II) chloride H Fe H (Not formed) H11001 2NaCl (Benzene)tricarbonylchromium HH HH HH Cr CO COOC Fe Ferrocene Cyclopentadienylsodium is ionic. Its anion is the cyclo- pentadienide ion, which con- tains six H9266 electrons. The first page of this chapter displayed an electrosta- tic potential map of ferrocene. You may wish to view a molecu- lar model of it on Learning By Modeling. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 568 CHAPTER FOURTEEN Organometallic Compounds AN ORGANOMETALLIC COMPOUND THAT OCCURS NATURALLY: COENZYME B 12 P ernicious anemia is a disease characterized, as are all anemias, by a deficiency of red blood cells. Unlike ordinary anemia, pernicious anemia does not respond to treatment with sources of iron, and before effective treatments were developed, was often fatal. Injection of liver extracts was one such treatment, and in 1948 chemists succeeded in isolat- ing the “antipernicious anemia factor” from beef liver as a red crystalline compound, which they called vitamin B 12 . This compound had the formula C 63 H 88 CoN 14 O 14 P. Its complexity precluded structure determination by classical degradation techniques, and spectroscopic methods were too primitive to be of much help. The structure was solved by Dorothy Crowfoot Hodgkin of Oxford University in 1955 using X-ray diffraction techniques and is shown in Figure 14.3a. Structure determination by X-ray crystallogra- phy can be superficially considered as taking a photo- graph of a molecule with X-rays. It is a demanding task and earned Hodgkin the 1964 Nobel Prize in chemistry. Modern structural studies by X-ray crystal- lography use computers to collect and analyze the diffraction data and take only a fraction of the time required years ago to solve the vitamin B 12 structure. The structure of vitamin B 12 is interesting in that it contains a central cobalt atom that is sur- rounded by six atoms in an octahedral geometry. One substituent, the cyano (±CN) group, is what is known as an “artifact.” It appears to be introduced into the molecule during the isolation process and leads to the synonym cyanocobalamin for vitamin B 12 . This material is used to treat pernicious anemia, but this is not the form in which it exerts its activity. The biologically active material is called coenzyme B 12 and differs from vitamin B 12 in the substituent at- tached to cobalt (Figure 14.3b). Coenzyme B 12 is the only known naturally occurring substance that has a carbon–metal bond. Moreover, coenzyme B 12 was discovered before any compound containing an alkyl group H9268-bonded to cobalt had ever been isolated in the laboratory! N N N N O O O P O H11002 HO O O HN O O O H 2 N H 2 N H 2 N HOCH 2 H 3 C O CH 3 CH 3 N N N O O N R Co H11001 (a) O N N H 2 N CH 2 OHHO (b) R H11005 R H11005H11002C P N CH 3 CH 3 CH 3 CH 3 CH 3 NH 2 H 3 C NH 2 NH 2 CH 3 CH 3 FIGURE 14.3 The structures of (a) vitamin B 12 and (b) coenzyme B 12 . Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website In the early 1950s, Karl Ziegler, then at the Max Planck Institute for Coal Research in Germany, was studying the use of aluminum compounds as catalysts for the oligomer- ization of ethylene. Ziegler found that adding certain metals or their compounds to the reaction mixture led to the formation of ethylene oligomers with 6–18 carbons, but others promoted the for- mation of very long carbon chains giving polyethylene. Both were major discoveries. The 6–18 carbon ethylene oligomers constitute a class of industrial organic chemicals known as linear H9251 olefins that are produced at a rate of 10 9 pounds/year in the United States. The Ziegler route to polyethylene is even more important because it occurs at modest temperatures and pressures and gives high-density polyethylene, which has prop- erties superior to the low-density material formed by free-radical polymerization described in Section 6.21. A typical Ziegler catalyst is a combination of titanium tetrachloride (TiCl 4 ) and diethylaluminum chloride [(CH 3 CH 2 ) 2 AlCl], but other combinations such as TiCl 3 /(CH 3 CH 2 ) 3 Al also work as do catalysts based on metallocenes. Although still in question, a plausible mechanism for the polymerization of ethylene in the presence of such catalysts has been offered and is outlined in Figure 14.4. Al(CH 2 CH 3 ) 3 Ethylene nH 2 C CH 2 Ethylene oligomers CH 3 CH 2 (CH 2 CH 2 ) nH110022 CH CH 2 14.15 Ziegler–Natta Catalysis of Alkene Polymerization 569 Step 1: A titanium halide and an ethylaluminum compound combine to place an ethyl group on titanium, giving the active catalyst. Titanium has one or more vacant coordination sites, shown here as an empty orbital. Step 2: Ethylene reacts with the active form of the catalyst. The π orbital of ethylene with its two electrons overlaps with the vacant titanium orbital to bind ethylene as a ligand to titanium. Step 3: The flow of electrons from ethylene to titanium increases the electron density at titanium and weakens the TiQCH 2 CH 3 bond. The ethyl group migrates from titanium to one of the carbons of ethylene. Step 4: The catalyst now has a butyl ligand on titanium instead of an ethyl group. Repeating steps 2 and 3 converts the butyl group to a hexyl group, then an octyl group, and so on. After thousands of repetitions, polyethylene is formed. CH 3 CH 2 Cl n Ti W H11001 H 2 C?CH 2 X CH 2 CH 2 CH 3 CH 2 W CH 2 Cl n Ti±CH 2 CH 3 CH 2 Cl n Ti W CH 3 CH 2 Cl n Ti W X CH 2 CH 2 CH 3 CH 2 Cl n Ti W FIGURE 14.4 A proposed mechanism for the polymerization of ethylene in the presence of a Ziegler–Natta catalyst. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Ziegler had a working relationship with the Italian chemical company Montecatini, for which Giulio Natta of the Milan Polytechnic Institute was a consultant. When Natta used Ziegler’s catalyst to polymerize propene, he discovered that the catalyst was not only effective but that it gave mainly isotactic polypropylene. (Recall from Section 7.15 that free-radical polymerization of propene gives atactic polypropylene.) Isotactic polypropylene has a higher melting point than the atactic form and can be drawn into fibers or molded into hard, durable materials. Before coordination polymerization was discovered by Ziegler and applied to propene by Natta, there was no polypropylene indus- try. Now, more than 10 10 pounds of it are prepared each year in the United States. Ziegler and Natta shared the 1963 Nobel Prize in chemistry: Ziegler for discovering novel cat- alytic systems for alkene polymerization and Natta for stereoregular polymerization. 14.16 SUMMARY Section 14.1 Organometallic compounds contain a carbon–metal bond. They are named as alkyl (or aryl) derivatives of metals. Section 14.2 Carbon is more electronegative than metals and carbon–metal bonds are polarized so that carbon bears a partial to complete negative charge and the metal bears a partial to complete positive charge. Section 14.3 See Table 14.4 Section 14.4 See Table 14.4 Section 14.5 Organolithium compounds and Grignard reagents are strong bases and react instantly with compounds that have ±OH groups. These organometallic compounds cannot therefore be formed or used in solvents such as water and ethanol. The most commonly employed sol- vents are diethyl ether and tetrahydrofuran. Section 14.6 See Tables 14.3 and 14.5 Section 14.7 See Table 14.5 Section 14.8 See Table 14.5 Section 14.9 When planning the synthesis of a compound using an organometallic reagent, or indeed any synthesis, the best approach is to reason backward from the product. This method is called retrosynthetic analysis. Retro- synthetic analysis of 1-methylcyclohexanol suggests it can be prepared by the reaction of methylmagnesium bromide and cyclohexanone. RHRM H11001H11001 H11002 ORH11032M H11001 HORH11032 HC Na H11001 C H11002 Sodium acetylide has an ionic bond between carbon and sodium. H9254H11002 C Li H9254H11001 H H H Methyllithium has a polar covalent carbon–lithium bond. Butyllithium CH 3 CH 2 CH 2 CH 2 Li Phenylmagnesium bromide C 6 H 5 MgBr 570 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Section 14.10 See Table 14.5 Section 14.11 See Tables 14.4 and 14.5 Section 14.12 See Tables 14.4 and 14.5 Section 14.13 Carbenes are species that contain a divalent carbon; that is, a carbon with only two bonds. One of the characteristic reactions of carbenes is with alkenes to give cyclopropane derivatives. KOC(CH 3 ) 3 (CH 3 ) 3 COH H11001 Cl CH 3 CH 3 Cl 1,1-Dichloro-2,2-dimethylcyclopropane (65%) 2-Methylpropene CH 3 CH 3 H 2 C C CHCl 3 CH 3 MgBr Methylmagnesium bromide H11001O Cyclohexanone1-Methylcyclohexanol CH 3 OH 14.16 Summary 571 TABLE 14.4 Preparation of Organometallic Reagents Used in Synthesis Type of organometallic reagent (section) and comments Organolithium reagents (Section 14.3) Lithi- um metal reacts with organic halides to pro- duce organolithium compounds. The organic halide may be alkyl, alkenyl, or aryl. Iodides react most and fluorides least readily; bro- mides are used most often. Suitable solvents include hexane, diethyl ether, and tetrahy- drofuran. Lithium dialkylcuprates (Section 14.11) These reagents contain a negatively charged cop- per atom and are formed by the reaction of a copper(I) salt with two equivalents of an organolithium reagent. Iodomethylzinc iodide (Section 14.12) This is the Simmons–Smith reagent. It is prepared by the reaction of zinc (usually in the pres- ence of copper) with diiodomethane. Grignard reagents (Section 14.4) Grignard reagents are prepared in a manner similar to that used for organolithium compounds. Diethyl ether and tetrahydrofuran are appro- priate solvents. General equation for preparation and specific example H11001 Magnesium Mg RMgX Alkylmagnesium halide (Grignard reagent) RX Alkyl halide H11001 Copper(I) halide CuX2RLi Alkyllithium H11001 Lithium halide LiXR 2 CuLi Lithium dialkylcuprate CH 3 CH 2 CH 2 Br Propyl bromide CH 3 CH 2 CH 2 Li Propyllithium (78%) Li diethyl ether Lithium 2Li H11001 Lithium halide LiX Alkyl halide RX Alkyllithium RLiH11001 2CH 3 Li Methyllithium CuI Copper(I) iodide H11001 (CH 3 ) 2 CuLi Lithium dimethylcuprate LiI Lithium iodide H11001 diethyl ether C 6 H 5 CH 2 Cl Benzyl chloride C 6 H 5 CH 2 MgCl Benzylmagnesium chloride (93%) Mg diethyl ether H11001CH 2 I 2 Diiodomethane ICH 2 ZnI Iodomethylzinc iodide Zn Zinc diethyl ether Cu Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website Certain organometallic compounds resemble carbenes in their reactions and are referred to as carbenoids. Iodomethylzinc iodide (Section 14.12) is an example. Section 14.14 Transition-metal complexes that contain one or more organic ligands offer a rich variety of structural types and reactivity. Organic ligands can be bonded to a metal by a H9268 bond or through its H9266 system. Metallocenes are transition-metal complexes in which one or more of the ligands is a 572 CHAPTER FOURTEEN Organometallic Compounds TABLE 14.5 Carbon–Carbon Bond-Forming Reactions of Organometallic Reagents Reaction (section) and comments Alcohol synthesis via the reaction of Grignard reagents with carbonyl com- pounds (Section 14.6) This is one of the most useful reactions in synthetic organ- ic chemistry. Grignard reagents react with formaldehyde to yield primary alco- hols, with aldehydes to give secondary alcohols, and with ketones to form terti- ary alcohols. Synthesis of alcohols using organolithi- um reagents (Section 14.7) Organolithi- um reagents react with aldehydes and ketones in a manner similar to that of Grignard reagents to produce alcohols. Reaction of Grignard reagents with esters (Section 14.10) Tertiary alcohols in which two of the substituents on the hydroxyl carbon are the same may be prepared by the reaction of an ester with two equivalents of a Grignard reagent. (Continued) General equation and specific example Aldehyde or ketone RH11032CRH11033 O X Grignard reagent RMgX Alcohol RCOH W W RH11032 RH11033 H11001 1. diethyl ether 2. H 3 O H11001 Ester RH11032CORH11033 O X Grignard reagent 2RMgX Tertiary alcohol RCOH W W RH11032 R H11001 1. diethyl ether 2. H 3 O H11001 Aldehyde or ketone RH11032CRH11033 O X Alkyllithium RLi Alcohol RCOH W W RH11032 RH11033 H11001 1. diethyl ether 2. H 3 O H11001 Butanal CH 3 CH 2 CH 2 CH O X Methylmagnesium iodide CH 3 MgI 2-Pentanol (82%) CH 3 CH 2 CH 2 CHCH 3 W OH H11001 1. diethyl ether 2. H 3 O H11001 Ethyl benzoate C 6 H 5 COCH 2 CH 3 O X Phenylmagnesium bromide 2C 6 H 5 MgBr Triphenylmethanol (89–93%) (C 6 H 5 ) 3 COHH11001 1. diethyl ether 2. H 3 O H11001 3,3-Dimethyl- 2-butanone CH 3 CC(CH 3 ) 3 O X H11001 1. diethyl ether 2. H 3 O H11001 Li Cyclopropyllithium CC(CH 3 ) 3 W W OH CH 3 2-Cyclopropyl- 3,3-dimethyl- 2-butanol (71%) Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website cyclopentadienyl ring. Ferrocene was the first metallocene synthesized; its structure is shown on the opening page of this chapter. Section 14.15 Coordination polymerization of ethylene and propene has the biggest eco- nomic impact of any organic chemical process. Ziegler–Natta polymer- ization is carried out in the presence of catalysts derived from transition metals such as titanium. H9266-Bonded and H9268-bonded organometallic com- pounds are intermediates in coordination polymerization. Problems 14.13 Write structural formulas for each of the following compounds. Specify which compounds qualify as organometallic compounds. (a) Cyclopentyllithium (d) Lithium divinylcuprate (b) Ethoxymagnesium chloride (e) Sodium carbonate (c) 2-Phenylethylmagnesium iodide (f) Benzylpotassium Problems 573 TABLE 14.5 Carbon–Carbon Bond-Forming Reactions of Organometallic Reagents (Continued) Reaction (section) and comments Synthesis of acetylenic alcohols (Section 14.8) Sodium acetylide and acetylenic Grignard reagents react with aldehydes and ketones to give alcohols of the type CPC±COH. The Simmons-Smith reaction (Section 14.12) Methylene transfer from iodo- methylzinc iodide converts alkenes to cyclopropanes. The reaction is a stereo- specific syn addition of a CH 2 group to the double bond. Preparation of alkanes using lithium di- alkylcuprates (Section 14.11) Two alkyl groups may be coupled together to form an alkane by the reaction of an alkyl hal- ide with a lithium dialkylcuprate. Both alkyl groups must be primary (or meth- yl). Aryl and vinyl halides may be used in place of alkyl halides. General equation and specific example Aldehyde or ketone RCRH11032 O X Sodium acetylide NaCPCH Alcohol HCPCCRH11032 W W OH R H11001 1. NH 3 , H1100233°C 2. H 3 O H11001 2-Butanone CH 3 CCH 2 CH 3 O X Sodium acetylide NaCPCH H11001 1. NH 3 , H1100233°C 2. H 3 O H11001 3-Methyl-1-pentyn-3-ol (72%) HCPCCCH 2 CH 3 W W OH CH 3 H11001 RH11032CH 2 X RCH 2 RH11032 Alkane R 2 CuLi Lithium dialkylcuprate Primary alkyl halide (CH 3 ) 2 CuLi Lithium dimethylcuprate C 6 H 5 CH 2 Cl Benzyl chloride H11001 C 6 H 5 CH 2 CH 3 Ethylbenzene (80%) diethyl ether Iodomethylzinc iodide ICH 2 ZnI Alkene R 2 C?CR 2 H11001 Zinc iodide ZnI 2 H11001 diethyl ether R RR R Cyclopropane derivative CH 2 I 2 , Zn(Cu) diethyl ether Bicyclo[3.1.0]hexane (53%) Cyclopentene Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 14.14 Dibal is an informal name given to the organometallic compound [(CH 3 ) 2 CHCH 2 ] 2 AlH, used as a reducing agent in certain reactions. Can you figure out the systematic name from which “dibal” is derived? 14.15 Suggest appropriate methods for preparing each of the following compounds from the start- ing material of your choice. (a) CH 3 CH 2 CH 2 CH 2 CH 2 MgI (c) CH 3 CH 2 CH 2 CH 2 CH 2 Li (b) CH 3 CH 2 CPCMgI (d) (CH 3 CH 2 CH 2 CH 2 CH 2 ) 2 CuLi 14.16 Which compound in each of the following pairs would you expect to have the more polar carbon–metal bond? Compare the models on Learning By Modeling with respect to the charge on the carbon bonded to the metal. (a) CH 3 CH 2 Li or (CH 3 CH 2 ) 3 Al (c) CH 3 CH 2 MgBr or HCPCMgBr (b) (CH 3 ) 2 Zn or (CH 3 ) 2 Mg 14.17 Write the structure of the principal organic product of each of the following reactions: (a) 1-Bromopropane with lithium in diethyl ether (b) 1-Bromopropane with magnesium in diethyl ether (c) 2-Iodopropane with lithium in diethyl ether (d) 2-Iodopropane with magnesium in diethyl ether (e) Product of part (a) with copper(I) iodide (f) Product of part (e) with 1-bromobutane (g) Product of part (e) with iodobenzene (h) Product of part (b) with D 2 O and DCl (i) Product of part (c) with D 2 O and DCl (j) Product of part (a) with formaldehyde in ether, followed by dilute acid (k) Product of part (b) with benzaldehyde in ether, followed by dilute acid (l) Product of part (c) with cycloheptanone in ether, followed by dilute acid (m) Product of part (d) with in ether, followed by dilute acid (n) Product of part (b) with (2 mol) in ether, followed by dilute acid (o) 1-Octene with diiodomethane and zinc–copper couple in ether (p) (E)-2-Decene with diiodomethane and zinc–copper couple in ether (q) (Z )-3-Decene with diiodomethane and zinc–copper couple in ether (r) 1-Pentene with tribromomethane and potassium tert-butoxide in tert-butyl alcohol 14.18 Using 1-bromobutane and any necessary organic or inorganic reagents, suggest efficient syn- theses of each of the following alcohols: (a) 1-Pentanol (d) 3-Methyl-3-heptanol (b) 2-Hexanol (e) 1-Butylcyclobutanol (c) 1-Phenyl-1-pentanol 14.19 Using bromobenzene and any necessary organic or inorganic reagents, suggest efficient syn- theses of each of the following: (a) Benzyl alcohol (b) 1-Phenyl-1-hexanol C 6 H 5 COCH 3 O X CH 3 CCH 2 CH 3 O X 574 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website (c) Bromodiphenylmethane (e) 1-Phenylcyclooctanol (d) 4-Phenyl-4-heptanol (f) trans-2-Phenylcyclooctanol 14.20 Analyze the following structures so as to determine all the practical combinations of Grig- nard reagent and carbonyl compound that will give rise to each: (a) (d) 6-Methyl-5-hepten-2-ol (b) (e) (c) (CH 3 ) 3 CCH 2 OH 14.21 A number of drugs are prepared by reactions of the type described in this chapter. Indicate what you believe would be a reasonable last step in the synthesis of each of the following: (a) (b) (c) 14.22 Predict the principal organic product of each of the following reactions: (a) (b) (c) (d) CH 2 I 2 Zn(Cu) diethyl ether CH 2 CH CH 2 1. Mg, THF 2. HCH O X 3. H 3 O H11001 Br 1. diethyl ether 2. H 3 O H11001 O H11001 CH 3 CH 2 Li C O H11001 NaC CH 1. liquid ammonia 2. H 3 O H11001 CH 3 O CH 3 OH CCH Mestranol, an estrogenic component of oral contraceptive drugs (C 6 H 5 ) 2 CCH OH CH 3 N Diphepanol, an antitussive (cough suppressant) CH 3 CH 2 CC CH 3 OH CH Meparfynol, a mild hypnotic or sleep-inducing agent OH CH OCH 3 OH CH 3 CH 2 CHCH 2 CH(CH 3 ) 2 OH Problems 575 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website (e) (f) (g) 14.23 Addition of phenylmagnesium bromide to 4-tert-butylcyclohexanone gives two isomeric ter- tiary alcohols as products. Both alcohols yield the same alkene when subjected to acid-catalyzed dehydration. Suggest reasonable structures for these two alcohols. 14.24 (a) Unlike other esters, which react with Grignard reagents to give tertiary alcohols, ethyl formate yields a different class of alcohols on treatment with Grignard reagents. What kind of alcohol is formed in this case and why? (b) Diethyl carbonate reacts with excess Grignard reagent to yield alcohols of a particular type. What is the structural feature that characterizes alcohols prepared in this way? 14.25 Reaction of lithium diphenylcuprate with optically active 2-bromobutane yields 2-phenylbu- tane, with high net inversion of configuration. When the 2-bromobutane used has the stereostruc- ture shown, will the 2-phenylbutane formed have the R or the S configuration? 14.26 Suggest reasonable structures for compounds A, B, and C in the following reactions: Compound C is more stable than compound A. OTs stands for toluenesulfonate. LiCu(CH 3 ) 2 (CH 3 ) 3 C OTs compound A (C 11 H 22 ) H11001 compound B (C 10 H 18 ) LiCu(CH 3 ) 2 (CH 3 ) 3 C OTs compound B H11001 compound C (C 11 H 22 ) CH 3 CH 2 CH 3 C Br H (CH 3 CH 2 OCOCH 2 CH 3 ) O X (HCOCH 2 CH 3 ) O X O C(CH 3 ) 3 4-tert-Butylcyclohexanone H11001 LiCu(CH 2 CH 2 CH 2 CH 3 ) 2 CH 3 O CH 2 OS O O CH 3 O I LiCu(CH 3 ) 2 H11001 CH 2 I 2 Zn(Cu) ether CH 2 H H CH 3 CC 576 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 14.27 The following conversion has been reported in the chemical literature. It was carried out in two steps, the first of which involved formation of a p-toluenesulfonate ester. Indicate the reagents for this step, and show how you could convert the p-toluenesulfonate to the desired product. 14.28 Sometimes the strongly basic properties of Grignard reagents can be turned to synthetic advantage. A chemist needed samples of butane specifically labeled with deuterium, the mass 2 isotope of hydrogen, as shown: (a) CH 3 CH 2 CH 2 CH 2 D (b) CH 3 CHDCH 2 CH 3 Suggest methods for the preparation of each of these using heavy water (D 2 O) as the source of deuterium, butanols of your choice, and any necessary organic or inorganic reagents. 14.29 Diphenylmethane is significantly more acidic than benzene, and triphenylmethane is more acidic than either. Identify the most acidic proton in each compound, and suggest a reason for the trend in acidity. 14.30 The 18-electron rule is a general, but not universal, guide for assessing whether a certain transition-metal complex is stable or not. Both of the following are stable compounds, but only one obeys the 18-electron rule. Which one? 14.31 One of the main uses of the “linear H9251-olefins” prepared by oligomerization of ethylene is in the preparation of linear low-density polyethylene. Linear low-density polyethylene is a copoly- mer produced when ethylene is polymerized in the presence of a “linear H9251-olefin” such as 1-decene [CH 2 ?CH(CH 2 ) 7 CH 3 ]. 1-Decene replaces ethylene at random points in the growing polymer chain. Can you deduce how the structure of linear low-density polyethylene differs from a linear chain of CH 2 units? 14.32 Make a molecular model of 7,7-dimethylbicyclo[2.2.1]heptan-2-one. Two diastereomeric alcohols may be formed when it reacts with methylmagnesium bromide. Which one is formed in greater amounts? 7,7-Dimethylbicyclo[2.2.1]heptan-2-one CH 3 H 3 C O HH HH Fe CO COOC Ti Cl Cl C 6 H 6 Benzene K a H11015 10 H1100245 (C 6 H 5 ) 2 CH 2 Diphenylmethane K a H11015 10 H1100234 (C 6 H 5 ) 3 CH Triphenylmethane K a H11015 10 H1100232 O OH O two steps Problems 577 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website 14.33 Make molecular models of the product of addition of dichlorocarbene to: (a) trans-2-Butene (b) cis-2-Butene Which product is achiral? Which one is formed as a racemic mixture? 14.34 Examine the molecular model of ferrocene on Learning By Modeling. Does ferrocene have a dipole moment? Would you expect the cyclopentadienyl rings of ferrocene to be more reactive toward nucleophiles or electrophiles? Where is the region of highest electrostatic potential? 14.35 Inspect the electrostatic potential surface of the benzyl anion structure given on Learning By Modeling. What is the hybridization state of the benzylic carbon? Does the region of highest electrostatic potential lie in the plane of the molecule or perpendicular to it? Which ring carbons bear the greatest share of negative charge? 578 CHAPTER FOURTEEN Organometallic Compounds Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website