http://www.courses.fas.harvard.edu/~chem206/ OH NH2 NaNO2 Me O Me Me R HOAc/H2O CHO EtAlCl2 OH NH2 CMe3 Me O Me R Me NaNO2 HOAc/H2O O CMe3 Chem 206D. A. Evans Matthew D. Shair Wednesday, December 4, 2002 Reading Assignment for this Lecture: Other Relevant Background Reading Chemistry 206 Advanced Organic Chemistry Lecture Number 30 Introduction to Carbonium Ions a73 Carbocation Stabilization a73 Carbocation Structures by X-ray Crystallography a73 Vinyl & Allyl Carbonium Ions Carbocations: Stability & Structure March, Advanced Organic Chemistry, 4th Ed. Chapter 5, pp165-174. Lowery & Richardson, Mech. & Theory in Org, Chem., 3rd Ed. pp 383-412. Arnett, Hoeflich, Schriver in Reactive Intermediates Vol 3, Wiley, 1985, Chapter 5, p 189. Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part A Chapter 5, "Nucleophilic Substitution", 263-350 . Walling, C. (1983). “An Innocent Bystander Looks at the 2-Norbornyl Cation.” Acc. Chem. Res. 16: 448. Olah, G. A. and G. Rasul (1997). “Chemistry in superacids .26. From Kekule's tetravalent methane to five-, six- and seven-coordinate protonated methanes.” Acc. Chem. Res. 30(6): 245-250. Saunders, M. and H. A. Jimenez-Vazquez (1991). “Recent studies of carbocations.” Chem. Rev. 91: 375. Stang, P. J. (1978). “Vinyl Triflate Chemistry: Unsaturated Cations and Carbenes.” Acc. Chem. Res. 11: 107. Olah, G. A. (1995). “My search for carbocations and their role in chemistry (Nobel lecture).” Angew. Chem., Int. Ed. Engl. 34, 1393-1405. (CCB library) Laube (1995). “X-Ray Crystal Structures of Carbocations Stabilized by Bridging or Hyperconjugation.” Acc. Chem. Res. 28,: 399 (pdf) Olah, G. A. (2001). “100 Years of Carbocations and their Significance in Chemistry.” J. Org. Chem. 2001, 66, 5944-5957. (pdf) Qumulative Exam Question Fall, 2001. The reaction illustrated below was recently reported by Snider and co-workers (Org. Lett. 2001, 123, 569-572). Provide a mechanism for this transformation. Where stereochemical issues are present, provide clear three dimensional drawings to support your answer. CH2Cl2, 0 °C Carey & Sundberg-A, p 337: Provide mechanisms for the following reactions. C C C C C C C C C C C C ⊕ ⊕ ⊕ ⊕ R3 R2 R1 R3 R2 OR1 R3 R2 NR R H3C CH2 Me CH2 H2C CH Me2 CH R R R H R R H H R H H H C C+H Ph CH2 Me CH2 PhCH2–Br CH=CH–CH2–Br HI ?-HI rel rate Me CH2 Me–CH2 CH2 Hydride Affinity = –?G° C C C C CH3+ CH3CH2+ (CH3)2CH+ (CH3)3C+ H2C=CH+ PhCH2+ R R–H Me3 C Me2CH–Br HC C CH CH2H2C D. A. Evans. B. Breit Chem 206 Carbocation Subclasses ⊕ R–R3 = alkyl or aryl ⊕ R–R3 = alkyl or aryl ⊕ R–R3 = alkyl or aryl Carbon-substituted Heteroatom–stabilized The following discussion will focus on carbocations unsubstitutred with heteroatoms Stability: Stabilization via alkyl substituents (hyperconjugation) Order of carbocation stability: 3?>2?>1? >> > Due to increasing number of substituents capable of hyperconjugation 314 276 249 231 287 386 239 Hydride ion affinities The relative stabilities of various carbocations can be measured in the gas phase by their affinity for hydride ion. J. Beauchamp, J. Am. Chem. Soc. 1984, 106, 3917. 276 287 +21 386 +81 276 249 –27 231 –18 239 276 –37 –20 256 Hydride ion affinities (HI) Hydride ion affinities versus Rates of Solvolysis Relative Solvolysis rates in 80% EtOH, 80 °C 100 52 0 +17 239 256 A. Streitwieser, Solvolytic Displacement Reactions, p75 Conclusion: Gas phase stabilities do not always correlate with rates of solvolysis 0.7 +10 249 + H 276 270 –7 The effect of beta substituents: Rationalizeopentrivalent hyperconjugationno bridging unsymmetrical bridging symmetrical bridging classical nonclassical increasing nonclassical character Classical vs nonclassical carbonium ions Note: As S-character increases, cation stability decreases due to more electronegative carbon. + HI HI increases C(+) stability decreases Carey & Sundberg–A, pp 276- Carbocations: Stability CH2 CHPh R3C R3C R3C R3C X X Fe R3C H H7C3 H7C3 C3H7 R3C H H H Fe Ph3C H H (3-Cl-C6H4)3C Cr(CO)3 CHPh RS RS H H R2N R2N H H Ph2CH R CPh2 Co2(CO)6 HC CH2OH R R R3C OH R3C X R R R R R3C X Br H–X H H H2SO4 R R R R H R H R Me O M. Shair, D. Evans Chem 206Carbocation Generation & Stability Carbocation Stability: The pKR+ value Definition: R+ + H2O ROH + H+ KR+ = aROH ? aH+a R+ ? aH2O a = activity pKR+ = – log KR+ (4-MeO-C6H4)3C + 0.82 – 6.63 – 11.0 – 13.3 0.40 0.75 –10.4 –7.4 7.2 4.77 Table: pKR+ values of some selected carbenium salts Hydride abstraction from neutral precursors + Lewis-Acid = etc. Lewis-Acid: Ph3C BF4, BF3, PCl5 Removal of an energy-poor anion from a neutral precursor via Lewis Acids + LA LA–X LA: Ag , AlCl3, SnCl4, SbCl5, SbF5, BF3, FeCl3, ZnCl2, PCl3, PCl5, POCl3 ... X: F, Cl, Br, I, OR Acidic dehydratization of secondary and tertiary alcohols - H2O R: Aryl + other charge stabilizing substituents X: SO42-, ClO4-, FSO3-, CF3SO3- From neutral precursors via heterolytic dissociation (solvolysis) - First step in SN1 or E1 reactions solvent Ability of X to function as a leaving group: -N2+ > -OSO2R' > -OPO(OR')2 > -I ≥ -Br > Cl > OH2+ ...Carbocation Generation + + + + Addition of electrophiles to -systems chemistry chemistry J.C.S.,CC 1971, 556 Provide a Mechanism of this transformation Carey & Sundberg, A, p 277 Carey & Sundberg, A, pp 276- C C Me H H MeMe Me Me Me H C HHC HH Me Me Me C [F5Sb–F–SbF5]– C HHC H C C R H H HH R D. A. Evans, B. Breit Chem 206 Take linear combination of σ C–R (filled) and C pz-orbital (empty): σ C–R + σ? C–R σ C–R σ? C–R + Syn-planar orientation between interacting orbitals a73 FMO Description E ++ Carbocation Stabilization Through Hyperconjugation C–H versus C–C Hyperconjugation:The t-Pentyl Cation + 1.582 ? + 1.107 ? 1.092 ? R. P von Schleyer in Stable Carbocation Chemistry, 1997, p 46-47 Calculated carbocation agrees with solution structure Physical Evidence for Hyperconjugation: The Adamantyl Cation T. Laube, Angew. Chem. Int. Ed. 1986, 25, 349 First X-ray Structure of an Aliphatic Carbocation 100.6 ° 1.608 ? 1.431 ? + Bonds participating in the hyperconjugative interaction, e.g C–R, will be lengthened while the C(+)–C bond will be shortened. The Adamantane Reference(MM-2) 110 ° 1.530 ? 1.528 ? + Carbocations: Structure 1.508 ? 1.342 ? Me Me Me F [F 5Sb–F–SbF5]– F Me Me Me SbF5 Me Me Me C F5Sb F SbF5 2 SbF5 C MeMeMe F5Sb F SbF5 D. A. Evans, K. Scheidt Chem 206 + T. Laube, Angew. Chem. Int. Ed. 1986, 25, 349 98.2 °1.621 ? 1.466 ? + 1.551 ? 1.608 ? 1.622 ? 1.421 ? T. Laube, JACS 1993, 115, 7240 C–C1: 1.439 ? C–C2: 1.446 ? C–C3: 1.442 ? + – –+ 1.439 ? reference structure:CSP3–Csp2 bond length Carbocations: Structure 1.508 ? 1.342 ? 1.505 ? Cl Cl Cl SbF5 Cl Cl Cl Cl SbClF5– F Me Ph Me SbF5 C PhMeMe SbF6– D. A. Evans, K. Scheidt Chem 206 + + + + + T. Laube, JACS 1993, 115, 7240 1.408 ? 1.491 ? 1.432 ? 1.371 ? 122 ° + 1.446 ? 1.439 ? 1.442 ? 121.0 ° 121.2 ° 117.8 ° + 1.432 ? 1.422 ? 1.725 ? 1.668 ? reference structure:CSP 3–Csp2 bond length reference structure:CSP 2–Csp2 bond length Carbocations: Structure C C C C C C ⊕ ⊕ Me Me Me H Me Me Me Ph Cl AgSbF6 Me H Me Me Me F [F5Sb–F–SbF5]– 2 SbF5 C Me Me Ph F5Sb F SbF5 D. A. Evans, K. Scheidt Chem 206Carbonium Ion X-ray Structures: Bridged Carbocations – 1.467 ? + 1.855 ? 1.503 ? 1.495 ? T. Laube, JACS 1989, 111, 9224 + 1.467 ? 1.442 ? 1.739 ?**2.092 ? + + T. Laube, Angew. Chem. Int. Ed. 1987, 26, 560 **One of the longest documented C–C bond lengths. hyperconjugationno bridging unsymmetrical bridging D. A. Evans, K. Scheidt Chem 206Carbonium Ion X-ray Structures: A Summary 1.467 ? 1.855 ? 1.503 ? 1.495 ? 1.467 ? 1.442 ? 1.739 ?2.092 ? + + + 1.408 ? 1.432 ?1.371 ? 1.446 ? 1.439 ? 1.442 ? + 98.2 °1.621 ? 1.466 ? + 1.551 ? 1.608 ? 1.622 ? 1.421 ? 1.432 ? 1.422 ? 1.725 ? 1.668 ? Cl Cl + 1.508 ? 1.342 ? (ref 1.513 ?)Ph–C(Me)=CH2 1.491 ? C C C ⊕ C C C ⊕ C C C ⊕ C C C ⊕ opentrivalent hyperconjugationno bridging unsymmetrical bridging symmetrical bridging classical nonclassical increasing nonclassical character Nomenclature: classical vs nonclassical OTf D R OTf R H+ H3C CH2 H2C CH H2C CH OSolv C CDR R HC C HI ?-HI R R PhCH2–Br Me2CH–Br R R Ph CH2 CH=CH–CH2–Br Me3 C D. A. Evans, B. Breit Chem 206Vinyl & Allyl Carbocations Vinyl & Phenyl Cations: Highly Unstable Evidence suggests that vinyl cations are linear. As ring size decreases, the rate of hydrolysis also diminishes. Implying that the formation of the linear vinyl cation is disfavored due to increasing ring strain. Hyperconjugation P. J. Stang J. Am. Chem Soc. 1971, 93, 1513; P. J. Stang J.C.S. PT II 1977, 1486. A secondary kinetic isotope effect was measured to be KH/KD = 1.5 (quite large) indicating strong hyperconjugation and an orientation of the vacant p orbital as shown above. HOSolv Phenyl Cations The ring geometry opposes rehybridization (top) so the vacant orbital retains sp2 character. Additionally, the empty orbital lies in the nodal plane of the ring, effectively prohibiting conjugative stabilization. 276 287 +21 386 +81 Hydride ion affinities (HI) 287 +11 298 Allyl & Benzyl Carbocations Carbocation Stabilization via pi-delocalization a73 Stabilization by Phenyl-groups The Benzyl cation is as stable as a t-Butylcation. This is shown in the subsequent isodesmic equations: (CH3)3C + PhCH3 (CH3)3CH + PhCH2 ?H0r [kcal/mol] 3.8 (CH3)3C + PhCH2Cl (CH3)3CCl + PhCH2 - 0.8 allyl cation 239 Hydride ion affinities (HI) 231 –8 Hydride ion affinities versus Rates of Solvolysis Relative Solvolysis rates in 80% EtOH, 80 °C 100 0.7 52 0 +10 +17 239 249 256 A. Streitwieser, Solvolytic Displacement Reactions, p75 H Me Me C R O R X Me Me Me OTs Me Me OTs OTs TsO X OTs OTs TsO Cl Cl TsO X H H D. A. Evans, B. Breit Chem 206Cyclopropyl-carbinyl Carbocations Carbocation Stabilization via Cyclopropylgroups A rotational barrier of about 13.7 kcal/mol is observed in following example: NMR in super acids δ(CH3) = 2.6 and 3.2 ppm R. F. Childs, JACS 1986, 108, 1692 1.464 ? 1.409 ? 1.534 ? 1.541 ? 1.444 ? 24 ° 1.302 ? 1.222 ? 1.474 ? 1.517 ? 1.478 ? X-ray Structures support this orientation Carbocation Stabilization - Aromaticity Some Hückel aromatic cations (4n+2) pi-electrons are isolable as salts with non-nucleophilic anions. Solvolysis rates represent the extend of that cyclopropyl orbital overlap contributing to the stabiliziation of the carbenium ion which is involved as a reactive intermediate: krel = 1 krel = 1 krel = 106 krel = 10-3 krel = 1 krel = 108 + = BF4, SbCl6 ++ ++ generated in SbF5-SO3 in SbF5-SO2ClFstable, isolable salts Bridgehead Carbocations 1 10-7 10-13 104 Bridgehead carbocations are highly disfavored due to a strain increase in achieving planarity. Systems with the greatest strain increase upon passing from ground state to transition state react slowest. why so reactive? See Lecture 5, slide 5-05 for discussion of Walsh orbitals OMe OMeCO2Me Me3O+BF4– O OC OMeMeOMe Me B2F7– D. A. Evans, J.Tedrow Chem 206A Stable Hypervalent Carbon Compound ? + 2.428 ? 2.452 ? 1.483 ? 2.428 ? 2.452 ? + + "The relevant C–O distances are longer than a covalent C–O bond (1.43 ?) but shorter than the sum of the van der Waals radii (3.25 ?)." "The Synthesis and Isolation of Stable Hypervalent Carbon Compound (10-C-5) Bearing a 1,8-Dimethoxyanthrecene Ligand" Akibe, et al. JACS 1999, 121, 10644-10645 For a recent monograph on hypervalent Compounds see:"Chemistry of Hypervalent Compounds", K. Akiba, Wiley-VGH, 1999 C CH C CH2 C RR C RR Fe Ph Ph Fe CF3CO2H Fe Fe Fe R OH R' R'' C C Co(CO)3(OC)3Co R R R D. A. Evans, J.Tedrow Chem 206Transition Metal-Stablized Carbocations-1 a73 Transition metal not bound directly to carbenium ion: Ferrocenes Carbocation Stabilization - d( ) stabilization via Transition metal Fragments stable in CF3COOH + 1.412 ? 1.389 ? 1.428 ? 1+ an important resonance contribution J. Lukasser, etal. Organometallics 1995, 14, 5566-5578 1.385 ? 1.391 ? 1.376 ? + 1.297 ? 1.509 ? CyclopropeneMM 2 1) Co2(CO)8 2) HX isolable, basis of the Nicholas reaction a73 Transition metal not bound directly to carbenium ion: Colbalt-Acetylenes R. L. Sime, etal. JACS 1974, 96, 892 See Houk etal. JACS 1999, 121, 3596-3606 Ph Ph OAc R OAc OAc– H R PdL L S P C1 C2 Nu Ph Ph Nu C1 CHMe2 Me O S CMe 3 P Ph Pd Ph PhPh H H C2 R Nu CHMe2 MeO S R Ar2P AcO BocN OCO2Et OAc OAc C1 CHMe2 Me O S CMe 3 PPh Pd Ph C2 Nu BocN Nu Nu Nu C1 C2 Nu CHMe2 MeO S CMe3 Ar2P D. A. Evans, J. Tedrow Chem 206Transition Metal-Stablized Carbocations-Pd Catalysis Transition metals bound to carbenium ions: –Allyl Pd(II) Complexes Carbocation Stabilization - d( ) stabilization via Transition metal Fragments L4Pd(0) 1+ Nu Nu, CH2Cl2, –20 °C 2 mol% [C3H5-PdCl]2, 1 Nu = CH(CO2Me)2 Nu = BnNH 1a Ar = Ph 1b, Ar = α-naphthyl Nu = CH(CO2Me)2 94% ee 91% ee 94% ee 91% ee 96% ee 97% ee 94% ee 94% ee conditions: 2 mol% [C3H5-PdCl]2, 2b Nu, CH2Cl2, -20 °C Nu, CH2Cl2, -20 °C Nu, CH2Cl2, -20 °C Nu, CH2Cl2, -20 °C Nu = BnNH 1b 98% ee95% ee Selected Bond Lengths: Pd-C1, 2.16?; Pd-C2, 2.28? Pd-P, 2.29 ?; Pd-S, 2.38 ? Pd-C2, 2.28? Selected Bond Lengths: Pd-C1, 2.17?; Pd-C2, 2.26? Pd-P, 2.25 ?; Pd-S, 2.36 ? Pd-C2, 2.26? Pd-C1, 2.17?Evans, Campos,Tedrow, Michael, Gagné, JACS 2000, 122, 7905 inversion inversion 1b Pd-C1, 2.16?