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?