Chem 206D. A. Evans Carbocations: Stability & Structure

Other Relevant Background Reading

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.

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

D. A. EvansMondayDecember 11, 2006

Reading Assignment for this Lecture:

Chemistry 206

Advanced Organic Chemistry

Lecture Number 33

Introduction to Carbonium Ions

! Carbocation Stabilization

! Carbocation Structures by X-ray Crystallography

! Vinyl & Allyl Carbonium Ions

Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part A Chapter 5, "Nucleophilic Substitution", 263-350 .

Laube (1995). “X-Ray Crystal Structures of Carbocations Stabilized by Bridging or Hyperconjugation.” Acc. Chem. Res.1995, 28,: 399 (electronic pdf)

Olah, G. A. (2001). “100 Years of Carbocations and their Significance in Chemistry.” J. Org. Chem. 2001, 66, 5944-5957. (handout)

Walling, C. (1983). “An Innocent Bystander Looks at the 2-Norbornyl Cation.” Acc. Chem. Res. 1983, 16, 448. (handout)

Birladeanu, L. (2000). "The Story of the Wagner-Meerwein Rearrangement.” J. Chem. Ed. 2000, 77, 858. (handout)

http://www.courses.fas.harvard.edu/colgsas/1063

Problem 17: The reaction illustrated below was recently reported by Snider and co-workers (Org. Lett. 2001, 123, 569-572). Provide a mechanism for this transformation. Wherestereochemical issues are present, provide clear three dimensional drawings to supportyour answer.

Me

O

Me Me

R EtAlCl2

CH2Cl2, 0 °C

Me

O

Me

R

Me

Carey & Sundberg-A, p 337: Provide mechanisms for the following reactions.

OH

NH2 NaNO2

HOAc/H2O

CHO

OH

NH2 NaNO2

HOAc/H2O

CMe3

O

CMe3

The Gathering at The Gathering at JDRJDR’’s s 70th70th Birthday CelebrationBirthday Celebration19881988

DervanDervan, Ireland, Evans, Bergman, Grubbs, JDR, Myers, Dougherty, Hammond, Ireland, Evans, Bergman, Grubbs, JDR, Myers, Dougherty, HammondRecent organic faculty at CIT, present and departedRecent organic faculty at CIT, present and departed

Chem 206D. A. Evans John D. Roberts, Institute Professor of Chemistry, Emeritus, Caltech

B.A., 1941, University of California (Los Angeles)Ph.D. 1944, University of California (Los Angeles)

John D. Roberts was born in 1918.

He became Prof. at MIT and then Prof. at Caltech where he is still active. His work has been centered on mechanisms of organic reactions.

One of the joys of being a professor is when an exceptional student comes along and wants to work

with you.

J.D. Roberts, The Right Place at the Right Time. p. 63.

John D. Roberts graduated from the University of California at Los Angeles where he had received A. B. (hons) degree in 1941 and the Ph. D. degree in 1944. In 1945-1946 he was a National Research Council Fellow and Instructor at Harvard. Later on, he went to MIT in 1946 as an Instructor. He had introduced the terms "nonclassical" carbocations and "benzyne" into organic chemistry. He had won numerous awards; he is a member of the National Academy of Sciences (1956) and the American Philosophical Society (1974). He received the Welch Award (1990, with W. E. Doering), the National Medal of Science (1990), and the ACS Arthur C. Cope Award (1994). Since 1939 his research has been concerned with the mechanisms of organic reactions and the chemistry of small-ring compounds. His current work involves applications of nuclear magnetic resonance spectroscopy to physical organic chemistry.

Roberts made major research and pedagogic contributions to mechanisticorganic chemistry. He pioneered the use of 14C and other isotopic labels tofollow molecular rearrangements as, for example, in the complex and subtle solvolysis of cyclopropyl-carbinyl systems. He introduced the terms"nonclassical" carbocations and "benzyne" into organic chemistry, and usedisotopic labeling to establish the intermediacy of each. Roberts was early torecognize NMR's potential, and used 1H NMR to study nitrogen inversion,long-range spin-spin coupling and conformational isomerism, and later 13Cand 15N NMR to study other reactions, including the active sites of certainenzymes. Roberts' superb short books on "Nuclear Magnetic Resonance"(1959), "Spin-Spin Splitting in High Resolution NMR" (1961) and "Notes onMolecular Orbital Calculations" (1961) did much to popularize and clarifythese subjects for organic chemists. His highly successful text "BasicPrinciples of Organic Chemistry" (1964), written with Marjorie Caserio,introduced spectroscopy early to undergraduates. Roberts received manyawards, including the Roger Adams (1967) and Priestley (1987) Medals. Anexcellent photographer, Roberts graciously supplied several of thephotographs for the MSU collection.

D. A. Evans. B. Breit Chem 206Carbocations: Stability

Carbocation Subclasses

R3 R2

R1

!

R–R3 = alkyl or aryl

R3 R2

O!

R–R3 = alkyl or aryl

R1

R3 R2

N!

R–R3 = alkyl or aryl

R R

Carbon-substituted Heteroatom–stabilized

The following discussion will focus on carbocations unsubstitutred with heteroatoms

C C

C!

C C

C!

C C

C

!C C

C

!

opentrivalent

hyperconjugationno bridging

unsymmetrical bridging

symmetrical bridging

classical nonclassical

increasing nonclassical character

Classical vs nonclassical carbonium ions

Stability: Stabilization via alkyl substituents (hyperconjugation)

R

R

R

H

R

R

H

H

R

H

H

H

Order of carbocation stability: 3˚>2˚>1˚

>> > Due to increasing number of substituents capable of hyperconjugation

C C+H

314

276

249

231

287

386

239

Hydride ion affinities

The relative stabilities of various carbocations can be measured in the gas phase by theiraffinity for hydride ion.

J. Beauchamp, J. Am. Chem. Soc. 1984, 106, 3917.

+ H

Note: As S-character increases, cation stability decreases due to more electronegative carbon.

+ HI

!HI increases " C(+) stability decreases

Hydride Affinity = –!G°

Carey & Sundberg–A, pp 276-

C C C C

CH3+

CH3CH2+

(CH3)2CH+

(CH3)3C+

H2C=CH+

PhCH2+

R R–H

Me CH2

276 249

–27

231

–18Me2 CH Me3 C

Hydride ion affinities (HI)

H3C CH2

276

H2C CH

287

+21

HC C

386

+81

Ph CH2

239 276

–37 –20Me CH2

256

CH CH2H2C

Me CH2

276 270

–7Me–CH2 CH2

The effect of beta substituents: Rationalize

Hydride ion affinities versus Rates of Solvolysis

PhCH2–Br CH=CH–CH2–Br

Relative Solvolysis rates in 80% EtOH, 80 °C

100 52

0 +17

239 256HI

!-HI

A. Streitwieser, Solvolytic Displacement Reactions, p75

Conclusion: Gas phase stabilities do not always correlate with rates of solvolysis

Me2CH–Br

0.7

+10

249

rel rate

M. Shair, D. Evans Chem 206Carbocation Generation & Stability

Carbocation Stability: The pKR+ value

Definition: R+ + H2O ROH + H+

KR+ =aROH ! aH+

aR+ ! aH2O

a = activity

pKR+ = – log KR+ Carey & Sundberg, A, p 277

(4-MeO-C6H4)3C Ph3C (3-Cl-C6H4)3C Ph2CH

Fe

CH2

Fe

CHPh CHPh

Cr(CO)3

R CPh2

Co2(CO)6

+

H7C3

H7C3

C3H7

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

Carey & Sundberg, A, pp 276-

most stable

least stable

Hydride abstraction from neutral precursors

R3C H + Lewis-Acid

R3C H =

HH

H

RS

RS

H

H

R2N

R2N

H

Hetc.

Lewis-Acid: Ph3C BF4, BF3, PCl5

Carbocation Generation

R3C

H

Removal of an energy-poor anion from a neutral precursor via Lewis Acids

R3C X + LA LA–X

LA: Ag , AlCl3, SnCl4, SbCl5, SbF5, BF3, FeCl3, ZnCl2, PCl3, PCl5, POCl3 ...X: F, Cl, Br, I, OR

R3C +

Acidic dehydratization of secondary and tertiary alcohols

R3C OH- H2O

R: Aryl + other charge stabilizing substituents

X: SO42-, ClO4

-, FSO3-, CF3SO3

-

+ R3C +H–X X

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

+ ...

R3C X R3C + X

Addition of electrophiles to !-systems

R

R

R

R

H R

R

R

R

H chemistry

R RH R

H

R chemistry

Br

H2SO4

Me

O

HC C CH2OH

J.C.S.,CC 1971, 556

Problem 897: Provide a Mechanism of this transformation

D. A. Evans, B. Breit Chem 206Carbocations: Structure

+

C C

R

H

HH

HC

H

HC

H

R

Carbocation Stabilization Through Hyperconjugation

Take linear combination of ! C–R (filled) and C pz-orbital (empty):

! C–R

!" C–R

+

! FMO Description

CH

H

E

! C–R

+

!" C–R

Syn-planar orientation between interacting orbitals

CH

H

D. A. Evans, K. Scheidt Chem 206Carbonium Ion X-ray Structures: Bridged Carbocations

1.467 Å

1.442 Å

1.739 Å**2.092 Å

+

+[F5Sb–F–SbF5]–

T. Laube, Angew. Chem. Int. Ed. 1987, 26, 560

Me

Me

Me

H

MeMe

H

Me

Me

Me

F

**One of the longest documented C–C bond lengths.

C C

C!

C C

C

!

hyperconjugationno bridging

unsymmetrical bridging

2 SbF5

F5Sb F SbF5–

1.467 Å

+

1.855 Å

1.503 Å

1.495 Å

T. Laube, JACS 1989, 111, 9224

Me

Me

Ph Cl

C

Me

Me

Ph

+

AgSbF6

D. A. Evans, K. Scheidt Chem 206Carbonium Ion X-ray Structures: A Summary

1.467 Å

1.855 Å

1.503 Å

1.495 Å

1.467 Å

1.442 Å

1.739 Å2.092 Å

+

+

+

1.408 Å

1.432 Å1.371 Å

1.446 Å

1.439 Å

1.442 Å

+

98.2 °1.621 Å

1.466 Å

+

1.551 Å

1.608 Å

1.622 Å

1.421 Å

1.432 Å

1.422 Å

1.725 Å

1.668 Å

Cl

Cl

+

1.508 Å

1.342 Å

(ref 1.513 Å)Ph–C(Me)=CH2

1.491 Å

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

Chem 30D. A. Evans Chapter 18: Chemistry of Aryl & Vinyl Halides

Me

R

X H CMe

RFavorable

H2C

R

XUnfavorable CC R

H

H

–X–

–X–

Substitution (SN1)

Substitution Reactions

Sp hybridized Carbonis more electronegative

CSp2 Carbonium Ions do exist!

1.221 Å

Si

Si

1.946 Å

Si Si

CMe3

Me

Me Me

Me

Normal CC triple bond lengths are ~1.21 Å

D. A. Evans, B. Breit Chem 206Vinyl & Allyl Carbocations

D

R

OTf

R C CD

RR

OTf OSolv

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

H+

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.

H3C CH2

276

H2C CH

287

+21HC C

386

+81

Hydride ion affinities (HI)

H2C CH

287

+11

298

Allyl & Benzyl Carbocations

R

R

R

R

Carbocation Stabilization via !-delocalization

allyl cation

! Stabilization by Phenyl-groups

The Benzyl cation is approximately as stable as a t-Butylcation.

(CH3)3C + PhCH3 (CH3)3CH + PhCH2

!H0r

[kcal/mol]

3.8

(CH3)3C + PhCH2Cl (CH3)3CCl + PhCH2– 0.8

Ph CH2

239

Hydride ion affinities (HI)

231

Me3 C–8

Hydride ion affinities versus Rates of Solvolysis

PhCH2–Br Me2CH–Br CH=CH–CH2–Br

Relative Solvolysis rates in 80% EtOH, 80 °C

100 0.7 52

0 +10 +17

239 249 256HI

!-HI

A. Streitwieser, Solvolytic Displacement Reactions, p75

D. A. Evans Chem 206The Johnson Longifolene Synthesis

Volkman, Andrews, Johnson, JACS 1975, 97, 4777

The plan ( According to Volkman):

Me Me

Me

CH2

H

Me Me

Me

HO

Me Me

Me

Me Me

Me

Me Me

Me

H

Me Me

Me

H

HO

longfifolene

TFA, K2CO375%

Me Me

Me

HO

Me Me

Me

H

NaBH3CN

ZnBr2

94%

Me Me

CH2

H

H

H+

91%

Me Me

Me

ZnBr2NaBH3CN

longfifolene

steps

Ho, Nouri, Tantillo, JOC 2005, 70, 5139-5143

W. S. Johnson!s total synthesis of the sesquiterpenoid longifolene is a classic example of the power of cationic polycyclizations for constructing complex molecular architectures. Herein we revisit the key polycyclization step of this synthesis using hybrid Hartree-Fock/density functional theory calculations and validate the feasibility of Johnson!s proposed mechanism. We also explore perturbations to the 3-center 2 electron bonding array in a key intermediate that result from changing the polycyclic framework in which it is embedded.

The Cationic Cascade Route to Longifolene

FIGURE 1. Relative energies (kcal/mol) of stationary points for the mechanism shown in Scheme 2 (B3LYP/6-31G(d) zero-point corrected energies in italics, B3LYP/6-31G(d) free energies at 0 °C in bold, and CPCM-B3LYP/6-31G(d) energies in water underlined).

D. A. Evans, B. Breit Chem 206Cyclopropyl-carbinyl & Bridgehead Carbocations

Carbocation Stabilization via Cyclopropylgroups

C

A rotational barrier of about 13.7 kcal/mol is observed in

following example:H

Me

Me NMR in super acids!(CH3) = 2.6 and 3.2 ppm

R. F. Childs, JACS 1986, 108, 1692

1.464 Å

1.409 Å

1.534 Å

1.541 Å

1.444 Å

24 °

1.302 Å

R

O1.222 Å

1.474 Å

1.517 Å

1.478 Å

X-ray Structures support this orientation

See Lecture 5, slide 5-05 for discussion of Walsh orbitals

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:

Me

Me

OTs

OTs

Cl

Cl

krel = 1 krel = 1

krel = 106 krel = 10-3

OTs

OTs

krel = 1

krel = 108

Why??

Carey–A, p 286

Me

Me

Me

OTs

TsO TsO TsO

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?

TsO

why so reactive?

–TsO

D. A. Evans, J.Tedrow Chem 206A Stable Hypervalent Carbon Compound ?

+

2.428 Å

2.452 Å

1.483 Å

2.428 Å

2.452 Å

+

OMe OMeCO2Me

Me3O+BF4– O OC

OMeMeOMe Me

+

B2F7–

"The relevant C–O distances are longer than a covalent C–O bond (1.43 Å) but shorter than the sum of the van der Waals radii (3.25 Å)."

"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