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Nonclassical H H C From Controversy to Convention H H H A Stoltz Group Literature Meeting brought to you by

Chris Gilmore

June 26, 2006 8 PM 147 Noyes Outline

1. Introduction

2. The Nonclassical Controversy - Winstein, Brown, and the Great Debate - George Olah and ending the discussion - Important nonclassical carbocations

3. The Nature of the Nonclassical Carbocation - The 3-center, 2-electron bond - Cleaving C-C and C-H σ−bonds - Intermediate or Transition state? Changing the way we think about carbocations

4. Carbocations, nonclassical intermediates, and synthetic - Biosynthetic Pathways - Steroids, by W.S. Johnson - Corey's foray into carbocationic cascades - Interesting rearrangements - Overman and the Prins-Pinacol Carbocations: An Introduction

Traditional carbocation is a low-valent, trisubstituted electron-deficient center:

R R R LG R R R R R R "carbenium LGH "

- 6 e- - planar structure - empty p orbital

Modes of stabilization:

Heteroatomic Assistance π-bond σ-bond Participation R X H2C X

Allylic Lone Pair Anchimeric Homoconjugation Non-Classical Resonance Assistance Stabilization Interaction Outline

1. Introduction

2. The Nonclassical Carbocation Controversy - Winstein, Brown, and the Great Debate - George Olah and ending the discussion - Important nonclassical carbocations

3. The Nature of the Nonclassical Carbocation - The 3-center, 2-electron bond - Cleaving C-C and C-H σ−bonds - Intermediate or Transition state? Changing the way we think about carbocations

4. Carbocations, nonclassical intermediates, and synthetic chemistry - Biosynthetic Pathways - Steroids, by W.S. Johnson - Corey's foray into carbocationic cascades - Interesting rearrangements - Overman and the Prins-Pinacol The Nonclassical Problem: Early Curiosities

Wagner, 1899: 1,2 shift OH H

- H+

Meerwein, 1922:

1,2 shift

OH

Meerwin, H. Chem. Ber. 1922, 55B, 2500. Ruzicka, 1918: Nuc

Nuc OH Nuc

Ruzicka, L. Helv. Chim. Acta, 1918, 1, 110. The Nonclassical Problem: An Indecent Proposal

Winstein and Trifan, 1949

Rates of

aqueous solvent aqueous solvent

OBs OBs 350 1

O O S Br O

= OBs

Winstein, Trifan. J. Am. Chem. Soc., 1949, 71, 2953. The Nonclassical Problem: An Indecent Proposal

Winstein and Trifan, 1949

Rates of solvolysis

aqueous solvent aqueous solvent

OBs OBs 350 1

Enantiomerically pure starting material...

7 7 5 3 Acetone, H2O OAc 4 5 3 2 6 OBs KOAc 1 2 1 6 OAc

3 O 6 4 5 O S Br 7 2 6 O AcO 1 = OBs 2 1 1:1 Mixture of enantiomers OAc

Winstein, Trifan. J. Am. Chem. Soc., 1949, 71, 2953. The Nonclassical Problem: An Indecent Proposal Winstein and Trifan, 1949

Rates of solvolysis

aqueous solvent aqueous solvent

OBs OBs 350 1 Enantiomerically pure starting material... 7

5 3 7 6 2 OBs Acetone, H2O OAc 4 1 5 3 KOAc 1 2 6 OAc

O 3 6 O S Br 4 7 5 O AcO 2 6 1 = OBs 2 1

1:1 Mixture of enantiomers OAc Winstein, Trifan. J. Am. Chem. Soc., 1949, 71, 2953. The Nonclassical Problem: An Indecent Proposal

HOAc OAc

OBs OAc

aqueous solvent aqueous solvent

OBs OBs 350 1

"It is attractive to account for these results by way of the bridged (nonclassical) formulation for the norbornyl cation involving accelerated rate of formation from the exo precursor by anchimeric assistance." -Saul Winstein The Nonclassical Problem: An Indecent Proposal

HOAc OAc

OBs OAc

aqueous solvent aqueous solvent

OBs OBs 350 1

"It is attractive to account for these results by way of the bridged (nonclassical) formulation for the norbornyl cation involving accelerated rate of formation from the exo precursor by anchimeric assistance." -Saul Winstein The Response of the Traditionalists- H. C. Brown

Strain release improves exo to endo ratio:

OBs OBs OBs PNB Exo/Endo 350 13 78

Not only must strain have some impact, but direct ionization hinders rate of solvolysis of endo norbornyl system.

exo endo

H LG H H

H H H LG Solvolysis proceeds through unassisted ionization: - relief of strain accelerates endo ionization - steric effects hinder ionization of endo isomer - exo is not fast, endo is slow

Brown, H.C. J. Am. Chem. Soc. 1964, 86, 1248-1250. A Bonding Experience- Brown's Challenge

Brown insisted upon two stable, equilibrating classical carbocaitonic forms for the norbornyl cation:

"The norbornyl cation does not possess sufficient electrons to provide a pair for all of the bonds required by the proposed bridged structures. One must propose a new bonding concept, not yet established in carbon structures." - H. C. Brown, 1965 A Bonding Experience- Brown's Challenge

Brown insisted upon two stable, equilibrating classical carbocaitonic forms for the norbornyl cation:

"The norbornyl cation does not possess sufficient electrons to provide a pair for all of the bonds required by the proposed bridged structures. One must propose a new bonding concept, not yet established in carbon structures." - H. C. Brown, 1965

So, if not classical carbenium , what must nonclassical carbocations be?

R R - a pentavalent carbon - distinct 3-center, 2-electron bond - 8 valence e- between 6 R R R means electron-poor carbon ""

Brown, H. C. J. Am. Chem. Soc. 1965, 87, 2137-2153. P.D. Bartlett, Nonclassical Ions, W.A. Benjamin, New York, 1965. A Bonding Experience- Brown's Challenge

Brown insisted upon two stable, equilibrating classical carbocaitonic forms for the norbornyl cation:

"The norbornyl cation does not possess sufficient electrons to provide a pair for all of the bonds required by the proposed bridged structures. One must propose a new bonding concept, not yet established in carbon structures." - H. C. Brown, 1965

So, if not classical carbenium ions, what must nonclassical carbocations be?

R H H H isoelectronic R - a pentavalent carbon B B - distinct 3-center, 2-electron bond - 8 valence e- between 6 atoms R R H H H R means electron-poor carbon

Contain too few electrons to allow a pair for each "bond"; must have delocalized σ electrons

P.D. Bartlett, Nonclassical Ions, W.A. Benjamin, New York, 1965. Enter George Olah

- Previous work with isolable carbocations possible because of and stable ion media.

- Isolated the first stable carbocation in 1964 and was able to characterize with 13C NMR

Me 13 SbF5 C shift was 300 ppm Me F Me SbF6 downfield from SM! Me Me (335.2 ppm) Me J. Am Chem. Soc. 1964, 86, 1360

- Superacids designed to prevent proton elimination to quench carbocations

H Me Me H Me Me

- pKa's are measured anhydrously by Hammet acidiy function Ho Ho anhydrous sulfuric -11.9 16 perchloric acid -13.0 Superacids can reach acidities of Ho= -28, or 10 times acidity of triflic acid -14.1 anhydrous . magic acid (FSO3H•SbF5) -21.0 Proving the Existence of the Carbonium Ion

1H NMR Studies of Olah, Saunders and Schleyer

SbF5 Broad singlet corresponds 6,2 shift 3,2 shift to fast Wagner-Meerwein F 25 °C and hydride shifts, -3.75 — 7 -3.1 ppm W-M 3 6 1 2

SbF5, SO2 Resolves 3 singlets, 4:1:6 at -5.35, -3.15, -2.20 ppm -60 to -120°C F Shows 2-norbornyl ion stable in solution as equilibrating Wagner-Meerwein shifts OR mesomeric intermediate

Saunders, M.; Schleyer, P.; Olah, G. A. J. Am. Chem. Soc. 1964, 86, 5680. Proving the Existence of the Carbonium Ion

1H NMR Studies of Olah, Saunders and Schleyer

SbF5 Broad singlet corresponds 6,2 shift 3,2 shift to fast Wagner-Meerwein 25 °C F and hydride shifts, -3.75 — 7 -3.1 ppm W-M 3 6 1 2

H H H H H H SbF5, SO2 H H H H 4 (-5.35 ppm) H H F -60 to -120°C H H H H 1 (-3.15 ppm) H H H H H H 6 (-2.20 ppm)

Saunders, M.; Schleyer, P.; Olah, G. A. J. Am. Chem. Soc. 1964, 86, 5680. Proving the Existence of the Carbonium Ion

7 1H spectra at low temps 5 3 6 2 1

A 1,2,6 4 3,5,7 SbF5, SO2

F -100 °C

3,5

1,2 6 4 7

B SbF5, SO2

F -157 °C

Olah, G. A. J. Am. Chem. Soc. 1982, 104, 7105. Proving the Existence of the Carbonium Ion

7

13 C spectra at low temps 5 3 6 2 1 1,2,6 4 3,5,7 A

SbF5, SO2

F -80 °C

1,2 4

B

3,5 SbF5, SO2 7,6 F -158 °C

Olah, G. A. J. Am. Chem. Soc. 1982, 104, 7105. Proving the Existence of the Carbonium Ion Core Electron Spectroscopy for Chemical Analysis (ESCA) - Exploits photoelectric effect to measure ion affinity for electrons. - Trivalent classical carbocation shows charge localization on 1 increases e- binding energy by ~5eV - Timescale is ~ 1018 Hz, much faster than NMR and Wagner-Meerwein shifts Δ eV

Me Me Me Δ eV = 3.4

Δ eV = 4.2 - 4.3

H

Δ eV Δ eV = 3.7

Me

Olah, G. A.; Mateescu, L. A. J. Am. Chem. Soc. 1970, 92, 7231. Olah, G. A.; Mateescu, L. A. J. Am. Chem. Soc. 1972, 94, 2529. Proving the Existence of the Carbonium Ion

Core Electron Spectroscopy for Chemical Analysis (ESCA) - Exploits photoelectric effect to measure ion affinity for electrons. - Trivalent classical carbocation shows charge localization on 1 atom increases e- binding energy by ~5eV - Timescale is ~ 1018 Hz, much faster than NMR and Wagner-Meerwein shifts Δ eV

Me Me Me Δ eV = 3.4

Δ eV = 4.2 - 4.3

H Δ eV

Me

Δ eV = 1.7

Olah, G. A.; Mateescu, L. A. J. Am. Chem. Soc. 1970, 92, 7231. Olah, G. A.; Mateescu, L. A. J. Am. Chem. Soc. 1972, 94, 2529. Closing the Debate

7 5 3 vs. 6 2 1

13 Solid-state C NMR studies at 5 K Isolated crystals allowed x-ray determination of ion's structure: Me Me

Me 1.442 Å Calculations reveal 1.739 Å that Wagner-Meerwein 2.092 Å 1.467 Å shifts would require a Me barrier of 0.2 kcal/mol 5 and occur at 10 Hz to Laube, T. Angew. Chem. Int. Ed. Engl. 1987, 26, 560 avoid resolution at 5 K, setting migration equal to a vibrational transition For an excellent review of the nonclassical ion controversy:

- Olah, G. A.; Prakash, G. K. S.; Saunders, M. Acc. Chem. Res. 1983, 16, 440-449. - Olah, G. A. Angew. Chem. Int. Ed. Engl. 1995, 34, 1393- 1405

Yannoni, C. S.; Myhre, P. C. J. Am. Chem. Soc. 1982, 104, 7381-7383 Other Important Nonclassical Carbocations

H H C H H H methonium

H H - Parent for all nonclassical carbocations. H H C H C - 8 Valence electrons rendered deficient by electron pair H H H sharing between 3 atoms H H trigonal C Geometry: bipyramidal s H - initially suggested trigonal bipyramidal structure H - Ab initio calculations postulated C symmetry (as shown) C s H H - Low bond-bond proton migration barriers lend to completely H delocalized theory of bonding delocalized

H H H H H H+ H H H H C C H H H H H H H H H H

Olah, G. A.; Klopman, G. J. Am. Chem. Soc. 1969, 91, 3261 Other Important Nonclassical Carbocations

H H C H H H cyclopropylcarbinyl OH Studies by Roberts in 1951: 48%

EtOH, Cl OH H2O 47%

unsymmetrical stabilization 5%

OH

Roberts, J.D.; et. al. J. Am. Che. Soc. 1951, 73, 3542. Other Important Nonclassical Carbocations

H H C H H H cyclopropylcarbinyl OH Studies by Roberts in 1951: 48%

EtOH, Cl OH H2O 47%

unsymmetrical stabilization 5% Schleyer's Solvolytic Studies and Structural Revision in 1966: OH

OH DNB krel = 1

DNB OH Me krel = 11 Me

DNB OH R R R R Me krel = 82 Me Me Me symmetrical stabilization DNB OH Me krel = 490 Me Me Me Schleyer, P. v. R. J. Am. Chem. Soc. 1966, 88, 2321. Me Me Other Important Nonclassical Carbocations

H H C H H H 7-norbornenyl Solvolytic studies by Winstein (JACS 1956, 78, 592) TsO AcO HOAc 11 k2/k1 = 10 k1 Norbornene Solvolysis occurs with complete TsO AcO HOAc retention of stereo- chemistry! k2 Other Important Nonclassical Carbocations

H H C H H H 7-norbornenyl Solvolytic studies by Winstein (JACS 1956, 78, 592) TsO AcO HOAc 11 k2/k1 = 10 k1 Norbornene Solvolysis occurs with complete TsO AcO HOAc retention of stereo- chemistry! k2

1H NMR study of norbornadienyl model system proved nonequivalence of protons in norbornenyl cation

2,3 @ 2.54 ppm, 5,6 @ 3.90 ppm 5 3 6 2 Winstein, S.; Brookhart, M. J. Am. Chem. Soc. 1972, 94, 2347. Other Important Nonclassical Carbocations

H H C H H H

phenonium ion Aromatic group participation

Walden Inversion:

Ph HOAc Ph Ph OTs OAc OAc

1 1

racemization

Me Me H Me Me H H H

Cram, D. D. J. Am. Chem. Soc. 1949, 71, 3183 Other Important Nonclassical Carbocations

H H C H H H

cyclopropyl assistance Properties of Cyclopropane are similar to an olefin:

~ ~ Other Important Nonclassical Carbocations

H H C H H H

cyclopropyl Problem solved by solvolysis assistance k OBs OAc rel HOAc 1

OBs OAc HOAc 1014

OBs OAc HOAc 0.333

BsO OAc HOAc 5

Tsuji, et. al. J. Am. Chem. Soc. 1967, 89, 1953.; Wells, et. al. Tetrahedron, 1966, 22, 2007. Outline

1. Introduction

2. The Nonclassical Carbocation Controversy - Winstein, Brown, and the Great Debate - George Olah and ending the discussion - Important nonclassical carbocations

3. The Nature of the Nonclassical Carbocation - The 3-center, 2-electron bond - Cleaving C-C and C-H σ−bonds - Intermediate or Transition state? Changing the way we think about carbocations

4. Carbocations, nonclassical intermediates, and synthetic chemistry - Biosynthetic Pathways - Steroids, by W.S. Johnson - Corey's foray into carbocationic cascades - Interesting rearrangements - Overman and the Prins-Pinacol The 3-Center, 2-electron Bond

Diborane and the stable 3-center 2-electron bond.

H H H H H H B B B B H H H H BR3 H H

R2B H - Borane dimers consist of two 3-center 2-electron bonds - Delocalized electron-poor region at center of dimer

Electon-poor carbon analogs: π-bond donors

Postulated first by DeWar in 1945 as π-complex Cationic π−complexes and MO theory

E+ + + E+ E E R C CR 2 2 R2C CR2 Protonating an

Much less nucleophilic than π-bonds, σ C-C and C-H bonds donate as well: CH4 H+ H H H HF-SbF5 H Me3C CH3 Me C CH 3 2 Me3C CH2 Me3C CH3 Me Me Me

Calculated Protonolysis Activation Calculated C-C Cracking Activation . . Barriers (Sb2F11 HF2 @ 298K) Barriers (Sb2F11 HF2 @ 298K) o Alkane ΔH (kcal/mol) H H Alkane Ho (kcal/mol) 2 Me3C Δ CH4 21.0 H C2H6 35.0 C2H6 19.3 C3H8 30.0 ∗ 19.3 * 18.7 28.7

19.9 ∗

* 18.3

Mota, et. al. J. Phys. Chem. B 2001, 105, 4331. Ramsden Tetrahedron 2004, 60, 3293. Olah, et al. Angew. Chem. Int. Ed. Eng. 1973, 12, 173. Protonating an Alkane

Much less nucleophilic than π-bonds, σ C-C and C-H bonds donate as well:

Linear or bridged transition state in σ protonation?

Olah vs. Hogeveen R A H H R R R R H H+ H R R R R B H R

R H R

Olah, 1971 R R R + Me + H D2, H Me D2, H H D R Me R R R A B R R

Olah's general order of alkane σ−bond reactivity: H H H H

> R3C CR3 > > > R H H H R R R R R H H H

Olah, et al. J. Am. Chem. Soc. 1971, 93, 1251. Hogeveen, et al. Recl. Trav. Chim. Pays-Bas. 1969, 88, 703. Olah, et al. Angew. Chem. Int. Ed. Eng. 1973, 12, 173. Leveling the Field

The 3-center, 2-electron bond changes how all carbocations are precieved

Ethyl cation: hyperconjugation or hypervalence?

H H - Carbenium ions are prone to rearrangement H vs. H H - Rapid scrambling of 5 H's in ethyl cation indicative H H H H H of some delocalized intermediate

- Hydride shifts in such cations are illustrative of the low energy barriers between cabenium and carbonium ions H H Me vs. H Me - Carbonium intermediate is calculated as favorable for H Me all but most stabilized carbocations H H Me Leveling the Field

The 3-center, 2-electron bond changes how all carbocations are precieved

Ethyl cation: hyperconjugation or hypervalence?

H H - Carbenium ions are prone to rearrangement H vs. H H - Rapid scrambling of 5 H's in ethyl cation indicative H H H H H of some delocalized intermediate

- Hydride shifts in such cations are illustrative of the low energy barriers between cabenium and carbonium ions H H Me vs. H Me - Carbonium intermediate is calculated as favorable for H Me all but most stabilized carbocations H H Me Leveling the Field

The 3-center, 2-electron bond changes how all carbocations are precieved

Ethyl cation: hyperconjugation or hypervalence?

H H - Carbenium ions are prone to rearrangement H vs. H H - Rapid scrambling of 5 H's in ethyl cation indicative H H H H H of some delocalized intermediate

- Hydride shifts in such cations are illustrative of the low energy barriers between cabenium and carbonium ions H H Me vs. H Me - Carbonium intermediate is calculated as favorable for H Me all but most stabilized carbocations H H Me Leveling the Field

The 3-center, 2-electron bond changes how all carbocations are precieved

Ethyl cation: hyperconjugation or hypervalence?

H H - Carbenium ions are prone to rearrangement H vs. H H - Rapid scrambling of 5 H's in ethyl cation indicative H H H H H of some delocalized intermediate

- Hydride shifts in such cations are illustrative of the low energy barriers between cabenium and carbonium ions H H Me vs. - Carbonium intermediate is calculated as favorable for H Me H Me all but most stabilized carbocations H H Me

Wagner-Meerwein shifts and isomerization

H H - 1 13C NMR Shift at -139 °C H - Rearrangements occur ~ 3.1 x 107 Hz A Whole New Ballgame...

Delocalized intermediates also participate in assisting departure

Nuc Prins-Pinacol reaction intermediate resembles a momentarily delocalized cation: OH

O

O O OH LA LA

Nuc

Many of the carbocationic rearrangements basic to organic chemistry can be associated with nonclassical carbocationic intermediates. Outline

1. Introduction

2. The Nonclassical Carbocation Controversy - Winstein, Brown, and the Great Debate - George Olah and ending the discussion - Important nonclassical carbocations

3. The Nature of the Nonclassical Carbocation - The 3-center, 2-electron bond - Cleaving C-C and C-H σ−bonds - Intermediate or Transition state? Changing the way we think about carbocations

4. Carbocations, nonclassical intermediates, and synthetic chemistry - Biosynthetic Pathways - Steroids, by W.S. Johnson - Corey's foray into carbocationic cascades - Interesting rearrangements - Overman and the Prins-Pinacol Carbocationic Cascades- Biosynthesis

- isolated from streptomyces OPP - precursor to pentalenolactone antibiotics farnesyl diphosphate

pentalenene

H H 1,2 shift

H H

H H 1,2 shift H - H+ H H H H

H H

H

H

H

Tantillo J. Am. Chem. Soc. 2006, 128, 6172. Carbocationic Cascades- Biosynthesis

OPP farnesyl diphosphate

H

H humulene

H H

H H H Δ6- protoilludene

H H

Tantillo J. Am. Chem. Soc. 2006, 128, 6172. H H H asteriscadiene W.S. Johnson's Approach to Steroid Skeletons

O

TFA, nitroethane O N Johnson, W. S.; et. al. -78°C, 15 min H Journ. Am. Chem. Soc. HO 1973, 95, 4417. 80% yield H H

O

TFA, TFE -100 °C Johnson, W. S.; et. al. Journ. Am. Chem. Soc. 1976, 98, 1038. 66% yield H H

OH OH

SnCl4, DCM 30 min, -100 °C H Johnson, W. S.; et. al. Journ. Am. Chem. Soc. 1973, 95, 7501. 59% yield H H HO HO W.S. Johnson's Approach to Steroid Skeletons

O

TFA, nitroethane O N Johnson, W. S.; et. al. -78°C, 15 min H Journ. Am. Chem. Soc. 1973, 95, 4417. 80% yield H H

O

TFA, TFE -100 °C Johnson, W. S.; et. al. Journ. Am. Chem. Soc. 1976, 98, 1038. 66% yield H H

SnCl4, DCM 30 min, -100 °C H Johnson, W. S.; et. al. Journ. Am. Chem. Soc. 1973, 95, 7501. 59% yield H H HO HO Carbocationic Cascades- Corey and Oleananes

O MeO MeAlCl3 AlMeCl2 -78 °C O O

PhCOCl DMAP H H HO BzO H BzO H

(+) β-amyrin R= CH3 R (+) erthrodiol R= CH2OH (+) oleanolic acid R= COOH H HO H

Corey, E.J J. Am. Chem. Soc. 1993, 115, 8873-8874 Some other unique rearrangements

H

MeAlCl2 -95 °C O Ph Ph HO 50% yield

H Me H Cl MeAl Ph H H 2 O O Cl MeAl O 2 Cl2MeAl Ph Ph H Me H

Me Me Me Me Cl2MeAl Ph Cl2MeAl Ph Cl2MeAl Ph Me O O O Me

H H H H H H H H H H H

Me H Cl2MeAl Ph Me O

H H Ph H HO

Corey, E. J.; Roberts, B.E. Tetrahedron Lett. 1997, 38, 8921. Some other unique rearrangements

R R N N RO RO

O H O HO O O DAST O O F

O O O O O O

O R O R O O

Et

N SF3 Et

Lartey, et. al. J. Org. Chem. 1996, 61, 5153. Some other unique rearrangements

R R N N RO RO

O H O HO O O DAST O O F

O O O O O O

O R O R O O

Et F F F N S O O O Et Et Et F N S O O N S O O Et F Et F O O

O Lartey, et. al. J. Org. Chem. 1996, 61, 5153. Cationic Cascade to Longifolene

HO TFA, Et2O 0 °C, 3 min

K2CO3 workup O HO 76% yield longifolene

H+

HO H+

K2CO3 HO

Johnson, W. S., et. al. J. Am. Chem. Soc. 1975, 97, 4777. Tantillo, D. J., et al. J. Org. Chem. 2005, 70, 5139. Larry Overman and the Prins-Pinacol N H O H H OH Me H (—)-magellanine H TIPSO H O H SnCl4 H -78 °C OH O H 57% yield H O O

Overman, L. E. J. Am. Chem. Soc. 1993, 115, 2992. Larry Overman and the Prins-Pinacol N H O H H OH Me H (—)-magellanine H TIPSO H O H SnCl4 H -78 °C OH O H 57% yield H O O

Me Me Me Me O O O O

TIPSO TIPSO TIPSO O

Overman, L. E. J. Am. Chem. Soc. 1993, 115, 2992. Larry Overman and the Prins-Pinacol AcO O

H O H OAc

H

shahamin K

O O OTMS DMTSF H H SPh SPh O -45 °C to 0 °C SPh Me Me 80% yield H H

Overman, L.E. J. Am. Chem. Soc. 2001, 123, 4851 Larry Overman and the Prins-Pinacol AcO O

H O H OAc

H

shahamin K

O O OTMS DMTSF H H SPh SPh O -45 °C to 0 °C SPh Me Me 80% yield H H

OTMS OTMS Me Me

Me Me H SPh H SPh

Overman, L.E. J. Am. Chem. Soc. 2001, 123, 4851 Summary and Parting Thoughts

- The nonclassical carbocation controversy opened the realm of physical organic chemistry, established the idea of delocalized, electron-poor bonding in intermediates and transition states for organic reactions, and encouraged an intense debate that has led to the affirmation of many instrumental and experimental techniques used today

- The 3-center, 2-electron bond is prevalent in carbocation chemistry, often as a stable intermediate or transition state, and sometimes as a stable molecule itself

- Carbocation chemistry and its variants have found an effective place in synthesis, but there exists a large gap in controlled carbocationic methodology that has only recently been explored.

Thanks to JT for the Carbocation book and Meyer for helpful advice