Experimental and theoretical investigation of the enantiomerization of Lithium α-tert-butylsulfonyl carbanion salts and the determination of their structures in solution and in the crystal

FULL PAPER

DOI: 10.1002/ejoc.201000409

Experimental and Theoretical Investigation of the Enantiomerization of

Lithium α-tert-Butylsulfonyl Carbanion Salts and the Determination of Their

Structures in Solution and in the Crystal

Roland Scholz,^[a][‡]Gunther Hellmann,^[a][‡‡]Susanne Rohs,^{[a][‡‡‡]}Gerhard Raabe,^[a]

Jan Runsink,^[a]Diana Özdemir,^{[a][‡‡‡‡]}Olaf Luche,^{[a][‡‡‡‡‡]}Thomas Heß,^{[a][‡‡‡‡‡‡]}

Alexander W. Giesen,^{[a][‡‡‡‡‡‡‡]}Juliana Atodiresei,^[a]Hans J. Lindner,^[b]and

Hans-Joachim Gais*^[a]

Keywords: Carbanions / Chirality / Enantiomerization / Ab initio calculations / Cryoscopy

Dynamic NMR (DNMR) spectroscopy of [R¹C(R²)SO₂R³]Li

(R¹, R²= alkyl, phenyl; R³= Ph, tBu, adamantyl, CEt₃) in

[D₈]THF has shown that the S-tBu, S-adamantyl, and S-CEt₃

derivatives have a significantly higher enantiomerization

barrier than their S-Ph analogues. C_α–S bond rotation is most

likely the rate-determining step of the enantiomerization of

the salts bearing a bulky group at the S atom and two substit-

uents at the C_αatom. Ab initio calculations on [Me(Ph)-

S–O angle and a significantly shortened C_α–S bond. The C_α

atom of [R¹C(R²)SO₂R³]Li·L_n(R¹= Ph; R³= Ph, tBu) is planar,

whereas the C_αatom of [R¹C(R²)SO₂R³]Li·L_n(R¹= R²= alkyl)

is strongly pyramidalized in the case of R³= Ph and most

likely planar for R³= tBu. Ab initio calculations on [MeC-

(Me)SO₂R]^–gave a pyramidalized C_αatom for R = Me and a

nearly planar one for R = CF₃and tBu. The [R¹C(R²)SO₂-

tBu]Li salts were characterized by ¹H, ¹³C, and ⁶Li NMR

SO₂tBu]^–gave information about the two C_α–S rotational bar- spectroscopy. ¹H{¹H} and ⁶Li{¹H} NOE experiments are in ac-

riers, which are dominated by steric effects. Cryoscopy of

[R¹C(R²)SO₂tBu]Li in THF at –108 °C revealed the existence

of monomers and dimers. X-ray crystal structure analysis of

the monomers and dimers of [R¹C(R²)SO₂tBu]Li·L_n(R¹= Me,

Et, tBuCH₂, PhCH₂, tBu; R²= Ph, L = THF, 12-crown-4,

PMDTA) and [R¹C(R²)SO₂Ph]Li·2diglyme [R¹= R²= Me, Et;

R¹–R²= (CH₂)₅] showed them to be O–Li contact ion pairs

(CIPs). The monomers and dimers have a C_α–S conformation

in which the lone-pair orbital at the C_αatom bisects the O–

cordance with the existence of O–Li CIPs. ¹H and ¹³C NMR

spectroscopy of [R¹C(R²)SO₂tBu]Li in [D₈]THF at low tem-

peratures showed equilibrium mixtures of up to five different

species being most likely monomeric and dimeric O–Li CIPs

with different configurations. According to ⁷Li NMR spec-

troscopy, the addition of HMPA to [MeC(Ph)SO₂tBu]Li in

[D₈]THF at low temperatures causes the formation of the sep-

arated ion pair [MeC(Ph)SO₂tBu]Li(HMPA)₄.

Introduction

It is therefore not surprising that their structure and reactiv-

ity have been continuously studied both by experimental^[3–5]

and theoretical^[3k,3q,6]methods. One of the most captivating

structural features of salts I (planar C_αatom) and II (py-

ramidalized C_αatom) bearing two different substituents (R¹

϶ R²) at the C_αatom is the chirality of the carbanion.

Whereas the carbanion of salt I has a stereogenic axis, that

of II has both a stereogenic axis and a stereogenic center.

A decisive factor for the stereogenicity of I and II is the

Lithium α-sulfonyl carbanion salts I and II (Figure 1)

have found wide-spread application in organic synthesis.^[1,2]

[a] Institute of Organic Chemistry, RWTH Aachen University,

Landoltweg 1, 52056 Aachen, Germany

Fax: +49-241-8092665

E-mail: gais@rwth-aachen.de

[b] Clemens-Schöpf-Institut, TU Darmstadt,

Petersenstrasse 22, 64287 Darmstadt, Germany

[‡] Current address: Kelheim Fibres, Regensburger Strasse 109,

93309 Kelheim, Germany

[‡‡] Current address: DSM Nutritional Products Ltd., Wurmisweg

576, 4002 Kaiseraugst, Switzerland

[‡‡‡] Current address: ICG-1: Stratosphäre, Forschungszentrum

Jülich, 52425 Jülich, Germany

[‡‡‡‡] Current address: Lummus Novolen Technology GmbH,

Gottlieb-Daimler-Strasse 8, 68165 Mannheim, Germany

[‡‡‡‡‡] Current address: Lisi Automotive (Beijing) Co Ltd., 28

Linhe Street, Linhe Industrial Development Zone Shunyi

District, Beijing, PRC 101300, P. R. China

[‡‡‡‡‡‡] Current address: Jaspertstrasse 5 H, 60435 Frankfurt,

Germany

[‡‡‡‡‡‡‡] Current address: Merianstrasse 16, 41749 Viersen,

Germany

Figure 1. Chiral lithium α-sulfonyl carbanion salts (priority:

SϾR¹ϾR²).

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.201000409.

Eur. J. Org. Chem. 2010, 4559–4587

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C_α–S conformation of the carbanions in which the lone- tronegative than the CF₃group. Derivatives of I and II that

pair orbital at the C_αatom bisects the O–S–O angle. This carry a bulky alkyl group at the S atom should be much

conformation is generally preferred for steric reasons more reactive towards electrophiles than their S-trifluoro-

and stabilization by negative hyperconjugation (n_C– methyl-substituted analogues because of the reduced stabili-

σ*_SR3).^[3k,3q,6]The chirality of α-sulfonyl carbanions was zation by negative hyperconjugation and electrostatic inter-

first inferred from base-mediated H/D-exchange experi- action. Although the decreased hyperconjugation provided

ments of optically active sulfones, which proceeded with a by the bulky S-alkyl group is expected to lower the C_α–S

high degree of retention of configuration.^[7]Final proof of rotational barrier,^[6h,6j]this effect should be outweighed, at

the chirality of I and II was provided by X-ray crystal struc- least in part, by a higher torsional effect.

ture analysis.^[3]Previous attempts towards an enantioselec-

In this paper we describe the results of an investigation

tive synthesis of S-phenyl-substituted derivatives of I and II into the enantiomerization of lithium α-tert-butylsulfonyl

have been uniformly unsuccessful,^[1j,8]presumably because carbanion salts. It is shown that lithium α-sulfonyl carb-

of fast racemization even at low temperatures (see below). anion salts have a barrier that should allow the attainment

A few enantioselective reactions of magnesium and lithium of derivatives that are configurationally stable at low tem-

α-sulfonyl carbanion salts have been achieved by treatment peratures on the timescale of the synthesis. Therefore the

with electrophiles in the presence of chiral ligands on the structures of lithium S-tert-butylsulfonyl carbanion salts

metal atom.^[6r,9,10]These interesting reactions presumably both in solution and in the crystal form were determined.^[13]

follow dynamic kinetic^[9]and dynamic thermodynamic^[6r]This work was undertaken to provide the basis for a study

resolution pathways. In the course of our structural studies of their enantioselective synthesis, configurational stability,

of α-sulfonyl carbanions and their salts^{[3b–3i,3k,3m,6h,6j]}we and reactivity, the results of which will be described in a

became interested in the design and enantioselective synthe- separate paper.^[14]

sis of derivatives of I and II that are configurationally stable

on the timescale of their synthesis, reaction with electro-

philes, and structural investigation. The availability of such

lithium α-sulfonyl carbanion salts would not only allow a

study of their dynamics and reactivity, but could perhaps

Results and Discussion

also lead to interesting applications in stereoselective syn-

thesis. A prerequisite to an enantioselective synthesis and

Enantiomerization Barriers of α-Sulfonyl Carbanions

study of I and II is a sufficiently high configurational sta-

bility at low temperatures. The enantiomerization of (P)-

and (M)-I has to include, besides perhaps other steps, a C_α–

S bond rotation, and the enantiomerization of (P,S)- and

(M,R)-II both a C_α–S bond rotation and an inversion of

the C_αatom (not shown in Figure 1). Ab initio calculations

on counterion-free S-methylsulfonyl carbanions have re-

vealed a small barrier towards inversion and a much

higher barrier towards C_α–S rotation, the latter being

determined by both steric effects and the n_C–σ*_SR3inter-

action.^{[6a,6b,6h,6j]}Based on the results of our ab initio calcu-

lations on fluorine-substituted α-sulfonyl carbanions,^[6h,6j]

we speculated that salts I and II carrying the strongly elec-

tronegative and sterically demanding trifluoromethyl

group^[11]at the S atom should have a significantly higher

configurational stability than their S-phenyl derivatives. In-

deed, the S-trifluoromethyl-substituted salts (P)-Ia (R¹=

Ph, R²= CH₂Ph, R³= CF₃) and (M)-IIa (R¹= CH₂Ph, R²

= Me, R³= CF₃) exhibited such a configurational stability

at low temperatures, which allowed their enantioselective

synthesis and structural study.^[3f,3g]Unfortunately, the

strong n_C–σ*_SCF3interactions in (P)-Ia and (M)-IIa be-

stows the salts not only with a relatively high configura-

tional stability, but also with a low reactivity towards elec-

trophiles at low temperatures.^{[3f,3g,6r,10,12]}Therefore deriva-

tives of I and II were sought that would combine both a

relatively high configurational stability and a high reactivity

at low temperatures. To meet these requirements we envi-

sioned the introduction of a group at the S atom of I and

Enantiomerization and Topomerization of Nuclei

To gain general information about the influence of the

substituents at the S and C_αatoms of salts I and II upon

their configurational stability, the enantiomerization of the

racemic salts rac-1–10 (Figure 2) was investigated by ¹H

and ¹³C dynamic NMR (DNMR) spectroscopy.

Figure 2. Lithium salts of chiral S-phenyl-, S-tert-butyl-, S-ada-

II that is sterically more demanding^[11]but much less elec- mantyl-, and S-triethylmethyl-substituted α-sulfonyl carbanions.

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Eur. J. Org. Chem. 2010, 4559–4587

Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

The anions of rac-1–10 carry a Ph, tBu, adamantyl, or C_α–Ph rotation is higher than that to C_α–S rotation. Finally,

Et₃C group at the S atom. These substituents were selected it was of interest to determine the C_α–Ph rotational barriers

on the basis of their increasing steric size according to the for the salts rac-1–9 as a probe for the benzylic conjugation

Taft parameters [E_s(Ph) = –1.01/–3.82, E_s(CMe₃) = –2.78, and its influence on the configurational stability. Rotation

E_s(adamantyl) = –4.0, and E_s(CEt₃) = –5.04].^[11]Whereas around the C_α–Ph bond leads to topomerization of the nu-

the salts rac-1, rac-3–5, and rac-8–10 are also benzylic carb- clei of the phenyl ring in the ortho and meta positions, as

anions, the salts rac-2, rac-6, and rac-7 carry only alkyl depicted for rac-3, which can, in principle, also be moni-

groups at the C_αatom. The different substituents at the C_αtored by DNMR spectroscopy.

atom were chosen to study the influence of the coordination

geometry of the anionic C atom and the benzylic conjuga-

Synthesis of Racemic Sulfones

The racemic S-tert-butyl sulfones rac-17 and rac-18 were

prepared starting from the corresponding sulfides 11^[15a]

and 12^[15b](Scheme 1). Oxidation of sulfides 11 and 12 gave

the corresponding sulfones 13^[15c]and 14^[15d]in 79 and 81%

yields, respectively. Deprotonation of sulfones 13 and 14

with nBuLi in THF afforded the corresponding racemic

salts rac-15 and rac-16. Treatment of these salts with

PhCH₂Br and MeI, respectively, furnished the correspond-

ing sulfones rac-17 and rac-18 in 86 and 93% yields, respec-

tively. A substitution approach was followed for the synthe-

sis of the racemic S-tert-butyl sulfones rac-27–30. This ap-

proach was chosen because of its proposed use in the syn-

thesis of the corresponding enantiomerically pure sulfones.

Treatment of the racemic bromide rac-19 and chlorides rac-

20,^[16a]rac-21,^[16b]and rac-22^[16b]with sodium tert-butyl-

thiolate in dimethylformamide (DMF) gave the correspond-

ing racemic sulfides rac-23,^[15b,17a]rac-24, rac-25, and rac-

tion upon the configurational stability of the salts. The en-

antiomerization of salts rac-1–10 has to involve a C_α–S

bond rotation and that of rac-2, in addition, a C_αinversion

(not shown in Figure 3) because its C_αatom is most likely

pyramidalized. Although the configurations of the C_α

atoms of the S-tert-butyl- and S-adamantyl-substituted

salts rac-6 and rac-7 have not been experimentally deter-

mined, there is evidence to suggest that they are planar or

nearly planar (see below). Furthermore, the salts rac-1–8

undergo C_α–CH₂bond rotation during enantiomerization.

Because the anions of rac-1–8 each have a CH₂R group (R

= Ph, Me, tBu) at the C_αatom, their enantiomerization is

accompanied by topomerization of the diastereotopic meth-

ylene protons H_aand H_b, as highlighted for rac-3 and rac-

6 in Figure 3. This should provide a means of studying the

enantiomerization of the salts rac-1–8 by temperature-de-

pendent NMR spectroscopy. In addition, the tert-butyl-

substituted salt rac-10 was investigated. Whereas the salts

rac-1, rac-3, and rac-4 have and rac-8 and rac-9 are expected

to have a C_α–Ph conformation as depicted, the phenyl ring

of the salt rac-10 is orthogonal to the C_i–C_α–S plane (see

below). Therefore enantiomerization of rac-10 is ac-

companied by topomerization of the nuclei at the ortho and

meta positions of the phenyl ring. This process should be

accessible by DNMR spectroscopy provided the barrier to

Figure 3. Topomerization of nuclei in the enantiomerization and

C_α–Ph rotation of α-sulfonyl carbanions.

Scheme 1. Synthesis of sulfones rac-17, rac-18, rac-27–30, and rac-

31–34.

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H.-J. Gais et al.

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26^[17b]in 99, 94, 51, and 98% yields, respectively. Finally, [E_s(CMe₃) = –2.78 and E_s(Ph) = –1.01/–3.82].^[11]The ben-

oxidation of the sulfides furnished the corresponding zylic S-tert-butyl-substituted salt rac-3 in [D₈]THF has, at

sulfones rac-27,^[18]rac-28, rac-29, and rac-30 in 80, 69, 74, a concentration of c = 0.28 molL^–l, an estimated activation

and 84% yields, respectively. The racemic sulfones rac- free energy of enantiomerization ∆G^‡_enantof 13.5 kcalmol^–1

31,^[19a]rac-32,^[19b]rac-33, and rac-34 were prepared follow- at the coalescence temperature of 283 K (entry 4). This

ing similar routes (see the Supporting Information).

translates into an estimated half-life of enantiomerization

for rac-1 of τ = 3.22ϫ10^–3s at 283 K. The estimated bar-

½

DNMR Spectroscopy

rier for the C_α-ethyl-substituted derivative rac-4 is

14.2 kcalmol^–1at 295 K (entry 5). Thus, the barriers to the

enantiomerization of the S-tert-butyl-substituted salts rac-3

and rac-4 are, as envisioned, significantly higher than those

of the S-phenyl-substituted derivatives rac-1 and rac-2. A

change in solvent from [D₈]THF to [D₁₄]diglyme had no

significant effect on the enantiomerization barrier of rac-4

(entry 6). The enantiomerization barrier for the C_α-neopen-

tyl- and S-tert-butyl-substituted salt rac-5 in [D₈]THF

could not be determined because of the relatively low boil-

ing point of the solvent. However, because of a coalescence

1

The H NMR spectra of the salts rac-1–8, which were

prepared from the corresponding sulfones rac-31, rac-32,

rac-17, rac-28, rac-29, rac-18, rac-33, and rac-34 with nBuLi

and nPrLi in [D₈]THF and [D₁₄]diglyme, showed in all

cases a temperature-dependent reversible coalescence phe-

nomenon for the signals of the diastereotopic protons of

the methylene group. The activation free energies for the

enantiomerization of rac-1–8 at the coalescence temperature

were estimated^[20]based on the assumption that the process

follows first-order kinetics (see below). DNMR spec-

troscopy of the benzylic S-phenyl-substituted salt rac-1 in

[D₈]THF at a concentration of c = 0.32 molL^–1gave an

temperature of Ն333 K, the activation free energy ∆G^‡

enant

of rac-5 was estimated to be Ն15.7 kcalmol^–1(entry 7).

DNMR spectroscopy of rac-5 in [D₁₄]diglyme at a concen-

tration of c = 0.10 molL^–lgave an estimated activation free

estimated

enantiomerization

barrier

∆G^‡

of

enant

9.5 kcalmol^–1at the coalescence temperature of 210 K

(Table 1, entry 1). This translates into an estimated half-life

energy ∆G^‡

of 16.2 kcalmol^–1at the coalescence tem-

enant

of enantiomerization (τ ) for rac-1 of only 1.12ϫ10^–3s at

perature of 343 K (entry 8). DNMR spectroscopy of the S-

tert-butyl-substituted salt rac-6, the C_αatom of which car-

ries a methyl and a benzyl group, revealed an activation free

½

210 K. Lowering the concentration of rac-1 to c =

0.20 molL^–1and finally to 0.06 molL^–1had no influence on

the height of the estimated enantiomerization barrier. Next

the influence of HMPA upon the enantiomerization barrier

of rac-1 was probed. In the presence of 2 equiv. of [D₁₈]-

energy of enantiomerization ∆G^‡

of 13.6 kcalmol^–1at

enant

the coalescence temperature of 288 K (entry 9). Thus, the

benzylic salt rac-5, the C_αatom of which is planar, and the

non-benzylic salt rac-6, the C_αatom of which is most likely

also planar (see below), have similar enantiomerization bar-

riers. Finally, the two salts rac-7 and rac-8, which carry a

sterically demanding adamantyl and triethylmethyl group

at the S atom, respectively, and a C_αatom that is most likely

planar, were studied. Their enantiomerization barriers

HMPA, the barrier of rac-1 increased to ∆G^‡

=

enant

9.9 kcalmol^–1at the coalescence temperature of 218 K (en-

try 2). Whereas the anionic C atom of the benzylic salt rac-

1 should be planar, that of the non-benzylic S-phenyl-sub-

stituted salt rac-2 is expected to be strongly pyrami-

dalized^[3d](see below). DNMR spectroscopy of rac-2 in

[D₈]THF at a concentration of c = 0.28 molL^–lgave an esti-

∆G^‡

were estimated by DNMR spectroscopy to be

enant

13.9 kcalmol^–1at 297 K and 15.1 kcalmol^–1at 325 K (en-

tries 10 and 11).

mated activation barrier of ∆G^‡

= 9.6 kcalmol^–1at the

enant

coalescence temperature of 213 K (entry 3). Thus, the

planar and pyramidalized lithium salts rac-1 and rac-2,

respectively, have similar barriers to enantiomerization.

Next the benzylic S-tert-butyl-substituted salts rac-3 and

rac-4 were studied by DNMR spectroscopy. The tert-butyl

group has a higher Taft parameter than the phenyl group

The activation parameter for the enantiomerization of

the tert-butyl-substituted salt rac-10 was not accessible by

DNMR spectroscopy because of the lack of different chem-

ical shifts for the diastereotopic nuclei in the ortho and meta

positions of the phenyl group (see below). Neither could

Table 1. Estimation of the enantiomerization barriers of the salts rac-1–8 by DNMR spectroscopy.

Entry

Salt

Solvent

c [molL^–1]

∆ν [Hz]

J_AB[Hz]

k_enant[s^–1]

T_c[K]

∆G^‡

[kcalmol^–1]

enant

1

2

3

4

5

6

7

8

rac-1

rac-2

rac-3

rac-4

rac-5

rac-6

rac-7

rac-8

[D₈]THF

[D₈]THF^[a]

[D₈]THF

[D₁₄]Diglyme 0.10

[D₈]THF 0.10

[D₁₄]Diglyme 0.10

0.32, 0.20, 0.06 225

14.5

16.2

14.5

17.9

15

14

15

506

553

550

214

176

231

339

350

343

377

455

210Ϯ5

218Ϯ5

213

283Ϯ5

295Ϯ5

Ն333

343Ϯ10

288Ϯ5

297

9.5Ϯ0.2

9.9Ϯ0.3

9.6Ϯ0.2

13.5Ϯ0.2

14.2Ϯ0.3

14.1Ϯ0.3

Ն15.7

16.2Ϯ0.5

13.6Ϯ0.2

13.9Ϯ0.3

15.1Ϯ0.3

0.16

0.28

0.10

246

225

86

70^[b]

98^[b]

148

153

150

162

201

15

9

10

11

[D₈]THF

0.31

0.16

15.3

16.9

16.4

325

[a] In the presence of 2equiv. of HMPA. [b] With selective spin-decoupling of the β-methyl group.

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Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

the activation parameter for the enantiomerization of the the C_αatom cannot be rate-determining. This is in accord-

methyl-substituted salt rac-9 be determined by this tech- ance with theoretical^[6b,6c]and chemical evidence^{[1c,3k,3m,21]}

nique because of a lack of suitable diastereotopic nuclei.

that suggests that the inversion barrier of a pyramidalized

A more detailed comparison of the enantiomerization C_αatom is small. Finally, there seems to be no significant

barriers of the salts and the half-lives of enantiomerization difference in the enantiomerization barriers of the benzylic

is precluded because of the widely differing coalescence and non-benzylic α-sulfonyl carbanion as a comparison of

temperatures. The activation parameters ∆H^‡

and the pairs of the salts rac-1/rac-2 and rac-3/rac-6 shows.

enant

∆S^‡

of the salts were not determined by DNMR spec-

enant

troscopy because of the determination of the racemization

dynamics of the salt (P)-6 by polarimetry.^[14]The data col-

lected in Table 1 clearly show that there is no chance of

obtaining chiral S-phenyl-substituted lithium salts of types

I and II for further studies in enantiomerically enriched

form even at low temperatures because of their fast racemi-

zation. Whereas the S-phenyl-substituted salt rac-2 has a

Aggregation in Solution

The S-tert-butyl-substituted lithium α-sulfonyl carbanion

salts 3–10 are promising candidates for the attainment of

nonracemic salts of types I and II and the study of their

reactivity. Thus, a determination of their aggregation in

THF solution was deemed necessary. Knowledge of the spe-

cies that prevail in solution should facilitate a rationaliza-

tion of the enantioselectivity of their reactions with electro-

philes. The aggregation of the salts rac-3–6 and rac-9 was

studied by cryoscopy and low-temperature NMR spec-

troscopy (see below). Cryoscopic measurements of the salts

rac-3, rac-4, rac-6, and rac-9 in THF were successfully per-

formed by the method described by Bauer and Seebach.^[22]

The cryoscopic constant of THF was determined by mea-

surements with naphthalene and stilbene. As a test, the ag-

gregation of nBuLi in THF was determined, which gave

good agreement with the literature data (n = 2.43Ϯ0.07 at

c = 96.4 mmolkg^–1vs. 2.38Ϯ0.13 at c = 92.9 mmolkg^–1).^[22]

The cryoscopy measurements were carried out in THF

solutions of the salts, which had been prepared with the

half-life τ of enantiomerization in THF of ca. 1.25ϫ10^–3

s

½

at 213 K, that of the corresponding S-tert-butyl-substituted

salt rac-6, calculated under the assumption that ∆S^‡

=

enant

0, is about 16.8 s at 213 K. Thus, an enantioselective synthe-

sis and study of S-tert-butyl-substituted salts of type I

should be feasible at low temperatures as far as configura-

tional stability is concerned.

Mechanism of Enantiomerization

The activation parameters for the enantiomerization of

the salts rac-1–8 were estimated based on the assumption

that the process follows first-order kinetics. This raises the

question as to the nature of the rate-determining step of the

enantiomerization process. The lithium salts rac-1–8 exist

in THF solution as a mixture of THF-solvated monomeric

and dimeric contact ion pairs (CIPs), the Li atom of which

is bonded to the O atom(s) (see below). The enantiomeri-

zation of rac-1–8 has, in principle, to involve (1) a rotation

around the C_α–SR³bond, (2) an inversion of the C_αatom

in the case of a nonplanar coordination geometry, (3) per-

haps a conversion of the O–Li CIP carrying, for example,

two THF molecules to the CIP with only one THF mole-

cule, or (4) the conversion of the dimeric into the mono-

meric CIP. The formation of the less solvated CIP could

perhaps minimize the steric interaction between the THF-

coordinated Li atom and the C_αsubstituents during C_α–

SR³bond rotation (see below). The similar barriers for the

enantiomerization of rac-1 at different concentrations may

be taken as an indication that the establishment of the equi-

librium between dimers and monomers is not rate-de-

termining. It is assumed that at least in the case of the salts

rac-3–8, which carry the sterically demanding tert-butyl

group at the S atom, C_α–S bond rotation is the rate-de-

termining step. Polarimetric measurements of the dialkyl-

substituted salt (P)-6 at low temperatures showed that its

racemization is mainly an enthalpic process with a very

small entropic contribution.^[3f,3g]Previous studies of the S-

trifluoromethyl-substituted lithium salts (P)-Ia and (M)-IIa

and the corresponding potassium and tetrabutylammonium

salts in THF and DMSO led to a similar conclusion.^[3f,3g]

The barriers to enantiomerization for the salts rac-1 and

rac-2, the C_αatoms of which should be planar and pyrami-

Scheme 2. Synthesis of the salts (M/P)-3·4THF, rac-3·12-crown-4,

(M/P)-4·4THF, (M/P)-5·4THF, (M/P)-6·4THF, rac-9·PMDTA,

dalized, respectively, show furthermore that the inversion of (M/P)-9·4THF, and (M/P)-10·2THF.

Eur. J. Org. Chem. 2010, 4559–4587

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4563

H.-J. Gais et al.

FULL PAPER

crystalline salts (M/P)-3·4THF, (M/P)-4·4THF, (M/P)- nBuLi in THF/n-hexane and recrystallization from n-hex-

6·4THF, and (M/P)-9·4THF. The THF content of the salts ane/THF (cf. Scheme 2). Each salt crystallized with four

was determined by NMR spectroscopy. The salts were pre- molecules of THF as a THF-solvated heterochiral dimer

pared from the corresponding racemic sulfones rac-17, rac- (Figures 4, 5, and 6)^[24]in a structure similar to that of the

28, rac-18, and rac-27 as shown in Scheme 2. Several mea- S-phenyl-substituted salt (M/P)-1·4THF.^[3d,3g]The Li atoms

surements were taken for each salt. After the measurements are coordinated in a tetrahedral fashion by only four O

were completed, the integrity of the salts was checked by atoms. The two anions of the dimer are held together by

deuteriation with CF₃CO₂D and the D content of the cor- four O–Li bonds, and each anion is coordinated by two Li

responding sulfone determined by NMR spectroscopy. atoms. Thus, a characteristic eight-membered ring is

Table 2 shows that the salts rac-3, rac-4, rac-6, and rac-9 formed, the O–Li bond lengths of which are between

(entries 1–4) exist in THF at low temperatures as mixtures 1.88(1) and 1.900(6) Å (see the Supporting Information).

of monomers and dimers in ratios ranging from 85:15 to The puckering of the ring of the dimeric salts differs only

33:67 depending on the substituents on the C_αatom (see slightly. The similarity of the rings is reflected by their tor-

below). These results are in accordance with those obtained sion angles and the deviation of the S and Li atoms from

in previous cryoscopy experiments of lithium salts of chiral the plane defined by the four O atoms. The anions have a

and achiral α-sulfonyl carbanions^{[1c,3f,3g,6k,23]}and acidity

measurements of sulfones in THF.^[5a,5d,5g]

Table 2. Aggregation of the S-tert-butyl-substituted salts rac-3, rac-

4, rac-6, and rac-9 at –108 °C in THF.

Entry

Salt

c [mmolkg^––1

]

NϮσ

Monomer/dimer

1

2

3

4

rac-3

rac-4

rac-6

rac-9

86.6

54.1

49.9

49.7

1.14Ϯ0.15

1.36Ϯ0.04

1.60Ϯ0.06

1.67Ϯ0.18

ca. 85:15

ca. 64:36

ca. 40:60

ca. 33:67

Figure 4. View of the crystal structure of the dimeric benzyl-substi-

tuted salt (M/P)-3·4THF with H atoms omitted for clarity. Color

code: C, black; S, yellow; O, red; Li, pink.

Structures of Lithium α-tert-Butylsulfonyl Carbanion Salts

in the Crystal

Cryoscopy of the S-tert-butyl-substituted lithium salts

rac-3, rac-4, rac-6, and rac-9 in THF revealed the existence

of monomers and dimers in THF solution. Thus, the ques-

tion arose as to the structures of the monomeric and di-

meric salts. Knowledge of the crystal structures of the lith-

ium salts of S-tert-butylsulfonyl carbanions was required

because of the enantioselective synthesis of 3–6, 9, and 10

and the study of their dynamics and reactivity towards

electrophiles.^[14]Therefore the crystal structures of the di-

meric lithium salts (M/P)-3·4THF, (M/P)-4·4THF, (M/P)-

5·4THF, and (M/P)-10·2THF and the monomeric lithium

salts rac-3·12-crown-4 and rac-9·PMDTA were determined.

Figure 5. View of the crystal structure of the dimeric ethyl-substi-

tuted salt (M/P)-4·4THF with H atoms omitted for clarity. Color

Although much is known about the structures of the dimers code: C, black; S, yellow; O, red; Li, pink.

of S-aryl-substituted lithium α-sulfonyl carbanion salts in

the crystal form,^[3]those of S-tert-butyl-substituted α-sulfon-

yl carbanion salts were, with one exception, unknown.^[3m]

Most importantly, however, in general, the structures of the

monomers of lithium α-sulfonyl carbanion salts, which are

expected to play an important role in reactions with electro-

philes, were unknown.^[3m]

Dimeric Salts

Single crystals of the dimeric C_α-benzyl-, C_α-ethyl-, and

C_α-neopentyl- and S-tert-butyl-substituted benzylic lithium

salts (M/P)-3·4THF, (M/P)-4·4THF, and (M/P)-5·4THF,

Figure 6. View of the structure of the dimeric neopentyl-substituted

salt (M/P)-5·4THF with H atoms omitted for clarity. Color code:

sponding racemic sulfones rac-17, rac-28, and rac-29 with C, black; S, yellow; O, red; Li, pink.

respectively, were obtained by deprotonation of the corre-

4564

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Eur. J. Org. Chem. 2010, 4559–4587

Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

typical C_α–S conformation in which the orbital at the C_α1.842(7) and 1.885(7) Å, that is, in the normal range. The

atom is gauche to both O atoms (see the Supporting Infor- anion has the typical C_α–S conformation. However, this salt

mation). They adopt a C_α–CH₂conformation in which the shows a further interesting structural feature. The following

group in the β position (phenyl, methyl, tert-butyl) is anti parameter seems to indicate a stabilizing interaction be-

to the S-tert-butyl group. There are no bonds between the tween the Li atom and the phenyl ring,^[26a]which is not in

C_αatom and the Li atoms in the dimeric S-tert-butyl salts, conjugation with the lone-pair orbital at the C_αatom (see

as indicated by C_α–Li nonbonding distances between below). First, the nonbonding distance between the coordi-

4.190(4) and 4.424(7) Å.

natively unsaturated Li atom and the C_oatom of the phenyl

Finally, the dimeric C_α,S-di-tert-butyl-substituted lith- ring is, at 2.652(9) Å, smaller than the sum of the

ium salt (M/P)-10·2THF was synthesized and its crystal van der Waals radii of Li (1.60 Å) and C (1.70 Å); optimiza-

+

structure analyzed. The anion of the salt (M/P)-10·2THF tion of the model complex C₆H₆·Li(H₂O)₃(see the Sup-

carries the sterically demanding tert-butyl group at the C_αporting Information) at the MP2/6-31+G* level resulted in

atom, which could influence the C_α–S and C_α–Ph confor- a Li···C distance of 2.447 Å and a binding energy of

mation (see above). The salt (M/P)-10·2THF was obtained –13.9 kcalmol^–1relative to benzene and Li(H₂O)₃⁺. Sec-

without difficulty in the usual manner by deprotonation of ondly, the phenyl group bends towards the Li atom.

the racemic sulfone rac-30 with nBuLi in THF/n-hexane Thirdly, the eight-membered ring is strongly puckered. Al-

solution and recrystallization from n-hexane. The salt (M/ though these parameters point to a stabilizing C_o···Li inter-

P)-10·2THF also crystallized as a THF-solvated hetero- action, a purely steric origin of the relatively short C_o···Li

chiral dimer (Figure 7).^[24]However, presumably for steric distance cannot be excluded.^[26b]

reasons, the Li atoms of (M/P)-10·2THF are each coordi-

Monomeric Salts

nated by only one THF molecule. Thus, the Li atoms

achieve a less common tricoordination by O atoms^[25]in a

Having obtained a general picture of the structures of

slightly nonplanar fashion (ΣЄLi = 354°). Of all the di- the dimeric lithium S-tert-butyl salts in the crystal form, it

meric salts studied, the salt (M/P)-10·2THF has the most was important to gather information about the structures

puckered eight-membered ring (see the Supporting Infor- of the monomeric salts. Because the structure of the dimer

mation) as revealed by the torsion angles and the deviation (M/P)-3·4THF was known, we chose to synthesize the mo-

of the S atoms from the plane defined by the O atoms. The nomeric salt rac-3. To attain a monomer of rac-3, our pre-

S-tert-butyl groups occupy the pseudoequatorial and the vious experience of the preparation of the monomeric po-

tBu(Ph)C fragments the pseudoaxial positions of the chair- tassium salt of a α-sulfonyl carbanion^[3e]suggested the use

like ring.

of the lithium-ion-specific 12-crown-4 as donor ligand to

prevent dimer formation for steric reasons. Single crystals

of the C_α-benzyl- and S-tert-butyl-substituted lithium salt

rac-3·12-crown-4 were obtained by deprotonation of sulfone

rac-17 with nBuLi in THF/n-hexane solution in the pres-

ence of 12-crown-4 and crystallization from THF. The X-

ray structure analysis of rac-3·12-crown-4 revealed a mono-

mer with the Li atom coordinated to only one O atom of

the anion in addition to the four O atoms of the crown

ether molecule (Figure 8).^[24]Interestingly, the two known

crystal structures of monomeric 18-crown-6-coordinated

potassium salts of α-sulfonyl carbanions feature a coordina-

tion of the K atom to both sulfonyl O atoms as well as the

ether O atoms.^[3e,3j]One has to consider, however, that in

addition to the different coordination numbers of the Li

and K atoms, the O–K bond length of 2.808(3) Å (average

Figure 7. View of the crystal structure of the dimeric tert-butyl-

substituted salt (M/P)-10·2THF with H atoms omitted for clarity.

Color code: C, black; S, yellow; O, red; Li, pink.

An additional structural feature, however, in which the value) is much longer than the average O–Li bond length

salt (M/P)-10·2THF differs structurally most significantly of 2.10(1) Å. Thus, one reason for this striking structural

from the other benzylic salts (M/P)-3·4THF, (M/P)- difference between the crown ether coordinated monomeric

4·4THF, and (M/P)-5·4THF is the orientation of the α- potassium and lithium salts might be that a monomer of

phenyl ring, which is almost orthogonal to the S–C_α–C_β12-crown-4-coordinated rac-3 in which both sulfonyl O

plane (see the Supporting Information). Consequently, at atoms are coordinated to the Li atom is energetically less

1.508(5) Å the C_α–Ph bond in (M/P)-10·2THF is the long- favorable than rac-3·12-crown-4 because of van der Waals

est among the benzylic salts described in this paper. There repulsion between the anion and the crown ether. The dia-

are no C_α–Li bonds as the C_α–Li nonbonding distances of stereomer of rac-3·12-crown-4 having the relative

3.639(8) and 3.688(8) Å show. Because of the pseudoaxial P(M),S_S(R_S) configuration crystallized preferentially. Pre-

position of the C_αatoms of (M/P)-10·2THF, this salt has sumably for steric reasons the S, O, and Li atoms are ar-

the shortest C_α–Li nonbonding distances of all the dimeric ranged in a nearly linear fashion, as revealed by the Li–O–

salts described. The O–Li bond lengths for the ring are S angle of 166.4(6)°. The sulfonyl O–Li bond length

Eur. J. Org. Chem. 2010, 4559–4587

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4565

H.-J. Gais et al.

FULL PAPER

[1.864(1) Å] is slightly shorter than the average sulfonyl O– stituted lithium salt rac-9·PMDTA were obtained by depro-

Li bond length in (M/P)-3·4THF [1.983(4) Å]. The average tonation of the racemic sulfone rac-27 with nBuLi in

O–Li bond length to the crown ether [2.10(1) Å] is some- PMDTA solution and recrystallization from PMDTA/THF.

what longer than the average O–Li bond length of the coor- X-ray structure analysis of rac-9·PMDTA revealed a mono-

dinated THF molecules in (M/P)-3·4THF. This feature is, mer with the Li atom coordinated to only one O atom of

however, in perfect agreement with the Li–O bond lengths the anion in addition to the three N atoms of the triamine

in other lithium–crown ether complexes.^[25c]The anion of (Figure 9).^[24]The diastereomer of rac-9·PMDTA having

rac-3·12-crown-4 also has the typical C_α–S conformation the relative M(P),S_S(R_S) configuration had preferentially

(see the Supporting Information). The β-phenyl ring is anti crystallized. The S, O, and Li atoms are not arranged in an

to the tert-butyl group and there are no C_α–Li bonds as the almost linear fashion as in rac-3·12-crown-4, as revealed by

C_α–Li nonbonding distance of 4.099(13) Å shows.

the average Li–O–S angle of 138.5(3)°. The sulfonyl O–Li

bond length of 1.850(8) Å is slightly shorter than the O–Li

bond length of rac-3·12-crown-4 [1.86(1) Å]. The anion of

rac-9·PMDTA also has the typical C_α–S conformation (see

the Supporting Information). There are no C–Li bonds as

the C_α–Li nonbonding distance of 3.647(9) Å shows.

Figure 8. View of the crystal structure of the monomeric benzyl-

substituted salt rac-3·12-crown-4 with H atoms omitted for clarity.

Color code: C, black; S, yellow; O, red; Li, pink.

The crystal structure of the salt rac-3·12-crown-4, which

carries a benzyl and phenyl group at the C_αatom, is only

the second monomeric acyclic lithium α-sulfonyl carbanion

salt known.^[3m]Because the monomeric salts are expected

to play a crucial role in the reactions of the salts with elec-

trophiles (see below), knowledge of the structure of a fur-

ther monomeric S-tert-butylsulfonyl carbanion salt was de-

sirable in order to have a more general picture. The salt rac-

9, which carries a methyl and phenyl group at the C_αatom,

was chosen as a model because of the enantioselective syn-

Figure 9. View of the crystal structure of the monomeric methyl-

substituted salt rac-9·PMDTA with H atoms omitted for clarity.

Color code: C, black; S, yellow; O, red; N, green; Li, pink.

C_α–S Conformation and C_αConfiguration of the Dimeric

Lithium Salts

The anions of the dimeric S-tert-butyllithium salts (M/

thesis and reactivity study of (P)-9.^[14]Because of our pre- P)-3·4THF, (M/P)-4·4THF, (M/P)-5·4THF, and (M/P)-

vious success in the synthesis of the monomeric PMDTA- 10·2THF all have a similar C_α–S conformation irrespective

coordinated lithium salt of a bicyclic allylic S-tert-butyl- of the second substituent at the C_αatom (Table 3) and the

sulfonyl carbanion,^[3m]this ligand was also used in this case. conformation of the eight-membered (Li–O–S–O)₂coordi-

Single crystals of the C_α-methyl- and S-tert-butyl-sub- nation ring (see the Supporting Information). The lone-pair

Table 3. Torsion angles α and β,^[a]sum of the angles |α|+|β|, torsion angles S–C_α–C_i–C_o, and S–C_α–CH₂–R,^[a]and sum of the bond angles

ΣЄC_αof the salts (M/P)-3·4THF, rac-3·12-crown-4, (M/P)-4·4THF, (M/P)-5·4THF, rac-9·PMDTA, (M/P)-10·2THF, (M/P)-40·2diglyme,

(41·diglyme)₂, and (42·diglyme)₂.^[b]

Salt

R¹

R²

R³

α [°]

β [°]

|α|+|β| [°] S–C_α–C_i–C_o[°] S–C_α–CH₂–R [°]

ΣЄC_α[°]

(M/P)-3·4THF

rac-3·12-crown-4

(M/P)-4·4THF

(M/P)-5·4THF

rac-9·PMDTA

(M/P)-10·2THF

(M/P)-40·2diglyme

(41·diglyme)₂

PhCH₂

MeCH₂

tBuCH₂

Me

tBu

Et

–(CH₂)₅–

Ph

Me

Et

tBu

Ph

83.1

–93.3

176.4

173.8

179.6

162.7

179.5

194.4

146.9

141.6

149.9

10.5

–5.9(8)

6(1)

38.9(5)

4.6(7)

77.0(4)

–

–108.5

–109.5(7)

–107.3(7)

–114.3(3)

–

359.9

359.7

360.0

357.6

360.0

358.5

351.1

88.6(7)

86.6(7)

68.7(3)

–87.7(4)

101.7(3)

73.8(7)

68.0(2)

77.7(5)

–85.2(5)

–93.0(6)

–94.0(3)

91.8(4)

–92.7(3)

–73.1(9)

–73.6(2)

–72.2(4)

–

–148.3(6)

–148.3(2), 112.9(2) 348.2

–158.4(4), 151.1(5) 353.2

Ph

–

(42·diglyme)₂

[a] Calculated neglecting standard deviations. [b] Charges of the structural formulae have been omitted for clarity.

4566 Eur. J. Org. Chem. 2010, 4559–4587

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Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

orbital at the C_αatom is gauche to both O atoms, as judged C_α–Ph bond length in (M/P)-3·4THF, (M/P)-4·4THF, and

by the torsion angles α and β. This allows a stabilization (M/P)-5·4THF. Not surprisingly, the C_α-tert-butyl-substi-

of the anions by n_C–σ*_SR3hyperconjugation.^[6]Because of tuted salt (M/P)-10·2THF has the longest C_α–Ph bond,

different van der Waals repulsion within the benzylic anions which is, however, shorter than in the corresponding sul-

and the aggregates these torsion angles differ in magnitude. fone. Of all the S-tert-butyl-substituted lithium salts

Not surprisingly, the deviation is the strongest for the C_α- studied, the salt (M/P)-10·2THF has the shortest C_α–S

tert-butyl- and C_α-neopentyl-substituted salts (M/P)- bond and the longest S–O and C_α–Ph bonds. In addition,

10·2THF and (M/P)-5·4THF, respectively.

the lengthening of the S–O bond in (M/P)-10·2THF in

Because of the stabilization of the negative charge by comparison with the parent sulfone rac-30 is, although

conjugation with the phenyl group, the C_αatoms of the small, the strongest observed for the lithium salt of an α-

anions are almost planar-coordinated, as shown by the sum sulfonyl carbanion. Noticeable changes in bond angles at

of their bond angles ΣЄC_α. The phenyl rings at the C_αthe S atom of the parent sulfones rac-17 and rac-30 occur

atoms of the benzyl- and ethyl-substituted salts (M/P)- upon deprotonation. In the S-tert-butyl-substituted salts

3·4THF and (M/P)-4·4THF, respectively, are nearly co- (M/P)-3·4THF and (M/P)-10·2THF the C_α–S–tBu, C_i–C_α–

planar with the S–C_α–C_iplane, as revealed by the torsion S, and S–C_α–tBu angles are increased and the O–S–O angle

angles S–C_α–C_i–C_o. Deviation from coplanarity is such that is slightly reduced.

the conjugative interaction is not significantly hampered.

For the neopentyl- and tert-butyl-substituted salts (M/P)-

Comparison of the Monomeric and Dimeric Salts

5·4THF and (M/P)-10·THF, however, these torsion angles

The monomeric and dimeric salts are generally expected

are 38.9(5) and 77.0(4)°. This large deviation from copla- to have CIP structures (see below) in which the C_α–S con-

narity most likely results from a steric interaction between formation and the position of the Li atom are very similar.

the phenyl ring and the tert-butyl group. As a consequence, Indeed, the anions of the monomer rac-3·12-crown-4 and

stabilization of the negative charge by the p_π–p_πinteraction dimer (M/P)-3·4THF have a very similar conformation.

should be diminished in (M/P)-5·4THF and nearly absent The smaller value of β and the larger value of α in rac-

in (M/P)-10·2THF (see below). Therefore the C_αatoms of 3·12-crown-4 seems to be the consequence of van der Waals

(M/P)-10·2THF ought to be significantly pyramidalized. repulsion between the benzyl group and the neighboring

However, the resulting steric interaction between the tert- crown ether molecule. The decisive bond lengths and angles

butyl groups prevents pyramidalization (see below). Thus, in (M/P)-3·4THF and rac-3·12-crown-4 are almost iden-

the size of the alkyl substituent at the C_αatom has no tical. Thus, the structure of the anion of dimer (M/P)-

significant bearing upon the C_α–S conformation of the 3·4THF is retained in the monomer rac-3·12-crown-4.

anion.

Furthermore it is apparently of no consequence for the

structure of the anion whether it is coordinated either to

one or two Li atoms. The crystal structures of rac-3·12-

crown-4 and rac-9·PMDTA can thus serve as appropriate

Comparison of the Bonding Parameters of the Salts and

Parent Sulfones

A comparison of the structure of the lithium salt (M/P)- models for the structure of the monomeric lithium salt I in

3·4THF (Table 4) with that of the parent sulfone rac-17^[14]THF solution. Although the crystal structure of the dimeric

reveals a considerable shortening of the C_α–S bond by ap- salt (M/P)-9·4THF is not available for comparison, there is

proximately 10% (0.18 and 0.19 Å). The S–O bonds are little doubt that the structure of the anion in the monomer

slightly longer. The shortening of the C_α–S bond and the is not significantly different to that of the dimer. This no-

lengthening of the S–O bond are general phenomena for α- tion is corroborated by the bonding parameters of rac-

sulfonyl carbanions.^[3]The C_α–Ph bond in (M/P)-3·4THF 9·PMDTA. It should be emphasized, however, that rac-

is also shortened significantly in comparison with the corre- 3·12-crown-4 and rac-9·PMDTA are only models for the

sponding sulfone. There are only minor differences in the monomeric O–Li CIPs in THF solution. Crystallization of

Table 4. Selected bond lengths and bond angles for the salts (M/P)-3·4THF, rac-3·12-crown-4, (M/P)-4·4THF, (M/P)-5·4THF, rac-

9·PMDTA, (M/P)-10·2THF, (M/P)-40·2diglyme, (41·diglyme)₂, and (42·diglyme)₂.

Bond lengths [Å]

Bond angles [°]

Salt

C_α–S

S–R³

S–O

C_α–Ph

Li–O

C_α–S–R³

O–S–O

(M/P)-3·4THF

rac-3·12-crown-4

(M/P)-4·4THF

(M/P)-5·4THF

rac-9·PMDTA

1.659(2)

1.68(1)

1.671(7)

1.652(3)

1.675(5)

1.667(5)

1.630(4)

1.838(2)

1.841(8)

1.830(7)

1.842(4)

1.832(5)

1.836(5)

1.847(4)

1.793(9)

1.802(2)

1.780(5)

1.457(2), 1.458(2)

1.465(9), 1.46(1)

1.465(5), 1.450(5)

1.459(3), 1.461(3)

1.444(3), 1.466(3)

1.438(3), 1.466(3)

1.483(2), 1.475(2)

1.450(7), 1.455(6)

1.458(2), 1.466(1)

1.459(4), 1.461(4)

1.451(3)

1.45(1)

1.43(1)

1.467(5)

1.430(6)

1.440(6)

1.508(5)

–

1.878(4), 1.891(4)

1.86(1)

1.888(12), 1.877(12)

1.900(6), 1.879(6)

1.828(8)

113.5(1)

112.2(4)

112.3(3)

112.9(2)

112.6(2)

117.0(2)

113.1(4)

111.5(1)

112.4(2)

115.1(1)

114.9(6)

115.1(3)

114.5(1)

115.3(2)

115.2(2)

113.6(2)

115.9(3)

116.5(1)

117.1(2)

1.871(8)

(M/P)-10·2THF

(M/P)-40·2diglyme 1.643(7)

(41·diglyme)₂

(42·diglyme)₂

1.885(7), 1.842(7)

1.898(11), 1.940(18)

1.894(4), 1.943(4)

1.914(11), 1.912(8)

1.636(2)

1.641(4)

–

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4567

H.-J. Gais et al.

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the monomer of a lithium α-sulfonyl carbanion salt that is geometry of the C_αatom of dialkyl-substituted α-phenyl-

coordinated only by THF molecules has yet to be ac- sulfonyl carbanions. These salts were chosen because of our

complished.

previous determination of the structure of 35 and the corre-

sponding C_α-phenyl- and -methyl-substituted salt.^[3d]

Sulfones rac-46,^[27a]47,^[27b]and 48^[27c](Scheme 3) were syn-

thesized from the corresponding bromides via the corre-

sponding sulfides by standard procedures (see the Support-

ing Information). Single crystals of the salts (M/P)-

40·2diglyme, (41·diglyme)₂, and (42·diglyme)₂were ob-

tained by deprotonation of the corresponding sulfones with

nBuLi in diglyme and recrystallization of the salts from di-

glyme.

Configuration of the Anionic C Atom of the C_α-Dialkyl-

Substituted Salts

Crystal analysis of the dimeric S-tert-butyl-substituted

benzylic salts (M/P)-3·4THF, (M/P)-4·4THF, and (M/P)-

5·4THF had revealed structures with a planar anionic C

atom, a feature that can now be regarded as a general one

for benzylic lithium α-sulfonyl carbanion salts. In contrast,

the question of the coordination geometry of the C_αatom

of the lithium salts of α,α-dialkyl-substituted α-sulfonyl

carbanions remained largely unanswered. Although X-ray

crystal structure analysis of the S-phenyl-substituted lith-

ium salt 35 (dimeric O–Li CIP; ΣЄC_α= 346.5°),^[3d]the cor-

responding salt 36 [solvent-separated ion pair (SIP);

351.7°],^[3h]and, to a lesser extent, the bicyclic allylic salts

rac-37 (dimeric O–Li CIP; ΣЄC_α= 349.8°) and rac-38 (di-

meric O–Li CIP; ΣЄC_α= 355.2°)^[3k]revealed strongly py-

ramidalized C_αatoms, that of the bicyclic allylic S-tert-bu-

tyl-substituted salt rac-39 (monomeric O–Li CIP; ΣЄC_α=

359.7°) is planar (Figure 10).^[3m]Ab initio calculations on

the counterion-free carbanions 37(–Li) and 38(–Li) also

showed their anionic C atoms to be pyramidalized.^[3k]Be-

cause of this seemingly contradictory evidence and the per-

haps nonrepresentative structures of the bicyclic salts (al-

lylic conjugation), it was desirable to obtain further infor-

mation about the coordination geometry of the dialkyl-sub-

stituted C_αatom of the S-phenyl- and especially S-tert-

butylsulfonyl carbanions. First, the S-phenyl-substituted

salts (M/P)-40·2diglyme, (41·diglyme)₂, and (42·diglyme)₂

were prepared and their crystal structures determined in

order to acquire a general picture of the coordination

Scheme 3. Synthesis of the salts (M/P)-40·2diglyme, (41·diglyme)₂,

and (42·diglyme)₂.

Each salt crystallized together with two molecules of di-

glyme as the diglyme-solvated dimer^[3d](Figures 11, 12, and

13).^[24]The Li atoms are coordinated by five O atoms. The

two anions of the dimer are held together by four O–Li

bonds, each anion carrying two Li atoms. Thereby the di-

mer has the characteristic eight-membered ring (see the

Supporting Information), the O–Li bond lengths of which

are between 1.894(4) and 1.943(4) Å. Whereas the coordi-

nation ring of (M/P)-40·2diglyme and (41·diglyme)₂

shows only a small deviation from planarity, that of

(42·diglyme)₂is strongly puckered. The anions of (M/P)-

40·2diglyme, (41·diglyme)₂, and (42·diglyme)₂adopt the

typical C_α–S conformation (see the Supporting Infor-

mation) and their C_α–S bond lengths (cf. Table 4) are also

in the typical region. However, the C_αatoms of (M/P)-

40·2diglyme, (41·diglyme)₂, and (42·diglyme)₂are strongly

Figure 11. View of the crystal structure of the dimeric salt (M/P)-

40·2diglyme with H atoms omitted for clarity. Color code: C, black;

S, yellow; O, red; Li, pink.

Figure 10. α,α-Disubstituted non-benzylic lithium α-sulfonyl carb-

anion salts.

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Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

pyramidalized in the direction of the O atoms, as revealed

by the dihedral angles α and β and the sum of the bond

angles around the C_αatom (cf. Table 3). The C_αatom of

the α,α-dimethyl-substituted salt 35 shows a similar degree

of pyramidalization with dihedral angles of α = 72.9° and

β = –66.4° and a sum of bond angles of 346.5°.^[3d,3h]Be-

cause of these results and those obtained previously, it can

now be safely stated that the C_αatoms of dialkyl-substi-

tuted S-phenylsulfonyl carbanions and perhaps also S-aryl-

sulfonyl carbanions are generally pyramidalized (half-way

between sp²and sp³).

Ab initio geometry optimizations at the MP2/6-31+G*

level of theory were performed for the carbanions 43, 44,

and 45 (Figure 14). Calculation and diagonalization of the

force constant matrices of the obtained stationary points

showed that they were local minima. The molecular ener-

gies were at minima for structures in which the sums of the

bond angles at the anionic carbon atom are 344.6° for the

S-methyl carbanion 43, 354.1° for the S-trifluoromethyl

carbanion 44, and 356.1° for the S-tert-butyl carbanion 45

(Table 5). The corresponding C_α–S bond lengths correlate

with the energy of interaction between the lone pair at the

C_αatom (n_Cα) and the antibonding orbital of the S–CR₃

(R = H, F, Me) bond (σ*_S–CR3; see ∆E_nǞσ*, footnote d,

Table 10) in that a more negative value of ∆E_nǞσ*corre-

sponds to a shorter C_α–S bond. Consequently the length of

the S–CR₃bond increases in the same direction. Delocaliza-

tion of the anionic lone pair into the σ*_S–CR3orbital is also

reflected by a decrease in the charge on the CMe₂group.

According to the NBO calculation there is no such lone

pair at the C_αatom of carbanion 45 but a S–C π bond

instead. However, almost 90% of this π bond is located at

the C_αatom so that it can be considered a lone pair. Thus,

comparison of the S-tert-butyl carbanion 45 with the S-

methyl carbanion 43 shows the C_αatom of the former is

planar and the C_α–S bond is shorter. A similar situation

exists in the case of the S-trifluoromethyl carbanion 44.

However, carbanion 44 is a special case because of the

strong effect exerted by the fluorine atoms upon the struc-

ture and stabilization.^{[3f,3g,6h,6j]}

Figure 12. View of the crystal structure of the dimeric salt

(41·diglyme)₂with H atoms omitted for clarity. Color code: C,

black; S, yellow; O, red; Li, pink.

Figure 13. View of the crystal structure of the dimeric salt

(42·diglyme)₂with H atoms omitted for clarity. Color code: C,

black; S, yellow; O, red; Li, pink.

Ab Initio Calculations of C_α-Dialkyl-Substituted

Counterion-Free Carbanions

Left open was the question of the coordination geometry

of the C_αatom of the dialkyl-substituted S-tert-butylsulfon-

yl carbanion. Unfortunately, we could not obtain suitable

single crystals of the S-tert-butyl-substituted salt rac-6.

Therefore calculations on the counterion-free carbanions

43, 44, and 45, which carry a methyl, trifluoromethyl, and

tert-butyl group at the S atom, respectively, were carried out

to see whether the steric size of the S substituent [E_s(Me)

= –1.24, E_s(CF₃) = –2.4, E_s(CMe₃) = –2.78]^[11]has a bear-

ing on the coordination geometry of the anionic C atom.

Figure 14. Structure of the S-methylsulfonyl carbanion 43 (top), S-

trifluoromethylsulfonyl carbanion 44 (middle), and S-tert-butylsul-

fonyl carbanion 45 (bottom) obtained at the MP2/6-31+G* level

of theory. Color code: C, black; S, yellow; O, red; F, green; H, grey.

Eur. J. Org. Chem. 2010, 4559–4587

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4569

H.-J. Gais et al.

FULL PAPER

Table 5. Selected bond angles and lengths, energies, and charges for models of the salts (M/P)-3·3THF, (M/P)-3·4THF, and rac-

the carbanions 43, 44, and 45.

3·12-crown-4 furthermore shows a strong steric shielding of

one side of the anionic C_αatom by the S-tert-butyl group.

Thus, reactions of S-tert-butyl-substituted α-sulfonyl carb-

anions with electrophiles at the C_αatom should take place

nearly exclusively syn to the O atoms and anti to the tert-

butyl group.

Parameter

43

44

45

ΣЄC_α[°]

C_α–S [Å]

S–CR₃[Å]

344.6

1.674

1.835

–0.87

–35.1

354.1

1.640

1.904

–0.75

–65.9

356.1

1.660

1.887

–0.83

–43.8

q(C_αMe₂) [e]

σ*_S–CR3[kcalmol^–1]

In summary, there is much experimental and theoretical

evidence showing that dialkyl-substituted α-sulfonyl carb-

anions generally have a strongly pyramidalized C_αatom ex-

cept for when the S atom bears a bulky substituent, in

which case the C_αatom is planar. The planarization of the

C_αatom of the dialkyl-substituted α-sulfonyl carbanion

causes an energy increase, which is outweighed by the de-

crease in the steric interaction between all substituents and

the increase in negative hyperconjugation. The experimental

and theoretical data point to a small intrinsic energy differ-

ence between pyramidalized and planar dialkyl-substituted

α-sulfonyl carbanions.^[3h,6b,6c]

Figure 16. Space filling model of the crystal structure of the dimeric

tricoordinated salt (M/P)-3·4THF with H atoms and one THF mo-

lecule omitted. Color code: C, black; S, yellow; O, red; Li, pink.

Accessibility of the Anionic C Atom of the Monomeric and

Dimeric Salts for Electrophiles

What can be predicted about the reactivity of the mono-

meric and dimeric lithium α-tert-butylsulfonyl carbanion

salts towards electrophiles? An inspection of the space-fill-

ing models of the dimeric salts in the crystal form shows

that the C_αatoms are completely shielded by THF mole-

cules, as highlighted by the space-filling model of the salt

(M/P)-3·4THF (Figure 15). Thus, the reactions of (M/P)-

3·4THF with electrophiles at the anionic C atom should be

very slow if not impossible. Therefore for a reaction of the

dimeric salt with an electrophile to occur at least one THF

molecule must dissociate with the formation of the corre-

sponding tricoordinated dimer. The C_αatom of the tricoor-

dinated salt is less shielded, as hinted by in the space-filling

model of (M/P)-3·3THF (Figure 16), which was generated

as a model from (M/P)-3·4THF by omitting one of the

THF molecules. However, the monomeric lithium salt is ex-

pected to have a higher reactivity than the dimeric salt if

only the shielding of the C_αatom is considered. The space-

filling model of rac-3·12-crown-4 (Figure 17), which may be

considered as a model for the THF-coordinated monomer

(see below), shows that the C_αatom is less shielded than

that in (M/P)-3·3THF. An inspection of the space-filling

Figure 17. Space filling model of the crystal structure of the mono-

meric salt rac-3·12-crown-4 with H atoms omitted for clarity. Color

code: C, black; S, yellow; O, red; Li, pink.

Structures of Lithium α-tert-Butylsulfonyl Carbanion Salts

in Solution

The Anionic C Atom Ϫ Coordination Geometry and

Negative Charge

Cryoscopy of the methyl-, ethyl-, benzyl-, and dialkyl-

substituted salts rac-9, rac-4, rac-3, and rac-6, respectively,

in THF revealed monomeric and dimeric CIPs, and X-ray

analysis of rac-9·PMDTA, (M/P)-4·4THF, and rac-3·12-

crown-4 provided models for their structures. Therefore the

structures of the salts rac-9, rac-4, and rac-3 in [D₈]THF

and [D₆]benzene solution were investigated by NMR spec-

troscopy. The salts rac-5 and rac-10 were also included in

this study. Although the crystalline THF-solvated dimeric

salts dissolved in [D₈]THF solution form dimer/monomer

mixtures, they are expected to retain their dimeric structure

in [D₆]benzene solution because of the low polarity of the

solvent. The ¹³C NMR spectra of the salts rac-9, rac-4, rac-

3, rac-5, rac-10, and rac-6 (cf. Figure 2) each showed, in

comparison with those of the corresponding sulfones, the

expected upfield shift^{[3k,3m,4a,4b,4e,4g,5g,5k]}of the signal of the

anionic C_αatom (Table 6). Interestingly, although the up-

field shifts are similar in magnitude for the methyl-, benzyl-

, ethyl-, and neopentyl-substituted benzylic salts rac-9, rac-

4, rac-3, and rac-5, respectively, that of the tert-butyl-substi-

Figure 15. Space filling model of the crystal structure of the dimeric

tetracoordinated salt (M/P)-3·4THF with H atoms omitted for

clarity. Color code: C, black; S, yellow; O, red; Li, pink.

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Eur. J. Org. Chem. 2010, 4559–4587

Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

Table 6. ¹³C NMR chemical shifts of the C_αatoms of the salts rac-9, rac-4, rac-3, rac-5, and rac-10 and the corresponding sulfones rac-

27, rac-28, rac-17, rac-29, rac-18, and rac-30.

Chemical

shift

Salt

rac-9

Sulfone

rac-27

Salt

rac-4

Sulfone

rac-28

Salt

rac-3

Sulfone

rac-17

Salt

rac-5

Sulfone

rac-29

Salt

rac-6

Sulfone

rac-18

Salt

rac-10

Sulfone

rac-30

δ [ppm]

53.1^[a]

59.9^[b]

60.8^[a]

66.6^[b]

–5.8

66.6^[d]

–7.1

57.8

62.3

58.4^[a]

63.2^[b]

–4.8

63.1^[d]

–8.4

37.9^[a]

55.3^[b]

57.8^[a]

71.8^[b]

∆δ [ppm]^[c]

δ [ppm]

–6.8

–4.5

–17.4

–14.0

52.2^[d,e]

–

59.5^[d]

56.7^[d]

–

54.7^[d]

–

58.0^[d]

71.8^[d]

∆δ [ppm]^[c]

–

–13.8

[a] In [D₈]THF at room temperature. [b] In CDCl₃at room temperature. [c] ∆δ = δ (salt) – δ (sulfone). [d] The crystalline THF-solvated

dimeric salt was dissolved in [D₆]benzene at room temperature. [e] In the presence of 2 equiv. of TMEDA.

tuted benzylic salt rac-10 is larger and that of the non-benz- Benzylic Conjugation and C_α–Ph Conformation

ylic salt rac-6 is larger still. These high-field shifts can be

Because of the mode of stabilization of the negative

mainly ascribed to the following factors. First, the accumu-

charge of the α-sulfonyl carbanion, much of the negative

lation of negative charge at the C_αatom causes a high-field

charge resides on the anionic C_αatom, which can interact

shift, the magnitude of which depends on the electron de-

with the phenyl group. This interaction is described in one

mands of the sulfonyl group, secondly, the interaction of the

model as conjugation between the lone-pair orbital at the

negative charge with the phenyl group (see below) causes a

C_αatom and the orbitals of the phenyl ring. The conjuga-

downfield shift, and thirdly, the change in the coordination

tion leads to charge transfer to the phenyl ring and thus to

geometry of the C_αatom from sp³to sp²or sp^3–xresults in

a higher electron density at the C_oand C_patoms. Therefore

a downfield shift of the signal. The sulfonyl group stabilizes

the changes in the chemical shifts of H_pand C_p[∆δ(H_p),

∆δ(C_p)] on going from the corresponding sulfone to the

salts rac-9, rac-4, rac-3, rac-5, and rac-10 act as probes for

the negative charge mainly by electrostatic and hyperconju-

gative interactions.^[6]Therefore much of the negative charge

at the C_αatom is available for interaction with the phenyl

group. Although the C_αatom of the salt rac-10 is nearly

the interaction between the negative charge at the C_αatom

and the phenyl ring.^[4e]Table 7 shows that the signals of H_p

planar, its ¹³C NMR signal experiences a significantly

and C_pof rac-9, rac-4, rac-3, and rac-5 experience a strong

larger high-field shift than those of the other C_α-phenyl-

high-field shift relative to the corresponding sulfones. With

substituted salts. This seems to be the result of a higher

regard to the magnitude of this effect, sulfonyl-substituted

negative charge at the C_αatom of rac-10 in comparison

with rac-9, rac-4, rac-3, and rac-5. Because of the C_α–Ph

conformation of rac-10, an optimal co-alignment of the

lone-pair orbital and the orbitals of the phenyl ring is not

possible (see below) and benzylic conjugation is strongly

reduced (see below). The salt rac-6, which carries two alkyl

benzylic carbanions behave quite differently, for example,

from nitro-substituted benzylic carbanions.^[4e]The nitro

group stabilizes the negative charge mainly by π conjuga-

tion, which leaves less negative charge at the C_αatom and

thus less charge is transferred to the C_p(o)atom than in the

case of the sulfonyl group. As a result, the nitro-substituted

groups at the C_αatom, shows the largest upfield shift. Al-

C_αatom of the benzyl carbanion experiences a much larger

though the C_αatom of this S-tert-butyl-substituted salt is

expected to be planar, a charge-reducing interaction with

the phenyl ring, as in rac-9, rac-4, rac-3, and rac-5, is not

low-field shift and the C_patom a much smaller high-field

shift.^[4e]

Interestingly, although the C_patoms of the methyl-, eth-

available. It is interesting to note that for the non-

yl- and benzyl-substituted salts rac-9, rac-4, and rac-3,

benzylic S-phenyl-substituted salts (M/P)-40·2diglyme,

(41·diglyme)₂, and (42·diglyme)₂, the C_αatoms of which are

significantly pyramidalized, the changes in the chemical

shifts of the C_αatoms on going from the sulfone to the salt

are ∆δ = –14.0, –12.7, and –11.0, respectively. These values

are similar in magnitude to those of rac-6 and rac-10.

respectively, experience a high-field shift of similar magni-

tude, that of the neopentyl-substituted salt rac-5 shows a

smaller high-field shift, and that of the tert-butyl-substi-

tuted salt rac-10 even smaller. The conjugative interaction

between the anionic C_αatom and the phenyl group also

1

Table 7. Chemical shifts of H_oand H_pin the H NMR spectra and of C_oand C_pin the ¹³C NMR spectra of the salts rac-9, rac-4, rac-

3, rac-5, and rac-10 and the corresponding sulfones rac-27, rac-28, rac-17, rac-29, and rac-30 in [D₈]THF.

Chemical shift

Salt

rac-9

Sulfone

rac-27

Salt

rac-4

Sulfone

rac-28

Salt

rac-3

Sulfone

rac-17

Salt

rac-5

Sulfone

rac-29

Salt

rac-10

Sulfone

rac-30

δ(H_o) [ppm]^[a]

∆δ(H_o) [ppm]^[a,b]

δ(H_p) [ppm]^[a]

∆δ(H_p) [ppm]^[a,b]

δ(C_o) [ppm]^[a]

7.09

7.50

7.13

7.48

7.05

7.35

7.38

7.53

7.39

7.55

–0.41

–0.35

7.36

–1.17

129.5

–9.3

128.7

–14.7

–0.30

–0.15

–0.16

6.18

7.35

128.9

128.7

6.19

6.15

7.27

6.22

7.34

130.1

128.6

6.82

7.34

131.1

128.1

–1.17

–9.6

–1.12

–7.0

–0.52

+7.4

–4.8

[c]

119.2

113.7

120.2

114.0

120.1

114.0

–

123.1

115.3

138.5

123.3

∆δ(C_o) [ppm]^[a,b]

δ(C_p) [ppm]^[a]

–

128.7

–14.7

∆δ(C_p) [ppm]^[a,b]

–15.0

–13.4

[a] Sulfone in CDCl₃at room temperature. [b] ∆δ = δ(salt) – δ(sulfone). [c] Signal could not be assigned.

Eur. J. Org. Chem. 2010, 4559–4587

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4571

H.-J. Gais et al.

FULL PAPER

depends on the proper co-alignment of the p orbital of the ingly, the magnitude of the high-field shifts of C_pand C_o

C_αatom and the orbitals of the phenyl group. In a first for rac-9, rac-4, rac-3, rac-5, and rac-10 show a rough corre-

approximation, the quality of this alignment can be judged lation with the deviation of the lone-pair orbital from co-

by the dihedral angles S–C_α–C_i–C_oof the salts rac-9, rac- planarity with the p orbital of the phenyl ring, as judged by

4, rac-3, rac-5, and rac-10 in the crystal form (Figure 18). the dihedral angles S–C_α–C_i–C_oof the corresponding salts

Although the dihedral angles of the salts rac-9·PMDTA, in the crystal form (Figure 18a–c).

(M/P)-4·4THF, (M/P)-3·4THF, and rac-3·12-crown-4 are

small and similar in magnitude (5–10°; cf. Table 3), that of

(M/P)-5·4THF is large (37°) and that of (M/P)-10·2THF

Benzylic Rotation

1

Temperature-dependent H and ¹³C NMR spectroscopy

of the methyl-, ethyl-, and neopentyl-substituted salts rac-9,

rac-4, and rac-5, respectively, in [D₈]THF and [D₁₄]diglyme

showed reversible coalescence phenomena of the H_o, H_m,

C_o, and C_msignals, which indicates a hindered rotation

around the C_α–C_ibond. The topomerization of these nuclei

has to involve a rotation around the C_α–C_ibond. This pro-

vided a means to study the benzylic rotation by DNMR

spectroscopy. Information about the C_α–C_irotational bar-

rier of benzylic carbanions carrying an additional carban-

ion-stabilizing group at the C_αatom is scarce. The barriers

for the sulfonyl-substituted carbanion [CF₃SO₂C₆H₄C(H)-

even larger (77°) (see the Supporting Information). Interest-

SO₂CF₃)]^–[∆G^‡

(256 K) = 11.5 kcalmol^–1, DMSO]^[4f]

rot

and cyano-substituted carbanion [PhC(H)CN]Li [∆G^‡

rot

(213 K) = 10.7 kcalmol^–1, THF]^[28]have previously been re-

ported. The activation free energies for the rotation of the

phenyl ring of rac-9, rac-4, and rac-5 at the coalescence tem-

perature were estimated^[20]based on the assumption that

the topomerization follows first-order kinetics. Although

barriers of ∆G^‡= 9.6–9.9 and 9.7 kcalmol^–1were esti-

rot

mated for the methyl- and ethyl-substituted salts rac-9 and

rac-4, respectively, the barrier for the neopentyl-substituted

salt rac-5 was significantly higher at ∆G^‡

= 11.0–

rot

11.2 kcalmol^–1at 223 K (Table 8). Although a direct com-

parison of the barriers for rac-4, rac-5, and rac-9 is pre-

cluded because of the different coalescence temperatures,

the higher barrier for rac-5 is perhaps due to the steric hin-

drance posed by the tert-butyl group. For comparison, the

barrier for the S-phenyl-substituted salt rac-1 towards C_α–

C_irotation in the presence of 2 equiv. of HMPA was also

Figure 18. (a) Dihedral angles S–C_α–C_i–C_oof the salts rac-

9·PMDTA (Me), (M/P)-4·4THF (Et), (M/P)-3·4THF (CH₂Ph),

(M/P)-5·4THF (CH₂tBu), and (M/P)-10·2THF (tBu) in the crystal

form. (b) Chemical shifts of C_m(ᮀ), C_o(᭺), and C_p(᭹) of the

salts rac-9, rac-4, rac-3, rac-5, and rac-10 in [D₈]THF at room tem-

perature. (c) Chemical shift differences for C_pin the salts rac-9, rac-

4, rac-3, rac-5, and rac-10 ([D₈]THF, room temperature) and the

corresponding sulfones rac-27, rac-28, rac-17, rac-29, and rac-30

(CDCl₃, room temperature).

1

determined. H DNMR spectroscopy showed a reversible

coalescence phenomenon of the H_msignals, the analysis of

which gave an activation free energy of ∆G^‡

=

rot

9.5 kcalmol^–1at the coalescence temperature of 196 K,

which is in good agreement with those of rac-9 and rac-4.

A particularly interesting case is the C_α-tert-butyl-substi-

tuted benzylic salt rac-10, which has an unusual C_α–C_icon-

1

Table 8. Estimated activation free energies ∆G^‡(T_c) for the rotation of C_α–Ph in the salts rac-9, rac-4, rac-5, and rac-1·2HMPA by H

rot

and ¹³C DNMR spectroscopic analysis (500 and 125 MHz).

Parameter

rac-9^[a]

C_o

rac-4^[b,c]

H_o

rac-5^[a]

rac-1·2HMPA^[a]

H_m

H_o

C_m

H_o

C_o

C_m

∆ν [Hz]

T_c[K]

k_rot[s]

700

228Ϯ5

1555

356

218Ϯ10

791

154

208Ϯ10

342

700

223Ϯ10

1555

460

253Ϯ5

1022

276

243Ϯ10

613

65

228Ϯ10

144

47

196Ϯ10

104

∆G^‡(T_c)

9.9Ϯ0.2

9.7Ϯ0.5

9.6Ϯ0.5

9.7Ϯ0.5

11.2Ϯ0.3 11.0Ϯ0.5

11.0Ϯ0.5

9.5Ϯ0.3

rot

[kcalmol^–1]

[a] In [D₈]THF. [b] In [D₁₄]diglyme. [c] Upon cooling a solution of rac-4 in [D₈]THF to – 40 °C the same changes in the H_osignal were

observed as in [D₁₄]diglyme.

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Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

formation. Determination of its enantiomerization barrier Low-Temperature NMR Spectroscopy in [D₈]THF Ϫ

by DNMR spectroscopy was not possible because of the Monomer–Dimer Equilibria

nonobservance of different chemical shifts for the dia-

The possible structures of the monomers of the salts rac-

stereotopic nuclei at the ortho and meta positions of the

3–6, rac-9, and rac-10 in THF solution are the O–Li CIPs

1

phenyl group. The variable-temperature H and ¹³C NMR

III–V and the O,C–Li CIPs VI and VII (Figure 19). Mono-

spectra of rac-10 in [D₈]THF showed no coalescence phe-

mer III features a coordination of the Li atom to both O

nomena due to hindered C_α–C_irotation at low tempera-

atoms. The Li atoms of the diastereomeric monomers IV

tures. The ¹H NMR spectrum at –100 °C displayed only

and V, which have a stereogenic S atom, are only coordi-

nated to one of the O atoms in the anions. Structures IV

and V resemble those found for the monomers rac-3·12-

crown-4 and rac-9·PMDTA in the crystal form. Monomers

minor line-broadening for the signal of H_o, whereas the

doubling of the signal of H_pis due to the presence of several

CIPs (see below). Furthermore, the number of signals of C_o

and C_mdid not exceed those of C_pand C_i. The lack of

VI and VII exhibit a coordination of the Li atom to both

doubling of the signals of H_o, H_m, C_m, and C_oof the salt

the O atom and the anionic C_αatom. In addition to the

rac-10 in equal intensity at –100 °C can be rationalized as

monomers, four dimers of salts rac-3Ϫ6, rac-9, and rac-10

are conceivable, the achiral dimers anti-(P/M)-VIII (C_i) and

syn-(P/M)-IX (C_s) and the chiral dimers anti-(P/P)-X (C₂)

follows. First, the signals of H_o, H_m, C_m, and C_oare inci-

dentally isochronous under the conditions of measurement.

This is not very likely given the structure of rac-10 (see

and syn-(P/P)-XI (C₂).^[29]In the crystal form, the dimers

above and below). In strong contrast to the salts rac-9, rac-

adopt a structure of the type anti-(P/M)-VIII. The results

4, rac-3, and rac-5, the salt rac-10 adopts in the crystal form

of the ⁶Li{¹H} NOE experiments on rac-3, rac-5, rac-6, and

and most probably also in solution a C_α–Ph conformation

rac-10 in [D₈]THF are more in favor with the Li atom being

in which the phenyl ring is almost orthogonal to the C_tBu

–

positioned at the O atom of the carbanion, as in structures

C_α–S plane (cf. Figure 7). Thus, one H_ois syn to the Li-

coordinated O atom, whereas the other one is syn to the S-

tert-butyl group. The same holds true for the H_m, C_o, and

C_matoms. The different chemical environments of the nu-

clei should be manifested in different chemical shifts. Sec-

ondly, the barrier towards C_α–C_irotation could be much

lower than that of rac-9, rac-4, and rac-5. Although the

ground states of the salts rac-9, rac-4, and rac-5 are stabi-

lized through the conjugation of the lone-pair orbital at the

C_αatom with the phenyl ring, it is the transition state of

the C_α–C_irotation of the salt rac-10 that will be stabilized

by benzylic conjugation. Thus, the NMR spectra of rac-10

at –100 °C could still be a reflection of a fast exchange re-

gime. It is more than questionable, however, whether this

energy-lowering effect of the transition state is sufficient to

overcome the destabilization by the severe interaction of H_o

with the C_α-tert-butyl group. Even in the ground state of

rac-10 there is a significant interaction between the C_α-tert-

butyl and phenyl groups, as indicated by the rather small

C_i–C_α–S angle of 115.2°. The corresponding angles for the

salts rac-3·12-crown-4, (M/P)-4·4THF, and (M/P)-5·4THF

are 124.6, 124.5, and 119.9°, respectively, and are, thus, sig-

nificantly larger. Thirdly, and most importantly, because of

the C_α–Ph conformation of rac-10, topomerization of the

H_o, H_m, C_m, and C_oatoms of the phenyl ring can also occur

by rotation around the C_α–S bond. Thus, the absence of any

dynamic phenomenon in the temperature-dependent NMR

spectra of rac-10 could imply that at –100 °C the topomer-

ization of the nuclei is still in the fast exchange regime be-

cause of the low enantiomerization barrier of the salt. Be-

cause the phenyl ring is fixed in a position almost orthogo-

nal to the C_tBu–C_α–S plane, C_α–S rotation can take place

whereby the tert-butyl group attached to the S atom can get

past the face of the phenyl ring but not the tert-butyl group.

A phenyl group in such a position is smaller sterically than

a methyl group, as shown by E_svalues of –1.01 and –1.24,

respectively.^[11]

III–V and VIII–XI, than at the O and C_αatom, as in VI

6

and VII. However, because the Li{¹H} NOE experiments

were conducted at room temperature, only information con-

cerning the averaged structures of the various monomers

and dimers was obtained (see the Supporting Information).

Therefore NMR experiments on the benzylic salts rac-4,

rac-5, rac-9, and rac-10 at low temperatures were performed

to seek more information about the monomers and dimers

Figure 19. Possible structures of the monomers and dimers of lith-

ium α-tert-butylsulfonyl carbanion salts (priority: R¹ϾR²).

Eur. J. Org. Chem. 2010, 4559–4587

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4573

H.-J. Gais et al.

FULL PAPER

and to find a correlation with the results of the cryoscopy

experiments.

The ¹H and ¹³C NMR spectra of the methyl-, ethyl-, and

neopentyl-substituted salts rac-9, rac-4, and rac-5, respec-

tively, showed at low temperatures, in addition to the co-

alescence phenomena originating from a reduction of the

frequency of the C_α–S and C_α–C_ibond rotations, further

line-broadenings and reversible coalescence phenomena.

This caused the appearance of further signals in addition

to those originating from a slowing of the bond rotation.

Finally, the spectra of rac-9, rac-4, rac-5, and rac-10 at

–100 °C revealed the presence of two to five different equi-

librium species in various ratios (Table 9). In several cases,

the sample of the salt used for the low-temperature NMR

studies also contained some of the corresponding sulfone.

However, the NMR spectra of the mixtures at the various

temperatures and ratios gave no indication of complex for-

mation between the salt and the corresponding sulfone.

Table 9. Number of species of the salts rac-4–6, rac-9, and rac-10

present at –100 °C in [D₈]THF according to ¹H, ¹³C, and ⁶Li NMR

spectroscopy.

Species (Ratio)

Salt

¹H NMR

(500 MHz)

¹³C NMR

(125 MHz)

⁶Li NMR

(75 MHz)

[b]

rac-9

rac-4

rac-5

3^[a](75:15:10)

4 (45:30:15:10)

2 (85:15)

2 (60:40)

–

[b]

2^[c](85:15)

–

3 (55:40:5)

2 (60:40)

rac-10 Ն2^[d,e](–)

5 (50:20:10:10:10)

3 (70:20:10)

[b]

rac-6

2^[e](60:40)

–

[a] Four C_α-methyl signals were observed in a ratio of 45:30:15:10.

[b] Not investigated. [c] At –80 °C in [D₁₄]diglyme. [d] Because of

the large line width, the number of signals and their intensity could

not be determined with certainty. [e] At –60 °C.

1

Figure 20. H NMR (500 MHz) spectra (in part) of the salt rac-9

in [D₈]THF at ca. 25 °C and –100 °C.

The H NMR spectrum of the α-methyl-substituted salt

rac-9 in [D₈]THF at –100 °C exhibited a three-fold splitting

of the signals of H_o, H_oЈ, H_p, H_m, and H_mЈ. In addition, a

four-fold splitting of the signal of the C_α-methyl group was

observed. This splitting points to the presence of four spe- ting of the signals of H_o, H_p, H_oЈ, and the methylene group

cies in a ratio of 45:30:15:10 (Figure 20). The ¹³C NMR and thus indicates the presence of three species in a ratio of

spectrum exhibited two signals for C_i, three signals for C_oapproximately 55:40:5 (Figure 22). The ¹³C NMR spectrum

and C_oЈ, four signals for C_p, four signals for S-tBu, and four exhibited two complete and very similar signal sets in ac-

signals for C_α, which indicates the presence of four species cord with the presence of two species in a ratio of 60:40

in a ratio of approximately 45:30:15:10 (Figure 21). Cryos- (Figure 23).

1

copy of rac-9 in THF at –100 °C had shown a dimer-to-

The H NMR spectrum of the C_α-tert-butyl-substituted

monomer ratio of approximately 70:30.

salt rac-10 in [D₈]THF at –100 °C showed a doubling of the

1

The H NMR spectrum of the C_α-ethyl-substituted salt signals for the tert-butyl groups and thus the presence of at

rac-4 in [D₁₄]diglyme at –80 °C showed, according to the least two species. The ¹³C NMR spectrum, however, exhib-

doubling of the signals of H_o, H_oЈ, and H_p, the presence of ited four signals for C_i, five signals for C_o, three signals for

two species in a ratio of 85:15. Similarly, a doubling of the C_p, two signals for the S-tert-butyl group, three signals for

¹³C NMR signals of C_i, C_o, C_oЈ, C_p, and C_αalso revealed C_α, and three signals for the C_α-tert-butyl group. This split-

the presence of two species in approximately the same ratio. ting points to the presence of five species in a ratio of

The differences in the shifts of the ¹H and ¹³C NMR signals 50:20:10:10:10.

for the two species are only small.

The H NMR spectrum of the α-neopentyl-substituted rac-6 in [D₈]THF at –60 °C showed, according to a doub-

salt rac-5 in [D₈]THF at –100 °C featured a three-fold split- ling of the signals of the methyl and methylene groups, the

The ¹H NMR spectrum of the C_α-dialkyl-substituted salt

1

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Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

Figure 21. ¹³C NMR (125 MHz) spectra (in part) of the salt rac-9

in [D₈]THF at ca. 25 °C and –100 °C.

1

Figure 22. H NMR (500 MHz) spectra (in part) of the salt rac-5

in [D₈]THF at ca. 25 °C and –100 °C (the expanded spectrum was

obtained with resolution enhancement).

presence of two species in a ratio of 60:40. Cryoscopy of

rac-6 in THF at –100 °C had shown the existence of dimers

and monomers in a ratio of approximately of 60:40.

1

The low-temperature H and ¹³C NMR experiments on

the salts rac-9, rac-4, rac-5, and rac-10 were complemented cryoscopic aggregation numbers of rac-4, rac-9, and rac-5,

6

by Li NMR experiments on the salts rac-5 and rac-10 in (2) the ⁶Li{¹H} NOE experiments on rac-3 and rac-5 in

[D₈]THF at –100 °C. Although the low-temperature spec- [D₈]THF (see the Supporting Information), and (3) the low-

trum of the C_α-neopentyl-substituted salt rac-5 exhibited temperature NMR investigation, which revealed up to five

two signals in a ratio of 60:40, that of the C_α-tert-butyl- different species of the salts. However, it should be emphas-

substituted salt rac-10 showed three signals in a ratio of ized that cryoscopy only gives aggregation numbers that are

70:20:10.

an average over all monomers and possible aggregates. In

The H and ¹³C NMR spectra of the racemic salts rac- addition, the ⁶Li{¹H} NOE experiments only provided

9, rac-4, rac-5, and rac-10 in [D₈]THF at –100 °C showed averaged information because they were performed at room

the existence of up to five different species. The chemical temperature (see the Supporting Information) at which a

shifts of the various species are very similar. Low-tempera- fast equilibration of all species takes place. Nevertheless, the

ture ⁷Li, ¹H, and ¹³C NMR studies of other lithium α-sulfon- crystal structures of (M/P)-3·4THF, (M/P)-4·4THF, (M/P)-

yl carbanion salts have also indicated the existence of sev- 5·4THF, (M/P)-10·2THF, rac-3·12-crown-4, and rac-

eral species in [D₈]THF and THF/Et₂O at very low tem- 9·PMDTA can serve as models for the structures of the

peratures.^[3m,30]It is thus proposed that the monomers of dimers and monomers in THF solution. Although all avail-

the salts rac-9, rac-4, rac-5, and rac-10 adopt the structures able evidence points to CIP structures of the type III–V for

of the O–Li CIPs III–V and the dimers the structures of the the monomers in THF, which exhibit only O–Li and no C–

CIPs VIII–XI. This would be in accordance with (1) the Li bonds, the existence of C,O–Li CIPs of the type VI and

1

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4575

H.-J. Gais et al.

FULL PAPER

solution be demonstrated by NMR spectroscopy.^[31]Ab ini-

tio calculations on the monomeric salts 49·2THF^[6k]and

50·2Et₂O^[3q]gave the two structures 51 and 52 (Figure 24).

Whereas the Li atom of 52 is coordinated by one O atom

and the C_αatom, that of 51 is coordinated by both O atoms.

Interestingly, both structures have the typical C_α–S confor-

mation in which the lone-pair orbital at the C_αatom bisects

or nearly bisects the O–S–O angle. Although the allylic

CIPs 51a and 52a (S = THF) have the same energy, the

alkyl O,C–Li CIP 52b is 2.5 kcalmol^–1more stable than the

O–Li CIP 51b (S = OEt₂). There is, however, an important

structural difference between the salts studied in this work

and the salts 49 and 50. Although the C_αatoms of 49 and

50 carry only one substituent, those of the lithium tert-but-

ylsulfonyl carbanion salts bear either an alkyl and a phenyl

group or two alkyl groups. This could perhaps make, in the

case of the C_α-disubstituted carbanions, the C,O–Li CIPs

of the type VI and VII (cf. Figure 22) energetically less fa-

vorable than O–Li CIPs of the type III–V because of steric

interactions between the THF-coordinated Li atom and the

substituents R¹and R². Recently, the crystal structure of

50·THF, the Li atom of which carries only one THF mole-

cule, has been determined.^[3q]This salt is a polymer in the

crystal form that features a C–Li bond and two O–Li bonds

but contains no four-membered C_α–Li–O–S ring like 52b.

The C_αatom of 50·THF is pyramidalized and the salt has

a C_α–S conformation in which the C–Li bond almost bi-

sects the O–S–O angle. The coordination of the Li atom to

the C_αatom and thus the formation of a C–Li bond in the

crystal is most likely the result of a lack of solvating THF

molecules for the Li atom. In summary, all available data

on salts rac-1–10 point to the existence of monomeric and

dimeric O–Li CIPs of the type III–V and VIII–XI in THF

that are in fast equilibrium.

Figure 23. ¹³C NMR (125 MHz) spectra (in part) of the salt rac-5

in [D₈]THF at ca. 25 °C and –100 °C.

VII cannot be excluded. The ¹³C NMR spectra showed for

all the species present a singlet for the anionic C_αatom and

thus no splitting due to C–Li coupling. Low-temperature

¹³C NMR studies of the lithium salts of bicyclic α-sulfonyl

carbanions also failed to reveal J(¹³C,⁶Li) coupling.^[3m]

However, C,O–Li CIPs of the type VI and VII may be pres-

ent in only small amounts and escape detection. Alterna-

tively, they could be amongst the up to five species detected

by NMR spectroscopy at –100 °C and undergo a fast C–Li

exchange even at –100 °C, which would prevent the detec-

Figure 24. Calculated structures 51 and 52 of the salts 49 and

50.^[3q,6k]

Low-Temperature NMR Spectroscopy in the Presence of

HMPA Ϫ the CIP/SIP Equilibrium

Finally, low-temperature ⁷Li and ³¹P NMR spectroscopic

tion of C–Li coupling in the ¹³C and ⁶Li NMR spectra. All experiments on the methyl-substituted salt rac-9 were con-

attempts to detect a species of the type VI or VII, either as ducted in [D₈]THF in the presence of HMPA. It was of

a monomer or dimer, exhibiting a C–Li bond in solution interest to see whether this strongly Li-coordinating mole-

have thus far failed. Only in the case of an α,α-dilithio- cule would lead to the formation of SIPs.^[4d,32]DNMR

sulfone could the existence of a C–Li bond in THF spectroscopy of the benzylic S-phenyl salt rac-1 in [D₈]THF

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Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

in the presence and absence of HMPA has revealed a higher behavior of the S-phenyl-substituted salts rac-50, [HC(H)-

free energy of activation for the enantiomerization in the SO₂Ph]Li and [MeC(Ph)SO₂Ph]Li towards HMPA in [D₈]-

7

former case. The S-tert-butyl salt rac-9 was studied instead THF/Et₂O at –110 to –135 °C by Li and ³¹P NMR spec-

of rac-1 in more detail because of a higher configurational troscopy.^[4d,30]It was found that the monomeric and dimeric

7

stability. The Li NMR spectrum of the salt rac-9, which in CIPs are converted upon the addition of HMPA into the

THF at –108 °C is an equilibrium mixture of four different corresponding CIPs bearing one HMPA molecule. The fur-

monomers and dimers, in [D₈]THF/n-hexane (20:1) at ther addition of HMPA then transforms these CIPs into

–115 °C in the presence of 2 equiv. of HMPA showed a SIPs bearing three HMPA molecules and finally into SIPs

quintet (J = 7.6 Hz) at δ ≈ –0.70 ppm and a broad signal bearing four HMPA molecules. The CIPs with two HMPA

centered at δ ≈ –0.30 ppm in a ratio of approximately 50:50 molecules are not stable but disproportionate into the CIP

(external reference, LiBr in H₂O). Although the latter signal with one HMPA and the SIP with three HMPA molecules.

could not be assigned, it appeared to be a combination of

two signals, a doublet and a quartet. Warming the solution

of rac-9 to –60 °C resulted in the disappearance of the split-

ting of the signals and the appearance of two singlets, which

Ab initio Calculations on a Counterion-Free S-tert-Butyl

Carbanion Ϫ Electronic Structure and Roational Barrier

finally collapsed at room temperature to one singlet. The

³¹P NMR spectrum of rac-9 in [D₈]THF/n-hexane (20:1) at

Having obtained experimentally information about the

–115 °C in the presence of 2 equiv. of HMPA exhibited a structure of the salt rac-9 in the crystal form and in solu-

singlet at δ ≈ 23.1 ppm, presumably free HMPA, and a tion, ab initio calculations on its counterion-free carbanion

broader singlet at δ ≈ 23.7 ppm (external reference, H₃PO₄9(–Li) were undertaken. The rate-determining step of the

in H₂O) in a ratio of 45:55. Unfortunately, a splitting of the racemization of (M)-9 is the C_α–S bond rotation, which can

latter signal due to ³¹P,⁷Li-coupling could not be resolved. occur in a clockwise and counter-clockwise fashion. Be-

The two signals in the ³¹P NMR spectrum merged at –60 °C cause of the two different substituents at the C_αatom, there

into one singlet. Nearly the same ⁷Li and ³¹P NMR spectra are two different barriers and only the lowest barrier is ac-

of rac-9 in [D₈]THF at –115 °C were recorded in the pres- cessible by kinetic experiments. Theoretical calculations on

ence of 5 equiv. of HMPA, except that the apparent doub- 9(–Li) were expected to give not only information about

let/quartet-to-quintet signal ratio in the ⁷Li spectrum both barriers but also about the electronic structure of the

changed to a ratio of 30:70 in favor of the quintet. In the anion. In particular, information as to the magnitude of the

³¹P NMR spectrum the ratio of the two singlets increased benzylic conjugation was sought, which has already been

to 35:65. The quintet in the ⁷Li NMR spectrum arises from probed by NMR spectroscopy (see above). Previous ab ini-

a Li ion to which four HMPA molecules are coordinated. tio calculations on counterion-free α-sulfonyl carbanions

2

This is in accordance with the magnitude of the J(³¹P,⁷Li) dealt only with non-benzylic derivatives.^[6b,6c,6j]Ab initio

coupling of 7.6 Hz.^[30]Thus, this signal was assigned to the calculations at different levels of theory employing the

SIP rac-9·4HMPA (Figure 25). This result shows that rac-9 Gaussian 03 suite of quantum-chemical routines^[33]were

forms a SIP in the presence of HMPA. The apparent doub- carried out to elucidate the binding near the anionic C

7

let [²J(³¹P,⁷Li) = 12.1 Hz] in the low-temperature Li spec- atom. To determine the preferred relative orientation of the

trum could be caused by the monomeric CIPs rac- substituents we performed a complete rotation about the

9·THF·HMPA and rac-9·HMPA·THF or their dimers, the C_α–S bond starting from a structure fully optimized at the

Li atoms of which carry one HMPA molecule. The appar- HF/6-31+G* level with an equilibrium dihedral angle Θ(O–

ent quartet indicates the presence of the SIP rac-9·3HMPA, S–C_α–C_Me) of 15.4°. In these calculations the C_αatom was

which has three HMPA molecules. The signals of the forced into the plane defined by its nearest neighbors (S,

HMPA-coordinated monomers and dimers were, however,

C_Me, and C_i). Moreover, the phenyl group was constrained

not resolved. Reich and co-workers previously studied the to planarity but allowed to rotate freely about the C_α–C_i

bond. The dihedral angle Θ was changed in steps of 10°

and by freezing this angle at the corresponding value we

optimized the remaining structural parameters at the HF/

6-31+G* level under the constraints described above. The

resulting potential curve is shown in Figure 26 (dotted).

To obtain more reliable relative energies we then per-

formed single-point calculations employing the larger 6-

311++G** basis set, including the correlation energy by

means of the second-order Møller–Plesset perturbation

theory (MP2).^[34]The potential curve obtained in this way

is also shown in Figure 26 (solid line). The curve calculated

upon including the correlation energy in single-point calcu-

lations is quite similar to that obtained at the HF/6-31+G*

level. Both curves have two minima, 9A(–Li) and 9B(–Li),

and two maxima, 9C(–Li) and 9D(–Li). The structures of

Figure 25. Structures of the HMPA-coordinated SIPs and CIPs of

the salt rac-9.

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4577

H.-J. Gais et al.

FULL PAPER

Figure 26. Energies (kcalmol^–1) of 9(–Li) relative to the most stable

conformer as a function of the dihedral angle Θ(O1–S–C_α–C_Me)-

(dotted: HF/6-31+G*//HF/6-31+G*; solid: MP2/6-311++G**//

HF/6-31+G*).

the four conformations viewed along the C_α–S axis are

shown in Figure 27. At the MP2/6-311++G**//HF/6-

31+G* level, the energetically most favorable conformer

9A(–Li) was found at Θ = 15.4° (∆E_HF= 0.25 kcalmol^–1).

The other minimum, 9B(–Li) (∆E_MP2= 0.14 kcalmol^–1),

occurs at 205.4° (∆E_HF= 0.00 kcalmol^–1). At both levels of

theory the energetically least favorable conformation,

9D(–Li), was found at Θ = 295.4° corresponding to an en-

ergy of ∆E_MP2= 20.82 kcalmol^–1(∆E_HF= 22.10 kcalmol^–1)

relative to 9A(–Li). An energetically somewhat lower maxi-

mum, 9C(–Li) (∆E_MP2= 17.30 kcalmol^–1), occurs at Θ =

115.4° (∆E_HF= 16.64 kcalmol^–1; Table 10).

Striking structural differences between the minima and

maxima were found. First, the orientation of the phenyl

ring relative to the plane of the C_αatom as defined by the

dihedral angle Φ = C_Me–C_α–C_i–C_oas a function of the di-

hedral angle Θ is shown in Figure 28. The dotted curve is

Figure 27. Structures of the conformations 9A(–Li) (top), 9C(–Li)

(middle), 9B(–Li) (lower middle), and 9D(–Li) (bottom) obtained

at the HF/6-31+G* level employing the constraints described in the

text. Color code: C, black; S, yellow; O, red; H, grey.

the potential curve obtained at the MP2/6-311++G**//HF/ average, the C–C bonds of the phenyl ring are slightly

6-31+G* level of theory. Note that the dihedral angles Φ in longer for the maxima [9C(–Li): 1.399 Å; 9D(–Li): 1.401 Å]

9A(–Li), 9B(–Li), 9C(–Li), and 9D(–Li) are less than 10° than for the minima [9A(–Li): 1.398 Å; 9B(–Li): 1.398 Å].

and therefore the phenyl ring and the plane defined by the Secondly, on average, the S–C_αbonds are 0.034 Å longer in

nearest neighbors of the C_αatom are more or less coplanar. the maxima than in the minima. The lengths of these bonds

The largest deviation from the value of 0°, ideal for a conju- will be discussed below in the description of the interactions

gative interaction between the anionic C_αatom and the of the bonding and antibonding MOs within the framework

phenyl group, occurs for the minima 9A(–Li) (9.5°) and of the NBO method.^[35]Figure 28 reveals interesting

9B(–Li) (–5.8°), whereas smaller values were found for the changes in the C_α–C_iand C_α–S conformations on going

maxima 9C(–Li) (0.3°) and 9D(–Li) (–4.8°). Consequently from the minimum 9B(–Li) via the maximum 9D(–Li) to

the phenyl groups of the minimum structures carry a less the minimum 9A(–Li), which involves a higher C_α–S rota-

negative (natural) charge [9A(–Li), 9B(–Li): –0.25e] than tional barrier. Upon rotation around the C_α–S bond of

those of the maxima [9C(–Li): –0.27e; 9D(–Li): –0.36e; for 9B(–Li), a simultaneous rotation around the C_α–C_ibond

the special case of 9D(–Li): see below]. Moreover, on occurs up to a maximum value of Θ = –30°, which corre-

Table 10. Energies, angles, bond lengths, charges (q) and occupation numbers (n) for 9A(–Li), 9B(–Li), 9C(–Li), and 9D(–Li).

[a]

[c]

[d]

9(–Li)

∆E_HF

Θ^[b][°]

∆E_MP2

C_α–S [Å] C_α–C_i[Å] q (C_α) [e]

n_n(C_α)

∆E_n(Cα)ǞRy

*

∆E_n(Cα)ǞBD

*

n_σS–Cα

n_σ*S–Cα

[kcalmol^–1]

A

B

C

D

0.25

0.00

16.64

22.10

15.4

205.4

115.4

295.4

0.00

0.14

17.30

20.82

1.693

1.717

1.736

1.441

1.432

1.416

–0.6784

–0.6771

–0.6389

–0.5933

1.5881

1.5872

1.5871

–18.67

–18.97

–15.02

–8.94^[e]

–166.74

–167.97

–174.34

–50.10^[e]

1.9785

1.9784

1.9773

1.9763

0.1024

0.1020

0.1038

0.1068

[a] Relative to the most stable conformer. [b] Dihedral angle C_Me–C_α–S–O. [c] For the HF/6-31+G*-optimized geometry relative to the

most stable conformer. [d] ∆E_nǞσ*= –q_n‹n|F|σ*›²/(ε_σ*– ε_n), in which F is the Fock operator of the molecule and q_nthe occupation

number of the lone pair. ε_σ*and ε_nare the NBO orbital energies of the σ* and the nonbonding orbital n, respectively. [e] Interaction of

π_Cα-Ciwith Ry* and BD*.

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Eur. J. Org. Chem. 2010, 4559–4587

Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

sponds to the conformation 9E(–Li) (Figure 29). Further 9B(–Li), and 9C(–Li), there is no such lone pair at C_αin

C_α–S rotation sees a simultaneous rotation around the the case of 9D(–Li) but an additional π bond to the C_i

C_α–C_ibond in the opposite direction with the attainment atom. This π bond, however, is largely located at C_α

of conformation 9D(–Li) in which the phenyl ring adopts a (74.4%). Note that at 1.416 Å this conformer also has the

conformation optimal for benzylic conjugation (Θ = 300° shortest C_α–C_ibond and that the C_αatom of 9D(–Li) also

and Φ = 0°) and the tert-butyl group and phenyl ring are carries the least (natural) negative charge of all four struc-

synperiplanar. Upon further rotation around the C_α–S tures. In all four cases the S atom is bonded to C_αby a σ

bond of 9D(–Li) again simultaneous rotation around the bond between two hybrid orbitals (approximately sp³) with

C_α–C_ibond occurs up to a maximum value of Φ = 30° coefficients of about equal size at both atoms. According to

with the attainment of conformation 9F(–Li). Further C_α– the NBO analyses there is no additional π bond. The S–O

S rotation sees a simultaneous rotation around the C_α–C_ibonds are σ bonds between an sp³hybrid at sulfur and an

bond in the opposite direction with the attainment of con- sp^2.3orbital at oxygen with no additional π bond. Each O

former 9A(–Li). The C_α–S and C_α–C_irotations are most atom carries three lone pairs one of which has about 70%

likely accompanied by simultaneous rotation around the s and 30% p character, whereas the other two are essentially

S–tBu bond.

pure p orbitals. The potential curve obtained at the corre-

lated level (MP2/6-311++G**//HF/6-31+G*) was also sub-

jected to a Fourier analysis employing a five-term Fourier

series [Equation (1)].^[36,37]

V(Θ) = 0.5V₁(1 – cosΘ) + 0.5V₂(1 – cos2Θ) + 0.5V₃(1 – cos3Θ)

+ V₄sinΘ + V₅sin2Θ

(1)

The resulting V_iparameters are collected in Table 11.

The potential curve is dominated by a strongly positive V₂

(17.6 kcalmol^–1), which results in minima at Θ = 0 and 180°

and maxima at 90 and 270°. The large and positive V₂

might indicate a stabilizing interaction between the lone

pair at C_αand the σ* orbital of the S–C_tBubond (negative

hyperconjugation).^[6]Indeed, the NBO analyses indicate

significant interactions between these orbitals in 9A(–Li)

(–24.6 kcalmol^–1) and 9B(–Li) (–24.8 kcalmol^–1), whereas

interactions of the lone pair of 9C(–Li) or the C_α–S π or-

bital in the case of 9D(–Li) with the S–C_tBuσ* orbital are

negligible. However, the different degrees of nǞσ* inter-

action in 9A(–Li) and 9B(–Li) on the one hand and in

9C(–Li) on the other is not reflected by the S–C_tBubond

lengths in 9A(–Li), 9B(–Li), and 9C(–Li), which are com-

parable [9A(–Li): 1.846 Å; 9B(–Li): 1.844 Å; 9C(–Li):

1.846 Å], nor by the occupation numbers of n(C_α) which

are also similar for all three conformers (see Table 11).

Moreover, the total energies of the interactions between the

lone pair at C_αand the weakly occupied antibonding (BD*)

and Rydberg-like orbitals (Ry*) are comparable (–185 to

–189 kcalmol^–1) for structures 9A(–Li), 9B(–Li), and

9C(–Li), and even slightly more stabilizing for the maxi-

mum 9C(–Li) (–189 kcalmol^–1) than for the minima

Figure 28. The dihedral angle Φ = C_Me–C_α–C_i–C_oof 9(–Li) as a

function of Θ = O1–S–C_α–C_Me[°] (solid).

Figure 29. Structures of conformations 9E(–Li) (Θ = –30°) (top)

and 9F(–Li) (Θ = 30°) (bottom) obtained at the HF/6-31+G* level 9A(–Li) (–185 kcalmol^–1) and 9B(–Li) (–187 kcalmol^–1). At

–8.9 and –50.1 kcalmol^–1the interactions of the C_α–C_iπ

bond, mostly located at C_α, of 9D(–Li) with the Ry* and

employing the constraints described in the text. Color code: C,

black; S, yellow; O, red; H, grey.

BD* orbitals are much weaker. The σ* orbital of the C_α–S

To gain a deeper insight into the electronic structures of bond interacts more strongly with the occupied NBOs in

9A(–Li), 9B(–Li), 9C(–Li), and 9D(–Li) we analyzed the the maxima, which results in higher/lower occupation num-

corresponding molecular wavefunctions using the NBO bers of the σ*_Cα–S/σ_Cα–Sbonds and therefore larger C_α–S

method (version 3.1, as implemented in Gaussian 03)^[34]at bond lengths in these conformers. It therefore appears that

the MP2/6-311++G**//HF/6-31+G* level. The NBO analy- the shapes of the curves shown in Figure 26 are not deter-

ses gave a single σ bond without an additional π component mined by different degrees of negative hyperconjugation in

between the C_αand C_iatoms of 9A(–Li), 9B(–Li), and the four structures but rather by repulsive interactions be-

9C(–Li). The C_αatoms in these conformations carry a lone tween the substituents. Thus, in the maxima, the tert-butyl

pair of essentially pure p character. In contrast to 9A(–Li), group on the one hand and the methyl or phenyl group on

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4579

H.-J. Gais et al.

FULL PAPER

the other are in a synperiplanar orientation in which repul- Me- to the S-CF₃- and S-tBu-substituted carbanions. The

sion between the groups should be strong. Moreover, this planarization the C_αatom with increasing steric size of the

repulsive interaction should be stronger between the phenyl S substituent seems to be a result of a minimization of the

substituent and the tert-butyl group in 9D(–Li) than be- steric interaction between the S and C_αsubstituents in com-

tween the methyl and the tert-butyl group in 9C(–Li). Con- bination with a small intrinsic energy difference between the

sequently, conformation 9D(–Li), in which the phenyl sub- planar and pyramidal coordination geometry. Because of

stituent and the tert-butyl group are oriented synperiplanar, shielding of the anionic C atom by the S-tert-butyl group,

is higher in energy than the maximum 9C(–Li), in which we the lithium α-tert-butylsulfonyl carbanion salts are expected

have such a relative orientation of the methyl and tert-butyl to react with electrophiles with high stereoselectivity. The

groups. Such an interpretation of the potential curve does addition of HMPA to the CIP causes the formation of SIPs,

not contradict the large and positive V₂term because this a feature that is perhaps of importance in the case of insuf-

quantity merely describes the angular dependence of the ficient reactivity of nonracemic CIPs at low temperatures.

energy and does not imply any stabilizing or destabilizing The crystal structures of the lithium salts of the benzylic α-

mechanism in the minima and maxima.

tert-butylsulfonyl carbanions revealed an increasing devia-

tion of the coplanarity of the phenyl ring with the C_i–C_α–

S plane with increasing steric size of the substituent at the

C_αatom. This feature results in a gradual decrease in benz-

ylic conjugation, as shown by the NMR spectroscopic data

of the salts in solution. Ab initio calculations on [MeC(Ph)-

SO₂tBu]^–in combination with a NBO analysis showed that

the C_αatom carries a lone pair of pure p character. There

is neither a π bond between the C_αand C_iatoms nor be-

tween the C_αand S atoms. The lack of a π bond, however,

does not preclude an interaction between the lone pair and

the phenyl group leading to charge transfer, as revealed by

NMR spectroscopy.

Table 11. Potential constants obtained from a fit of the five-term

Fourier series to the potential curve of 9(–Li) calculated at the

MP2/6-311++G**//HF/6-31+G* level.

V_i[kcalmol^–1]

V₁

V₂

V₃

V₄

V₅

–0.3

17.6

1.3

–0.1

–3.0

Conclusions

Because of their relatively high enantiomerization barri-

ers, lithium α-tert-butylsulfonyl carbanion salts bearing two

substituents at the C_αatom should have at low temperatures

a configurational stability sufficient for enantioselective

synthesis and a study of the racemization dynamics and re-

activity. The rate-determining step of the enantiomerization

of the lithium α-tert-butylsulfonyl carbanion salts is the C_α–

S bond rotation and not C_αatom inversion or dimer-to-

monomer conversion. Ab initio calculations on the counter-

ion-free benzylic α-sulfonyl carbanion [MeC(Ph)SO₂tBu]^–

gave two different C_α–S rotational barriers, which are

Experimental Section

General: All manipulations with the lithium α-sulfonyl carbanion

salts were performed in oven-dried glassware under dry argon or

nitrogen using Schlenk and syringe techniques unless otherwise

stated. Solvents were purified and dried prior to use by distillation

from an appropriate drying agent under argon. [D₆]Benzene, [D₁₄]-

diglyme, and diglyme were distilled from potassium benzophenone

ketyl. n-Hexane and n-pentane were distilled from sodium benzo-

phenone ketyl and tetrahydrofuran (THF) was distilled from

mainly determined by steric interaction in the transition potassium benzophenone ketyl. N¹,N¹,N²,N²-Tetramethylethane-

1,2-diamine (TMEDA), dimethylformamide (DMF), 12-crown-4

(12-crown-4), hexamethylphosphoric triamide (HMPA), and N¹-[2-

(dimethylamino)ethyl]-N¹,N²,N²-trimethylethane-1,2-diamine

(PMDTA) were distilled from calcium hydride. Diethyl ether was

distilled from sodium benzophenone ketyl. The starting materials

were obtained from commercial sources and used without further

purification unless otherwise stated. A solution of n-butyllithium

(nBuLi) in n-hexane was purchased from Chemmetall and stan-

dardized by titration with diphenylacetic acid.^{[38] 6}Li-Labeled n-

state. Lithium S-tert-butylsulfonyl carbanion salts form in

THF monomeric and dimeric O–Li CIPs. X-ray crystal

structure analysis of a number of monomeric and dimeric

salts of type [R¹C(R²)SO₂tBu]Li (R¹϶ R²) gave a general

picture of their structures, which can serve as a solid basis

for the structures of the monomers and dimers in solution.

The monomeric and dimeric S-tert-butyl-substituted O–Li

CIPs are devoid of a C_α–Li bond. They feature a planar C_α

atom in the case of a phenyl substituent and exhibit, be-

propyllithium (nPr⁶Li) in n-pentane was prepared from 1-chloro-

6

cause of the C_α–S conformation, a stereogenic axis. There propane and Li and standardized by titration with diphenylacetic

acid. nBu⁶Li in n-hexane was prepared from 1-chlorobutane and

is a high degree of similarity in the structures of the lithium

salts of α-sulfonyl carbanions irrespective of the substitu-

⁶Li^[39]and standardized by titration with diphenylacetic acid. Ana-

lytical thin-layer chromatography (TLC) was performed on E.

ents at the S and C_αatoms. An exception is the configura-

Merck precoated TLC plates (silica gel 60 F₂₅₄, layer thickness

tion of the anionic C atom. Crystal structure analysis and

0.2 mm). Column chromatography was performed with Merck sil-

ab initio calculations show that dialkyl-substituted α-phen-

ica gel 60 (70–230 mesh). Temperatures were measured with a

yl- and α-methylsulfonyl carbanions have a strongly pyram-

idalized anionic C atom. Ab initio calculations on counter-

ion-free dimethyl-substituted α-sulfonyl carbanions re-

vealed a change in the coordination geometry of the C_α

Lauda TP10 digital thermometer and a Pt-82 thermosensor. Melt-

ing points were determined using a Büchi SMP-20 apparatus and

are uncorrected. ¹H, ¹³C, ⁶Li, and ³¹P NMR spectra were recorded

with Bruker AM 400, Bruker, WM 300, Bruker WM 250, Varian

atom from pyramidalized to planar on going from the S- Unity 500, Varian Inova 400, Varian VXR 300, and Varian Gemini

4580 Eur. J. Org. Chem. 2010, 4559–4587

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Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

300 instruments. ¹H NMR chemical shifts of measurements in

CDCl₃, are reported in ppm relative to Me₄Si (δ = 0.00 ppm) as

the internal standard. ¹H NMR chemical shifts of measurements

in [D₆]benzene, [D₈]THF, and [D₁₄]diglyme are reported in ppm

relative to [D₅]benzene (δ = 7.12 ppm), [D₇]THF (δ = 3.56 ppm),

and [D₁₃]diglyme (δ = 3.22 ppm), respectively, as the internal stan-

dards. Splitting patterns are designated as follows: s singlet, d

doublet, dd double doublet, t triplet, q quartet, quint quintet, sext

sextet, sept septet, m multiplet, br. broad, ps pseudo in the case

that the apparent multiplicity is a result of the overlap of several

multiplets or additional couplings are not resolved because of line-

broadening; sh., shoulder; unsym., unsymmetrical; hn, hidden;

app., apparent. ¹³C NMR chemical shifts of measurements in

CDCl₃are reported in ppm relative to Me₄Si (δ = 0.00 ppm) as the

internal standard. ¹³C NMR chemical shifts of measurements in

[D₆]benzene, [D₈]THF, and [D₁₄]diglyme are reported in ppm rela-

tive to [D₅]benzene (δ = 128.0 ppm), [D₇]THF (δ = 25.5 ppm), and

[D₁₃]diglyme (δ = 57.9 ppm), respectively, as the internal standard.

Peaks in the ¹³C NMR spectra are denoted as “u” for carbons with

zero of two attached protons and as “d” for carbons with one or

three attached protons, as determined from the attached proton

test (APT) pulse sequence. The following abbreviations are used to

designate the peaks: br. broad, vbr. very broad, t triplet. ⁶Li NMR

chemical shifts are reported in ppm relative to LiBr in water (δ =

0.00 ppm) as the external standard. ³¹P NMR chemical shifts are

reported in ppm relative to H₃PO₄in water (δ = 0.00 ppm) as the

external standard. Low-resolution mass spectra were recorded with

a Varian MAT 212 mass spectrometer. Only peaks of m/z Ն 80 and

an intensity of Ն5%, except decisive ones, are listed. IR spectra

were recorded with Perkin–Elmer FT 1760 S and 1760 instruments.

a cannula under argon. The solutions were kept under a slight ar-

gon pressure and then the thermometer was inserted into the sep-

tum. The insulating jacket was evacuated with a high-vacuum

pump and the vacuum was maintained throughout the measure-

ments. Then the apparatus was placed in the Dewar flask, which

was subsequently filled with liquid nitrogen. During the measure-

ments the solutions were stirred. The cooling rate was 5 Kmin^–1at

the beginning, which declined to 1 Kmin^–1at the freezing point. In

each cryoscopy experiment at least seven freeze/thaw cycles of the

solution of the salt were performed, whereby care was taken that

during freezing no salt deposited.

Crystallographic Structure Determination and Refinement: Different

techniques were employed to mount crystals for X-ray structure

determination. Crystals of (M/P)-40·2diglyme, (41·diglyme)₂, and

(42·digylme)₂were transferred into a glass capillary, which was then

sealed. Irregular crystals of rac-3·12-crown-4 were cut and a rod-

like specimen was transferred into a glass capillary with a diameter

of 0.5 mm, which was sealed under nitrogen. Crystals of (M/P)-

3·4THF were transferred into a glass capillary with a diameter of

0.5 mm, which was then sealed under argon. In the cases of (M/

P)-4·4THF, (M/P)-5·4THF, rac-9·PMDETA, and (M/P)-10·2THF,

the crystals were transferred directly under a stream of nitrogen

from the flask to the top of a glass fiber tipped with a droplet of

highly viscous silicon grease. In these cases, data were collected

under a stream of cooled nitrogen. The structure of (M/P)-3·4THF

was solved by direct methods (SHELXL-86) and refined with

SHELX-76.^[41]The structures of rac-3·12-crown-4, (M/P)-4·4THF,

(M/P)-5·4THF,

rac-9·PMDETA,

(M/P)-10·2THF,

(M/P)-

40·2diglyme, (41·diglyme)₂, and (42·digylme)₂were solved by direct

methods as implemented in the Xtal 3.2 package of crystallo-

graphic routines: GENSIN^[42]was employed to generate structure

invariant relationships and GENTAN^[43]for the general tangent

phasing procedure. The final refinements were performed using

Xtal 3.7.^[44]Crystallographic data are summarized in the Support-

ing Information

Only peaks of ν Ն 800 cm^–1are listed. The following abbreviations

˜

are used to designate the peaks: vs very strong, s strong, m medium,

w weak. Elemental analyses were performed by the Institute of Or-

ganic Chemistry Microanalytical Laboratory.

The cryoscopy experiments of the lithium α-sulfonyl carbanion

salts were carried out by the method described by Bauer and Seeb-

ach.^[40]The cryoscopy apparatus consisted of a cryoscopy flask

with an outside joint, which allowed its insertion into a Schlenk-

type conical glass jacket. The outer jacket-flask, which served as a

thermo-insulating device, was evacuated. The whole apparatus was

placed in a Dewar flask, which had an alumina bottom and was

filled with liquid nitrogen. A Schlenk-type steep-breasted flask was

used as the cryoscopy flask, which contained a Teflon-coated mag-

netic stirring bar in a vertical alignment. A magnet (adhering force

470 N) connected to an IKA mixer RW20 served as a stirrer. The

steep-breasted flask was closed with a rubber septum, which was

fitted with a thermoelement reaching to 5 mm above the bottom

of the flask. Temperatures were measured with a Kelvimat type

4321 (Burster Präzisionsmeßtechnik, Gernsbach, Germany) pre-

cision digital thermometer, which had an accuracy of measurement

of 10 mK and a reproducibility of Ϯ2 mK. A Pt-100 thermocouple

of type 42943 (Burster Präzisionsmeßtechnik, Gernsbach, Ger-

many) was used as the thermoelement, which was suitable for mea-

surements in the range –200 to +500 °C. According to the specifica-

tions it had for temperatures of approximately –100 °C a deviation

from the actual value of ∆T Յ 200 mK. An additional maximal

distortion of the real temperature of 2 mK was produced by the

necessary measurement current of 1 mA. The measurement data

were transferred via an RS232C interface to a computer and pro-

cessed. Every three seconds a measurement with a resolution of

1 mK was recorded. The cryoscopy measurements of the salt solu-

tions in THF were performed by introducing the solution into the

cryoscopy flask to the gauge mark (approximately 60 mL) through

General Procedure for the Preparation of Solutions of Salts rac-1–8

for DNMR Spectroscopy (GP1): A Schlenk flask equipped with a

Teflon-coated magnetic stirring bar and a septum, which had been

dried with a heat gun in vacuo and filled with argon, was charged

with nPrLi (0.12–0.22 mL of 0.89  in n-hexane, 0.1–0.2 mmol).

The solvent was removed in vacuo and the remaining oil was dried

for 5 min at 133 Pa. After cooling the flask to –90 °C, it was filled

with argon and [D₈]THF (0.4 mL) was added. In a separate

Schlenk flask, which had been dried with a heat gun in vacuo and

filled with argon, the sulfone (0.1–0.2 mmol) and [D₈]THF

(0.5 mL) were successively added under argon. Then the solution

of the sulfone was added at –90 °C with a syringe to the solution

of nPrLi in [D₈]THF. After stirring the mixture for 5 min, it was

warmed to room temperature and concentrated in vacuo to a vol-

ume of 0.6 mL. Then the solution was transferred under argon with

a syringe to an NMR tube (from the bottom), which had been

dried with a heat gun under vacuum and filled with argon. The

NMR tube contained a ground joint carrying a three-way Teflon

stopcock. The NMR tube with the solution of the salt was cooled

to –90 °C, evacuated twice for 5 s, filled with argon, evacuated a

third time, and then sealed with an acetylene/oxygen microburner.

{[PhCH₂C(Ph)SO₂tBu]Li·2THF}₂

[(M/P)-3·4THF]:

nBuLi

(0.20 mL of 1.59  in n-hexane) was added dropwise to a solution

of sulfone rac-35 (100 mg, 0.33 mmol) in THF (0.8 mL) at –90 °C.

The solution was stirred for 20 min at this temperature and then

warmed to room temperature over 15 min. After the addition of n-

hexane (1 mL), the solution was concentrated at room temperature

Eur. J. Org. Chem. 2010, 4559–4587

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4581

H.-J. Gais et al.

FULL PAPER

in vacuo to a volume of 1 mL and kept for 2 d at 2 °C. The crystals

formed were freed from the mother liquor with a syringe, washed

with n-hexane, and dried at room temperature in vacuo at 133 Pa

for 2 min. the salt (M/P)-3·4THF (130 mg, 90%) was obtained as

J = 7.0 Hz, 3 H, CH₃), 1.42 (s, 9 H, S-tBu), 1.44 (m, 8 H, β-THF),

2.91 (br. q, J = 7.0 Hz, 2 H, CH₂), 3.70 (m, 8 H, α-THF), 6.80 (m,

1 H, p-Ph), 7.30 (m, 2 H, m-Ph), 7.61 (m, 2 H, o-Ph) ppm. ¹³C

NMR (125 MHz, [D₆]benzene): δ = 16.0 (CH₃, d), 24.4 (CH₂, u),

25.5 (β-THF, u), 25.7 (S-tBu-CH₃, d), 59.5 (C_α, u), 64.0 (S-tBu-C,

u), 68.1 (α-THF, d), 115.0 (p-Ph, d), 120.2 (o-Ph, d), 145.0 ppm (i-

Ph, u) (the signal of m-Ph was hidden below the signal of [D₅H]-

benzene at δ = 128.0 ppm).

1

pale-yellow crystals. H NMR (250 MHz, [D₈]THF): δ = 1.31 (s, 9

H, tBu), 3.98 (s, J = 49 Hz, 2 H, CH₂), 6.16 (m, 1 H, p-α-Ph), 6.69

(m, 2 H, m-α-Ph), 6.94 (m, 1 H, p-β-Ph), 7.00–7.12 (m, 4 H, o-α-

Ph, m-β-Ph), 7.32 (m, 2 H, o-β-Ph) ppm. ¹³C NMR (100 MHz, [D₈]-

THF): δ = 26.0 (tBu-CH₃, d), 58.0 (C_α, u), 64.6 (CH₂, u), 114.2 (p-

α-Ph, d), 120.3 (o-α-Ph, d), 125.1 (p-β-Ph, d), 127.4 (m-α-Ph, d),

128.0 (m-β-Ph, d), 129.2 (o-β-Ph, d), 145.8 (i-Ph, u), 146.1 (i-Ph,

u) ppm. Single crystals of (M/P)-3·4THF were obtained by dissolv-

ing the above crystals in n-hexane/THF (1:1; 1 mL) until only a few

crystals remained by warming the suspension to 50 °C. The solu-

tion was cooled over 5 h to room temperature, whereupon crystals

were formed. The mother liquor was removed with a syringe and

the crystals were washed with n-hexane (4ϫ1 mL) and dried at

room temperature for 1 min at 133 Pa.

{[tBuCH₂C(Ph)SO₂tBu]Li·2THF}₂

[(M/P)-5·4THF]:

nBuLi

(7.5 mL, 11.3 mmol of 1.5  in n-hexane) was added dropwise over

10 min to a suspension of sulfone rac-29 (2.82 g, 10 mmol) in THF

(20 mL) at –66 °C. A clear yellow solution was formed from which,

after stirring for 1 h at –75 °C, the salt (M/P)-5·4THF partially

crystallized. After the addition of n-hexane (40 mL) the mixture

was warmed to room temperature, whereupon the solid dissolved.

The clear solution was concentrated in vacuo to a volume of

20 mL, whereupon a partial crystallization took place. After the

addition of n-hexane (40 mL) the suspension was heated slowly to

60 °C, whereupon the solid dissolved completely. The heating de-

vice was removed and the solution was kept for 1 d at room tem-

perature. Crystallization of (M/P)-5·4THF as colorless crystals up

to 1 mm in length started after several hours. The pale-yellow

mother liquor was removed by the aid of a syringe and the crystals

were washed with n-hexane (4ϫ10 mL) and dried at room tem-

perature in vacuo for 10 min. The salt (M/P)-5·4THF (2.35 g, 54%)

was obtained as pale-yellow crystals. ¹H NMR (500 MHz, [D₆]ben-

zene): δ = 1.17 (s, 9 H, β-tBu), 1.32 (s, 9 H, S-tBu), 1.45 (m, 8 H,

β-THF), 2.57 (unsym. br. s, 1 H, CH₂), 3.14 (unsym. br. s, 1 H,

CH₂), 3.79 (m, 8 H, α-THF), 6.90 (app. t, 1 H, p-Ph), 7.29 (m, 2

H, m-Ph), 7.87 (app. br. d, 2 H, o-Ph) ppm. ¹³C NMR (125 MHz,

[D₆]benzene): δ = 25.5 (β-THF, u), 26.1 (S-tBu, d), 30.5 (β-tBu, d),

35.0 (β-tBu, d), 43.5 (CH₂), 54.7 (C_α, u), 64.9 (S-tBu-C, u), 68.2

[PhCH₂C(Ph)SO₂tBu]Li·12-crown-4 (rac-3·12-crown-4): nBuLi

(0.66 mL of 1.5  in n-hexane) was added to a solution of sulfone

rac-35 (300 mg, 0.99 mmol) and freshly distilled 12-crown-4

(262 mg, 1.49 mmol) in THF (10 mL) at –78 °C. After the addition

a microcrystalline solid was formed, which did not dissolve even at

room temperature. The suspension was concentrated in vacuo to a

volume of 3 mL. The mother liquor was removed with the aid of

a syringe. The crystals were washed with n-hexane and dried in

vacuo. The salt rac-3·12-crown-4 (366 mg, 75%) was isolated as

pale-yellow crystals. Single crystals were obtained by the addition

of THF (20 mL) to the above crystals to give a clear solution,

which was kept at –15 °C for 2 d. The irregular colorless crystals

that were formed were freed from the mother liquor by the aid of

1

a syringe and dried in a stream of argon at room temperature. H

NMR ([D₈]THF, 500 MHz): δ = 1.28 (s, 9 H, tBu), 3.58 (s, 16 H, (α-THF, d), 117.4 (p-Ph, d), 124.1 (o-Ph, d), 127.6 (m-Ph, d), 146.4

12-crown-4), 3.70–4.08 (br. s, 2 H, CH₂), 6.12 (tt, 1 H, p-α-Ph),

6.65 (tm, 2 H, m-α-Ph), 6.92 (tm, 1 H, p-β-Ph), 7.02–7.06, 7.16–

(i-Ph, u) ppm. For the preparation of single crystals, (M/P)-

5·4THF was dissolved in n-hexane/THF (6:1; 35 mL) by slowly

7.24, 7.30–7.34 (m, 6 H, Ph) ppm. ¹³C NMR ([D₈]THF, 125 MHz): warming the suspension in an oil bath to 60 °C. The heat supply

δ = 26.9 (tBu-CH₃, d), 39.0 (CH₂, u), 65.2 (tBu-C, u), 72.6 (12-

crown-4, u), 114.7 (d), 121.0 (d), 125.9 (d) (p-β-Ph, m-β-Ph, o-α-

Ph), 128.3 (d), 128.8 (d), 130.1 (d) (p-β-Ph, m-β-Ph, o-β-Ph), 147.0

(u), 147.3 (u) (i-Ph, u) ppm. The signal of C_αcould not be detected.

to the oil bath was removed, and the pale-yellow solution was al-

lowed to cool slowly to room temperature. After 24 h some only

slightly distorted octahedral crystals of 1 mm in diameter had been

formed. The mother liquor was removed by a syringe and heated

to 60 °C to dissolve any crystalline material that had formed. The

resulting solution was cooled slowly to room temperature, upon

which crystallization started again. Once again the mother liquor

was removed and warmed to dissolve any crystals that had formed.

Cooling the solution slowly to room temperature gave faint yellow

octahedral crystals of up to 5 mm in length.

{[MeCH₂C(Ph)SO₂tBu]Li·2THF}₂

[(M/P)-4·4THF]:

nBuLi

(14.5 mL, 22 mmol of 1.52  in n-hexane) was added dropwise over

15 min to a suspension of sulfone rac-28 (4.83 g, 20 mmol) in THF

(40 mL) at –75 °C. After stirring the mixture for 20 min at –75 °C,

n-hexane (80 mL) was added and the yellow-orange solution was

warmed to room temperature. The solution was concentrated in

vacuo to a volume of 40 mL and n-hexane (100 mL) was added.

After 2 d at 2 °C the mother liquor was removed with the aid of a

syringe and the crystals were washed with n-hexane (3ϫ15 mL).

The salt (M/P)-4·4THF was obtained as colorless crystals. For the

preparation of single crystals, THF (1 mL) and n-hexane (25 mL)

were added to the crystalline salt (M/P)-4·4THF obtained above

and the suspension was slowly heated to 50 °C. The clear solution

formed was slowly cooled to room temperature and kept for 1 d at

2 °C. The microcrystalline material formed was dissolved by the

addition of THF (1 mL) and heating the suspension to 50 °C. The

solution was slowly cooled to room temperature and kept for 3 d

at 2 °C. After repeating this procedure twice and extending the

crystallization time in the last run to 1 week, (M/P)-4·4THF was

obtained as bundles of needles or rods up to 0.5 mm in diameter

and 4 mm in length. The mother liquor was removed with the aid

of a syringe and the crystals (3.08 g, 39%) were washed with n-

{[tBuC(Ph)SO₂tBu]Li·THF}₂[(M/P)-10·2THF]: nBuLi (7.0 mL,

11.3 mmol of 1.62  in n-hexane) was added dropwise to a suspen-

sion of sulfone rac-30 (2.73 g, 10.2 mmol) in THF (20 mL) at

–69 °C whilst stirring (the mixture remained a suspension because

of the salt that deposited). After stirring the suspension for 2.5 h

at –74 °C, n-hexane (40 mL) was added and the suspension was

warmed to room temperature, whereupon the solid dissolved com-

pletely at –30 °C. The pale-yellow solution was concentrated in

vacuo at room temperature to a volume of 10 mL. After the ad-

dition of n-hexane (60 mL), a suspension formed, which was heated

in an oil bath to 65 °C upon which a clear solution was obtained.

The heat supply to the oil bath was removed, and the solution was

allowed to cool to room temperature. After 4 h colorless crystals

up to 3 mm in diameter had formed. The mother liquor was re-

moved with a syringe and the crystals were washed with n-hexane

(3ϫ10 mL) and dried in vacuo for 10 min. The salt (M/P)-

10·2THF (1.63 g, 49%) was obtained as pale-yellow crystals. ¹H

1

hexane (4ϫ5 mL). H NMR (500 MHz, [D₆]benzene): δ = 1.40 (t,

4582

www.eurjoc.org

Eur. J. Org. Chem. 2010, 4559–4587

Enantiomerization of Lithium α-tert-Butylsulfonyl Carbanion Salts

NMR (500 MHz, [D₆]benzene): δ = 1.27 (m, 4 H, β-THF), 1.55 (s,

9 H, S-tBu), 1.58 (s, 9 H, α-tBu), 3.31 (m, 4 H, α-THF), 7.09 (app.

t, 1 H, p-Ph), 7.31 (m, 2 H, m-Ph), 7.81 (app. br. d, 2 H, o-Ph) ppm.

{[(CH₂)₅CSO₂Ph]Li·diglyme}₂(42·diglyme)₂: nBuLi (2.84 mL of

1.38  in n-hexane, 3.92 mmol) was added dropwise to a solution

of sulfone 48 (800 mg, 3.57 mmol) in diglyme (4.5 mL) at 0 °C. The

¹³C NMR (125 MHz, [D₆]benzene): δ = 25.2 (β-THF, u), 27.0 solution turned orange and an orange solid deposited. n-Hexane

S-tBu-CH₃, d), 34.6 (α-tBu-CH₃, d), 34.7 (α-tBu-CH₃, d), 58.0 and n-butane were removed by a concentration of the mixture in

(C_α,u), 61.9 (S-tBu-C, u), 67.9 (α-THF, u), 124.9 (p-Ph, d), 127.5

(m-Ph, d), 138.8 (o-Ph, d), 145.4 (i-Ph) ppm. For the preparation

vacuo at room temperature for 1 min. The orange suspension was

slowly warmed to 100 °C (oil bath) whereupon an orange solution

of suitable single crystals, THF (1 mL) and n-hexane (30 mL) were was obtained. Upon cooling the solution in the oil bath to room

added to the crystals and the suspension slowly warmed to 65 °C,

temperature orange rod-like crystal were formed. Removal of the

mother liquor and washing the crystals with cold diethyl ether gave

whereupon a clear solution was formed. Upon cooling the solution

to room temperature, pale-yellow, strongly distorted octahedral the salt (42·diglyme)₂(950 mg, 82%) as orange rod-like crystals. ¹H

crystals were formed. The mother liquor was removed with a sy-

ringe and the crystals were washed with n-hexane (3ϫ10 mL) and

dried.

NMR (300 MHz, [D₈]THF): δ = 1.28–1.35 (m, 6 H, CH₂), 1.89–

1.93 (m, 4 H, CH₂), 3.28 (s, 6 H, OMe, diglyme), 3.45 (m, 4 H,

diglyme), 3.53 (m, 4 H, diglyme), 7.06 (m, 1 H, p-Ph), 7.18 (m, 2 H,

m-Ph), 7.50 (m, 2 H, o-Ph) ppm. ¹³C NMR (75 MHz, [D₈]THF): δ

= 28.5 (CH₂, u), 28.6 (CH₂, u), 30.0 (CH₂, u), 52.5 (C_α, d), 58.8

(OMe, diglyme, d), 71.3 (OCH_2,u), 72.8 (OCH₂, u), 124.9 (m-Ph,

u), 126.9 (p-Ph, u), 128.1 (o-Ph, u), 150.6 (i-Ph, u) ppm.

[MeC(Ph)SO₂tBu]Li·PMDTA (rac-10·PMDTA): nBuLi (0.64 mL

of 1.60  in n-hexane, 1.03 mmol) was added dropwise to a suspen-

sion of sulfone rac-27 (226 mg, 1 mmol) in PMDTA (2 mL) under

argon at –70 °C. After stirring the suspension at –70 °C for 20 min,

the cooling bath was removed and the mixture was warmed to

room temperature. Upon the addition of THF (0.68 mL) the milky

mixture turned to a yellow solution within 10 min. The solution

was kept at 2 °C for 4 d whereupon colorless platelet-like crystals

of rac-10·PMDTA were formed. The mother liquor was removed

with a syringe and the crystals were dried in a stream or argon.

Cryoscopy of [PhCH₂C(Ph)SO₂tBu]Li (rac-3) in THF: nBuLi

(10.4 mL of 1.52  in n-hexane, 15.8 mmol) was added to a suspen-

sion of sulfone rac-35 (4.54 g, 15 mmol) in THF (30 mL) under

argon at –90 °C. Then n-hexane (30 mL) was added dropwise,

whereupon a white solid deposited. Subsequently the suspension

was heated at 60 °C until a clear solution was formed. The solution

was slowly cooled to room temperature and kept at 4 °C for 4 d,

whereupon colorless crystals were formed. The mother liquor was

removed with a syringe. Washing of the crystals with n-hexane and

{[MeCH₂C(Me)SO₂Ph]Li·diglyme}₂[(M/P)-40·2diglyme]: nBuLi

(2.6 mL of 1.5  in n-hexane, 3.97 mmol) was added dropwise to a

solution of sulfone rac-46 (767 mg, 3.87 mmol) in diglyme (4.9 mL)

at 0 °C. The solution turned yellow-orange and a yellow solid de-

posited. n-Hexane and n-butane were removed by concentration of

the mixture in vacuo at room temperature for 1 min. The yellow

suspension was slowly warmed to 30 °C, whereupon a yellow-

orange solution was obtained. Upon cooling the solution to room

temperature yellow rod-like crystals were formed. Removal of the

mother liquor and washing the crystals with cold diethyl ether gave

the salt (M/P)-40·2diglyme (1.14 g, 87%) as yellow needle-like crys-

1

drying in vacuo for 15 min gave the salt (M/P)-3·4THF. H NMR

(300 MHz, [D₈]THF): δ = 1.26 (s, 9 H, tBu), 3.83 (br. s, 2 H, CH₂),

6.12 (t, J = 7.1 Hz, 1 H, p-α-Ph), 6.64 (dd, J = 8.5, J = 7.1 Hz, 2

H, m-α-Ph), 6.90 (t, J = 7.1 Hz, 1 H, p-β-Ph), 7.01–7.04 (m, 4 H,

o-α-Ph, m-β-Ph) ppm. The ¹H NMR spectrum of (M/P)-3·4THF

showed it to contain four molecules of THF (δ = 1.73, 3.58 ppm)

and the presence of 4% of sulfone rac-35. ¹³C NMR (75 MHz,

[D₈]THF): δ = 26.2 (tBu-CH₃, d), 58.2 (C_α, u), 64.8 (CH₂, u), 114.4

(p-α-Ph, d), 120.5 (o-α-Ph, d), 125.3 (p-β-Ph, d), 127.6 (d), 128.2

(d), 129.4 (d) (m-α-Ph, o-β-Ph, m-β-Ph), 146.1 (u), 146.3 (u)

(i-α-Ph, i-β-Ph) ppm. Three independent experiments with a solu-

tion of rac-3 in THF (70 mL) of different concentrations were per-

formed. Experiment 1: c = 86.6 mmolkg^–1; experiment 2: c =

44.2 mmolkg^–1; experiment 3: c = 41.0 mmolkg^–1. The solution

was transferred through a cannula to the cryoscopy flask up to

the graduation. Then the insulating jacket was evacuated and the

apparatus was cooled with liquid nitrogen. Several cooling curves

were recorded in each experiment. Determination of the melting

points in experiments 2 and 3 proved not to be possible because of

the occurrence of a two-phase undercooling. Several cooling curves

were recorded in experiment 1. Analysis of the curves gave the melt-

ing points listed in Table 12. After the experiment had finished, the

solution of rac-3 in THF was treated at –80 °C with [D]TFA

(12.5 mL of 2  [D]TFA in THF, 25 mmol). Work-up and ¹H NMR

spectroscopy of the crude material revealed the presence of rac--

35 and 4% of sulfone rac-35.

1

tals. H NMR (300 MHz, [D₈]THF): δ = 0.84 (t, J = 7.4 Hz, 3 H,

CH₃), 1.54 (s, 3 H, CH₃), 1.96 (q, J = 7.4 Hz, 2 H, CH₂), 3.27 (s,

OMe, diglyme), 3.43 (m, diglyme), 3.53 (m, diglyme), 7.04 (m, 1 H,

p-Ph), 7.15 (m, 2 H, m-Ph), 7.51 (m, 2 H, o-Ph) ppm. ¹³C NMR

(75 MHz, [D₈]THF): δ = 15.6 (CH₃, d), 16.1 (CH₃, d), 26.9 (CH₂,

u), 47.5 (C_α, u), 59.1 (OMe, diglyme, d), 71.6 (OCH₂, diglyme, u),

73.1 (OCH₂, diglyme, u), 125.3 (m-Ph, d), 127.1 (p-Ph, d), 128.3

(o-Ph, d), 132.5 (i-Ph, u) ppm.

{[MeCH₂C(CH₂Me)SO₂Ph]Li·diglyme}₂(41·diglyme)₂: nBuLi

(12.23 mL of 1.5  in n-hexane, 18.35 mmol) was added dropwise

to a solution of sulfone 47 (3.90 g, 18.35 mmol) in diglyme (22.5 m)

at 0 °C. The solution turned yellow and a yellow solid deposited.

n-Hexane and n-butane were removed by concentration of the mix-

ture in vacuo at room temperature for 1 min. The yellow suspen-

sion was slowly warmed to 80 °C, whereupon a yellow-orange solu-

tion was obtained. Upon cooling the solution to room temperature

yellow rod-like crystals were formed. Removal of the mother liquor

and washing the crystals with cold diethyl ether gave the salt

(41·diglyme)₂(5.06 g, 78%) as yellow needle-like crystals. ¹H NMR

(300 MHz, C₆D₆): δ = 1.23 (t, J = 7.15 Hz, 6 H, CH₃), 2.26 (q, J

= 7.32 Hz, 4 H, CH₂), 3.17 (s, OMe, diglyme), 3.27 (m, diglyme),

3.35 (m, diglyme), 7.01 (m, 1 H, p-Ph), 7.17 (m, 2 H, o-Ph), 7.93

(m, 2 H, m-Ph) ppm. ¹³C NMR (75 MHz, C₆D₆): δ = 15.4 (CH₃,

d), 22.9 (CH₂, u), 54.3 (C_α, u), 58.7 (OMe, diglyme, u), 70.1 (OCH₂,

u), 71.4 (OCH₂, u), 125.0 (m-Ph, d), 127.1 (p-Ph, d), 128.1 (o-Ph,

d), 153.7 (i-Ph, u) ppm.

Table 12. Cryoscopy of the salt rac-3 in THF under conditions of

experiment 1 (c = 86.6 mmolkg^–1).

Measurement

T [K]

a

b

c

164.417

164.435

165.427

164.426

Mean value

Eur. J. Org. Chem. 2010, 4559–4587

www.eurjoc.org

4583

H.-J. Gais et al.

FULL PAPER

The experiments were performed with the cryoscopy set-up of T_THF

2 H, CH₂) ppm. ¹H NMR (250 MHz, [D₈]THF, –40 °C, in part): δ

= 164.566Ϯ0.003 K and E_K= 1.85 Kmol^–1kg. Calculation of the = 3.70 (d, J = 17.9 Hz, 1 H, CH₂), 4.03 (d, J = 17.9 Hz, 1 H,

¯

aggregation number (n): Experiment 1: ∆T = T_THF– T_exp

=

CH₂) ppm. J_AB= 17.9Ϯ0.2 Hz, ∆ν = 86Ϯ5 Hz, T_c= 283Ϯ5 K.

164.566 K – 164.426 K = 0.140 K, c¯_exp= ∆T/E_K= 75.7 mmolkg^–1,

n¯ = c_nom/c¯_exp= 1.14Ϯ0.15.

¯

K (T_c) = π(∆ν²+ 6J_AB^{2 1/2}/√2, k₂₈₃= 214Ϯ10 s^–1; ∆G^‡(T_c) =

)

4.57T[10.32 – log(k/T_c)], ∆G^‡= 13.5Ϯ0.2 kcalmol^–1.

283

DNMR Spectroscopy of [PhCH₂C(Ph)SO₂tBu]Li (rac-3): Accord-

ing to GP1, a solution of sulfone rac-35 (51 mg, 0.17 mmol) in [D₈]-

THF (6 mL) was treated with nPrLi (0.20 mL of 0.90  in n-hex-

NMR Spectroscopy of [MeC(Ph)SO₂tBu]Li (rac-9) at Low Tem-

peratures: According to GP1, a solution of sulfone rac-27 (22.7 mg,

0.10 mmol) in [D₈]THF (1 mL) was treated at –78 °C with nPr⁶Li

(1.48 mL of 0.088  in n-pentane, 0.130 mmol). After stirring the

ane, 0.18 mmol). The thus obtained solution of rac-3 was sealed in

1

an NMR tube. H NMR (250 MHz, [D₈]THF, room temperature): mixture at –78 °C for 10 min, it was concentrated in vacuo and the

δ = 1.31 (s, 9 H, tBu-CH₃), 1.73 (m, β-THF), 3.58 (m, α-THF),

residue dried in vacuo. The salt (M/P)-9·2THF was dissolved in

3.89 (s, ω = 49 Hz, 2 H, CH₂), 6.16 (m, 1 H, p-α-Ph), 6.69 (m, 2 [D₈]THF (0.5 mL) and the solution was sealed in an NMR tube.

H, m-α-Ph), 6.94 (m, 1 H, p-β-Ph), 7.00–7.12 (m, 4 H, o-α-Ph), ¹H NMR (300 MHz, [D₈]THF): δ = 1.25 (s, 9 H, S-tBu), 1.95 (s, 3

7.32 (m, 2 H, o-β-Ph) ppm. ¹³C NMR (100 MHz, [D₈]THF, room H, α-CH₃), 6.18 (ps.-t, 1 H, p-Ph), 6.77 (ps.-t, 2 H, m-Ph), 7.09 (ps.-

temperature): δ = 25.3 (quint, β-THF, u), 26.0 (tBu-CH₃, d), 58.0

(C_α, u), 64.6 (CH₂, u), 67.4 (quint, α-THF, u), 114.2 (p-α-Ph, d),

120.3 (o-α-Ph, d), 125.1 (p-β-Ph, d), 127.4 (m-α-Ph, d), 128.0 (m-

β-Ph, d), 129.2 (o-β-Ph, d), 145.8 (i-Ph, u), 146.1 (i-Ph, u) ppm. ¹H

d, 2 H, o-Ph) ppm. ¹³C NMR (75 MHz, [D₈]THF): δ = 18.6 (α-

CH₃, d), 26.1 (S-tBu-CH₃d), 53.0 (C_α, u), 64.8 (S-tBu-C, u), 113.7

(p-Ph, d), 119.2 (o-Ph, u), 127.7 (m-Ph, d), 147.3 (i-Ph, u) ppm.

1

Tables 13, 14, and 15 list the H and ¹³C NMR spectroscopic data

NMR (250 MHz, [D₈]THF, 17 °C, in part): δ = 3.88 (s, ω = 67 Hz, at low temperatures.

1

Table 13. H NMR spectroscopy (500 MHz) of the salt rac-9 in [D₈]THF at various temperatures.

T [°C]

o-Ph: δ [ppm] (signal), species m-Ph: δ [ppm] (signal),

p-Ph: δ [ppm] (signal), species α-CH₃: δ [ppm] (signal),

S-tBu: δ [ppm]

species

(signal)

ca. 22

–40

–50

7.09 (ps.-d)

7.07 (br.)

6.77 (ps.-t)

6.77 (br. ps.-t)

6.77 (br. s)

6.67 (br., sh)

6.82 (br.), 6.72 (br.)

6.18 (ps.-t)

6.18 (br. s)

6.18 (br. t), 6.15 (br. t)

6.09 (br. s)

6.19 (br.), 6.16 (br.)

6.08 (br. s)

6.18 (t), 9–1/2

6.16 (t), 9–4

1.95 (s)

1.93 (s)

1.93 (br. s)

1.25 (s)

1.24 (s)

1.24 (br. s)

7.8–6.2 (br.)^[a]

7.73 (br. s), 6.34 (br.)

6.28 (br.)

–70

1.92 (br., sh), 1.91 (br.)

1.90 (br., sh)

1.92 (br. s), 1.91 (br. s)

1.89 (br., sh)

1.92 (s), 9–2

1.90 (s), 9–1

1.89 (s), 9–4

1.87 (s), 9–3

–80

7.73 (br.), 6.36 (br.)

6.27 (br.)

1.25 (br. s)

1.24 (s)

–100

7.75 (d, oЈ), 9–3^[b]

7.73 (d, oЈ), 9–1/2

7.70 (d, oЈ), 9–4

6.35 (d, o), 9–1/2

6.32 (d, o), 9–4

6.25 (d, o), 9–3

6.84 (m, mЈ), 9–1/2

6.82 (m, mЈ), 9–4

6.79 (t, mЈ), 9–3

6.72 (m, m), 9–1/2

6.68 (t, m), 9–4

6.08 (t), 9–3

6.65 (t, m), 9–3

[a] Coalescence range with very broad singlets at δ = 7.71 and 6.32 ppm. [b] The ratio of the species 9–1/2, 9–3, and 9–4 at –100 °C was

75:15:10 according to the intensity of the o-Ph signals. The ratio of the species 9–1, 9–2, 9–3, and 9–4 at –100 °C was 45:30:15:10

according to the intensity of the β-CH₃signals.

Table 14. ¹³C NMR spectroscopy (125 MHz) (aromatic region) of the salt rac-9 in [D₈]THF at various temperatures.

T [°C]

i-Ph: δ [ppm] (signal),

m-Ph: δ [ppm] (signal),

o-Ph: δ [ppm] (signal), species

p-Ph: δ [ppm] (signal), species

species

ca. 22^[a]

–50

147.3

147.0 (br.)

127.7

127.8 (br.)

119.2

119.1 (br. s)

113.7

113.8 (br.)

–80

–100

147.5 (br.), 146.8

147.5, 9–3; 146.8, 9–1/2

128.4 (br.), 127.2 (br.)

128.5, 9–2; 127.3, 9–1

120.2 (br.), 117.5 (br.), 116.5

120.2 (oЈ), 9–2; 120.2 (oЈ), 9–1; 119.6

113.8, 113.7, 112.4 (br. d)

113.7, 9–2; 113.6, 9–1 113.3, 9–4;

(oЈ), 9–3; 117.4 (o), 9–1/2; 116.4 (o), 9–3 112.2, 9–3

[a] 75 MHz NMR spectrum.

Table 15. ¹³C NMR spectroscopy (125 MHz) (aliphatic region) of the salt rac-9 in [D₈]THF at various temperatures.

T [°C]

S-tBu-C: δ [ppm] (signal), species

C_α: δ [ppm] (signal)

S-tBu-CH₃: δ

CH₃: δ [ppm] (signal),

[ppm]

species

ca. 22^[a]

–50

–80

64.8

64.7 (br.)

53.0

52.3 (br.)

52.3, 52.2

26.1

25.8

25.7

25.5

18.6

18.8 (br.)

18.9, 18.7

19.0, 9–1; 18.8, 9–2

64.7, 64.7, 63.7 (br.)

–100

64.7, 9–2^[b]; 64.6, 9–1; 64.3, 9–4; 63.5, 9–3

53.9, 9–3; 52.7, 9–4; 52.3, 9–1; 52.2, 9–2

[a] 75 MHz NMR spectrum. [b] The ratio of the species 9–1, 9–2, 9–3, and 9–4 at –100 °C was 45:30:15:10.

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Supporting Information (see also the footnote on the first page of

this article): General experimental procedures, experimental pro-

cedures and characterization data for rac-17, rac-18, rac-23–34, 46,

47, 59, 60, rac-62, 64, and 66; synthetic scheme for rac-31–34 and

rac-45–47; general cryoscopy data; cryoscopy data for rac-4, rac-6,

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temperatures; chemical shifts of H_o, H_p, C_o, and C_pof the salts rac-

3, rac-4, rac-9, and rac-10 and sulfones rac-17, rac-27–30; NOE

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data for rac-9 in the presence of HMPA at low temperatures; tor-

sion angles and deviation of the S and Li atoms from the O₄plane

for the eight-membered ring of the salts in the crystal form; figures

showing the structures of the salts in the crystal form; discussion

of the NOE data of the salts; views of the structures of complex

C₆H₆·Li(H₂O)₃⁺; crystal data and experimental details of the struc-

ture determination of the salts.

Acknowledgments

This research was supported by the Deutsche Forschungsgemein-

schaft (DFG), the Volkswagen Foundation, and Fonds der Chem-

ischen Industrie. We thank Professor Dr. H. Fritz and Dr. D.

Hunkler for NMR measurements, Professor Dr. W. Bauer for

cryoscopy measurements and valuable experimental advice, Dr. E.

Keller for a version of SCHAKAL, and C. Vermeeren and D. Wol-

ters for the preparation of the graphics. We are grateful to Professor

Dr. H. J. Reich for his assistance in the analysis of the NMR spec-

tra of the salt rac-9 in the presence of HMPA and for information

concerning his unpublished results of a NMR spectroscopic study

on the behaviour of lithium S-phenylsulfonyl carbanion salts

towards HMPA.

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Published Online: July 14, 2010

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4587

Article Doi

Experimental and theoretical investigation of the enantiomerization of Lithium α-tert-butylsulfonyl carbanion salts and the determination of their structures in solution and in the crystal

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