Chiral Lithiated Allylic α-Sulfonyl Carbanions: Experimental and Computational Study of Their Structure, Configurational Stability, and Enantioselective Synthesis

Article abstract of DOI:10.1002/chem.201503123

X-ray crystal structure analysis of the lithiated allylic α-sulfonyl carbanions [CH₂=CHC(Me)SO₂Ph]Li-diglyme, [cC₆H₈SO₂tBu]Li-PMDETA and [cC₇H₁₀SO₂tBu]Li-PMDETA showed dimeric and monomeric CIPs, having nearly planar anionic C atoms, only O-Li bonds, almost planar allylic units with strong C-C bond length alternation and the s-trans conformation around C1-C2. They adopt a C1-S conformation, which is similar to the one generally found for alkyl and aryl substituted α-sulfonyl carbanions. Cryoscopy of [EtCH=CHC(Et)SO₂tBu]Li in THF at 164K revealed an equilibrium between monomers and dimers in a ratio of 83:17, which is similar to the one found by low temperature NMR spectroscopy. According to NMR spectroscopy the lone-pair orbital at C1 strongly interacts with the C=C double bond. Low temperature ⁶Li,¹H NOE experiments of [EtCH=CHC(Et)SO₂tBu]Li in THF point to an equilibrium between monomeric CIPs having only O-Li bonds and CIPs having both O-Li and C1-Li bonds. Ab initio calculation of [MeCH=CHC(Me)SO₂Me]Li-(Me₂O)₂ gave three isomeric CIPs having the s-trans conformation and three isomeric CIPs having the s-cis conformation around the C1-C2 bond. All s-trans isomers are more stable than the s-cis isomers. At all levels of theory the s-trans isomer having O-Li and C1-Li bonds is the most stable one followed by the isomer which has two O-Li bonds. The allylic unit of the C,O,Li isomer shows strong bond length alternation and the C1 atom is in contrast to the O,Li isomer significantly pyramidalized. According to NBO analysis of the s-trans and s-cis isomers, the interaction of the lone pair at C1 with the π orbital of the CC double bond is energetically much more favorable than that with the "empty" orbitals at the Li atom. The C1-S and C1-C2 conformations are determined by the stereoelectronic effects n_C-σ_SR interaction and allylic conjugation. ¹H DNMR spectroscopy of racemic [EtCH=CHC(Et)SO₂tBu]Li, [iPrCH=CHC(iPr)SO₂tBu]Li and [EtCH=C(Me)C(Et)SO₂tBu]Li in [D₈]THF gave estimated barriers of enantiomerization of ΔG^≠=13.2kcal mol^-1 (270K), 14.2kcal mol^-1 (291K) and 14.2kcal mol^-1 (295K), respectively. Deprotonation of sulfone (R)-EtCH=CHCH(Et)SO₂tBu (94 % ee) with nBuLi in THF at -105 °C occurred with a calculated enantioselectivity of 93 % ee and gave carbanion (M)-[EtCH=CHC(Et)SO₂tBu]Li, the deuteration and alkylation of which with CF₃CO₂D and MeOCH₂I, respectively, proceeded with high enantioselectivities. Time-dependent deuteration of the enantioenriched carbanion (M)-[EtCH=CHC(Et)SO₂tBu]Li in THF gave a racemization barrier of ΔG^≠=12.5kcal mol^-1 (168K), which translates to a calculated half-time of racemization of t_1/2=12min at -105 °C.

Full text of DOI:10.1002/chem.201503123

DOI: 10.1002/chem.201503123
Full Paper
&
Lithiated Compounds
Chiral Lithiated Allylic a-Sulfonyl Carbanions: Experimental and
Computational Study of Their Structure, Configurational Stability,
and Enantioselective Synthesis
Frank Gerhards,[a, b] Nicole Griebel,[a, c] Jan Runsink†,[a] Gerhard Raabe,*[a] and
Hans-Joachim Gais*[a]
Abstract: X-ray crystal structure analysis of the lithiated allyl-
ic a-sulfonyl carbanions [CH2=CHC(Me)SO2Ph]Li·diglyme,
bonds. The allylic unit of the C,O,Li isomer shows strong
bond length alternation and the C1 atom is in contrast to
the O,Li isomer significantly pyramidalized. According to
NBO analysis of the s-trans and s-cis isomers, the interaction
of the lone pair at C1 with the p* orbital of the CC double
bond is energetically much more favorable than that with
the “empty” orbitals at the Li atom. The C1ÀS and C1ÀC2
conformations are determined by the stereoelectronic ef-
fects nC–sSR* interaction and allylic conjugation. 1H DNMR
spectroscopy of racemic [EtCH=CHC(Et)SO2tBu]Li, [iPrCH=
CHC(iPr)SO2tBu]Li and [EtCH=C(Me)C(Et)SO2tBu]Li in [D8]THF
[cC6H8SO2tBu]Li·PMDETA
and
[cC7H10SO2tBu]Li·PMDETA
showed dimeric and monomeric CIPs, having nearly planar
anionic C atoms, only OÀLi bonds, almost planar allylic units
with strong CÀC bond length alternation and the s-trans
conformation around C1ÀC2. They adopt a C1ÀS conforma-
tion, which is similar to the one generally found for alkyl
and aryl substituted a-sulfonyl carbanions. Cryoscopy of
[EtCH=CHC(Et)SO2tBu]Li in THF at 164 K revealed an equilib-
rium between monomers and dimers in a ratio of 83:17,
which is similar to the one found by low temperature NMR
spectroscopy. According to NMR spectroscopy the lone-pair
orbital at C1 strongly interacts with the C=C double bond.
¼
gave estimated barriers of enantiomerization of DG =
13.2 kcalmolÀ1 (270 K), 14.2 kcalmolÀ1 (291 K) and 14.2 kcal
molÀ1 (295 K), respectively. Deprotonation of sulfone (R)-
EtCH=CHCH(Et)SO2tBu (94% ee) with nBuLi in THF at
À1058C occurred with a calculated enantioselectivity of
93% ee and gave carbanion (M)-[EtCH=CHC(Et)SO2tBu]Li, the
deuteration and alkylation of which with CF3CO2D and
MeOCH2I, respectively, proceeded with high enantioselectivi-
ties. Time-dependent deuteration of the enantioenriched
carbanion (M)-[EtCH=CHC(Et)SO2tBu]Li in THF gave a racemi-
6
Low temperature Li,1H NOE experiments of [EtCH=CHC(Et)-
SO2tBu]Li in THF point to an equilibrium between monomer-
ic CIPs having only OÀLi bonds and CIPs having both OÀLi
and C1ÀLi bonds. Ab initio calculation of [MeCH=CHC(Me)-
SO2Me]Li·(Me2O)2 gave three isomeric CIPs having the s-trans
conformation and three isomeric CIPs having the s-cis con-
formation around the C1ÀC2 bond. All s-trans isomers are
more stable than the s-cis isomers. At all levels of theory the
s-trans isomer having OÀLi and C1ÀLi bonds is the most
stable one followed by the isomer which has two OÀLi
¼
zation barrier of DG =12.5 kcalmolÀ1 (168 K), which trans-
lates to a calculated half-time of racemization of t1/2 =12 min
at À1058C.
Introduction
Lithiated allylic a-sulfonyl carbanions I and II (Figure 1) have
found extensive application in organic synthesis.[1–3] This is
mainly due to their highly selective reactions with a wide
range of electrophiles at the a-position and the exceptional
nucleofugacity of the allylic sulfonyl group in, for example,
transition metal-mediated reactions with nucleophiles.[4] In
stark contrast stands the almost complete neglect of the as-
pects associated with the chirality of I[5] and II, including their
enantioselective synthesis and configurational stability.[6,7] In
addition, knowledge of the structure of I and II is, with the ex-
ception of some particular lithiated bicyclic allylic a-sulfonyl
carbanions,[8,9] rather limited.[5,10–13] It was found that chiral dia-
lkyl and alkyl-aryl substituted a-sulfonyl carbanions IIIa and
IIIb, which carry a S-tert-butyl and S-trifluoromethyl, are config-
[a] Dr. F. Gerhards, Dr. N. Griebel, Dr. J. Runsink, Prof. Dr. G. Raabe,
Prof. Dr. H.-J. Gais
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
E-mail: gais@rwth-aachen.de
[b] Dr. F. Gerhards
Present address: Philipp Reis Strasse 12
40215 Düsseldorf (Germany)
[c] Dr. N. Griebel
Present address: Kaiserstrasse 66
52080 Aachen (Germany)
[†] Deceased, 2012.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201503123.
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urationally stable at low temperatures.[7,14–20] They are available
through deprotonation of the corresponding chiral S-tert-butyl
and S-trifluoromethyl sulfones with organolithiums.[7,14–17,19,20]
We became therefore interested in a study of the configura-
tional stability, enantioselective synthesis and structure of the
S-tert-butyl and S-trifluoromethyl substituted allylic carbanions
I and II (R=R3 =tBu, CF3). Provided I and II are accessible in
enantioenriched and configurationally stable form, they will
constitute a new class of chiral heteroatom-stabilized allylli-
thiums,[1d,21,22] which could have a considerable synthetic po-
tential. We decided to first examine the acyclic and cyclic S-
tert-butyl substituted lithiated allylic carbanions I and II, re-
spectively. The corresponding chiral acyclic and cyclic allylic S-
tert-butyl sulfones IV and V, respectively, which are required as
starting material for the synthesis of I and II, can be readily ob-
tained by two different palladium catalyzed enantioselective
reactions, allylic alkylation of tert-butyl sulfinate with racemic
allylic carbonates[23–26] and rearrangement of racemic allylic S-
tert-butylsulfinates.[27–29]
Scheme 1. Palladium catalyzed enantioselective synthesis of allylic tert-butyl
sulfones.[24–26]
sponding racemic allylic carbonates and chloride with the sulfi-
nate in the presence of PPh3 or through racemization of the al-
lylic sulfones via deprotonation–protonation sequences at am-
bient temperatures. A palladium-catalyzed substitution of the
racemic allylic carbonate derived from the racemic allylic alco-
hol rac-16 with the sulfinate could not be achieved by using 3
or PPh3 as ligands. Therefore, alcohol rac-16 was treated with
racemic tert-butylsulfinyl chloride, which directly afforded via
the intermediate formation of the corresponding sulfinate and
its thermal sulfinate-sulfone rearrangement[31] the racemic allyl-
ic tert-butyl sulfone rac-17 albeit only in 33% yield (Scheme 2).
Figure 1. Chiral lithiated allylic and non-allylic a-sulfonyl carbanions.
Herein we describe the enantioselective synthesis, configura-
tional stability, reactivity, and experimental as well as theoreti-
cal structures of lithiated allylic a-sulfonyl carbanions.[30]
Scheme 2. Synthesis of the racemic allylic tert-butyl sulfone rac-17.
Results and Discussion
Structure in the crystal phase
Synthesis of enantiomerically enriched and racemic allylic
tert-butyl sulfones
Little information was available about the structure of lithiated
acyclic allylic a-sulfonyl carbanions in the crystal. We had previ-
ously determined the structure of the lithiated acyclic carban-
ion rac-18·diglyme, which crystallized from diglyme (diglyme
= diethylene glycol dimethyl ether) as a centro-symmetric di-
glyme-coordinated dimer that has only OÀLi bonds.[5] The
anionic C1 atom of rac-18·diglyme seems to be pyramidalized
as indicated by the dihedral angle C2-C1-S-Ci of 768. However,
the uncertainties associated with the determination of the po-
sition of the H atom at C1 did not allow a conclusion as to the
coordination geometry of the anionic
As described previously, the (R)-configured acyclic allylic tert-
butyl sulfones 4 and 5 and the (S)-configured cyclic allylic tert-
butyl sulfones 12–15 were synthesized through palladium cat-
alyzed alkylation of LiSO2tBu with the corresponding racemic
allylic carbonates rac-1, rac-2 and rac-8-11 in the presence of
the chiral bisphosphane 3 in yields of 50 to 98% with 89 to
98% ee (Scheme 1).[24–26]
The isopropyl-substituted allylic tert-butyl sulfone 7 was pre-
pared starting from the racemic allylic chloride rac-6 and Li-
SO2tBu through palladium catalysis in the presence of 3 fol-
lowing the published protocol in 58% yield with 87% ee.[25]
The corresponding racemic allylic sulfones were either synthe-
sized through palladium catalyzed substitution of the corre-
C atom of allylic a-sulfonyl carbanions.
The C2ÀC3 unit of rac-18·diglyme is
nearly in one plane with the C1ÀS unit
as shown by the dihedral angle S-C1-
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C2-C3 of 1698 and the carbanion adopts the s-trans conforma-
tion around the C1ÀC2 bond.
The smaller dihedral angle Me-C1-S-Ci is perhaps caused to
some extend by steric interaction between the methyl group
at the C1 atom and the methyl group of the diglyme mole-
cule.[18] The allyl unit of rac-20·diglyme shows with bond
lengths C1ÀC2 of 1.440(9) Š and C2ÀC3 of 1.35(1) Š a similar
bond length alternation as rac-18·diglyme (C1ÀC2 1.446(9) Š
and C2ÀC3 1.352(9) Š). The C1ÀS bond of rac-20·diglyme is
with 1.639(7) Š of similar length as the C1ÀS bonds of rac-
18·diglyme (1.668(6) Š) and of the lithiated bicyclic allylic a-
sulfony carbanions rac-23·diglyme (1.649(7) Š),[8] rac-24·di-
In order to obtain information about the structure of the
more relevant lithiated acyclic allylic a-sulfonyl carbanions car-
rying an alkyl group at C1, we determined in extension of the
study of rac-18·diglyme the crystal structure of the lithiated
methyl substituted carbanion rac-20. Single crystals of rac-
20·diglyme were obtained from sulfone rac-19 through treat-
ment with nBuLi in diglyme and recrystallization of the lithiat-
ed carbanion from diglyme (Scheme 3).[10d] The lithiated carb-
anion rac-20·diglyme is stable at room temperature under the
exclusion of water and dioxygen.
glyme
(1.633(3) Š)[8]
and
rac-25·PMDETA
(1.626(5) Š)
(PMDETA =pentamethyldiethylene-triamine) (Figure 3),[9] which
are also devoid of CÀLi bonds. The C2ÀC3 unit of rac-20·di-
glyme is nearly in one plane with the C1–S unit as shown by
the dihedral angle S-C1-C2-C3 of À166.2(6)8. Thus, the C=C
double bonds of rac-20·diglyme and rac-18·diglyme are
aligned in such a way as to allow for an interaction with the
lone pair orbital at the anionic C1 atoms. The lithiated carban-
ion rac-20·diglyme adopts the s-trans conformation around the
C1-C2 bond despite the presence of the methyl group at C1,
which could in principle destabilize the s-trans conformation
by steric interaction with the double bond.
Scheme 3. Synthesis of the lithiated allylic a-sulfonyl carbanions rac-20·di-
glyme, rac-21·PMDETA and rac-22·PMDETA.
The lithiated carbanion rac-20·diglyme is also a centro-sym-
metric diglyme-coordinated dimer, which has OÀLi but no CÀLi
bonds (Figure 2).[32] The carbanion has a similar chiral C1-S con-
formation as rac-18·diglyme. The anionic C1 atom of rac-20·di-
glyme is somewhat pyramidalized as shown by the dihedral
angles C2-C1-S-Ci of 86.5(6)8 and Me-C1-S-Ci of À70.6(6)8 and
the sum of the bond angles at C1 of 356.08 (Table 1).
Figure 2. Structure of the lithiated acyclic allylic a-sulfonyl carbanion rac-
20·diglyme in the crystal (colour code: black, carbon; red, oxygen; yellow,
sulphur; pink, lithium).
Table 1. Selected bond lengths [Š], bond angles [8] and dihedral angles
[8] of the lithiated carbanions rac-20·diglyme and rac-21·PMDETA.
Parameter
rac-20·diglyme
rac-21·PMDETA
C1ÀS
C1ÀC2
C2ÀC3
SÀO
1.639(7)
1.440(9)
1.35(1)
1.455(5)
1.471(5)
1.91(1)
1.622(5)
1.433(7)
1.352(8)
1.459(3)
1.478(3)
1.841(8)
Figure 3. Lithiated bicyclic s-cis allylic a-sulfonyl carbanions.
OÀLi
1.94(1)
Prior to our study, nothing was known about the structure
of monocyclic lithiated allylic a-sulfonyl carbanions in the crys-
tal. Therefore, the lithiated carbanions 21·PMDETA and
22·PMDETA were synthesized through deprotonation of the
corresponding sulfones rac-13 and rac-15 with nBuLi in
PMDETA and their structures determined by X-ray crystal struc-
ture analysis. PMDETA was chosen as ligand for the Li atom,
because it favors the crystallization of monomeric lithiated a-
sulfonyl carbanions by blocking three coordination sites at the
SÀCi(C)
1.790(6)
1.50(1)
128.0(7)
120.9(5)
117.5(7)
117.6(5)
1.832(5)
1.509(8)
123.8(5)
122.5(4)
116.6(4)
120.7(4)
114.7(2)
À83.9(4)
90.0(5)
SÀCH3(CH2)
C1-C2-C3
S-C1-C2
C2-C1-C
S-C1-C
C1-S-Ci(tBu)
Ci(tBu)-S-C1-C2
Ci(tBu)-S-C1-CH3(CH2)
S-C1-C2-C3
86.5(6)
À70.6(6)
À166.2(6)
À179.2(4)
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Li atom.[8,9] Single crystals of rac-21·PMDETA and rac-
22·PMDETA were attained through recrystallization from THF.
The crystalline lithiated carbanions are stable at room tempera-
ture under the exclusion of water and dioxygen. The lithiated
six-membered cyclic allylic carbanion rac-21·PMDETA crystal-
lized as a PMDETA-coordinated monomer.[32] Its Li atom is coor-
dinated only to one O atom but not to a C atom of the allylic
moiety (Figure 4).
Figure 5. Structure and bonding parameters (in Š and8) of the cyclic sulfone
(S)-13 in the crystal. Conformer A (shown): SÀtBu 1.826(4), C1ÀS 1.826(2),
C1ÀC2 1.515(5), C2ÀC3 1.327(3), C2-C1-C6 111.9(2), C2-C1-S 106.5(2), C6-C1-S
112.3(2), tBu-S-C1-C2 À155.6(1), tBu-S-C1-C6 81.6(2). Conformer B (not
shown): S-tBu 1.827(4), C1-S 1.811(2), C1-C2 1.505(3), C2-C3 1.325(3), C2-C1-
C6 111.1(2), CH2-C1-S 107.4(2), C2-C1-S 112.1(2), C1-S-tBu 109.5(2), tBu-S-C1-
C2 À85.8(2), tBu-S-C1-C6 151.8(1) (colour code: black, carbon; red, oxygen;
yellow, sulphur; white, hydrogen).
Figure 4. Structure of the monomeric lithiated six-membered cyclic allylic a-
sulfonyl carbanion rac-21·PMDETA in the crystal (colour code: black, carbon;
red, oxygen; yellow, sulphur; pink, lithium; green, nitrogen).
the bond angle C1-S-tBu considerably widens. Generally, a-sul-
fonylÀcarbanions have a larger bond angle C1-S-C than the
corresponding sulfones.[8,9,18] The C1ÀC2 bonds of the bicyclic
allylic carbanions rac-23·diglyme, rac-24·diglyme and rac-
25·PMDETA are also significantly shorter and the C2ÀC3 bonds
are only slightly longer than those of the corresponding sul-
fones.[8,9]
rac-21·PMDETA has the typical chiral C1ÀS conformation of
rac-18·diglyme and rac-20·diglyme. Its anionic C1 atom is
planar as revealed by dihedral angles CH2-C1-S-tBu of 90.0(5)8
and C2-C1-S-tBu of À83.9(4)8 and the sum of the bond
angles at C1 of 360.08. In contrast, the anionic C atom of
the saturated six-membered cyclic lithiated carbanion
l{[cC6H10SO2Ph]Li·digylme}2 is significantly pyramidalized
(SaC1=353.08).[18] The allylic unit of rac-21·PMDETA shows
with C1ÀC2 1.433(7) Š and C2ÀC3 1.352(8) Š a similar bond
length alternation as rac-18·diglyme and rac-20·diglyme. The
C1ÀS bond of rac-21·PMDETA is with 1.622(5) Š of similar
length as the C1ÀS bonds of rac-18·diglyme and rac-20·di-
glyme. The C2–C3 unit is in one plane with the C1–S unit as
shown by the dihedral angle S-C1-C2-C3 of À179.2(4)8. Thus,
the structural requirements for an optimal orbital interaction in
the allylic unit are given. Atom C5 of rac-21·PMDETA is disor-
dered, and atoms C4, C3, C1 and C6 almost lie in one plane as
indicated by the dihedral angles C1-C2-C3-C4 of À4.4(8)8 and
C6-C1-C2-C3 of 6.7(8)8.
From the crystal structure analyses follows that the mono-
meric and dimeric O,Li CIPs of lithiated allylic a-sulfonyl car-
banions, which carry a C-substituent at C1, have nearly planar
coordinated anionic C atoms. It seems interesting to note in
this context that the O,Li CIPs of lithiated alkyl substituted
benzylic a-sulfonyl carbanions have essentially planar anionic
C atoms,[18,33–35] while the anionic C atoms of the O,Li CIPs of
dialkyl substituted lithiated a-sulfonyl carbanions are strongly
pyramidalized (half-way between sp3 and sp2 hybridiza-
tion).[34,36]
The lithiated seven-membered cyclic allylic carbanion rac-
22·PMDETA also crystallized as a PMDETA-coordinated mono-
mer, the Li atom of which is coordinated to one O atom but
not to the C1 atom of the allylic moiety (Figure 6).[32,37] It has
a similar C1–S conformation as rac-21·PMDETA and an almost
planar anionic C atom.
The crystal structure of the parent sulfone (S)-13 (Figure 5)[32]
was also determined in order to obtain information about the
changes of the bonding parameter, which take place upon its
conversion to rac-21·PMDETA. In the crystal two independent
molecules of the sulfone exist, which mainly differ in regard to
the C1–S conformation (conformers A and B). The cyclohexene
rings of both molecules adopt half-chair conformations with
the sulfonyl groups in pseudo-equatorial position.
Structure in solution
The lithiated allylic a-tert-butylsulfonyl carbanions rac-21, rac-
22, rac-26, rac-27, rac-28, rac-29, rac-30 and rac-31, each con-
taining two molecules of THF, were prepared upon reaction of
the corresponding sulfones rac-4, rac-5, rac-7, rac-12, rac-13,
rac-14, rac-16 and rac-17 with nBuLi in THF at low tempera-
tures, removal of the solvent in vacuo at room temperature
and dissolution of the oily or crystalline residues in [D8]THF
(Scheme 4).
A comparison of the bonding parameters of sulfone (S)-13
and of rac-21·PMDETA shows that the C1ÀC2 bond of the lithi-
ated carbanion is significantly shorter, while the C2ÀC3 bond is
only slightly longer. On going from (S)-13 to rac-21·PMDETA
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different structures including monomers and dimers. Most
likely structures of the monomeric CIPs are A-P (Figure 7). The
CIPs differ in respect to the configurations of the C1 and S
atoms, the conformations around the C1ÀC2 and C1ÀS bonds,
the position of the Li atom and the number and type of bonds
between the Li atom and the carbanion and the number of co-
ordinated THF molecules. The cyclic lithiated carbanions rac-
21, rac-22, rac-30 and rac-31 can in principle attain structures
of type A–D and K–M (with a Z configured CC double bond).
The structures of rac-21·PMDETA and rac-22·PMDETA in the
crystal can be regarded as monomeric CIPs of type F and G.
In addition to the monomeric CIPs the lithiated carbanions
rac-21, rac-22, rac-26, rac-27, rac-28, rac-29, rac-30 and rac-31
can in principle form four different dimeric s-trans CIPs, having
the (anti,P,M), (anti,P(M),P(M), (syn,P,M) and (syn,P(M),P(M)) con-
figuration (not shown). The rac-18·diglyme and rac-21·diglyme
crystallized as (anti,P,M)-configured dimers, whereby P and M
designate the configurations of the carbanions and anti/syn
specify the position of the substituents at the S atoms relative
to the eight-membered ring composed of the S, O and Li
atoms. In addition to the dimeric s-trans CIPs the correspond-
ing dimeric s-cis and mixed s-trans/s-cis CIPs have to be consid-
ered as further possible species (not shown).
Figure 6. Structure of the monomeric lithiated seven-membered cyclic allylic
a-sulfonyl carbanion rac-22·PMDETA in the crystal (colour code: black,
carbon; red, oxygen; yellow, sulphur; pink, lithium; green, nitrogen).
Monomer–dimer equilibrium
Cryoscopy of the ethyl substituted lithiated carbanion rac-
27·2THF in THF at 164 K had yielded an aggregation number
of n=1.17Æ0.06 (c=50.0 mmolkgÀ1), which corresponds to
an equilibrium composed of 83Æ6% of monomeric CIPs and
17Æ6% of dimeric CIPs.[30a,39] Cryoscopy of the unsubstituted
lithiated allylic carbanion rac-18 in THF at 164 K had given sim-
ilar results (n=1.11Æ0.06).[12] The ratio of the monomer(s) and
the dimer(s) of rac-27 did not change in the concentration
range from c=0.10m to 0.50m. A similar observation was
made in the case of rac-18.[12]
Variable temperature 1H NMR spectroscopy of rac-27 in
[D8]THF showed at low temperatures a coalescence phenom-
enon, stemming from the hindered C1ÀS bond rotation (see
below), and a second coalescence phenomenon at even lower
1
temperatures. The H NMR spectrum of rac-27 in [D8]THF dis-
played two species in a ratio of approximately 3:1 at À788C,
which exhibited only small chemical shift differences for the
signals of 2-H, 3-H and the methylene group at C1 of Dd=
0.01 ppm. Similarly, 13C NMR spectroscopy of rac-27 in [D8]THF
showed a coalescence phenomenon at low temperatures. The
13C NMR spectrum of rac-27 featured two species in a ratio of
approximately 3:1 at À788C, which also displayed only small
chemical shift differences for Me, CMe3, C1 and C3 of Dd=
0.07–0.12 ppm. The two different species of rac-27 are most
likely the corresponding monomer(s) and the dimer(s), which
are in rapid dynamic equilibrium even at low temperatures. In
principle, the two equilibrium species of rac-27 could also be
the s-trans and s-cis isomers around the C1ÀC2 bond instead
of the monomer(s) and dimer(s). However, the s-trans and s-cis
isomers of carbanion rac-27 are expected to exhibit much
larger chemical shift differences for the allylic subunits than
Scheme 4. Synthesis of lithiated acyclic and cyclic allylic S-tert-butyl a-sulfo-
nyl carbanions.
6
Similarly, Li labeled rac-27 was synthesized from rac-5 and
nBu6Li in [D8]THF. The lithiated allylic carbanions were stable in
solution at room temperature under the exclusion of water
and dioxygen. The acyclic lithiated carbanions rac-26, rac-27,
rac-28 and rac-29, which are expected to form contact ion
pairs (CIPs) in THF solution,[18,38] can adopt a large number of
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Figure 7. Possible structures of the monomeric CIPs of the lithiated acyclic allylic a-sulfonyl carbanions (L=THF).
those observed. For example, the s-cis and s-trans isomers of
the CIPs as well as of the solvent separated ion pairs (SSIPs) of
1-(phenylthio)allyllithium and 1-(2-pyridylthio)allyllithium dis-
played chemical shift differences of Dd (1H) ꢀ 0.20 ppm and
Dd (13C) ꢀ 10 ppm for the signals of the H and C atoms, re-
spectively, of the allylic moieties.[40] Further support for the
designation of the low-temperature species of rac-27 as mono-
Figure 8. Lithiated bicyclic s-cis allylic S-tert-butyl a-sulfonyl carbanions.
1
mer(s) and dimer(s) comes from previous H and 13C NMR stud-
ies of the lithiated bicyclic allylic a-sulfonyl carbanions rac-25,
rac-32 and rac-33 (cf. Figure 3, Figure 8) in [D8]THF, which
cannot engage in a s-trans/s-cis equilibrium.[8,9] The NMR spec-
tra of the lithiated bicyclic carbanions displayed at À788C
monomers and dimers, having similar small chemical shift dif-
ferences as rac-27, in ratios comparable to those found by
tion around the C1ÀC2 bond. It also preferentially adopts in
THF solution at room temperature the s-trans conformation as
3
indicated by the magnitude of the coupling constant J(1-H,2-
H) of 10.9 Hz. Generally, the CIPs and SSIPs of metalated allylic
a-sulfonyl carbanions of type rac-34 (Scheme 5), carrying a H
atom at the anionic C1 atom, prefer the s-trans conformation
1
cryoscopy. In addition, H and 13C NMR investigations of lithiat-
3
ed alkyl substituted benzylic a-sulfonyl carbanions in [D8]THF
at À788C also showed the existence of two species, most
likely monomers and dimers, having only small chemical shift
differences, in ratios comparable to those determined by cryo-
scopy for the monomers and dimers.[18] Variable temperature
1H and 13C NMR spectroscopy of the diisopropyl substituted
carbanion rac-28 and the diethyl-methyl substituted carbanion
rac-29 in [D8]THF showed in addition to coalescence phenom-
ena, originating from the hindered C1ÀS bond rotation (see
below), further coalescence phenomena and in each case two
species at À858C, most likely monomers and dimers, which ex-
hibited only small chemical shift differences.
around the C1ÀC2 bond as shown by the magnitudes of J(1-
H,2-H), which are in the range of 10.5 to 11.0 Hz (Supporting
Information, Table S1).[5,10,11] 1H,1H NOE experiments of the di-
methyl substituted allylic a-sulfonyl carbanion rac-34 (M=Li,
R1 =R2 =Me; R3 =Ph) in [D8]THF at room temperature had also
given evidence for a preferred s-trans conformation around
the C1ÀC2 bond.[10c] Although the magnitudes of 3J(1-H,2-H)
for the s-cis conformers of rac-34 are not known, it is expected
that they are much smaller than those of the s-trans conform-
3
ers. For example, coupling constants J(1-H,2-H) of 11.1 Hz and
4.8 Hz had been measured for the s-trans and s-cis conformers,
respectively, of the CIPs and SSIPs of 1-(phenylthio)allyllithi-
um.[40] Typically, lithiated allylic a-sulfenyl carbanions from in
THF equilibrium mixtures of s-cis isomers as the major and s-
trans isomers as the minor species.[12,40–42]
C1ÀC2 conformation
The lithiated allylic a-sulfonyl carbanion rac-18·diglyme, which
carries a H atom at C1, has in the crystal the s-trans conforma-
The lithiated allylic S-phenyl carbanion rac-20·diglyme,
which carries a methyl group at the anionic C atom, has in the
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À908C showed besides the monomers and dimers no further
species, the spectra of the bicyclic s-cis allylic a-sulfonyl car-
banions rac-25, rac-32 and rac-33 in [D8]THF had revealed at
À908C besides the monomers and dimers further rapidly equi-
librating species, most likely different CIPs.[8,9] Similar observa-
tions were made by 13C NMR spectroscopy of lithiated benzylic
a-tert-butylsulfonyl carbanions in [D8]THF at À908C.[18]
Mixed aggregate with lithium ethenolate
The use of an excess of nBu6Li in the deprotonation of rac-5 in
[D8]THF led, besides rac-27, to the formation of deuterated
Scheme 5. Equilibrium of s-trans and s-cis Isomers of lithiated allylic a-sulfo-
nyl carbanions.
lithium ethenolate (ꢀ90% D)[43] as shown by H and H NMR
spectroscopy. Interestingly, the lithiated carbanion rac-27
formed besides the monomer(s) and dimer(s) a mixed aggre-
2
1
crystal also the s-trans conformation around the C1ÀC2 bond.
1H,1H NOE experiments of the C1 methyl substituted S-tert-
butyl carbanion rac-26 in [D8]THF at room temperature
showed strong effects between the methyl group at the anion-
ic C1 atom and 3-H, only a weak effect between the methyl
group at C1 and 2-H and a medium effect between 2-H and
the tert-butyl group (Scheme 5). These results would be com-
patible with a dynamic conformational equilibrium of rac-26,
in which the s-trans isomer is the major and the s-cis isomer is
the minor species. Similar 1H,1H NOE experiments of the C1
ethyl substituted S-tert-butyl carbanion rac-27 in [D8]THF at
room temperature gave strong effects between the H atoms
of the ethyl group at C1 and 3-H, medium effects between 2-H
and the tert-butyl group, medium effects between the ethyl
group at C1 and the tert-butyl group but no effect between
the C1 ethyl group and 2-H. These results indicate that rac-27
almost exclusively adopts the s-trans conformation.
1
gate with lithium ethenolate in [D8]THF, according to H, 13C
6
1
and Li NMR spectroscopy and 2D H,6Li HOESY experiments at
À788C.[30a,44,45] 2D Li EXSY experiments of the mixture of mon-
6
omer(s), dimer(s) and mixed aggregate at À908C revealed an
exchange of the Li atoms of the three species.[30a]
Allylic stabilization of the negative charge
The acidities of allyl phenylsulfone (DpKa =6.5) and benzyl
phenylsulfone (DpKa =5.6) are higher than the acidity of
methyl phenylsulfone (K+, DMSO).[46] This is commonly attrib-
uted to an increased stabilization of the corresponding allylic
and benzylic a-sulfonyl carbanions by conjugation of the nega-
tive charge with the double bond and phenyl group, respec-
tively. X-Ray crystal structure analyses of rac-20·diglyme and
rac-21·PMDETA had revealed dihedral angles S-C1-C2-C3 of
166.2 (6)8 and À179.2 (4)8. Thus, the orbitals of the allylic units
are properly aligned for an additional stabilization of the car-
Site of the Li atom in the CIP
1
banions by conjugative interaction. Table 2 lists the H and 13C
While monomeric CIPs of type K–P have like the corresponding
dimers only O–Li bonds, monomeric CIPs of type A–J exhibit
OÀLi and CÀLi bonds. In order to obtain structural information
chemical shifts of the allylic moieties of rac-21, rac-22, rac-26,
rac-27, rac-28, rac-29, rac-30 and rac-31 and the shift varia-
tions (Dd), which were observed in [D8]THF on going from the
sulfones rac-4, rac-5, rac-7, rac-12, rac-13, rac-14, rac-16 and
rac-17 to the corresponding lithiated carbanions. An inspection
of Table 2 reveals the following qualitative shift variations: 1)
small variations in the C1 and C2 signals, 2) strong up-field
shifts of the C3 signals, 3) medium down-field shifts of the 2-H
signals and 4) strong up-field shifts of the 3-H signals. Similar
chemical shift variations had been recorded for the bicyclic car-
banions rac-23, rac-24, rac-25, rac-32 and rac-33[8] and for allyl-
ic a-sulfonyl carbanions carrying a H atom at the anionic C1
atom (Supporting Information, Table S1).[10–12] Lithiated allylic
a-sulfonimidoyl carbanions rac-35,[3,10c,21b,47] lithiated allylic sul-
fenyl carbanions[12,40–42] and lithiated allylic diaminophosphonyl
carbanions[48] show similar NMR spectroscopic features.
6
about the CIPs of rac-27, Li,1H HOESY experiments were car-
ried out in [D8]THF at room temperature and at À908C. Be-
cause of the similar chemical shifts of the monomers and
6
dimers, a distinction between both in the 2D Li,1H HOESY ex-
periment was not possible and thus only averaged information
6
was obtained. The Li NMR spectrum showed a single peak at
6
room temperature and at À908C. The 2D Li,1H HOESY spectra
6
of Li labeled rac-27 at room temperature and at À908C re-
vealed correlations of the Li atom with the tert-butyl group,
the 2-H atom and the methylene group at C1. A correlation
between the Li atom and 3-H was not observed. These correla-
tions would be compatible with fast dynamic equilibria be-
tween O,C,Li CIPs of type A–D and O,Li CIPs of type K–M.
6Li,1H NOE experiments of rac-34 (M=Li, R1 =R2 =Me; R3 =Ph)
in [D8]THF at room temperature had also pointed to equilibria
The shifts variations recorded for the allylic a-sulfonyl car-
banions indicate 1) a hybridization of the anionic C atoms
somewhere between sp3 and sp2, 2) the accumulation of nega-
tive charge at C3, 3) the accumulation of positive charge at C2
and 4) the negative charge at C1. Charge distributions of the
type C1À-C2+-C3À, which are the result of allylic conjugation
and/or polarization of the double bond by the accumulation of
6
between O,Li CIPs and O,C,Li CIPs.[10c] Previous Li,1H NOE stud-
ies of lithiated benzylic a-trifluoromethylsulfonyl carbanions in
[D8]THF at low temperatures had indicated the existence of
equilibria between O,Li CIPs as major and O,C,Li CIPs as minor
components.[20] While the 13C NMR spectrum of rac-27 at
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troscopy, ab initio calculations of the
lithiated trimethyl substituted allylic
a-sulfonyl carbanion 36 were carried
out as model compound. In particular,
information was sought about the via-
bility and energies of monomeric CIPs
of the type shown in Figure 6.
Table 2. Selected 1H and 13C NMR data (d in ppm) of the lithiated allylic
S-tert-butyl a-sulfonyl carbanions rac-21, rac-22, rac-26, rac-27, rac-28,
rac-29, rac-30 and rac-31 in [D8]THF at room temperature.[a]
Lithiated carbanion
–
2-H(Dd)
C-2(Dd)
3-H(Dd)
C-3(Dd)
C-1(Dd)
–
6.25(0.69)
134.8(5.7)
6.14(0.69)
129.0(4.5)
6.03(0.53)
129.0(8.7)
–
134.6(4.2)
6.14(0.07)
137.6(13.8)
6.14(0.15)
131.3(À2.5)
6.25(0.25)
134.0(À1.5)
6.30(0.42)
136.6(3.4)
3.73(À2.03)
90.7(À37.5)
4.01(À1.74)
100.1(À39.4)
4.81(À0.69)
107.5(À36.9)
4.33(À1.21)
107.1(À29.6)
4.34(À1.47)
101.6(À37.5)
4.19(À1.51)
95.7(À26.2)
4.20(À1.80)
99.8(À29.3)
3.97(À1.71)
95.5(À32.1)
rac-26
52.7(À4.1)
The relative energies of all isomers of 36 obtained at differ-
ent levels of accuracy are listed in Table 3. Selected calculated
structural parameters of interest, dipole moments and energies
are given in Tables 4–6. The corresponding total energies of
the isomers are listed in Table S2 of the supporting informa-
tion, were also the optimized Cartesian coordinates of all local
minima are listed.
–
rac-27
61.3(À4.0)
–
rac-28
60.7(À4.9)
–
rac-29
63.3(À7.2)
–
rac-30
62.4(À2.4)
–
rac-21
55.5(0)
–
62.5(3.0)
–
rac-22
Table 3. Relative energies of the isomers A, B, E, J, K and N of the lithiat-
ed allylic a-sulfonyl carbanion 36 at different levels of theory in kcal
molÀ1. eo is the zero point energy.
rac-31
62.0(6.0)
Isomer MP2/6-
31+G*//
MP2/6-
31+G*//
MP2/6-
MP2/6-31+G*// MP2/6-31+G*//
MP2/6-31+G* MP2/6-31+
[a] Dd=dcarbanion À dsulfone
.
MP2/6-
+SCRF[a]
G*+SCRF[a] +e0
31+G*
31+G*+e0
negative charge at C1, lead to coulombic stabilization. Calcula-
tions of rac-23 and rac-24 had yielded a similar charge distri-
bution in the allylic moieties with an unequal distribution of
the negative charge between C1 and C3.[8,9] However, despite
the conjugative interaction in rac-18·diglyme, rac-20·diglyme,
s-trans/ Æ0.0
O,C1,Li
(36A)
s-trans/ 3.23
O,Li
(36K)
s-trans/ 6.59
O,C1,Li
(36B)
Æ0.0
2.74
6.47
6.06
3.45
5.92
Æ0.0
Æ0.0
2.82
2.87
4.03
4.31
6.41
2.33
2.75
3.86
4.12
5.74
rac-21·PMDETA,
rac-23·diglyme,
rac-24·diglyme
and
25·PMDETA, their allylic units show strong bond length alterna-
tion with long C1ÀC2 and short C2ÀC3 bonds.
Interestingly, the up-field shift of the signal of 3-H of the iso-
propyl substituted allylic carbanion rac-28 is significantly small-
er than the up-field shifts of 3-H of the other allylic a-sulfonyl
carbanions.
s-cis/
6.23
3.64
6.59
O,C3,Li
(36J)
s-cis/
O,C1,Li
(36E)
s-cis/
In summary, the NMR spectroscopic investigations of the
lithiated allylic S-tert-butyl carbanions rac-26, rac-27, rac-28
and rac-29 in THF point to the existence of rapid equilibria not
only between monomers and dimers, but also between mono-
meric O,Li and O,C,Li CIPs having the s-trans (major) and s-cis
(minor) conformation. Thus with the exception of the mono-
mers and dimers only averaged NMR data were obtained. This
holds also true for the other lithiated allylic a-sulfonyl carban-
ions described in this work.
O,Li
(36N)
[a] e=7.4257, THF, PCM model.[51]
At all levels of theory the s-trans/O,C1,Li isomer 36A is the
most stable species closely followed by the s-trans/O,Li isomer
36K (Figure 9), which is 2.82 and 2.33 kcalmolÀ1 higher in
energy at the MP2/6-31+G*//MP2/6-31+G*+SCRF and MP2/
Previous investigations of lithiated
allylic a-sulfonimidoyl carbanions rac-
35, the aza analogs of the sulfonyl
6-31+G*//MP2/6-31+G*+SCRF+e0
level,
respectively
carbanions, in the crystalline phase
(Table 3). Applying the same methods, the s-trans/O,C1,Li
isomer 36B is the next one on the energy scale (2.87 and
2.75 kcalmolÀ1). The s-trans/O,C1,Li isomer 36A and the s-
trans/O,C1,Li isomer 36B differ in regard to the C1–S confor-
mation. A strong solvent effect is observed for 36B which is
and in THF solution had also shown
a preference for the s-trans confor-
mation, equilibria between O(N),Li and O(N),C,Li CIPs, and
a similar C1–S conformation.[10c,21b,47,49,50]
the least stable one of all isomers without the SCRF corrections
[51]
(DESCRF
)
but is energetically similar to the s-trans/O,Li isomer
Theoretical structures of a lithiated allylic a-sulfonyl
carbanion
36K when SCRF corrections are included (2.87 and 2.75 kcal
molÀ1). The significant bulk effect of the solvent in this case is
due to the much higher dipole moment of the s-trans/O,C1,Li
isomer 36B (m=9.296 D) compared with the s-trans/O,Li
In order to corroborate the structural information gathered of
the CIPs of rac-26 and rac-27 in [D8]THF solution by NMR spec-
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SCRF corrections is obtained for the s-cis/O,C3,Li isomer 36J
(m=8.924 D, DESCRF =À10.68 kcalmolÀ1) (Figure 10). Of the s-cis
isomers s-cis/O,Li (36N), s-cis/O,C1,Li (36E) and s-cis/O,C3,Li
(36J) the later one, which has a CÀLi bond involving the termi-
nal C3 atom, has the lowest energy when the solvent is includ-
ed. A DFT calculation of s-cis isomers of the lithiated allylic a-
sulfonyl carbanion rac-18·2THF had found a structure similar
to 36J to be the most stable one.[12]
Table 4. Selected O(C)ÀLi bond lengths [Š] and the sums of bond angles
S [8] at the formally anionic carbon atom C1 in the geometries optimized
at the MP2/6-31+G* level of the isomers A, B, E, J, K and N of the lithiat-
ed allylic a-sulfonyl carbanion 36. Interatomic distances that might be
(2)
considered bonds are in italics. Sn*DEnn* is the energy of interaction be-
tween the anionic lone pair (n) and the formally empty atomic orbitals
(2)
(n*) at the Li atom, and DEnp* is the corresponding energy of interaction
between the anionic lone pair and the p* orbital of the CC double bond
(in kcalmolÀ1).
Ab initio calculation of the lithiated benzylic a-tert-butylsul-
fonyl carbanion [PhC(Me)SO2tBu]Li·(Me2O)2,[20] the Li atom of
which carries two ether molecules, had also yielded an ener-
getic preference for a CIP structure with OÀLi and C1ÀLi bonds
of type A. However, a similar calculation of the analogous lithi-
ated a-trifluormethylsulfonyl carbanion [PhC(Me)SO2CF3]-
(2)[a]
Isomer
r(OÀLi)
r(C1À r(C3À SaC1 Sn*DEnn*
Li) Li)
DEnp*
(2)
s-trans/O,C1,Li
(36A)
s-trans/O,Li (36K) 2.069/
1.979/
3.212
2.284 4.453 346.69 À28.04
3.407 5.495 356.41 À1.94
2.210 3.636 342.52 À11.79
2.341 2.438 349.79 À24.58
2.282 4.374 344.60 À29.60
3.441 4.730 353.36 À2.49
À40.22
À57.95
À41.66
À59.17
À37.47
À53.13
2.015
1.944/
3.937
s-trans/O,C1,Li
(36B)
s-cis/O,C3,Li (36J) 1.949/
3.930
s-cis/O,C1,Li (36E) 1.995/
3.184
[20]
Li·(OMe2)2 showed a CIP structure of type K with two OÀLi
s-cis/O,Li (36N)
2.044/
2.024
2
[a] DEnn* =Àqn·hnjFjn*i /(en*Àen), where F is the Fock operator of the
molecule and qn the occupation number of the lone pair. en* and en are
the NBO orbital energies of the n* orbitals at Li and the anionic lone pair
(n) at C1, respectively.
Table 5. Selected calculated (MP2/6-31+G*) bond lengths (Š) and dihy-
dral angles (8) of the isomers A, B, E, J, K and N of the lithiated allylic a-
sulfonyl carbanion 36.
Isomer
C1ÀS C1À C2À S-C1-C2- Me-S-C1- Me-C1-S-
C2
C3
C3
C2
O
s-trans/O,C1,Li
(36A)
1.699 1.457 1.357 154.5
À85.0
À58.1
s-trans/O,Li (36K) 1.655 1.445 1.360 165.6
À82.5
À41.5
s-trans/O,C1,Li
(36B)
1.722 1.463 1.359 À155.1
À177.1
159.0
s-cis/O,C3,Li (36J) 1.710 1.448 1.370 11.8
s-cis/O,C1,Li (36E) 1.700 1.469 1.357 À20.9
À170.1
À78.5
À68.7
À72.5
À56.1
À36.5
s-cis/O,Li (36N)
1.656 1.456 1.361 À25.3
Table 6. Calculated (MP2/6-31+G*) dipole moments (m) of the isomers
A, B, E, J, K and N of the lithiated allylic a-sulfonyl carbanion 36 (in D).
Isomer
m
s-trans/O,C1,Li (36A)
s-trans/O,Li (36K)
s-trans/O,C1,Li (36B)
s-cis/O,C3,Li (36J)
s-cis/O,C1,Li (36E)
s-cis/O,Li (36N)
5.605
6.316
9.296
8.924
5.653
6.038
isomer 36K (m=6.316 D), which is the second stable species
without the SCRF corrections. The stabilization energies due to
the bulk solvent effects are DESCRF =À12.20 for the s-trans/
O,C1,Li isomer 36B and DESCRF =À8.89 kcalmolÀ1 for the s-
trans/O,Li isomer 36K, respectively. A similarly strong, although
due to a slightly lower dipole moment weaker, effect of the
Figure 9. View of the calculated structures (MP2/G-31+G*) of the s-trans iso-
mers A, K and B of the lithiated allylic a-sulfonyl carbanion 36 (colour code:
black, carbon; red, oxygen; yellow, sulphur; pink, lithium; white, hydrogen).
Top, 36A; middle, 36K; bottom, 36B.
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the sum of bond angles at C1 is closest to the value for a sp3-
hybridized carbon atom (328.418). In the s-trans/O,Li structure
the sum of bond angles at the corresponding carbon atom
amounts to 356.418 and is, therefore, close to the value for an
atom in a perfectly planar environment. We thought that the
degree of pyramidalization might correlate with the results of
NBO analyses[53] of the corresponding molecular wave func-
tions especially with the second-order energies of interaction
between the anionic lone pair (n) with the formally empty or-
(2),
bitals at the Li atom (n*), Sn*DEnn* and between the lone pair
(2)
and the p* anti-bond of the olefinic double bond (p*), DEnp*
.
The corresponding values are listed in columns six and seven
of Table 4. However, it is obvious that there is no such
throughout correlation between the degree of pyramidaliza-
tion and these energetic quantities. Irrespective of the pres-
ence or absence of a CÀLi bond the interaction of the lone
pair with the p* orbital of the C=C double bond is in all CIPs
energetically much more favorable than that with the “empty”
orbitals at the Li atom. The allylic units of the isomers of 36
show a strong bond length alternation (Table 5) and all isomers
adopt a C1–C2 conformation, which allows for an interaction
of the lone-pair at C1 with the double bond. The C1ÀS bond
lengths of the isomers show marked differences. The isomers
with only O–Li bonds have the shortest C1ÀS bonds (36K,
36N), while the isomers in which the lone-pair orbital at C1 is
approximately periplanar to a SÀO bond (36B, 36J) have the
longest C1ÀS bonds. Isomers 36A, 36K, 36E and 36N adopt
a C1–S conformation in which lone-pair orbital at C1 is approx-
imately periplanar to the S-Me bond, while in isomers 36B and
36J the lone-pair orbital is approximately periplanar to a SÀO
bond.
In summary, the by far most stable isomer of the S-methyl
substituted lithiated carbanion 36 is the O,C,Li CIP A, having
besides the s-trans conformation C1ÀLi and OÀLi bonds, in-
cluding the effect of the solvent. The next stable isomer is the
O,Li CIP K, which has also the s-trans conformation and only O-
Li bonds followed by the O,C,Li CIP B, which is similar in
energy and has also the s-trans conformation and O,Li as well
as C1ÀLi bonds. All s-cis isomers of 36 are very much higher in
energy. Based on the relative energies of the CIP structures of
36 and the 6Li,1H HOESY experiments of rac-27, it is much
likely that the S-tert-butyl derivatives rac-26, rac-27, rac-28 and
rac-29 also preferentially form in THF solution rapidly equili-
brating s-trans CIPs (vide infra) of type A and K together with
perhaps CIPs of type L and M.
Figure 10. View of the calculated structures (MP2/G-31+G*) of the s-cis iso-
mers J, E and N of the lithiated allylic a-sulfonyl carbanion 36 (colour code:
black, carbon; red, oxygen; yellow, sulphur; pink, lithium; white, hydrogen).
Top, 36J; middle, 36E; bottom, 36N.
bonds to be the most stable one. While an initio calculation of
[PhC(H)SO2Ph]Li·(OMe2)2 also gave a structure of type A, that
of [PhC(H)SO2Ph]Li·(OMe2)3, which carries three ether molecules
at the Li atom, gave a structure of type L having no CÀLi
bond.[52] A DFT calculation of [MeC(H)SO2Ph]Li·(OMe2)2 found
a structure of type A to be more stable than a structure of
type K.[35]
Configurational stability
The calculated (MP2/6-31+G*) values of the interatomic dis-
tances between the anionic carbon atoms (C1) and the Li
atoms in Table 4 show that except for s-trans/O,Li (36K) and s-
cis/O,Li (36N) there are most likely bonding interactions be-
tween these atoms in the remaining structures, and the same
is true for at least one of the Li–O distances. The strongest pyr-
amidalization of the formally anionic carbon atom C1, which
correlates with the shortest calculated C1–Li distance (2.210 Š),
was obtained for the s-trans/O,C1,Li isomer 36B. At 342.528
The configurational stability of lithiated alkyl-phenyl and dialkyl
substituted a-sulfonyl carbanions is determined by the height
of the barrier towards rotation around the C1ÀS bond, which
is mainly an enthalpic process.[14,18,20] We had previously ob-
tained estimates of the height of the enantiomerization barrier
1
through H DNMR spectroscopy of derivatives containing dia-
stereotopic H atoms that undergo topomerisation during CaÀS
bond rotation.[14,15,18–20] 1H DNMR spectroscopy of the ethyl-
substituted lithiated carbanion rac-27, which carries the diaste-
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reotopic Ha and Hb atoms that undergo topomerisation during
enantiomerization, in [D8]THF under selective decoupling of
the methyl groups gave an estimated enantiomerization barri-
¼
er[54] DG enant =13.2Æ0.2 kcalmolÀ1 at the coalescence temper-
ature of 270 K (Scheme 6). The introduction of an isopropyl
group at the anionic C1 atom instead of the ethyl group in-
1
Scheme 7. Thermodymanic parameter of the enantiomerization of the lithi-
ated propargylic a-sulfonyl carbanion 37.
creased the barrier. H DNMR spectroscopy of the isopropyl-
substituted carbanion rac-28 in [D8]THF under selective decou-
pling of the H atom of the isopropyl group gave an estimated
¼
enantiomerization barrier DG enant =14.2Æ0.2 kcalmolÀ1 at the
13.5Æ0.2 kcalmolÀ1 at the coalescence temperature of 285 K.
The enantiomerization of rac-31 needs in addition to the CaÀS
bond rotation a ring inversion, the barrier of which should be,
however, much lower than the barrier estimated for CaÀS
bond rotation.[56]
1
coalescence temperature of 291 K. H DNMR spectroscopy of
carbanion rac-29, which carries an ethyl group at C1 and
a methyl group at C2, in [D8]THF under selective decoupling of
the methyl groups gave an estimated enantiomerization barri-
¼
er DG enant =14.2Æ0.2 kcalmolÀ1 at the coalescence tempera-
While the enantiomerization of the O,Li CIPs K of 26-29 and
36 involves two steps, rotation around the C1ÀS bond and C1
inversion, that of the O,C,Li CIPs A has to entail, in addition to
C1ÀS bond rotation and C1 inversion, the cleavage and the ref-
ormation of the C1ÀLi and OÀLi bonds (Scheme 8). A fast sol-
vent assisted topomerisation of the Li atom can be envisioned
for the cleavage and reformation of the bonds. Thus, coordina-
tion of a THF molecule to the O,C,Li CIP 26A gives 26A–L,
which experiences a de-coordination of the Li atom from C1 to
form 26M, because of the weaken C1ÀLi bond. Through loss
of a THF molecule 26M is converted to the O,Li CIP 26K
which undergoes C1ÀS bond rotation to furnish ent-26K. The
coordination of a THF molecule to the later yields ent-26K–L
and weakens the C1-Li bond, which leads to a de-coordination
of the Li atom from the O atom to yield ent-26M. Ring closure
of ent-26M with formation of the C1-Li bond gives ent-26A–L,
which upon loss of a THF molecule is converted to ent-26A.
The barriers for the de-coordination of the Li atom from C1
and its coordination to the O atom should be lower in energy
than the barrier for C1ÀS bond rotation since previous studies
of the CIPs and SSIPs of lithiated benzylic a-sulfonyl carbanions
had found similar enantiomerization barriers for both spe-
cies.[14,18,20] In accordance with the proposed fast C,O migration
of the Li atom of the lithiated allylic a-sulfonyl carbanions in
[D8]THF is the failure to observe by NMR spectroscopy, even at
low temperatures, different CIPs and 13C,6Li couplings.
ture of 295 K.
The enantiomerization of CIPs K and A of the cyclic lithiated
allylic a-sulfonyl carbanions 21, 22, 30 and 31 should proceed
in a similar manner except that as an additional step a ring in-
version is required.
Scheme 6. Thermodymanic parameters of the enantiomerization of lithiated
allylic a-sulfonyl carbanions.
1
Interestingly, H DNMR spectroscopy of the lithiated propar-
Enantioselective synthesis and electrophilic capture
gylic a-sulfonyl carbanion rac-37 (Scheme 7) in [D8]THF had
Deuteration and alkylation
previously given a significantly lower enantiomerization barrier
¼
of only DG enant =10.0Æ0.3 kcalmolÀ1 (208 K).[39,55]
Sulfone (R)-5 was treated with nBuLi (1.1 equiv) in THF at
À1058C and after 1 min had elapsed from the beginning of
the addition of the base the lithiated carbanion 27 was deuter-
ated at À1058C with CF3CO2D. This sequence led to the forma-
tion of a mixture of the allylic sulfone (R)-D-5 (96% D) of 81%
ee and the vinylic sulfone D-38 (97% D) in a ratio of 86:14
(Scheme 9). The configuration of the double bond of sulfone
D-38 was not determined. Both reactions were run under stan-
dard conditions and special experimental precautions were
1
The H NMR spectra of the six-membered cyclic allylic carb-
anion rac-21 in [D8]THF showed no line-broadening in the tem-
perature range from room temperature to À808C. Similarly,
the 13C NMR spectrum of rac-21 in [D8]THF remained un-
changed in this temperature range. In contrast, the 1H NMR
spectra of the eight-membered cyclic allylic carbanion rac-31
in [D8]THF displayed coalescence phenomena for the signals of
¼
4-H and 8-H. The estimation of the barrier gave DG
=
enant
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À1058C, the time of addition of
the base and the deuteration
reagent. The results show that
both deprotonation and deuter-
ation had occurred with high
enantioselectivities and pro-
ceeded with over-all retention
of configuration. The isolation
of sulfone (R)-D-5 of 81% ee
starting from (R)-5 of 94% ee
implies that both the deproto-
nation of (R)-5 and deuteration
of the lithiated carbanion 27
had occurred with calculated
selectivities of, for example,
93% ee. Based on our previous
results of the deprotonation of
chiral phenyl-alkyl and dialkyl
substituted sulfones,[7,15–17,19,20]
deprotonation of the (R)-config-
ured sulfone (R)-5 with nBuLi
had given the lithiated carban-
ion (M)-27, the deuteration of
Scheme 8. Enantiomerization and isomerisation of the O,C,Li and O,Li CIPs of 26 (L=THF) via solvent assisted top-
omerisation of the Li atom.
which at C1 had occurred from the direction anti to the
tert-butyl group and afforded sulfone (R)-D-5 (Scheme 9).
Phenyl-alkyl and dialkyl-substituted S-tert-butyl and S-trifluoro-
methyl a-sulfonyl carbanions also undergo a highly selective
anti attack by electrophiles.[7,15–17,19,20] Of the possible CIPs of
(M)-27, the O,Li CIP (M)-27K should be more reactive than
the O,C,Li CIP (R,R)-27A (cf. Figure 7), because of the lack of
steric hindrance and the negative charge at C1 lowering Li
atom.
We had proposed six-membered cyclic transition states (TSs)
for the enantioselective deprotonation of chiral benzylic sul-
fones with RLi.[19,20] The TS models are based on the assump-
tion of an intramolecular deprotonation, following complex
formation between the sulfone and nBuLi, either as monomer,
dimer or tetramer.[57] The developing negative charge of the TS
is stabilized by factors which also stabilize the carbanion, in-
cluding 1) coulombic interaction between the negative charge
at C1 and the positively charged S atom, 2) negative hypercon-
[18,20,58–60]
jugation nC–s*StBu
and 3) benzylic conjugation. Desta-
bilizing factors are mainly steric interactions around the C1ÀS
bond and 1,3-diaxial interactions. Based on these premises
transition states (Àsc,RS)-TS-5, (Àsc,SS)-TS-5, (+sc,SS)-TS-5 and
(ap,RS)-TS-5 are envisioned for the deprotonation of the allylic
sulfone (R)-5, which are all stabilized by coulombic interaction
and allylic conjugation. However, (Àsc,RS)-TS-5 and (Àsc,SS)-TS-
5, which both lead to the formation of (M)-27, should be pre-
ferred over (+sc,SS)-TS-5 and (ap,RS)-TS-5, which both afford
(P)-27. While (Àsc,RS)-TS-5 and (Àsc,SS)-TS-5 experience an ad-
ditional stabilization by nC–s*StBu interaction, (+sc,SS)-TS-5 and
(ap,RS)-TS-5 lack this extra stabilization. The nC–s*SO interaction
in (+sc,SS)-TS-5 and (ap,RS)-TS-5 should be less efficient than
the nC–s*StBu interaction.[18,20] Furthermore, (+sc,SS)-TS-5 and
(ap,RS)-TS-5 are destabilized by 1,3-interaction between the tBu
group and a THF molecule.
Scheme 9. Enantioselective deprotonation of sulfone (S)-13 and enantiose-
lective deuteration of carbanion (M)-27.
taken to ensure that both reactions were conducted at
À1058C. Deprotonation of (R)-5 and deuteration of the lithiat-
ed carbanion 27 were complete within less than 15 s at
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We had previously used time-dependent deuteration of
chiral dialkyl and alkyl-phenyl substituted a-sulfonyl carbanions
for the determination of the dynamic parameters of racemiza-
tion.[19,20] In order to determine the racemization dynamics of
(M)-27 by time-dependent deuteration, the successive depro-
tonation of sulfone (R)-5 of 94% ee and deuteration of the
thus generated carbanion (M)-27 after increasing delay time
with formation of sulfone (R)-D-5 were studied. The ee-value of
(R)-D-5 is a function of (1) the selectivity of the deprotonation
of sulfone (R)-5, (2) the selectivity of the deuteration of carban-
ion (M)-27 and (3) of the racemization of the carbanion. A
series of deprotonation-deuteration experiments was run, in
which all experimental parameters, including those of deproto-
nation and deuteration, were kept constant except the time
which elapsed after the addition of nBuLi to the sulfone and
the beginning of the addition of CF3CO2D to the lithiated carb-
anion, the racemization time trac. Six deprotonation-deuteration
experiments were carried out starting with sulfone (R)-5 (94%
ee) in THF at À1058C under variation of trac from 1 min to
10 min under otherwise identical conditions. The ee values of
(R)-D-5 (97% to 99% D) were determined by GC analysis on
a chiral stationary phase, which also served to prove the (R)
configuration of the deuterated sulfone by comparison with
the starting sulfone. From the slope of the linear plot of ln ee
versus trac the rate constant krac =2”10À3 sÀ1 was estimated
first of MeI (5.0 equiv) after 1 min and then of CF3CO2D after
2 min led to a mixture of 73% of the deuterated allylic sulfone
(R)-D-5 of 73% ee, 23% of the deuterated vinylic sulfone D-38
and 19% of the methylated allylic sulfone (R)-41 of 73% ee
(Scheme 11, Table 7). The composition of the mixture was de-
1
termined by H NMR spectroscopy and the ee values were de-
termined by GC on a chiral stationary phase. Formation of the
methylated vinylic sulfone 42 was not detected. The extension
of the methylation time to 10 min gave 53% of the methylated
sulfone (R)-41 with 64% ee. Finally, after a methylation time of
60 min sulfone (R)-41 of 30% ee was isolated in 98% yield.
Thus, the reactivity of (M)-27 towards MeI is not high enough
to successfully compete with its racemization.
and the activation free energy at 168 K was calculated with the
¼
aid of the Eyring equation to DG rac =12.5Æ0.2 kcalmolÀ1
,
which translates to a calculated half-life time of racemization
of (M)-27 to t1/2 =12 min at À1058C.
Previously, by time-dependent deuteration a racemization
barrier of DG rac =12.1Æ0.2 kcalmolÀ1 (166 K) had been deter-
¼
mined for the lithiated allylic-benzylic a-sulfonyl carbanion (P)-
40 (Scheme 10).[7] Deprotonation of sulfone (S)-39 (93% ee)
with nBuLi in THF at À1058C had afforded carbanion (P)-40,
the deuteration of which at À1078C with CF3CO2D (5 equiv)
after trac =1 min had yielded sulfone (S)-D-39 (ꢁ98% D) of
81% ee.[7] Thus, not only the deprotonation of sulfones (S)-13
and (S)-39 but also the deuteration of carbanions (M)-27 and
(P)-40 take the same stereochemical course and all four reac-
tions are highly enantioselective.
Scheme 11. Reactions of carbanion (M)-24 with C-electrophiles in THF at
À1058C.
The reactivity of (M)-27 towards methoxymethyl iodide was
much higher than towards MeI. Treatment of sulfone (R)-5 of
94% ee with nBuLi (1.1 equiv) in THF at À1058C for 1 min fol-
lowed by the addition of methoxymethyl iodide (5.0 equiv)
after 5 min and then of CF3CO2D after a reaction time of only
1 min gave a mixture composed of 86% of the alkylated allylic
sulfone (R)-43 of 86% ee and 14% of the alkylated vinylic sul-
fone 44 of 34% ee in 91% yield.
Carbanion (M)-27 displayed towards benzoxymethyl bro-
mide a similar high reactivity as towards methoxymethyl
iodide. Thus, treatment of sulfone (R)-5 of 94% ee with nBuLi
(1.1 equiv) in THF at À1058C followed by the addition of
PhCH2OCH2Br (5.0 equiv) after 5 min and then of CF3CO2D after
Scheme 10. Synthesis and deuteration of the lithiated carbanion (P)-40.[7]
Table 7. Methylation of carbanion (M)-27 with MeI in THF at À1058C.
trac [min]
(R)-D-5/D-38
[%]
((R)-D-5)
ee [%]
(R)-41
[%]
((R)-41 ee
[%]
The enantioselective synthesis of (M)-27 from sulfone (R)-5
with nBuLi provided the basis for a study of the reactivity of
the carbanion towards C-electrophiles. Deprotonation of sul-
fone (R)-5 of 94% ee with nBuLi (1.1 equiv) in THF at À1058C
with formation of (M)-27 followed by the successive addition
2
10
60
55:23
27:14
0:2
73
67
–
19
53
98
73
64
30
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5 min gave in 65% yield a mixture composed of 93% of the al-
kylated allylic sulfone (R)-45 of 69% ee and of 7% of the alky-
lated vinylic sulfone 46.
It is interesting to note that the a/g-selectivity of the reac-
tion of carbanion (M)-27 with methyl iodide was much higher
than of the reactions with the more reactive electrophiles
CF3CO2D, methoxymethyl iodide and benzoxymethyl bromide.
The double bond of the vinylic sulfone 44 has the (E) configu-
ration. NOE experiments of 44 revealed correlations between
2-H and tBu and between 3-H and the CH2 group at C1. Based
on this result the vinylic sulfone 46 was also assigned the (E)
configuration. Formation of the (E) configured vinylic sulfones
is a consequence of the higher reactivity of (M)-27 as com-
pared to its s-cis isomer. The configurations of the stereogenic
C atoms of 44 and 46 were not determined.
Scheme 12. Synthesis and reactions of carbanion (P)-21 in THF at À1058C.
signed the (R) and (S) configurations, respectively, on the basis
of the sterochemical course of the deuteration of carbanion
(M)-27. Previous studies of the deuteration and alkylation of di-
alkyl- and alkyl-phenyl-substituted chiral a-sulfonyl carbanions
had shown that both reactions always take the same stereo-
chemical course.[15–17,19,20]
Information about the configurational stability of the six-
membered cyclic carbanion (P)-21 could not be gained by
DNMR spectroscopy. Thus, deprotonation-deuteration experi-
ments starting with sulfone (S)-13 of 96% ee were carried out.
Sulfone (S)-13 was treated with nBuLi (1.1 equiv) in THF at
À1058C and after 1 min carbanion (P)-21 was deuterated at
À1058C with CF3CO2D (5 equiv), which gave a mixture of the
allylic sulfone D-13, the vinylic sulfone D-47 and sulfone (S)-13
in a ratio of 82:11:7 (Scheme 12). The mixture of D-13 and (S)-
13 had an ee value of only 15%. This result is compatible
either with a low configurational stability of the lithiated carb-
anion or with a low enantioselectivity of deprotonation. In
order to differentiate between the two possibilities, “external”
and “internal” trapping experiments[17,61] of carbanion (P)-21
with methyl iodide were carried out. In the “external” trapping
experiment sulfone (S)-13 was treated with nBuLi (1.1 equiv) in
THF at À1058C and after trac =5 min had elapsed methyl
iodide was added to carbanion (P)-21 at low temperature.
Then the mixture was kept for 15 min at low temperatures,
warmed to 08C and quenched with CF3CO2D. This procedure
gave the racemic sulfone rac-48 in 99% yield. Formation of
the vinylic sulfone 49 was not observed. A similar “external”
trapping experiment of (P)-21 starting with sulfone (S)-13
except that trac was only 1 min also afforded rac-48 in 98%
yield. In the “internal” trapping experiment nBuLi (1.1 equiv)
was added to a mixture of sulfone (S)-13 and methyl iodide
(4 equiv) in THF at À1058C. After the mixture was kept at low
temperature for 15 min, it was quenched at 08C with CF3CO2D.
This experiment gave the methylated sulfone (S)-48 with 62%
ee in 99% yield. The use of tBuLi in the deprotonation-methyl-
ation of sulfone (S)-13 under otherwise identical conditions af-
forded sulfone (S)-48 with 59% ee in 98% yield. The trapping
experiments of (P)-21 with methyl iodide indicate that the lithi-
ated carbanion (P)-21 has a low configurational stability, which
is the major cause for the medium overall selectivity in the de-
protonation-deuteration experiments starting with the cyclic
allylic sulfone (S)-13. The experiments with nBuLi and tBuLi
show that the enantioselectivity of the deprotonation does not
depend on RLi as previously observed in the case of the de-
protonation of alkyl-substituted benzylic tert-butyl sulfones. Al-
though the configurations of sulfones (R)-41, (R)-43, (R)-45 and
(S)-48 were not determined, the tertiary sulfones were as-
The deprotonation of the eight-membered cyclic sulfone (S)-
15 of ꢁ 98% ee with nBuLi was much slower than that of the
six-membered cyclic sulfone (S)-13. For example, treatment of
(S)-15 with nBuLi (1.2 equiv) in THF at À1058C and the subse-
quent deuteration of the carbanion (P)-31 with CF3CO2D at
À1058C after trac =1 min gave a mixture consisting of sulfone
D-15, the vinylic sulfone D-50 and (S)-15 in a ratio of 15:23:62
in 98% yield (Scheme 13). The mixture of D-15 and (S)-15 had
Scheme 13. Synthesis and deuteration of carbanion (P)-31 in THF at
À1058C.
an ee value of 79%. In a second experiment sulfone (S)-15
ꢁ98% ee) was treated with tBuLi (1.5 equiv) in THF at À858C
and after trac =3 min carbanion (P)-31 was deuterated with
CF3CO2D at À1058C. This sequence afforded a mixture of sul-
fone D-15 of only 20% ee together with D-50 in a ratio of
73:27 in 98% yield.
Conclusions
Lithiated alkyl substituted allylic S-tert-butyl a-sulfonyl carban-
ions are configurationally stable at low temperatures at the
time scale of their reactions with reactive electrophiles. Their
configurational stability is lower than that of dialkyl and alkyl-
aryl substituted S-tert-butyl a-sulfonyl carbanions. Lithiated
alkyl substituted allylic S-tert-butyl a-sulfonyl carbanions can
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very broad and combinations thereof. Peaks in the 13C NMR spectra
are denoted as “u” for carbons with zero or two attached protons
and as “d” for carbons with one or three attached protons, as de-
be obtained with high enantioselectivity through reaction of
the corresponding enantiopure allylic sulfones with organo-
lithiums and their reactions with reactive electrophiles are
highly enantioselective. The two-step sequence of deprotona-
tion and electrophilic capture proceeds with retention of con-
figuration. Deuteration and alkylation of the alkyl substituted
S-tert-butyl allylic a-sulfonyl carbanions are only of medium re-
gioselectivity. Although they have not been studied yet the re-
action of lithiated allylic S-tert-butyl a-sulfonyl carbanions with
aldehydes will be the most interesting ones. NMR spectrosco-
py, cryoscopy, ab initio calculation and X-ray crystal structure
analyses all suggest that lithiated allylic a-sulfonyl carbanions
form monomeric and dimeric CIPs in THF solution. The mono-
meric CIPs have either O-Li and C1-Li bonds or only O-Li and
are in rapid equilibrium even at low temperatures. The anions
preferentially adopt the s-trans conformation around the C1-C2
bond, have nearly planar allylic units, the typical C1–S confor-
mation and are stabilized by allylic conjugation, Coulomb in-
teraction and nC1–s*SR hyperconjugation. The ncÀs*SR interac-
tion (negative hyperconjugation) and allylic conjugation are
the stereoelectronic effects, which determine the conforma-
tions of the lithiated allylic a-sulfonyl carbanions around the
C1-S and C1-C2 bonds. These two effects are also responsible
for the conformations of the lithiated benzylic a-sulfonyl car-
banions around the C1ÀS and C1ÀCi bonds.
1
termined from the APT puls sequence. Assignments in the H NMR
spectra were made by GMQCOSY, GNOE, HETCOR experiments and
6
those in the 13C NMR spectra were made by DEPT experiments. Li
NMR spectra were run on a Varian Unity 500 (74 MHz) instrument.
IR spectra were recorded on a PerkinElmer PE 1760 S FT instru-
ment. Only peaks of n ꢁ 800 cmÀ1 are listed, vs=very strong, s=
strong, m=medium, w=weak. Low resolutions mass spectra were
recorded on a Varian MAT 212 S instrument using electron impact
ionization (EI, 70 eV). Only peaks of m/z ꢁ 80 and an intensity of ꢁ
10%, except decisive ones, are listed. Elemental analyses were per-
formed by the Institute of Organic Chemistry (RWTH Aachen Uni-
versity) micro analytical laboratory with PerkinElmer CHN-analyzer
240C and Heraeus CHN-Rapid analyzer. Optical rotations were mea-
sured with a PerkinElmer 241 instrument at approximately 208C,
[a]D in (grd ” dm3)/(dm ” g) and c in (g ” dmÀ3). GC MS analyses:
Varian Model 3700, Varian MAT 112 S, EI 70 eV. GC: Chrompack CP-
9000, FID. DB-5 (CP-9000): 30 m, 0.32 mm, 0.25 mm, H2, 60 kPa. Lip-
odex E (permethyl-b-cyclodextrin): 25 m, 0.25 mm, 15 mm, H2,
50 kPa. HPLC: Waters 600E system controller, waters 510, (S,S)-
Whelk-01 column. Cryoscopy was performed according to the
method,[65] which we had previously also used for lithiated benzylic
a-sulfonyl carbanions.[18,20] Single crystals of sulfone (S)-13 were ob-
tained through crystallization from EtOAc/n-hexane 1:1 at room
temperature.
The O,Li CIPs of type K should exhibit a higher reactivity to-
wards electrophiles than the O,C,Li CIPs of type A due to the
lack of a C1 bonded Li atom.
Computational methods
All calculations were performed with the Gaussian 09 suite of
quantum-chemical routines[66] running on the facilities of the IT
Center of RWTH Aachen University. Plausible initial structures were
defined using standard structural parameters. Specific interactions
between the solvent and the lithium compound were modelled by
adding two dimethyl ether molecules to each metal atom. The ge-
ometries of all species under consideration were then energetically
optimized at the MP2 level of ab initio theory employing the 6–
31+G* set of basis functions. The stationary points obtained in
this way were verified to be local minima by normal mode analy-
ses. In order to get a better description of the bulk solvent effects,
additional single point calculations at the optimized geometries of
the complexes consisting of the Li compounds and the two ether
molecules were performed at the PCM (polarizable continuum
model) level[51] of the SCRF method using the dielectric constant
for tetrahydrofuran as implemented in Gaussian 09 (e=7.4257).
Experimental Section
Experimental details
All reactions were carried out in absolute solvents under argon in
oven-dried and argon filled glassware by using Schlenk, cannula
and syringe techniques. Tetrahydrofuran (THF) was filtered through
alumina and distilled from potassium/benzophenone under argon.
Methyl iodide was distilled from CaH2 under argon. [D8]THF was
distilled from potassium in a micro solvent still under argon. Di-
glyme was distilled from calcium hydride. MeOCH2I and (allylsulfo-
nyl)benzene were obtained from commercial sources and
PhCH2OCH2Br[62] was synthesized according to the literature. nBuLi
(in n-hexane) and tBuLi (in n-pentane) were acquired from com-
mercial sources and were standardized by titration with diphenyl-
acetic acid.[63] nBu6Li in n-hexane was synthesized according to the
literature.[64] Analytical thin-layer chromatography (TLC) was per-
formed on E. Merck pre-coated TLC plates (silica gel 60 F254, layer
thickness 0.2 mm). Flash chromatography (denoted as chromatog-
raphy) was performed with E. Merck silica gel 60 (0.063–0.200 mm).
Gas chromatography was done with a Chrompack CP-9000 instru-
ment by using a DB 5 Carlo Erba CP-Sil-8 column: length 30 m, di-
ameter 0.32 mm, film thickness 0.25 mm. 1H and 13C NMR spectra
were recorded on Varian VXR 300 (300 MHz, 75 MHz), Varian
Gemini 300 (300 MHz, 75 MHz), Varian Unity 500 (500 MHz,
125 MHz) and Varian Inova 400 (400 MHz, 100 MHz) instruments.
Chemical shifts are reported relative to SiMe4 (d=0.00 ppm) CHCl3
(d=7.24 ppm, 77.1 ppm) and [D8]THF (d=1.72 ppm, 3.58 ppm,
25.3 ppm, 67.2 pm) as internal standards. Splitting patterns in the
1H NMR spectra are designated as s, singlet; d, doublet; t, triplet;
q, quartet; sept, septet; hept, heptet; m, multiplet; br, broad, vbr,
General procedure for the synthesis of lithiated allylic
a-sulfonyl carbanions for NMR spectroscopy (GP1)
To a solution of the sulfone (0.30 mmol) in THF (5 mL) at À758C
was added nBuLi (1 equivalent of 1.50m to 1.60m in n-hexane) or
nBu6Li (1 equivalent of 2.00m in n-hexane). After the mixture was
stirred for 5 min at low temperatures, the cooling bath was re-
moved and the volatiles were removed in vacuo. The oily residue
was dried at room temperature for 20 min in high vacuo. Then the
highly viscous residue was dissolved in [D8]THF (0.70 mL) and the
solution was transferred via cannula to an oven-dried and argon
filled Schlenk-type NMR tube. Then the NMR tube was cooled for
45 s to À758C, evacuated for 30 s in high vacuo and sealed with
a micro Bunsen burner.
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e) V. Sikervar, J. Fleet, P. L. Fuchs, J. Org. Chem. 2012, 77, 5132–5138;
f) E. Altenhofer, M. Harmata, Org. Lett. 2014, 16, 3–5.
General procedure for the enantioselective synthesis of
lithiated allylic a-sulfonyl carbanions and their reactions
with electrophiles (GP2)
[3] According to ab initio calculations of sulfones (see, for example: E. D.
Glendening, A. L. Shrout, J. Phys. Chem. A 2005, 109, 4966–4972) and
sulfoximines (see, for example: P. S. Kumar, P. V. Bharatam, Tetrahedron
2005, 61, 5633–5639) the sulfonyl and sulfonimidoyl groups have ylide
like SÀO and SÀN single bonds with negative charged O and N atoms
and double positive charged S atoms. For convenience, however, both
groups are depicted in all structural formulas with S=O and S=N
double bonds.
[4] For illustrative examples, see: a) B. M. Trost, N. R. Schmuff, M. J. Miller, J.
Am. Chem. Soc. 1980, 102, 5979–5981; b) H.-J. Gais, W. A. Ball, J. Bund,
Tetrahedron Lett. 1988, 29, 781–784; c) J. Clayden, M. Julia, J. Chem. Soc.
Chem. Commun. 1994, 1905–1907; d) W.-C. Cheng, C. Halm, J. B. Evarts,
M. M. Olmstead, M. J. Kurth, J. Org. Chem. 1999, 64, 8557–8562; e) X. Li,
D. Lantrip, P. L. Fuchs, J. Am. Chem. Soc. 2003, 125, 14262–14263; f) K.
Deng, J. Chalker, A. Yang, T. Cohen, Org. Lett. 2005, 7, 3637–3640;
g) A. L. Moure, P. Mauleón, R. G. Arrayµs, J. C. Carretero, Org. Lett. 2013,
15, 2054–2057.
[5] H.-J. Gais, J. Vollhardt, H. J. Lindner, Angew. Chem. Int. Ed. Engl. 1986, 25,
939–941; Angew. Chem. 1986, 98, 916–917.
[6] T. Akiyama, M. Shimizu, T. Mukaiyama, Chem. Lett. 1984, 611 –614.
[7] H. Eichelmann, Ph.D. thesis, RWTH Aachen (Germany) 1997.
[8] H.-J. Gais, M. Van Gumpel, G. Raabe, J. Müller, S. Braun, H. J. Lindner, S.
Rohs, J. Runsink, Eur. J. Org. Chem. 1999, 1627–1651.
[9] H.-J. Gais, M. Van Gumpel, M. Schleusner, G. Raabe, J. Runsink, C. Ver-
meeren, Eur. J. Org. Chem. 2001, 4275–4303.
[10] a) W. Ball, Ph.D. thesis, TU Darmstadt (Germany), 1987; b) J. Vollhardt,
Ph.D. thesis, TU Darmstadt (Germany), 1990; c) D. Lenz, Ph.D. thesis,
RWTH Aachen (Germany), 1995; d) T. Heß, Ph.D. thesis, RWTH Aachen
(Germany), 1998.
An oven-dried long-necked Schlenk flask, which was equipped
with a Teflon-coated magnetic stirring bar, was filled with argon.
The flask was charged with the sulfone and closed with a rubber
septum, which was fitted with a thermo-element reaching to 1 cm
above the bottom of the flask. The temperature measurements
were done with a precision thermometer Kelvimat Typ 4321 (Bur-
ster Präzisionsmeßtechnik, Gernsbach, Germany). Then the flask
was evacuated three times and refilled with argon, charged with
THF and the solution was cooled under argon to the given temper-
ature in a continuously stirred nitrogen/EtOH cooling bath (3 L).
Then the long-necked flask was immersed just below the joint into
the cooling bath and the solution of RLi was added via film-cooling
(the solution was allowed to run down the cooled long neck) to
the solution of the sulfone under rapid stirring. The solution of RLi
was added at such a rate that an efficient film-cooling was guaran-
teed. After the given time, the mixture was treated with a solution
of the electrophile under rapid stirring and film-cooling. Because of
the exothermic reactions, an efficient cooling is required in order
to achieve temperature control. Deuteration and quenching of re-
action mixture after the time given were carried out with a 2.00m
solution of CF3CO2D in THF except otherwise stated. Then ether
(20 mL) was added and the mixture was successively washed with
saturated aqueous NaHCO3, brine and water. In the case of halo-
gen containing electrophiles the organic phase was also washed
with aqueous Na2S2O3. The organic phase was dried (MgSO4) and
concentrated in vacuo.
[11] S. Bradamante, A. Mangia, G. Pagani, J. Chem. Soc. B 1971, 545–548.
[12] M. Pffl, J. Weston, W. Günther, E. Anders, J. Org. Chem. 2000, 65, 5942–
5950.
[13] a) P. Merino, V. Mannucci, T. Tejero, Tetrahedron 2005, 61, 3335–3347;
b) A. M. Belostotskii, A. Albeck, A. Hassner, Eur. J. Org. Chem. 2007,
4837–4844.
Synthesis and characterization
See Supporting Information.
[14] H.-J. Gais, G. Hellmann, H. Günther, F. Lopez, H. J. Lindner, S. Braun,
Angew. Chem. Int. Ed. Engl. 1989, 28, 1025–1028; Angew. Chem. 1989,
101, 1061–1063.
[15] H.-J. Gais, G. Hellmann, H. J. Lindner, Angew. Chem. Int. Ed. Engl. 1990,
29, 100–103; Angew. Chem. 1990, 102, 96–99.
Acknowledgements
Financial support by the Deutsche Forschungsgemeinschaft
(SFB 380, GK 440) and the Volkswagen Foundation is gratefully
acknowledged. We thank Cornelia Vermeeren for GC and HPLC
analyses and for the Schakal figures, Dr. Marcel Schleusner for
NMR measurements, Dr. Wolfgang Bettray for the MS spectra,
and Dr. Susanne Rohs for her cooperation in the cryoscopy of
the lithiated carbanion rac-27.
[16] H.-J. Gais, G. Hellmann, J. Am. Chem. Soc. 1992, 114, 4439–4440.
[17] H.-J. Gais, in Organosulfur Chemistry in Asymmetric Synthesis (Eds.: T.
Toru, C. Bolm), VCH-Wiley, Weinheim, 2008, pp. 375–398.
[18] R. Scholz, G. Hellmann, S. Rohs, G. Raabe, J. Runsink, D. Özdemier, O.
Luche, T. Heß, A. W. Giesen, J. Atodiresei, H. J. Lindner, H.-J. Gais, Eur. J.
Org. Chem. 2010, 4559–4587.
[19] R. Scholz, G. Hellmann, S. Rohs, D. Özdemir, G. Raabe, C. Vermeeren, H.-
J. Gais, Eur. J. Org. Chem. 2010, 4588–4616.
[20] G. Hellmann, A. Hack, E. Thiemermann, O. Luche, G. Raabe, H.-J. Gais,
Chem. Eur. J. 2013, 19, 3869–3897.
[21] For reviews, see: a) H. Ahlbrecht, U. Beyer, Synthesis 1999, 365–390;
b) M. Reggelin, C. Zur, Synthesis 2000, 1–64; c) D. Hoppe, F. Marr, M.
Brüggemann, Top. Organometal. Chem. 2003, 5, 61–138; d) P. Beak, T. A.
Johnson, D. D. Kim, S. H. Lim, Top. Organometal. Chem. 2003, 5, 139–
176; e) H.-J. Gais, in Asymmetric Synthesis with Chemical and Biological
Methods (Eds.: D. Enders, K.-E. Jäger), VCH-Wiley, Weinheim 2007,
pp. 75–115; f) H.-J. Gais, Heteroat. Chem. 2007, 18, 472–481; g) D.
Hoppe, Synthesis 2009, 43–55; h) M. Sasaki, K. Takeda, Synlett 2012, 23,
2153–2164.
[22] For the enantioselective synthesis, reactivity and configurational stabili-
ty of carbamoylthio stabilized lithiated allylic carbanions, see: a) F. Marr,
D. Hoppe, Org. Lett. 2002, 4, 4217–4220; b) F. Marr, R. Frçhlich, B. Wibb-
eling, C. Diedrich, D. Hoppe, Eur. J. Org. Chem. 2002, 2970–2988; c) R. P.
Sonawane, R. Frçhlich, D. Hoppe, Adv. Synth. Catal. 2006, 348, 1847–
1854.
Keywords: allyl anion
·
·
alpha-sulfonyl carbanion
·
chiral
compounds
elucidation
·
lithium
reaction mechanisms
· structure
[1] For reviews, see: a) J.-F. Biellmann, J.-B. Ducep, Org. React. 1982, 27, 1–
344; b) N. S. Simpkins, Sulphones in Organic Synthesis Pergamon,
Oxford, 1993; c) C. Nµjera, J. M. Sansano, Rec. Res. Dev. Org. Chem. 1998,
2, 637–683; d) A. R. Katritzky, M. Piffl, H. Lang, E. Anders, Chem. Rev.
1999, 99, 665–722; e) P. R. Blakemore, J. Chem. Soc. Perkin Trans.
1 2002, 2563–2585; f) A. El-Awa, M. Noshi, X. Mollat du Jourdin, P. L.
Fuchs, Chem. Rev. 2009, 109, 2315–2349; g) F. Martinelli, A. Palmieri, M.
Petrini, Phosphorous, Sulfur Silicon Rel. Elements 2011, 186, 1032–1045.
[2] For selected recent applications, see: a) V. Gembus, S. Postikova, V. Le-
vacher, J.-F. Bri›re, J. Org. Chem. 2011, 76, 4194–4199; b) T. Kimura, G.
Kobayashi, M. Ishigaki, M. Inumaru, J. Sakurada, T. Satoh, Synthesis
2012, 44, 3623–3632; c) N. R. Cichowicz, P. Nagorny, Org. Lett. 2012, 14,
1058–1061; d) V. Sikervar, P. L. Fuchs, Org. Lett. 2012, 14, 2922–2924;
[23] H. Eichelmann, H.-J. Gais, Tetrahedron: Asymmetry 1995, 6, 643–646.
[24] H.-J. Gais, H. Eichelmann, N. Spalthoff, F. Gerhards, M. Frank, G. Raabe,
Tetrahedron: Asymmetry 1998, 9, 235–248.
Chem. Eur. J. 2015, 21, 17904 – 17920
www.chemeurj.org
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[25] H.-J. Gais, T. Jagusch, N. Spalthoff, F. Gerhards, M. Frank, G. Raabe,
Chem. Eur. J. 2003, 9, 4202–4221.
[45] For a mixed aggregate of a dilithiated a,a-sulfonyl dicarbanion and lith-
ium oxide, see: H.-J. Gais, J. Vollhardt, H. Günther, D. Moskau, H. J. Lind-
ner, S. Braun, J. Am. Chem. Soc. 1988, 110, 978–980.
[26] H.-J. Gais, in Asymmetric Synthesis with Chemical and Biological Methods
(Eds.: D. Enders, K.-E. Jaeger), VCH-Wiley, Weinheim, 2007, pp. 215–250.
[27] T. Jagusch, H.-J. Gais, O. Bondarev, J. Org. Chem. 2004, 69, 2731–2736.
[28] Acyclic allylic S-tert-butyl sulfones IV carrying an unsubstituted double
bond (R2 =H) cannot be obtained by these methods. However,
a number of alternative methods for the enantioselective synthesis of
allylic sulfones have recently been described, which could perhaps also
give access to allylic tert-butyl sulfones of this type (see, for example:
M. Ueda, J. F. Hartwig, Org. Lett. 2010, 12, 92–94; N. Gao, S. Zheng, W.
Yang, X. Zhao, Org. Lett. 2011, 13, 1514–1516; X.-S. Wu, Y. Chen, M.-B.
Li, M.-G. Zhou, S.-K. Tian, J. Am. Chem. Soc. 2012, 134, 14694–14697; X.-
T. Ma, R.-H. Dai, J. Zhang, Y. Gu, S.-K. Tian, Adv. Synth. Catal. 2014, 356,
2984–2988; J. Choi, P. Martín-Gago, G. C. Fu, J. Am. Chem. Soc. 2014,
136, 12161–12165; A. B. Pritzius, B. Breit, Angew. Chem. Int. Ed. 2015,
54, 3121–3125; Angew. Chem. 2015, 127, 3164–3168).
[46] F. G. Bordwell, Acc. Chem. Res. 1988, 21, 456–463.
[47] H.-J. Gais, D. Lenz, G. Raabe, Tetrahedron Lett. 1995, 36, 7437–7440.
[48] S. E. Denmark, C. J. Cramer, J. Org. Chem. 1990, 55, 1806–1813.
[49] J. F. K. Müller, R. Batra, B. Spingler, M. Zehnder, Helv. Chim. Acta 1996,
79, 820–826.
[50] Low temperature 1H NMR spectroscopy of rac-35 (R1 =R2 =R4 =Me,
R3 =H) in [D8]THF, which can form diastereomers in regard to the C1ÀS
bond, revealed two coalescence phenomena (signals of 1-H and 2-H)
and dynamic equilibria between a major species and a minor species at
À1008C and two major species and one minor species at À1258C; see
ref. [10c].
[51] J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 2005, 105, 2999–3093.
[52] A. Streitwieser, J. R. Reyes, T. Singhapricha, S. Vu, K. Shah, J. Org. Chem.
2010, 75, 3821–3830.
[29] Until now, enantioselective syntheses of allylic S-trifluoromethyl sul-
fones are not available (see, for example: P. Nikolaienko, R. Pluta, M.
Rueping, Chem. Eur. J. 2014, 20, 9867–9870). However, 1,3-dialkyl sub-
stituted derivatives can perhaps be obtained through reaction of the
corresponding chiral allylic alcohols (see, for example: A. Lumbroso,
M. L. Cooke, B. Breit, Angew. Chem. Int. Ed. 2013, 52, 1890–1932;
Angew. Chem. 2013, 125, 1942–1986; B. J. Lüssem, H.-J. Gais, J. Am.
Chem. Soc. 2003, 125, 6066–6067; H.-J. Gais, O. Bondarev, R. Hetzer, Tet-
rahedron Lett. 2005, 46, 6279–6283) with CF3S(O)Cl followed by sigma-
tropic rearrangement of thereby formed allylic S-triflinates (see, for ex-
ample: S. Braverman, T. Pechenick, Y. Zafrani, ARKIVOC 2005, 51–63) or/
and through trifluoromethylation (see, for example: I. Kieltsch, P. Eisen-
berger, A. Togni, Angew. Chem. Int. Ed. 2007, 46, 754–757; Angew.
Chem. 2007, 119, 768–771, ref. [20]) of the corresponding chiral allylic
thiols (see, for example: A. Bçhme, H.-J. Gais, Tetrahedron: Asymmetry
1999, 10, 2511 –2514; H.-J. Gais, A. Bçhme, J. Org. Chem. 2002, 67,
1153–1161; B. J. Lüssem, H.-J. Gais, J. Org. Chem. 2004, 69, 4041–4052)
followed by oxidation of the corresponding allylic S-trifluoromethyl sul-
fides.
[30] a) Part of the Ph.D. thesis of F. Gerhards, RWTH Aachen (Germany),
2000; b) Part of the Ph.D. thesis of N. Griebel (nØe Spalthoff), RWTH
Aachen (Germany), 2002.
[31] A. C. Cope, D. Morrison, E. L. Field, J. Am. Chem. Soc. 1950, 72, 59–67.
[32] CCDC 1035284, 1035306, 1035720 and 1035288 contain the supple-
mentary crystallographic data for this paper. These data are provided
free of charge by The Cambridge Crystallographic Data Centre for rac-
20·diglyme, rac-21·PMDETA, rac-22·PMDETA, (S)-13, respectively.
[33] G. Boche, M. Marsch, K. Harms, G. M. Sheldrick, Angew. Chem. Int. Ed.
Engl. 1985, 24, 573–575; Angew. Chem. 1985, 97, 577–578.
[34] H.-J. Gais, J. Vollhardt, G. Hellmann, H. Paulus, H. J. Lindner, Tetrahedron
Lett. 1988, 29, 1259–1262.
[35] M. Linnert, C. Bruhn, C. Wagner, D. Steinborn, J. Organomet. Chem.
2006, 691, 2358–2367.
[36] H.-J. Gais, J. Müller, J. Vollhardt, H. J. Lindner, J. Am. Chem. Soc. 1991,
113, 4002–4003.
[37] Due to the low crystal quality combined with a disorder of the seven-
membered ring, which required isotropic refinement of this part of the
molecule, we could not refine to an R factor of better than 0.14.
[38] H. J. Reich, J. P. Borst, J. Am. Chem. Soc. 1991, 113, 1835–1837.
[39] S. Rohs. Ph.D. thesis, RWTH Aachen (Germany), 2000.
[40] M. M. Biddle, H. J. Reich, J. Org. Chem. 2006, 71, 4031–4039.
[41] L. Glendenning, L. D. Field, R. K. Haynes, Bull. Chem. Soc. Jpn. 1995, 68,
2739–2749.
[53] a) F. Weinhold, C. Landis, Valency and Bonding: A Natural Bond Orbital
Donor–Acceptor Perspective, Cambridge University Press 2005; b) A. E.
Reed, L. A. Curtiss, F. Weinhold, Chem. Rev. 1988, 88, 899–926; c) E. D.
Glendening, A. E. Reed, J. E. Carpenter, F. Weinhold, NBO 3.0 Program
Manual, Theoretical Chemistry Institute and Department of Chemistry,
University of Wisconsin, Madison, Wisconsin 53706.
[54] a) R. J. Kurland, M. B. Rubin, W. B. Wise, J. Chem. Phys. 1964, 40, 2426–
2427; b) G. Binsch, Top. Stereochem. 1968, 3, 97–192.
[55] Data of rac-37 ref. [39]: Cryoscopy: n=1.61Æ0.05 (THF, 164 K, c=
48.5 mmolkgÀ1); 1H NMR (500 MHz, [D8]THF, room temperature): d=
0.99 (d, J=6.7 Hz, 6H, iPr), 1.10 (s, 9H, tBu), 1.23 (s, 9H, tBu), 2.38 (sept,
J=6.7 Hz, 1H, iPr); 13C NMR (125 MHz, [D8]THF): d=25.5 (d, iPr), 26.3 (d,
tBu), 29.3 (d, iPr), 30.3 (u, tBu), 33.4 (d, tBu), 46.9 (u, CS), 63.0 (u, tBu),
87.0 (u, ꢂCCS), 94.5 (u, ꢂCtBu); Dd (C1)=À9.6, Dd (C2)=À4.6, Dd
(C3)=À3.7; 1H NMR (500 MHz, [D8]THF, À808C, decoupled): d=0.90 (s,
3H, iPr), 1.03 (s, 3H, iPr), 1.08 (s, 9H, tBu), 1.21 (s, 9H, tBu).
[56] M. von Büren, M. Cosandy, H. J. Hansen, Helv. Chim. Acta 1980, 63, 892–
898.
[57] A. C. Jones, A. W. Sanders, M. J. Bevan, H. J. Reich, J. Am. Chem. Soc.
2007, 129, 3492–3493.
[58] S. Wolfe, A. Stolow, L. A. LaJohn, Tetrahedron Lett. 1983, 24, 4071–4074.
[59] D. A. Bors, A. Streitwieser, J. Am. Chem. Soc. 1986, 108, 1397–1404.
[60] G. Raabe, H.-J. Gais, J. Fleischhauer, J. Am. Chem. Soc. 1996, 118, 4622–
4630.
[61] P. J. Cox, N. S. Simpkins, Tetrahedron: Asymmetry 1991, 2, 1–26.
[62] A. T. Blomquist, E. J. Moriconi, J. Org. Chem. 1961, 26, 3761–3769.
[63] W. G. Kofron, L. M. Baclawski, J. Org. Chem. 1976, 41, 1879–1880.
[64] D. Seebach, R. Hässig, J. Gabriel, Helv. Chim. Acta 1983, 66, 308–337.
[65] W. Bauer, D. Seebach, Helv. Chim. Acta 1984, 67, 1972–1988.
[66] Gaussian 09, Revision A.02, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.
Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Men-
nucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian,
A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro,
M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Ko-
bayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyen-
gar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B.
Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cio-
slowski, D. J. Fox, Gaussian, Inc., Wallingford CT, 2009.
[42] L. Glendenning, N. Bampos, L. D. Field, Bull. Chem. Soc. Jpn. 1996, 69,
2025–2029.
[43] a) R. B. Bates, L. M. Kroposki, D. E. Potter, J. Org. Chem. 1973, 37, 560–
562; b) J. Q. Wen, J. B. Grutzner, J. Org. Chem. 1986, 51, 4220–4224.
[44] For mixed aggregates of lithium enolates with halides, amines and lithi-
um amides, see: H. J. Reich, Chem. Rev. 2013, 113, 7130–7178.
Received: August 7, 2015
Published online on October 23, 2015
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