The synthesis and configurational stability of enantioenriched α-thioallyllithium compounds and the stereochemical course of their electrophilic substitution

Article abstract of DOI:10.1002/1099-0690(200209)2002:17<2970::AID-EJOC2970>3.0.CO;2-J

Deprotonation of enantioenriched S-allyl N-monoalkylmonothiocarbamates furnished the corresponding chiral lithium compounds. The α-thioallyllithium compounds 9 and 25 were found to be configurationally stable in THF solutions at -78 °C. These represent the first configurationally stable α-thio-substituted allyllithium compounds, and they can be utilized in asymmetric synthesis. Alkylations proceeded with stereo-inversion or in an anti-S_E′ process, while addition to carbonyl compounds took place in a syn-S_E′ process. Hydroxyalkylation products were employed as starting material for Ni⁰-catalyzed cross-coupling reactions.

Full text of DOI:10.1002/1099-0690(200209)2002:17<2970::AID-EJOC2970>3.0.CO;2-J

FULL PAPER
The Synthesis and Configurational Stability of Enantioenriched
α-Thioallyllithium Compounds and the Stereochemical Course of Their
Electrophilic Substitution
Felix Marr,[a] Roland Fröhlich,[a][‡] Birgit Wibbeling,[a][‡] Christian Diedrich,[a][‡‡] and
Dieter Hoppe*[a]
Dedicated to Professor Volker Jäger on the occasion of his 60th birthday
Keywords: Carbanions / Chirality / Cross-coupling / Electrophilic substitution / Sulfur compounds
Deprotonation of enantioenriched S-allyl N-monoalkylmono- in asymmetric synthesis. Alkylations proceeded with stereo-
thiocarbamates furnished the corresponding chiral lithium
compounds. The α-thioallyllithium compounds 9 and 25 were
found to be configurationally stable in THF solutions at −78
°C. These represent the first configurationally stable α-thio-
substituted allyllithium compounds, and they can be utilized
inversion or in an anti-SEЈ process, while addition to carbonyl
compounds took place in a syn-SEЈ process. Hydroxyalkyl-
ation products were employed as starting material for Ni0-
catalyzed cross-coupling reactions.
Introduction
Chiral, nonracemic α-heteroatom-substituted alkylli-
thium compounds are valuable chiral carbanion equiva-
lents,[1] as long as they react in a stereodefined manner.
Electrophilic substitution on these d1-synthons is generally
stereospecific. Consequently, configurational stability is de-
sirable for application in asymmetric synthesis, provided
that the carbanionic center is the sole source of chiral in-
formation (no further chiral centers in the substrate or any
chiral ligand). Some configurationally stable α-oxy- and α-
amino-substituted organolithium compounds of this type
are known. The enantioenriched 1-(alkoxymethoxy)alkylli-
thium compound 1a (Scheme 1) was prepared in 1980 and
shows configurational stability below Ϫ40 °C.[2] Lithium
cation chelating N,N-dialkylcarbamoyloxy groups give con-
figurationally stable α-oxy-substituted alkyllithium com-
pounds 1b[3,4] and Ϫ even more striking Ϫ configura-
tionally stable sec-benzyl- and sec-allyllithium species 1c[5]
and 1d,[6] respectively (Scheme 1).[7]
Scheme 1. Some chiral organolithium compounds 1Ϫ5
and 5 (Scheme 1) results in rapid enantiomerization even at
temperatures as low as Ϫ78 °C and below.[16] How should
a potentially configurationally stable thioallyllithium com-
pound be designed? This question can be addressed on the
basis of the mechanism of the enantiomerization, which has
to be suppressed. NMR and reactivity studies with racemic
samples of 4 and 5 and other compounds, performed by R.
W. Hoffmann et al. and H. J. Reich et al., together with
theoretical studies,[17] indicate that the interconversion of
the enantiomers here is different from those of other chiral
organolithium compounds. The process of enantiomeriz-
ation from 6 to ent-6 can be divided into three single steps:
A) the dissociation of the ion-pair, B) the inversion of the
carbanionic center, and C) rotation of the bond between
the carbanionic center and the heteroatom (Scheme 2).[7]
For α-thio- and α-seleno-substituted carbanions, step C
possesses the highest activation barrier and therefore be-
The N-Boc-α-aminoalkyllithium derivative 2[8] and the
N-Boc-α-aminoallyllithium derivatives 3a and 3b[9] show
similar properties (Scheme 1).[4,10] In sharp contrast, the
presence of α-thio[11Ϫ14] and α-seleno[13,15] substituents at
the carbanionic center of alkyllithium derivatives such as 4
[a]
Organisch-Chemisches Institut der Universität, Westfälische
Wilhelms-Universität Münster,
Corrensstraße 40, 48149 Münster, Germany
Fax: (internat.) ϩ 49-251/83-36531
E-mail: dhoppe@uni-muenster.de
[‡]
X-ray structure analysis.
[‡‡]
Theoretical computation of optical properties.
2970
 WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0917Ϫ2970 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2002, 2970Ϫ2988

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
way.[22] The rearrangement of thiocarbamic acid O-esters
into the corresponding S-esters is a well-investigated reac-
tion[21,23] for achiral or racemic substrates.[24] Here the re-
arrangement of the O-esters 12Ϫ13 into the corresponding
S-esters 14Ϫ15 was achieved by heating in a neat state
(Scheme 4),[21] with flash column chromatography (FCC)
then providing the white crystalline monothiocarbamates.
Yields are given in Table 1.
Scheme 2. Mechanism of enantiomerization
comes the rate-determining step for the enantiomerization.
Sterically demanding groups in the vicinity of the het-
eroatom hinder the torsion of the hyperconjugated SϪCϪ
bond and consequently increase the configurational
stability; we assume for these investigations that a branched
carbanionic center and a bulky protecting group for the
sulfhydryl group should result in a configurationally stable
organolithium compound. Evidence in support of this as-
sumption is provided by the configurational stability of the
enantioenriched α-lithiated thiocarbamate 7b.[18] The α-
branched compound 7b was prepared by deprotonation of
its corresponding thiocarbamate, which was in turn pre-
pared by silylation of the unbranched and configurationally
labile (Ϫ)-sparteine complex 7a.[18] The essentially enanti-
opure α-thio carbanion derivative (S)-8 was synthesized and
applied in electrophilic substitutions.[19] Encouraged by
these results, we designed and synthesized the enantioen-
riched α-thio-substituted species 9, in which the double
bond allows for further transformations (Scheme 3).[20]
Scheme 4. Synthesis of S-allyl N-monoalkylmonothiocarbamates;
reagents and conditions: (a) i) NaH, THF, 0 °C; ii) RϪNCS, THF,
0 °C; iii) H3Oϩ; (b) neat, 105Ϫ150 °C
We focussed our investigations on cyclic substrates be-
cause the reactions of acyclic thiocarbamates in lithiation
experiments proved to be more complicated, due to the
formation of (E)/(Z)-isomeric substitution products.
Enantioenriched sec-allyl alcohols are accessible by vari-
ous routes, and in this two-step sequence the enantioen-
riched alcohols 10 and 11 were employed. For the prepara-
tion of enantioenriched sec-allyl thiols only two procedures
have been published, both involving a route to cyclohex-
2-ene-1-thiol.[25,26] Optically active cyclohex-2-en-1-ol (10)
with an ee of up to 96% (e.r. ϭ 98:2) was prepared either
by kinetic resolution of a racemic cyclohexenol precursor,
through
lipase-catalyzed
enantioselective
transes-
terification[27] [(R) form], or by base-mediated rearrange-
ment of cyclohexene oxide with chiral lithium amide ba-
ses[28] [(R) and (S) forms]. (R)-Cyclohept-2-en-1-ol (11) was
prepared by kinetic resolution of rac-11 by Sharpless asym-
metric epoxidation.[29] In our hands, epoxidation at Ϫ30 °C
yielded 42% of enantiopure (R)-11; Sharpless et al. had re-
ported 80% ee (e.r. ϭ 90:10) when performing the reaction
at Ϫ20 °C and applying a slightly lower concentration.[29c]
Thermal rearrangement of enantioenriched O-(2-cyclo-
hexenyl) N-isopropylthiocarbamate (12b) at 105 °C for 3 h
produced the optically active S-(2-cyclohexenyl) N-isoprop-
ylthiocarbamate (14b) with smooth chirality transfer of
96Ϫ97% (Table 1, Entries 3 and 4). The rearrangement of
cycloheptenyl N-isopropylthiocarbamate (R)-13, prepared
from enantiopure alcohol (R)-11 in 87% yield, at 145 °C for
4.5 h gave the corresponding thiocarbamate (S)-15 in 74%
yield with somewhat lower enantiospecificity (91% ee, e.r. ϭ
Scheme 3. Lithiated monothiocarbamates
There is still only a small amount known about the ste-
reochemical course of electrophilic substitution reactions of
α-thio-substituted lithium compounds. In this investigation
some emphasis was therefore put on that point.
Results and Discussion
Preparation of S-Allyl N-Monoalkylmonothiocarbamates
Because of the unpleasant properties of sec-allyl thiols 95.5:4.5, Table 1, Entry 8). However, the rearrangement of
we were in favor of a synthetic approach from sec-allyl alco- N-tert-butylthiocarbamate (S)-12c, prepared from (S)-
hols, such as 10, towards the starting thiocarbamates. Addi- cyclohex-2-en-1-ol [(S)-10] with 77% ee (e.r. ϭ 88.5:11.5)
tion of sodium alkoxides to isothiocyanates in THF fur- and in 91% yield, took place at 110 °C in 3 h with complete
nished monothiocarbamic acid O-esters 12Ϫ13 in high conservation of the original enantioenrichment of 77% ee
yields (Scheme 4, Table 1).[21] N-Methyl-, N-isopropyl-, and (e.r. ϭ 88.5:11.5), in 93% yield (Table 1, Entry 6).
N-tert-butyl-substituted carbamoyl moieties were fused to
The stereochemical course of these rearrangements was
cyclohex-2-en-1-ol (10) or cyclohept-2-en-1-ol (11) in this elucidated on the basis of an X-ray crystal structure of (ϩ)-
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2971

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
FULL PAPER
Table 1. Results of carbamoylations and subsequent rearrangements
Entry
Alcohol
R
O-Ester
S-Ester
1
2
rac-10
Me
iPr
iPr
iPr
tBu
tBu
iPr
iPr
12a 99%
14a 80%
rac-10
12b 95%
14b 78%
3[a]
4[a]
5
(S)-10 82% ee
(R)-10 96% ee
rac-10
(S)-10 77% ee
rac-11
(R)-11 Ͼ 99% ee
(S)-12b 74% 82% ee
(R)-12b 80% 96% ee
12c 90%
(R)-14b 79% 79% ee
(S)-14b 86% 93% ee
14c 91%
6
7
8
(S)-12c 91% 77% ee
(R)-14c 93% 77% ee
13 68%[b]
15 64%[c]
(R)-13 87% Ͼ 99% ee
(S)-15 74% 91% ee
[a]
Carbamoylation and rearrangement was performed several times on different scales, with enantioenriched cyclohex-2-en-1-ol (10) of
[b]
[c]
varying enantiomeric purity; the given figures represent typical values. In addition, 25% of rac-11 was isolated. In addition, 32% of
rac-13 was isolated.
14c, which showed the (R) configuration (Figure 1). Thi- enantioenriched allylic thiocarbamates in a regioselective
ocarbamate (ϩ)-(R)-14c was furnished by thermal re- manner.
arrangement of the corresponding O-ester (Ϫ)-(S)-12c, the
Enantioenriched (S)-S-(2-cyclohexenyl) N-methylthiocar-
latter compound having been acquired by carbamoylation bamate [(S)-14a] was prepared by Pd0-catalyzed deracemiz-
of alcohol (Ϫ)-(S)-10 (vide supra). This is evidence for a ation of the corresponding O-ester 12a by an efficient
suprafacial rearrangement process of the N-tert-butyl-sub- method reported by Gais, furnishing yellowish (S)-14a in
stituted thiocarbamate (Ϫ)-(S)-12c. Saponification of the high yield.[25c] Unfortunately, we were not able to extend
thiocarbamate (ϩ)-(R)-14c with 2.0  sodium hydroxide so- this methodology to N-isopropyl derivatives without dra-
lution yielded (ϩ)-cyclohex-2-ene-1-thiol. An analogous re- matic losses in turnover or enantioselectivity.
action sequence starting with alcohol (ϩ)-(R)-10 and pro-
ceeding through the thiocarbamates (ϩ)-(R)-12b and (Ϫ)-
14b finally furnished (Ϫ)-(S)-cyclohex-2-ene-1-thiol. On the
basis of the optical rotation of the isolated thiol, the (S)
configuration was assigned to the thiocarbamate (Ϫ)-14b,
indicating a suprafacial rearrangement for N-isopropyl-sub-
stituted thiocarbamate as well.
Standard Deprotonation Conditions
Optimum deprotonation conditions for thiocarbamate
14b were established by a series of deuteration experiments
at Ϫ78 °C in toluene, ether, or THF. A slight excess of sec-
butyllithium for each of the two acidic protons of rac-14b
in the presence of an equal amount of N,N,NЈ,NЈ-tetra-
methylethylenediamine (TMEDA) proved to be well suited.
Each deprotonation series started with 60 min for lithiation
and subsequent quenching of the dilithiated species rac-9
with an excess of MeOD, followed by neutralization with
DOAc at Ϫ78 °C (Scheme 5).
Figure 1. X-ray crystal structure of thiocarbamate (ϩ)-(R)-14c
The slight loss of enantioenrichment during rearrange-
ment is assumed to be a consequence of partial dissociation
and nonenantiospecific recombination of the thiocarbamate
during the thermal rearrangement.[30] In general, this car-
bamoylation/rearrangement sequence should be applicable
Scheme 5. Lithiation and subsequent electrophilic substitution [the
(S) configuration for starting materials having been chosen arbit-
rarily]; ligands at the lithium centers are omitted for the sake of
clarity; reagents and conditions: (a) sBuLi/TMEDA, Ϫ78 °C,
5Ϫ240 min; (b) i) ElX, Ϫ78 °C, 15 min to 18 h; ii) HOAc (DOAc
to any enantioenriched allylic alcohol, providing access to for deuterations), Ϫ78 °C, 15 min; iii) NaHCO3 (aq), 0 °C
2972
Eur. J. Org. Chem. 2002, 2970Ϫ2988

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
The ratios of the regioisomeric products 20a and 21a
were determined by 1H NMR and GC, while the D content
was ascertained with the aid of calibrated GC-MS. The
duration of metallation was successively adjusted. Selected
values given in Table 2 indicate that deprotonation in tolu-
ene is sluggish and at least 2Ϫ4 h are required for almost
quantitative lithiation (Table 2, Entries 1 and 2). Depro-
tonation in diethyl ether occurs more readily and requires
30Ϫ60 min, the regioselectivity of deuterations is similar to
that observed in toluene (Table 2, Entries 3 and 4). Rapid
lithiation was observed in THF solution, slightly more than
5 min being sufficient for quantitative deprotonation, and
deuteration in the γ-position being more favored than in
toluene or ether (Table 2, Entries 5 and 6). This trend is
also reflected in the regioselectivities of the alkylations
(vide infra).
Table 3. Results of methylations of thiocarbamate 14b
Entry[a]
Solvent
Time
[min]
% stereospecificity[b] (% yield)[c]
20b
21b
1
2
3
toluene
toluene
Et2O
Et2O
THF
THF
THF
THF
THF
THF
THF
THF
270
45
60
180
5
60
3 (41)
66 (8)
3 (22)
52 (4)
60 (40)
53 (50)
96 (21)
96 (19)
96 (17)
94 (21)
97 (17)
81 (19)
Ͻ1 (18)
57 (31)
40 (31)
77 (43)
77 (28)
76 (21)
72 (45)
84 (40)
53 (19)
10 (13)
Ͻ1[j] (Ϫ)
4
5[d]
6
7
270
30
8[e]
9[f]
10
11
12
80
40[g]
40[h]
40[i]
3[j] (n.d.)
[a]
Thiocarbamate (R)- or (S)-14b of 30Ϫ75% ee was employed as
starting materials; 2.4Ϫ2.8 equivalents of sBuLi/TMEDA were
[b]
used.
Conservation of the original enantioenrichment, deter-
Table 2. Results of deuterations of thiocarbamate rac-14b
mined by GC and HPLC, respectively.[32] [c] Isolated yields. The
use of (S)-14b with 91Ϫ93% ee gave the same α-stereospecificity. [e]
(S)-14b with 80% ee (e.r. ϭ 90:10) from Pd0-catalyzed deracemiz-
[d]
Entry[a]
Solvent
Time
[min]
Products[b] (D content [%])[c]
rac-20a
:
rac-21a
[f]
[g]
ation was used. Performed at Ϫ90 °C. Warmed to Ϫ50 °C for
15 min.
15 min. Yield by calibrated GC; 36% of amide 24 were isolated
(vide infra).
[h]
[j]
[i]
Warmed to Ϫ26 °C for 15 min. Warmed to 0 °C for
1
2
3
4
toluene
toluene
Et2O
Et2O
THF
THF
THF
120
240
30
60
5
30
12
28 (73.5)
28 (85.0)
28 (88.8)
34 (93.0)
16 (78.3)
15 (84.4)
(S) 11[e] (Ϫ)
:
:
:
:
:
:
:
72 (95.7)
72 (96.1)
72 (98.0)
66 (94.5)
84 (83.9)
85 (98.0)
89[f] (Ϫ)
5
45 min gave markedly higher enantioenrichment of isolated
(R)-20b and (R)-21b (Table 3, Entry 2); this is evidence in
support of the assumption that low ees are due to racemiz-
ation rather than lack of stereospecificity of the methylation
in toluene. In ether, moderately stereospecificities of 60%
and 57% for the formation of carbamates (S)-20b and (S)-
21b were detected (Table 3, Entry 3), indicating that racem-
ization occurs perceptibly more slowly than in toluene. Pro-
longation of the reaction time by a factor of three caused a
decrease in enantioenrichment (Table 3, Entry 4). Di-
lithiated species 9 shows the highest configurational
stability in THF: methylation took place with the same high
stereospecificities[32] after 5, 60, or 270 min of lithiation
(Table 3, Entries 5Ϫ7).
The observed solvent dependence of the configurational
stability is consistent with results obtained by Reich et al.,
who reported that higher configurational stability arose
from increasing ion-pair separation by lithium cation solva-
tion.[12a]
Use of the enantioenriched thiocarbamate (S)-14b, syn-
thesized by Pd0-catalyzed deracemization, achieved com-
parable stereospecificities and yields (Table 3, Entry 8). A
reduction in the reaction temperature to Ϫ90 °C improved
6
7[d]
[a] 2.5Ϫ3.2 equivalents of sBuLi/TMEDA were employed. [b] Deter-
1
[c]
mined by H NMR and GC. Determined by calibrated GC-MS.
[d]
(R)-14b with 81% ee (e.r. ϭ 90.5:9.5) was the starting material;
[e]
MeOH was used as electrophile. 4% (S)-14b with 20% ee (e.r. ϭ
[f]
60:40) were isolated.
83% of the double bond regioisomer of
carbamate 14b were isolated.
Reprotonation of enantioenriched allyllithium com-
pound 9 should give quick access to information about con-
figurational stability, by determination of the optical purity
of the formed thiocarbamate 14b. Protonation of the en-
antiopure benzyllithium compound (S)-8 with methanol,
for instance, takes place with complete retention of config-
uration. However, quenching of the allylic thio carbanion
(R)-9 (81% ee, e.r. ϭ 90.5:9.5) with methanol under condi-
tions used for highly stereospecific alkylations[31] furnished
thiocarbamate (S)-14b with only 25% stereospecificity[32]
(20% ee, e.r. ϭ 60:40), Table 2, Entry 7).
Configurational Stability and Stereochemical Course of
Alkylations
The configurational stabilities of the enantioenriched di- the stereospecificity of the formation of the γ-product 21b
lithiated species (R)- and (S)-9 were investigated by methyl- slightly (Table 3, Entry 9). In comparison to that of α-thiob-
ation with methyl iodide[33] under different reaction condi- enzyllithium compound (S)-8,[19c] the configurational and
tions. The α-methylation product 20b and its γ-regioisomer chemical stability of the dianion (R)-9 at elevated temper-
21b (see Scheme 5) were separated by chromatography, and atures is quite limited. Warming of a THF solution of (R)-
the ees were determined by chiral GC and HPLC, respect- 9 to Ϫ50 °C for 15 min and subsequent methylation at Ϫ78
ively. The configurational stability of allyllithium com- °C resulted in a significantly lower overall stereospecific-
pound (R)-9 in toluene is quite low; alkylation after 4.5 h ity[32] (Table 3, Entry 10). A transitional temperature of
of metallation provided almost racemic products (Table 3, Ϫ26 °C resulted in almost entire loss of enantioenrichment
Entry 1). Quenching of the lithiated (S)-14b in toluene after (Table 3, Entry 11), and warming of (R)-9 to 0 °C for
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2973

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
FULL PAPER
15 min caused rearrangement to optically inactive carbox-
amide 24 in 36% yield (Table 3, Entry 12; Scheme 6).
The source of the configurational stability of dilithiated
species 9 is the branched carbanionic center. Our previous
findings with alkyllithium compounds 7a and 7b,[18] as well
as the observation by Hoffmann et al. that the configura-
tional stabilities of α-thioaryl-substituted alkyllithium com-
pounds are increased by sterically demanding substitu-
ents,[11c] support this assumption. The torsion (step C in
Scheme 2) of the SϪCϪ bond, abolishing the hyperconjug-
ation between the nC orbital and the SϪR σ* orbital in the
rotamer 9b, is regarded as the rate-determining step of the
racemization (Scheme 7).
Scheme 6. Rearrangement of (R)-9 on warming; ligands at the li-
thium centers are omitted for the sake of clarity; reagents and con-
ditions: (a) i) 10 min Ϫ78 °C; ii) 15 min 0 °C; iii) 15 min Ϫ78 °C;
(b) i) MeI, Ϫ78 °C, 15 h; ii) HOAc, Ϫ78 °C, 15 min; iii) NaHCO3
(aq), 0 °C
Scheme 7. Rate-determining step of racemization of dianion 9; li-
gands at the lithium centers are omitted for the sake of clarity
Further increased bulkiness of the carbamoyl moiety
should enhance the configurational stability. N-tert-Butyl-
substituted thiocarbamate 14c was quantitatively lithiated
to the dianion 17 under standard conditions, demonstrated
by a deuteration experiment in diethyl ether. Remarkably, a
change in the regioselectivity, relative to the deuteration of
dianion 9 (vide supra), was observed. Here the α-deutera-
tion product 22a was isolated in 84% yield (Ͼ 95% D con-
tent), whereas γ-isomer 23a was formed in only 4% yield
(Scheme 5). Unfortunately, methylation of carbanion (S)-
17 in order to check the configurational stability could not
be achieved.
Fractional crystallization of a dissolved sample of (S)-
21b with 63% ee (e.r. ϭ 81.5:18.5) afforded crystals of (S)-
21b with 54% ee (e.r. ϭ 77:23) to 70% ee (e.r. ϭ 85:15)
suitable for X-ray structure analysis.[34]
The stereochemical course of the methylation with
methyl iodide was elucidated by X-ray crystal structure ana-
lysis. Dianion (R)-9 gave the carbamates (S)-20b and (S)-
21b (Figure 2). Methylation with methyl iodide had there-
fore taken place with stereoinversion of configuration and
in an anti-SEЈ process, respectively.
The methylation of N-methyl-substituted rac-14a under
standard conditions worked very well. The formation of the
α-methylation product rac-18b was preferred over that of
the γ-product rac-19b (Scheme 5) in THF even more so
than in ether (Table 4, Entries 1 and 2). When thiocarba-
mate (S)-14a (isolated from Pd0-catalyzed deracemization
as a yellowish solid that gave satisfactory spectra and ele-
mental analysis) was used, only moderate stereospecificities
were obtained (Table 4, Entry 3).[32] A double recrystalliza-
tion/chromatography sequence yielded white thiocarbamate
(S)-14a, but the subsequent methylation experiment gave
higher but still unsatisfactory stereospecificities of 71% and
60%, respectively (Table 4, Entry 4). This indicates that even
traces of impurities from the Pd0-catalyzed deracemization
cause perceptible loss of stereospecificity. The addition of
hexamethylphosphoric triamide (HMPT) in order to en-
hance the configurational stability of carbanion (S)-16 by
ion-pair separation had only a marginal effect on the ste-
reospecificity (Table 4, Entry 5). The addition of 7 equiv. of
lithium chloride to a solution of (S)-16 in THF did not
cause loss of stereospecificity (Table 4, Entry 6).[35] The in
situ N-silylation of thiocarbamate (S)-14a with F3CSO3-
SiMe3 (TMSOTf; Table 4, Entry 7)[36] or other silylating re-
agents caused reduced stereospecificity.
Chemical correlation established the (R) absolute config-
uration for the thiocarbamate (ϩ)-18b as follows. A small
Figure 2. X-ray crystal structures of thiocarbamates (Ϫ)-(S)-20b
and (Ϫ)-(S)-21b[20]
2974
Eur. J. Org. Chem. 2002, 2970Ϫ2988

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
The absolute configuration of thiocarbamate (ϩ)-21d
was determined by X-ray structure analysis (Figure 3), con-
firming the (S) configuration and therefore once more the
stereoinversion of configuration during the electrophilic al-
kylation. The absolute configurations of further alkylation
products were assigned with the assumption, but without
any additional proof, of stereoinversion.
Table 4. Results of methylations of thiocarbamate (S)-14a
Entry[a] Solvent
Time
[min]
% stereospecificity[b] (% yield)[c]
(ϩ)-(R)-18b
(ϩ)-(R)-19b
1[d]
2[d]
3[e]
4
Et2O
THF
THF
THF
THF
THF
THF
120
10
10
50
55
50
10
rac (50)
rac (71)
63 (47)
71 (74)
77 (41)
82 (79)
28 (63)
rac (39)
rac (16)
52 (12)
60 (8)
40 (5)
70 (8)
5[f]
6[g]
7[h]
n.d. (4)
[a] (S)-14a of 94% ee (e.r. ϭ 97:3) was employed as starting material;
[b]
2.4Ϫ2.5 equivalents of sBuLi/TMEDA were used. Conservation
[c]
of the original enantioenrichment, determined by GC.[32]
Isol-
[d]
[e]
ated yields.
rac-14a was used.
Yellowish (S)-14a of 92% ee
[f]
(e.r. ϭ 96:4) from Pd0-catalyzed deracemization was used.
5.0
equivalents HMPT were used instead of TMEDA. [g] 7 equivalents
[h]
LiCl were added.
1.1 equivalents TMSOTf were added at 0 °C
prior to sBuLi at Ϫ78 °C.
amount of thiocarbamate (Ϫ)-(S)-20b (from the X-ray
structure determination) was saponified with 1  aqueous
sodium hydroxide solution to provide the corresponding
(Ϫ)-thiol and subjected to analytical GC on a chiral sta-
tionary phase (CPGC). A sample of compound (ϩ)-18b
was treated in the same way, resulting in a reversed order
of the major and the minor signal in the CPGC. Thus, the
dianionic species (S)-16 is alkylated by methyl iodide with
stereoinversion of configuration, as in the case of allylli-
thium compound 9. The (R) absolute configuration was as-
signed to thiocarbamate (ϩ)-19b by analogy.
Figure 3. X-ray crystal structure of thiocarbamate (ϩ)-(S)-21d
Lithiation was also carried out with the cycloheptenyl
thiocarbamate 15. Deuteration of allyllithium compound 25
under standard conditions in ether afforded a 41:59 mixture
of α-/γ-product, with 79% and Ͼ 99% D content, respect-
ively. Methylation furnished the α-methylation product 26
and its γ-isomer 27 in high yield (Scheme 8).
The steric demand of the isopropyl group seems to be
crucial for the configurational stability of the α-thiocarba-
moyl-substituted sec-allyllithium compounds. Thus, the
thiocarbamate (S)-14b (96% ee, e.r. ϭ 98:2) was lithiated
and subsequently alkylated with allyl bromide to provide
the thiocarbamates (ϩ)-20c and (ϩ)-21c or alkylated with
benzyl bromide to give the thiocarbamates (ϩ)-20d and
(ϩ)-21d, respectively. Alkylation products were separated
by column chromatography, and enantiomeric purity was
determined by GC or HPLC. The stereospecificities of al-
kylations are generally high (namely 96%, except for the γ-
allylation with 90% stereospecificity, Table 5, Entries 2 and
4).
The tendency of the regioselectivity of methylation of the
S-cycloheptenyl dianion 25 shows the same solvent depend-
ence as electrophilic substitutions of lithiated S-cyclohex-
enyl N-isopropylthiocarbamate 9. The γ-attack is more fav-
ored in THF solution than in ethereal solution (Table 6,
Entries 1 and 2). When thiocarbamate (Ϫ)-(S)-15 (91% ee,
e.r. ϭ 95.5:4.5) was subjected to methylation, optically act-
ive products were isolated: 21% of the α-methylation prod-
uct (ϩ)-(R)-26 with 87% ee (e.r. ϭ 93.5:6.5; 96% stereospec-
ificity) and 49% of the γ-isomer (ϩ)-(R)-27 formed with
88% ee (e.r. ϭ 94:6; 97% stereospecificity, Table 6, Entry
3).[37]
Table 5. Results of alkylations of thiocarbamate 14b
Entry[a,b]
Solvent
Et2O
Time [min]
ElX (equiv.)
AllylBr (1.5)
AllylBr (1.6)
BnBr (1.6)
Yield[c]
% stereospecificity[d]
1
80
15
80
15
32%
43%
18%
38%
13%
46%
7%
rac-20c
rac-21c
96 (ϩ)-(S)-20c
90 (ϩ)-(S)-21c
rac-20d
rac-21d
96 (ϩ)-(S)-20d
96 (ϩ)-(S)-21d
2[e]
3
THF
Et2O
4[e]
THF
BnBr (1.6)
59%
[a] See Table 3, entries 3 and 6 for related methylations. [b] 2.5 equivalents of sBuLi/TMEDA were used. [c] Isolated yields. [d] Conservation
of the original enantioenrichment, determined by GC or HPLC.[32] [e] (S)-14b of 96% ee (e.r. ϭ 98:2) was employed as starting material.
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2975

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
FULL PAPER
selectivity (d.r. ϭ 53:47). Consequently, we placed the em-
phasis on the addition of allyllithium compound 9 to sym-
metric ketones.[42] Adducts of acetone (21g), cyclohexanone
(21h), and benzophenone (21i) were isolated as white solids
by column chromatography in good yields (see Scheme 5;
Table 8, Entries 1, 2, 5Ϫ7).
The addition of acetone and cyclohexanone to the en-
antioenriched dianion 9 furnished adducts 21g and 21h,
with high stereospecificities of 97 and 94%, respectively
(Table 8, Entries 2 and 6).[43] When benzophenone was em-
ployed as electrophile, substantial loss of enantioenrich-
ment occurred; the addition might proceed via a radical
pair formed by single-electron transfer (SET),[44] causing
partial racemization (Table 8, Entry 8). The same observa-
tion has been made during addition of thiobenzyllithium
compound (S)-8 to benzophenone.[19c]
Scheme 8. Methylation of thiocarbamate (Ϫ)-(S)-15; ligands at the
lithium centers are omitted for the sake of clarity; reagents and
conditions: (a) sBuLi/TMEDA, Ϫ78 °C, 30 min; (b) i) MeI, Ϫ78
°C, 15 h; ii) HOAc, Ϫ78 °C, 15 min; iii) NaHCO3 (aq), 0 °C
Crystals suitable for X-ray structure analysis grown from
enantioenriched adduct (Ϫ)-(R)-21g turned out to be ra-
cemic. The obtained crystal structure, depicted in Figure 4,
shows hydrogen bonding between the NH protons and the
oxygen atoms of the introduced hydroxy groups.[45] These
interactions might give rise to higher crystallizability of
the racemate.
The N-methyl-substituted thiocarbamate 14a was hydro-
xyalkylated with acetone in the same manner as the N-iso-
propylthiocarbamate 14b, furnishing not only the γ-adduct
19g in high yield (87Ϫ90%), but, in addition, a small
amount of the α-product 18g when the reaction was run in
ether (Scheme 5; Table 8, Entries 3 and 4). Employment of
(S)-14a (95% ee, e.r. ϭ 97.5:2.5) as starting material yielded
thiocarbamate (ϩ)-(S)-19g in 87% yield and with 66% ste-
reospecificity (63% ee, e.r. ϭ 81.5:18.5). This represents the
same order of magnitude as found for methylations of dian-
ion (S)-16 (vide supra).
Attempts to determine the absolute configuration of hy-
droxyalkylation products through derivatization or correla-
tion with known compounds by independent synthesis
failed. Derivatization of thiocarbamate (ϩ)-19g by Ni0-cat-
alyzed cross-coupling with methylmagnesium bromide[46,47]
furnished isoterpineol (ϩ)-28[48] in 91% yield under optim-
ized conditions (Scheme 9). Isoterpineol (Ϫ)-28 was formed
from thiocarbamate (Ϫ)-21g under the same conditions in
74% yield. NOE experiments on the homoallylic alcohol 28
found that no isomerization of the double bond had oc-
curred during the cross-coupling reaction.
Table 6. Results of methylations of thiocarbamate 15
Entry[a] Solvent
Time
[min]
% stereospecificity,[b] (% yield)[c]
(ϩ)-(R)-26
(ϩ)-(R)-27
1
Et2O
THF
THF
80
60
30
rac (52)
rac (27)
96 (21)
rac (36)
rac (61)
97 (49)
2
3[d]
[a] 2.5 equivalents of sBuLi/TMEDA were used. [b] Conservation of
the original enantioenrichment, determined by GC.[32] [c] Isolated
[d]
yields. (S)-15 of 91% ee (e.r. ϭ 95.5:4.5) was employed as start-
ing material.
Hydroxyalkylations
The regioselective addition of benzaldehyde or 2-methyl-
propanal to the dianion rac-9 furnished diastereomeric mix-
tures of alcohols rac-21e (PhCHO) and rac-21f (iPrCHO),
respectively, in 55% yield in both cases. The diastereomeric
ratios are 55:45 in both cases (Table 7). Thiocarbamate anti-
rac-21f and its diastereoisomer syn-rac-21f could be separ-
ated by column chromatography. The anti/syn assignment
was made on the basis of an X-ray structure analysis of the
adduct syn-rac-21f. This matches with the previous assign-
3
ment[38] on the basis of the JH,H coupling constants of the
protons of the two newly formed stereocenters, taking liter-
ature references into account.[39]
Table 7. Addition of dianion rac-9 to aldehydes
The absolute configuration of hydroxyalkylation prod-
ucts is based on ab initio calculations by Grimme. It has
recently been shown[49] that reliable theoretical predictions
for the optical rotations of large chiral molecules can be
obtained by time-dependent density functional response
theory (TDDFT). By comparison of the theoretical calcu-
lated and the experimentally measured [α]D values, it is also
Entry ElX
Yield[a]
d.r.[b]
:
3JH,H [Hz]
anti-21 syn-21 anti-21
syn-21
1
2
PhCHO 55% 21e 55
iPrCHO 55% 21f 55
:
:
45
45
5.0
3.7
5.5
4.9
[a]
[b]
1
Isolated yields. Determined by H NMR.
Attempts to carry out a diastereoselective addition invol- easily possible to assign absolute configurations to noncrys-
ving a cyclic six-membered transition state[40] after trans- tallizable compounds. According to our computations,[50]
metallation from lithium to titanium or boron were less suc- the bulky 1-hydroxy-1-methylethyl substituent of 28 prefers
cessful.[41] Allyllithium compound rac-9 added to cyclohex- the pseudoequatorial position (population Ͼ 98% at room
2-en-1-one predominantly onto the carbonyl group (43% temp.), and so this conformer of the six-membered ring is
yield of the γ-1,2-adduct) with almost negligible diastereo- considered here exclusively. However, by rotation around
2976
Eur. J. Org. Chem. 2002, 2970Ϫ2988

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
Table 8. Addition of thioallyllithium compounds to ketones
Entry[a]
Starting compd.
Solvent
Time [min]
ElX (equiv.)
Adduct[b]
Specificity[d]
1
rac-14b
(R)-14b
rac-14a
Et2O
THF
Et2O
45
15
60
acetone (25)
acetone (1.5)
acetone (5.0)
rac-21g 64%
(Ϫ)-(R)-21g 47%
rac-18g 6%,
rac-19g 90%
(ϩ)-(S)-19g 87%
rac-21h 70%
(ϩ)-(S)-21h 80%
rac-21i 69%
(ϩ)-(S)-21i 74%
Ϫ
97%
Ϫ
2[c]
3
4[e]
5
(S)-14a
rac-14b
(S)-14b
rac-14b
(S)-14b
THF
Et2O
THF
Et2O
THF
15
50
8
45
15
acetone (5.9)
66%
Ϫ
94%
Ϫ
cyclohexanone (5)
cyclohexanone (5)
benzophenone (5)
benzophenone (5)
6[f]
7
8[f]
24%
[a]
[b]
[c]
[d]
2.1Ϫ2.5 equivalents of sBuLi/TMEDA were used. Isolated yields. (R)-14b of 75% ee (e.r. ϭ 87.5:12.5) was used. Conservation
[e]
[f]
of the original enantioenrichment, determined by GC or MPLC. (S)-14a of 95% ee (e.r. ϭ 97.5:2.5) was used. (S)-14b of 96% ee
(e.r. ϭ 98:2) was used.
Only 1.1 kJ/mol higher in energy is the conformer 28b,
with θ ഠ Ϫ120°. The third conformer, with θ ϭ ϩ50°, is
4.3 kJ/mol higher in energy and so is not considered further.
The computations were performed for both 28a and 28b,
and the theoretical [α]D values were weighted by the corres-
ponding Boltzmann populations at room temperature. Only
these averaged values are reported here for comparison with
the experimental data.[58] At the sodium D line frequency
we obtained a theoretical result of [α]D(theor.) ϭ ϩ76 for
the (S) enantiomer and so may assign the absolute config-
uration as (S) ϭ (ϩ). Keeping in mind that optical rotation
can be heavily influenced by solvation (the calculations refer
to the gas phase), the agreement with the experimentally
ascertained [α]D(exp.) ϭ Ϫ38 seems reasonable for the other
enantiomer. Inspection of the data at the other wavelengths
546 nm {[α](theor.) ϭ ϩ92, [α](exp.) ϭ Ϫ46}, 436 nm
{[α](theor.) ϭ ϩ164, [α](exp.) ϭ Ϫ92}, and 365 nm
{[α](theor.) ϭ ϩ277, [α](exp.) ϭ Ϫ146} clearly show that
the overestimation is systematic and that the frequency de-
pendence of [α] is described very well by theory. In sum-
Figure 4. X-ray crystal structure of thiocarbamate rac-21g
mary, we can conclude that thiocarbamate (ϩ)-19g, the
source of isoterpineol (ϩ)-(S)-28, possesses the (S) config-
uration, and the (R) configuration was assigned to thiocar-
bamate (Ϫ)-21g, the source of isoterpineol (Ϫ)-(R)-28. It is
concluded that the hydroxyalkylation of the dianionic spe-
cies (R)-9 and (S)-16 with acetone takes place suprafacially
through a syn-SEЈ process; the absolute configurations of
(ϩ)-(S)-21h and (ϩ)-(S)-21i were assigned in analogy, with-
out further proof.
Scheme 9. Ni0-catalyzed cross-coupling; reagents and conditions:
(a) i) 15 mol % Ni(dppe)Cl2, MeMgBr, toluene, 90 °C, 18 h; ii)
HCl (aq)
Conclusion
the C-1ЈϪC-1 bond three possible conformers possessing
Optically active S-(2-alkenyl) N-monoalkylmonothiocar-
relative minima in energy could be formed. In the lowest-
energy conformation 28a, the dihedral angle θ between the
oxygen atom and 1Ј-H is about Ϫ60° (Figure 5).
bamates 14aϪc and 15 as precursors for allyllithium com-
pounds have been synthesized starting from enantioen-
riched sec-allylic alcohols, by a carbamoylation/enantio-
specific rearrangement methodology, giving access to both
enantiomers. The rate of deprotonation, the configurational
stability of allyllithium compound 9, and the regioselectiv-
ity of electrophilic substitutions of all investigated lithiated
allylthiocarbamates show marked solvent dependence. Al-
Figure 5. Conformers of isoterpineol 28
Eur. J. Org. Chem. 2002, 2970Ϫ2988
kylations of configurationally stable allyllithium com-
2977

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
FULL PAPER
wise to the stirred suspension by syringe. A solution of the isothio-
cyanate in THF was added dropwise after 1 h of stirring, and after
an additional 1 h of stirring, the reaction mixture was carefully
hydrolyzed, still at 0 °C, with sat. NaHCO3 solution. The phases
were separated and the aqueous layer was extracted twice with ethyl
acetate. The combined organic layers were washed with brine, dried
with MgSO4, filtered, and concentrated in vacuo. The obtained
crude thiocarbamic acid O-esters were subjected to FCC, yielding
pure thiocarbamates 12aϪc and 13, respectively.
pounds 9 and 25 Ϫ each possessing an N-isopropyl-substi-
tuted carbamoyl group Ϫ proceed with high stereospecific-
ity and stereoinversion of configuration in both the α- and
the γ-positions.
Hydroxyalkylations of enantioenriched thioallyllithium 9
take place exclusively in the γ-position with high stereospec-
ificity in a suprafacial fashion, indicating a syn-SEЈ process.
Ni0-catalyzed cross-coupling of acetone adducts (ϩ)-19g
and (Ϫ)-21g with MeMgBr yielded optically active isoterpi-
neol 28, setting the stage for determination of absolute con-
figuration by DFT calculations of optical properties at the
aug-SV(p)/BH-LYP level.
rac-O-Cyclohex-2-enyl N-Methylmonothiocarbamate (rac-12a): So-
dium hydride (144 mg, 5.98 mmol, 1.19 equiv.), suspended in THF
(3 mL), rac-cyclohex-2-en-1-ol (rac-10, 488 mg, 4.97 mmol), dis-
solved in THF (1 mL), and methyl isothiocyanate (384 mg,
5.25 mmol, 1.06 equiv.), dissolved in THF (1 mL), were treated ac-
cording to General Procedure A. Purification by FCC (180 mL
SiO2; EE/cyclohexane, 1:4) yielded rac-12a (842 mg, 4.92 mmol,
99%) as a low-melting white solid (solid at Ϫ20 °C, colorless liquid
at room temp.). Rf ϭ 0.52 (EE/cyclohexane, 1:4). 1H NMR
(300 MHz, CDCl3): δ ϭ 1.54Ϫ2.14 (m, 6 H, 4CH2/5CH2/6CH2);
2.81/3.04 (each d, 3J ϭ 4.9/5.2 Hz, 3 H, NϪCH3); 5.71Ϫ5.84,
5.88Ϫ5.98 (each m, 2 H ϩ 1 H, 1CH/2CH/3CH); 6.31/6.85 (each
br. s, 1 H, NH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 18.8, 24.8,
28.2 (4CH2/5CH2/6CH2); 29.4/31.5 (NϪCH3); 73.7/75.5 (1CH);
125.3/125.6 (3CH); 132.6/132.9 (2CH); 189.7/190.6 (CϭS) ppm. IR
(film): ν˜ ϭ 3270 s [ν(NϪH)], 3033 m, 2940 s, 2868 m, 2835 w, 1657
m, 1525 s [ν(CϭS)], 1446 m, 1361 m, 1209 s [δ(NϪH)], 1144 s,
1045 s, 1005 s, 718 m, 663 m cmϪ1. MS (EI [70 eV]): m/z (%) ϭ
171 (68) [Mϩ]; 143 (6) [retro DielsϪAlder {M Ϫ C2H4}ϩ]; 112 (30)
[{M Ϫ MeNCO}ϩ]; 99 (35); 92 (45) [HS(COH)NHMeϩ]; 81 (100)
[{M Ϫ S(CO)NHMe}ϩ]; 57 (87) [MeNCOϩ]. C8H13NOS (171.26):
calcd. C 56.11 H 7.65 N 8.18; found C 55.97 H 7.42 N 8.33.
Experimental Section
General Remarks: All solvents were dried and purified prior to use:
toluene and Et2O were distilled from sodium benzophenone ketyl,
and THF was distilled from potassium benzophenone ketyl.
N,N,NЈ,NЈ-Tetramethylethylenediamine (TMEDA) was distilled
from powdered CaH2 and stored under Ar in the dark. Aldehydes
were distilled prior to use. Solutions of sec-butyllithium were pur-
chased (ca. 1.3  in cyclohexane/hexane, 92:8), filtered through a
pad of Celite under argon in order to remove any precipitate, and
stored in a freezer (Ϫ30 °C); only a slight yellow hue is acceptable.
The content of sBuLi was determined by titration.[59,60] All other
commercially available reagents were used as received. All reactions
were performed under Ar in flame-dried glassware. Flash column
chromatography (FCC) was performed on Merck 60 silica gel,
0.040Ϫ0.063 mm, and monitored by thin layer chromatography
(TLC) on Merck 60 F254 silica gel; PE: light petroleum ether, b.p.
36Ϫ46 °C; EE: ethyl acetate. NMR: Bruker ARX 300, AM 360
(NOE experiments), or AMX 400 (routine 2D spectra) and Varian
Unity Plus 600 (2D spectra, NOE experiments); spectra from solu-
tions in CDCl3 (δC ϭ 77.0 ppm) are calibrated relative to residual
content of CHCl3 (δH ϭ 7.24 ppm) or SiMe4 (δH ϭ 0.00 ppm),
spectra from solutions in other deuterated solvents are calibrated
to SiMe4 (δH ϭ 0.00 ppm; δC ϭ 0.00 ppm). Some resonance signals
for thiocarbamic acid O-esters are doubled due to (E)/(Z)-amide
isomers; the related signals are consequently given in groups, separ-
ated by a slash. IR: Nicolet 5 DXC. MS: Finnigan MAT 8200 (EI);
Finnigan MAT 8230 (GC-MS); Varian Saturn II (GC-MS); Micro-
mass Quattro LC (ESI). Optical rotations: PerkinϪElmer 341 po-
larimeter. Melting points: Gallenkamp MFB 595 (uncorrected
values). Elemental analyses: Elementar Analysensysteme Vario EL
III. GC: HewlettϪPackard 5890, 25 m ϫ 0.2 mm HP 1, 107 kPa
pre-column pressure N2, 1 min at 50 °C/10 °C ϫ minϪ1/15 min at
290 °C; Agilent 6890, 30 m ϫ 0.32 mm HP 5, 1.5 mL ϫ minϪ1 H2,
start at 50 °C/10 °C ϫ minϪ1/30 min at 300 °C; HewlettϪPackard
6890, 25 m ϫ 0.2 mm HP 1701, 100 kPa pre-column pressure N2,
1 min at 50 °C/10 °C ϫ minϪ1/20 min at 270 °C; HewlettϪPackard
rac-O-Cyclohex-2-enyl N-Isopropylmonothiocarbamate (rac-12b):
Sodium hydride (0.760 g, 19.0 mmol; 1.27 equiv.), suspended in
THF (8 mL), rac-cyclohex-2-en-1-ol (rac-10, 1.47 g, 15.0 mmol),
dissolved in THF (3 mL), and isopropyl isothiocyanate (1.61 g,
16.1 mmol, 1.07 equiv.), dissolved in THF (3 mL), were treated ac-
cording to General Procedure A. Purification by FCC (250 mL
SiO2; gradient Et2O/PE, 1:5 Ǟ 1:3) yielded rac-12b (2.83 g,
14.2 mmol, 95%) as a low-melting white solid (solid at Ϫ 25 °C,
colorless liquid at room temp.). Rf ϭ 0.37 (Et2O/PE, 1:5); Rf ϭ
0.48 (Et2O/PE, 1:3). 1H NMR (300 MHz, CDCl3): δ ϭ 1.12/1.19
3
[each d, J ϭ 6.6 Hz, 6 H, iPr(CH3)2]; 1.56Ϫ1.73, 1.75Ϫ2.14 (each
m, 2 H ϩ 4 H, 4CH2/5CH2/6CH2); 3.95/4.34 (each ψ-oct, 1 H,
iPrCH); 5.72Ϫ5.84 (m, 2 H, 1CH/2CH); 5.89Ϫ5.99 (m, 1 H, 3CH);
6.01/6.60 (each br. s, 1 H, NH) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 18.8 (5CH2); 21.8/22.2 [iPr(CH3)2]; 24.8 (4CH2); 28.2 (6CH2);
45.2/46.8 (iPrCH); 73.1/75.2 (1CH); 125.2/125.7 (2CH); 132.5/132.8
(3CH); 188.3 (CϭS) ppm. IR (film): ν˜ ϭ 3250 s [ν(NϪH)], 3039
m, 2973 s, 2940 s, 2868 m, 2835 w, 1650 m, 1519 s [ν(CϭS)], 1460
s, 1400 s, 1341 m, 1315 m, 1216 s [δ(NϪH)], 1147 s, 1131 s, 1045
m, 1006 m, 986 m, 120 w, 729 w cmϪ1. MS (EI [70 eV]): m/z (%) ϭ
199 (87) [Mϩ]; 120 (74) [HS(COH)NH-iPrϩ]; 97 (13) [SCNH-iPrϩ];
81 (100) [{M Ϫ S(CO)NH-iPr}ϩ]; 79 (58) [{M Ϫ S(CO)NH-iPr Ϫ
H2}ϩ]; 58 (32) [NH-iPrϩ]; 53 (20) [retro-DielsϪAlder {M Ϫ
S(CO)NH-iPr Ϫ C2H4}ϩ]. MS (ESI {MeOH/CHCl3}, [1.33 kV, 31
V], ESϩ): m/z (%) ϭ 222 (100) [M ϩ Naϩ] Ǟ {222 (80); 142 (100)
[HO(CS)NH-iPr ϩ Naϩ]; 81 (2) [{M Ϫ S(CO)NH-iPr}ϩ]; 79 (3)
[{M Ϫ S(CO)NH-iPr Ϫ H2}ϩ]; 23 (75) [Naϩ]}; 200 (25) [M ϩ
Hϩ] Ǟ {200 (2); 120 (85) [HO(CS)NH-iPr ϩ Hϩ]; 81 (100) [{M Ϫ
6890, cyclodextrins from Supelco (30
m ϫ 0.32 mm) or
MachereyϪNagel (25 m ϫ 0.2 mm), 100 kPa pre-column pressure
N2, isothermal runs. HPLC: A) Knauer WellChrom Maxi-Star K-
1000 pump with A0285 mixing unit and A0293 spectral photo-
meter at 220 nm; B) Waters 600E Multisolvent Delivery System
and 996 photodiode array detector.
Carbamoylation of Allylic Alcohols. General Procedure A: Sodium
hydride (60% in mineral oil, approx. 1.2 equiv.) was washed free of
mineral oil with two small portions of THF. The sodium hydride
was suspended in THF at 0 °C in a flask sealed with a rubber
septum. A solution of the allylic alcohol in THF was added drop-
S(CO)NH-iPr}ϩ]; 79 (20) [{M
Ϫ S(CO)NH-iPr Ϫ
H2}ϩ]}.
C10H17NOS (199.31): calcd. C 60.26, H 8.60, N 7.03; found C
60.38, H 8.83, N 7.36.
2978
Eur. J. Org. Chem. 2002, 2970Ϫ2988

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
1
Thiocarbamate (؊)-(S)-12b: Sodium hydride (96 mg, 2.4 mmol,
1.25 equiv.), suspended in THF (1 mL), (Ϫ)-(S)-cyclohex-2-en-1-ol
changed alcohol rac-11 was isolated. Rf ϭ 0.59 (Et2O/PE, 1:3). H
NMR (300 MHz, CDCl3): δ ϭ 1.11/1.17 (each d, 3J ϭ 6.5 Hz, 6
[(S)-10] (188 mg, 1.92 mmol, 82% ee, e.r. ϭ 91:9), dissolved in THF H, iPr(CH3)2]; 1.27Ϫ1.47, 1.56Ϫ1.75, 1.76Ϫ2.01, 2.02Ϫ2.22 (each
(1 mL), and isopropyl isothiocyanate (204 mg, 2.02 mmol, 1.05
equiv.), dissolved in THF (1 mL), were treated according to Gen-
eral Procedure A. Purification by FCC (91 mL SiO2; gradient Et2O/
m, 1 H ϩ 3 H ϩ 2 H ϩ 2 H, 4CH2/5CH2/6CH2/7CH2); 3.95/4.34
(each ψ-oct, 1 H, iPrCH); 5.59Ϫ5.84, 5.86Ϫ5.96 (each m, 2 H ϩ 1
H, 1CH/2CH/3CH); 6.06/6.79 (each br. s, 1 H, NH) ppm. 13C
PE, 1:10 Ǟ 1:3) yielded (Ϫ)-(S)-12b (282 mg, 1.41 mmol, 74%) as NMR (75 MHz, CDCl3): δ ϭ 21.9/22.3 [iPr(CH3)2]; 25.9/26.0, 26.5,
a viscous, colorless liquid and a few % of the corresponding S-ester
14b (8 mg, 0.04 mmol, 2%). [α]2D0 ϭ Ϫ149 [c ϭ 1.13, CHCl3, at 91%
ee (e.r. ϭ 95.5:4.5)].
28.4, 32.6/32.7 (4CH2/5CH2/6CH2/7CH2); 45.2/46.8 (iPrCH); 79.5/
81.4 (1CH); 131.0/131.7 (2CH); 132.7/133.4 (3CH); 188.0 (CϭS)
ppm. IR (film): ν˜ ϭ 3401 w, 3256 s [ν(NϪH)], 3033 w, 2973 s, 2934
s, 2855 s, 1657 w, 1512 s [ν(CϭS)], 1460 s, 1400 s, 1371 m, 1341 m,
1308 m, 1223 s [δ(NϪH)], 1170 m, 1151 s, 1131 s, 1032 s, 953 w
cmϪ1. C11H19HOS (213.34): calcd. C 61.93, H 8.98, N 6.57; found
C 62.13, H 9.17, N 6.49.
Thiocarbamate (؉)-(R)-12b: Sodium hydride (125 mg, 3.13 mmol,
1.20 equiv.), suspended in THF (2 mL), (ϩ)-(R)-cyclohex-2-en-1-ol
[(R)-10, 255 mg, 2.60 mmol, 96% ee, e.r. ϭ 98:2], dissolved in THF
(1 mL), and isopropyl isothiocyanate (276 mg, 2.73 mmol, 1.05
equiv.), dissolved in THF (1 mL), were allowed to react according
to General Procedure A. Purification by FCC (110 mL SiO2; Et2O/
PE, 1:5) yielded (ϩ)-(R)-12b (415 mg, 2.08 mmol, 80%) as a vis-
cous, colorless liquid; a further 4% of rearranged thiocarbamate
(S)-14b was isolated. [α]2D0 ϭ ϩ156 [c ϭ 1.13, CHCl3, at 95% ee
(e.r. ϭ 97.5:2.5)].
Thiocarbamate (؊)-(R)-13: Sodium hydride (73 mg, 1.8 mmol, 1.2
equiv.), suspended in THF (1 mL), (R)-cyclohept-2-en-1-ol [(R)-
11,[62] 170 mg, 1.52 mmol, Ͼ 99.6% ee, e.r. Ͼ 99.8:0.2],[63] dissolved
in THF (1 mL), and isopropyl isothiocyanate (162 mg, 1.60 mmol,
1.05 equiv.), dissolved in THF (1 mL), were treated according to
General Procedure A. Purification by FCC (35 mL SiO2; Et2O/PE
1:5) yielded (Ϫ)-(R)-12b (283 mg, 1.33 mmol, 87%) as a viscous,
colorless liquid. [α]2D0 ϭ Ϫ0.25 [c ϭ 1.19, CHCl3, at Ͼ 99.6% ee
rac-O-Cyclohex-2-enyl N-tert-Butylmonothiocarbamate (rac-12c):
Sodium hydride (240 mg, 6.00 mmol, 1.20 equiv.), suspended in
THF (3 mL), rac-cyclohex-2-en-1-ol (rac-10, 491 mg, 5.00 mmol),
dissolved in THF (1 mL), and tert-butyl isothiocyanate (625 mg,
5.43 mmol, 1.09 equiv.), dissolved in THF (1 mL), were treated ac-
cording to General Procedure A. Purification by FCC (160 mL
SiO2; Et2O/PE, 1:5) yielded rac-12c (955 mg, 4.48 mmol, 90%) as
colorless crystals. M.p. 102 °C (Et2O/PE). Rf ϭ 0.38 (Et2O/PE, 1:5).
1H NMR (300 MHz, CDCl3): δ ϭ 1.29 [s, 9 H, tBu(CH3)3];
1.60Ϫ1.74, 1.84Ϫ2.15 (each m, 2 H ϩ 4 H, 4CH2/5CH2/6CH2);
20
20
20
(e.r. Ͼ 99.8:0.2)]. [α]
[α] ϭ Ϫ9.7.
365
ϭ Ϫ0.34; [α]
ϭ Ϫ0.59; [α]
ϭ Ϫ3.4;
578
546
436
20
rac-S-Cyclohex-2-enyl N-Methylmonothiocarbamate (rac-14a): The
O-ester rac-12a (2.90 g, 16.9 mmol) was heated to 150 °C over 1 h
in a flask with a long neck. After 5 h, the flask was allowed to cool
to room temp. and the crude thiocarbamate rac-14a was purified
by FCC (210 mL SiO2; gradient Et2O/PE 1:10 Ǟ 1:5) to give rac-
14a (2.33 g, 13.6 mmol, 80%) as colorless crystals; a further 12% of
cyclohex-2-ene-1-thiol and 2% of starting material (rac-12a) were
isolated. M.p. 61 °C (Et2O/PE). Rf ϭ 0.31 (Et2O/PE, 1:1). tr (HP
1) ϭ 12.5 min; tr (HP 1701) ϭ 17.5 min. 1H NMR (300 MHz,
CDCl3): δ ϭ 1.55Ϫ1.72, 1.73Ϫ1.84, 1.92Ϫ2.05 (each m, 2 H ϩ 1
3
3
7.77Ϫ5.87 (m, 2 H, 1CH/2CH); 5.95 (dt, J2,3 ϭ 9.3 Hz; J3,4
ϭ
3.5 Hz, 1 H, 3CH); 6.68 (br. s, 1 H, NH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 19.0 (5CH2); 24.8 (4CH2); 28.2 (6CH2); 29.1
[tBu(CH3)3]; 54.4 (tBuC); 75.9 (1CH); 125.1 (2CH); 132.9 (3CH);
189.6 (CϭS) ppm. IR (KBr): ν˜ ϭ 3241 s [ν(NϪH)], 3033 s, 2993 s,
2983 s, 2970 s, 2948 s, 2933 s, 2917 s, 2869 s, 2834 m, 1652 m, 1538
s [ν(CϭS)], 1418 s, 1390 s, 1364 s, 1260 s, 1203 s [δ(NϪH)], 1169
3
H ϩ 3 H, 4CH2/5CH2/6CH2); 2.80/2.81 (each d, J ϭ 4.9 Hz, 3 H,
NϪCH3); 4.10Ϫ4.18 (m, 1 H, 1CH); 5.49 (br. s, 1 H, NH);
5.61Ϫ5.68 (ddtd, 3J1,2 ϭ 4.1, 3J2,3 ϭ 10.0, 4J2,6CH ϭ 0.5 Hz, 4J2,4 ϭ
4
3
s, 1055 s, 1021 s, 978 s, 934 m, 900 m, 734 m, 699 m, 654 m cmϪ1
.
2.0, 1 H, 2CH); 5.72Ϫ5.79 (dtd, J1,3 ϭ 1.5, J3,4 ϭ 3.6 Hz, 1 H,
3CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 19.7 (5CH2); 24.8
(4CH2); 27.7 (NϪCH3); 30.2 (6CH2); 40.7 (1CH); 126.8 (2CH);
130.4 (3CH); 167.8 (CϭO) ppm. IR (KBr): ν˜ ϭ 3283 s [ν(NϪH)],
3032 m, 2940 m, 2927 m, 2900 m, 2854 w, 2822 w, 1644 s [ν(Cϭ
O)], 1532 s [δ(NϪH)], 1406 m, 1242 s, 1230 s, 1203 m, 1038 w, 874
w, 827 m, 755 m, 630 m cmϪ1. MS (EI [70 eV]): m/z (%) ϭ 171 (37)
MS (EI [70 eV]): m/z (%) ϭ 213 (71) [Mϩ]; 134 (25) [HO(CSH)NH-
tBuϩ]; 114 (39); 97 (22) [SCNH-tBuϩ]; 81 (100) [{M Ϫ S(CO)NH-
tBu}ϩ]; 79 (44) [{M Ϫ S(CO)NH-tBu Ϫ H2}ϩ]; 57 (37) [tBuϩ]; 53
(7) [retro DielsϪAlder {M
Ϫ S(CO)NH-tBu Ϫ
C2H4}ϩ].
C11H19NOS (213.34): calcd. C 61.93, H 8.98, N 6.57; found C
61.92, H 8.85, N 6.56.
[Mϩ]; 138 (1); 114 (6) [{M
Ϫ
MeNCO}ϩ]; 92 (46)
[HS(COH)NHMeϩ]; 81 (100) [{M Ϫ S(CO)NHMe}ϩ]; 79 (43) [{M
Ϫ S(CO)NHMe Ϫ H2}ϩ]; 58 (22) [CONHMeϩ]; 53 (16) [retro
DielsϪAlder {M Ϫ S(CO)NHMe Ϫ C2H4}ϩ]. C8H13NOS (171.26):
calcd. C 56.11, H 7.65, N 8.18; found C 56.03, H 7.71, N 8.18.
Thiocarbamate (؊)-(S)-12c: Sodium hydride (390 mg, 9.75 mmol,
1.38 equiv.), suspended in THF (4 mL), (Ϫ)-(S)-cyclohex-2-en-1-ol
[(S)-10, 695 mg, 7.08 mmol, 77% ee, e.r. ϭ 88.5:11.5], dissolved in
THF (1.5 mL), and tert-butyl isothiocyanate (864 mg, 7.50 mmol,
1.06 equiv.), dissolved in THF (1 mL), were treated according to
General Procedure A. Purification by FCC (150 mL SiO2; gradient
Et2O/PE, 1:10 Ǟ 1:5) yielded (Ϫ)-(S)-12c (1.37 g, 6.42 mmol, 91%)
as colorless crystals. M.p. 96 °C (Et2O/PE). [α]2D0 ϭ Ϫ126 (c ϭ 1.22,
CHCl3, at 77% ee (e.r. ϭ 88.5:11.5)].
rac-S-Cyclohex-2-enyl N-Isopropylmonothiocarbamate (rac-14b):
The O-ester rac-12b (2.30 g, 11.5 mmol) was heated to 105 °C over
1 h. After 3 h, the flask was allowed slowly to come to room temp.
and the obtained solid was subjected to FCC (210 mL SiO2; gradi-
ent Et2O/PE, 1:5 Ǟ 1:3), yielding rac-14b (1.80 g, 9.03 mmol, 78%)
as colorless crystals. M.p. 96 °C (Et2O/PE). Rf ϭ 0.36 (Et2O/PE,
1:3). tr (HP 5) ϭ 13.2 min; tr (HP 1701) ϭ 17.9 min. 1H NMR
(300 MHz, CDCl3): δ ϭ 1.12 [d, 3J ϭ 6.3 Hz, 6 H, iPr(CH3)2];
1.55Ϫ1.72, 1.73Ϫ1.84, 1.93Ϫ2.04 (each m, 2 H ϩ 1 H ϩ 3 H,
4CH2/5CH2/6CH2); 3.99 (ψ-oct, 1 H, iPrCH); 4.09Ϫ4.15 (m, 1 H,
rac-O-Cyclohept-2-enyl N-Isopropylmonothiocarbamate (rac-13):
Sodium hydride (41 mg, 1.1 mmol, 1.2 equiv.), suspended in THF
(1 mL), rac-cyclohept-2-en-1-ol (rac-11,[61] 100 mg, 0.892 mmol),
dissolved in THF (1 mL), and isopropyl isothiocyanate (95 mg,
0.94 mmol, 1.05 equiv.), dissolved in THF (1 mL), were treated ac-
cording to General Procedure A. Purification by FCC (35 mL SiO2;
Et2O/PE, 1:5) yielded rac-13 [130 mg, 0.61 mmol, 68% (91% based
on conversion)] as a viscous, colorless liquid; a further 25% of un-
3
3
1CH); 5.24 (br. s, 1 H, NH); 5.64 (ddtd, J1,2 ϭ 4.0, J2,3 ϭ 10.0,
4J2,4 ϭ 2.1, J2,6CH ϭ 0.7 Hz, 1 H, 2CH); 5.75 (dtd, J1,3 ϭ 1.5,
4
4
3J3,4 ϭ 3.5 Hz, 1 H, 3CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2979

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
FULL PAPER
19.7 (5CH2); 24.7 (4CH2); 22.7 [iPr(CH3)2]; 30.2 (6CH2); 40.7 rac-S-Cyclohept-2-enyl N-Isopropylmonothiocarbamate (rac-15):
(1CH); 43.5 (iPrCH); 126.9 (2CH); 130.3 (3CH); 166.0 (CϭO) The O-ester rac-13 (120 mg, 0.562 mmol) was heated to 110 °C over
ppm. IR (KBr): ν˜ ϭ 3274 s [ν(NϪH)], 3030 m, 2968 s, 2937 s, 2924 1.5 h. After 1 h, the flask was allowed to cool to room temp. over
s, 2871 w, 2858 w, 1642 s [ν(CϭO)], 1626 s, 1535 s [δ(NϪH)], 1455
1 h, and the obtained solid was subjected to FCC (35 mL SiO2;
m, 1385 w, 1368 m, 1231 s, 1223 s, 1204 s, 867 m, 815 s, 751 m,
Et2O/PE, 1:5), giving rac-15 (77 mg, 0.36 mmol, 64%, 94% based
724 m, 638 m cmϪ1. MS (EI [70 eV]): m/z (%) ϭ 199 (86) [Mϩ]; on conversion) as colorless crystals; further starting material rac-
166 (1); 120 (55) [HS(COH)NH-iPrϩ]; 114 (21) [{M Ϫ CONH-
13 (38 mg, 0.18 mmol, 32%) was also isolated.[65] M.p. 65 °C (Et2O/
iPr}ϩ]; 113 (12) [{M Ϫ iPrNCO}ϩ]; 86 (15) [CONH-iPrϩ]; 81 (100) PE). Rf ϭ 0.48 (Et2O/PE, 1:3). tr (HP 1701) ϭ 19.1 min. 1H NMR
[{M Ϫ S(CO)NH-iPr}ϩ]; 79 (73) [{M Ϫ S(CO)NH-iPr Ϫ H2}ϩ];
(300 MHz, CDCl3): δ ϭ 1.29 [d, 3J ϭ 6.6 Hz, 6 H, iPr(CH3)2];
58 (9) [CONH-iPrϩ]; 53 (16) [retro DielsϪAlder {M Ϫ S(CO)NH- 1.44Ϫ1.66, 1.67Ϫ1.86, 1.87Ϫ1.94, 2.07Ϫ2.16 (each m, each 2 H,
iPr Ϫ C2H4}ϩ]. MS (ESI {MeOH/CHCl3}, [1.33 kV, 31 V], ESϩ): 4CH2/5CH2/6CH2/7CH2); 3.91Ϫ4.02 (m, 1 H, iPrCH); 4.26Ϫ4.32
m/z (%) ϭ 222 (100) [M ϩ Naϩ] Ǟ {222 (15); 142 (40)
(m, 1 H, 1CH); 5.20 (br. s, 1 H, NH); 5.73Ϫ5.77 (m, 2 H, 2CH/
[HO(CS)NH-iPr ϩ Naϩ]; 81 (3) [{M Ϫ S(CO)NH-iPr}ϩ]; 79 (1) 3CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 22.8 [iPr(CH3)2];
[{M Ϫ S(CO)NH-iPr Ϫ H2}ϩ]; 23 (100) [Naϩ]}; 200 (15) [M ϩ
27.0, 27.2, 28.3, 33.5 (4CH2/5CH2/6CH2/7CH2); 43.6 (iPrCH); 44.8
Hϩ] Ǟ {200 (2); 120 (90) [HO(CS)NH-iPr ϩ Hϩ]; 81 (100) [{M Ϫ (1CH); 132.1 (2CH); 133.4 (3CH); 166.0 (CϭO) ppm. IR (KBr):
S(CO)NH-iPr}ϩ]; 79 (20) [{M H2}ϩ]}. ν˜ ϭ 3322 s [ν(NϪH)], 3019 m, 2973 s, 2920 s, 2875 m, 2852 m,
S(CO)NH-iPr
Ϫ
Ϫ
C10H17NOS (199.32): calcd. C 60.26, H 8.60, N 7.03; found C
60.40, H 8.66, N 7.07.
1646 s [ν(CϭO)], 1519 s [δ(NϪH)], 1454 m, 1389 w, 1366 m, 1321
w, 1221 s, 1203 s, 1168 s, 1130 m, 1069 w, 1051 w, 956 m, 876 s,
817 s, 789 s, 691 m, 650 w, 610 s cmϪ1. MS (EI [70 eV]): m/z (%) ϭ
213 (20) [Mϩ]; 180 (1); 128 (11) [{M Ϫ iPrNCO}ϩ]; 120 (48)
[HS(COH)NH-iPrϩ]; 95 (100) [{M Ϫ SCONH-iPr}ϩ]; 94 (45) [{M
Ϫ HSCONH-iPr}ϩ]; 79 (32); 67 (40) [{M Ϫ SCONH-iPr Ϫ H2}ϩ].
C11H19NOS (213.34): calcd. C 61.93, H 8.98, N 6.57; found C
61.90, H 9.22, N 6.48.
Thiocarbamate (R)-14b: The thiocarbamate (S)-12b (280 mg,
1.40 mmol, 82% ee, e.r. ϭ 91:9) was heated to 105 °C for 5 h. Puri-
fication of the crude product by FCC gave (R)-14b (222 mg,
1.11 mmol, 79%) as colorless crystals.[64] 79% ee (e.r. ϭ 89.5:10.5);
96% stereospecificity. M.p. 92 °C (Et2O/PE).
Thiocarbamate (؊)-(S)-14b: The thiocarbamate (R)-12b (153 mg,
0.77 mmol, 96% ee, e.r. ϭ 98:2) was heated to 105 °C for 5 h in a
flask with a long neck. Purification of the crude product by FCC
afforded (S)-14b (132 mg, 0.66 mmol, 86%) as colorless crystals.
93% ee (e.r. ϭ 96.5:3.5); 97% stereospecificity. M.p. 91 °C (Et2O/
PE). tr (DEX β-120, 120 °C) ϭ 199/202 min. [α]2D0 ϭ Ϫ216 (c ϭ
1.06, CHCl3, at 96% ee (e.r. ϭ 98:2); synthesized starting from en-
antioenriched cyclohex-2-en-1-thiol).[25c]
Thiocarbamate (؊)-(S)-15: Thiocarbamate (Ϫ)-(R)-13 (270 mg,
1.27 mmol, Ͼ 99.6% ee, e.r. Ͼ 99.8:0.2) was brought to 145 °C over
30 min and, after 4.5 h, allowed to cool to room temp. over an
additional 30 min. The formed solid was subjected to FCC (95 mL
SiO2; Et2O/PE, 1:5), yielding thiocarbamate (Ϫ)-(S)-15 (200 mg,
0.937 mmol, 74%) as colorless crystals. 91% ee (e.r. ϭ 95.5:4.5);
91% stereospecificity. M.p. 71 °C (Et2O/PE). tr (DEX β-120, 135
°C) ϭ 149/151 min. [α]2D0 ϭ Ϫ217 [c ϭ 1.04, CHCl3, at 91% ee
(e.r. ϭ 95.5:4.5)].
rac-S-Cyclohex-2-enyl N-tert-Butylmonothiocarbamate (rac-14c):
The O-ester rac-12c (700 mg, 3.28 mmol) was heated to 110 °C for
3 h in a flask with a long neck. FCC of the crude thiocarbamate
(140 mL SiO2; gradient Et2O/PE, 1:20 Ǟ 1:3) gave rac-14c (637 mg,
2.99 mmol, 91%) as colorless crystals. M.p. 111 °C (Et2O/PE). Rf ϭ
0.52 (Et2O/PE, 1:5). tr (HP 1) ϭ 13.4 min; tr (HP 1701) ϭ 17.6 min.
1H NMR (300 MHz, CDCl3): δ ϭ 1.32 [s, 9 H, tBu(CH3)3];
1.57Ϫ1.73, 1.74Ϫ1.85, 1.94Ϫ2.06 (each m, 2 H ϩ 1 H ϩ 3 H,
4CH2/5CH2/6CH2); 4.03Ϫ4.10 (m, 1 H, 1CH); 5.09 (s, 1 H, NH);
Deuterations. General Method B: Lithiation and subsequent deu-
teration of thiocarbamate 14b was performed under varying condi-
tions. Detailed procedure for an experiment with preparative sep-
aration and characterization of the resulting products 20a and 21a:
A solution of thiocarbamate rac-14b (32 mg, 0.16 mmol) and
TMEDA (42 mg, 0.36 mmol, 2.2 equiv.) in toluene (1 mL) in a flask
with a magnetic stirrer bar and a rubber septum was cooled to
Ϫ78 °C in a dry ice/acetone bath. sBuLi (0.29 mL, 1.23  solution,
0.36 mmol, 2.2 equiv.) was added dropwise, the flask was sealed
with Parafilm, and stirring at Ϫ78 °C was continued for addi-
tional 14.5 h. MeOD (30 µL, 0.72 mmol, 4.5 equiv.) was then added
by syringe, and 10 min later the reaction mixture was neutralized
with DOAc (0.36 mL, 1.0  solution in Et2O, 0.36 mmol, 2.2
equiv.). The flask was removed from the cooling bath, and when
the reaction mixture had warmed to approx. 0 °C, sat. NaHCO3
solution (2 mL) was added. The combined organic layers of extrac-
tion with Et2O (3 ϫ 10 mL) were washed with brine (1 mL), dried
with MgSO4, and filtered, and the solvents were removed in vacuo.
3
3
4
4
5.65 (ddtd, J1,2 ϭ 4.0, J2,3 ϭ 10.0, J2,4 ϭ 2.0, J2,6CH ϭ 0.7 Hz,
4
3
1 H, 2CH); 5.77 (dtd, J1,3 ϭ 1.5, J3,4 ϭ 3.6 Hz, 1 H, 3CH) ppm.
13C NMR (75 MHz, CDCl3): δ ϭ 19.8 (5CH2); 24.7 (4CH2); 29.0
[tBu(CH3)3]; 29.6 (6CH2); 40.9 (1CH); 53.1 (tBuC); 126.9 (2CH);
130.3 (3 CH); 165.2 (CϭO) ppm. IR (KBr): ν˜ ϭ 3288 s [ν(NϪH)],
3029 s, 2965 s, 2936 s, 2919 s, 2854 s, 2831 s, 2717 w, 1649 s [ν(Cϭ
O)], 1524 s [δ(NϪH)], 1454 s, 1394 m, 1363 s, 1250 s, 1217 s, 1037
m, 997 m, 859 s, 760 s, 746 s, 724 m, 620 s cmϪ1. MS (EI [70 eV]):
m/z (%) ϭ 213 (16) [Mϩ]; 134 (2) [HO(CSH)NH-tBuϩ]; 114 (13);
97 (1) [SCNH-tBuϩ]; 81 (100) [{M Ϫ S(CO)NH-tBu}ϩ]; 79 (36)
[{M Ϫ S(CO)NH-tBu Ϫ H2}ϩ]; 57 (58) [tBuϩ]. C11H19NOS
(213.34): calcd. C 61.93, H 8.98, N 6.57; found C 61.76, H 8.94,
N 6.42.
1
A H NMR spectrum of the crude product was recorded, and ap-
prox. 1 mg was subjected to GC-MS analysis. FCC (31 mL SiO2;
gradient Et2O/PE, 1:20 Ǟ 1:5) provided the thiocarbamate rac-20a
(12 mg, 0.60 mmol, 37%) and its regioisomer rac-21a (13 mg,
0.65 mmol, 40%), both isolated as colorless crystals (formed in a
ratio of 48:52 by reference to GC).
Thiocarbamate (؉)-(R)-14c: In a flask with a long neck, the O-ester
(S)-12c (253 mg, 1.19 mmol, 77% ee, e.r. ϭ 88.5:11.5) was brought
to 110 °C over 1.5 h and then allowed to cool to room temp. over
3 h. The crude product was purified by FCC (35 mL SiO2; gradient
Et2O/PE, 1:20 Ǟ 1:3) to afford (ϩ)-(R)-14c (235 mg, 1.10 mmol, rac-S-(1-Deuteriocyclohex-2-enyl) N-Isopropylmonothiocarbamate
93%) as colorless crystals. 77% ee (e.r. ϭ 88.5:11.5); 100% stereo- (rac-20a): M.p. 89 °C (Et2O/PE). Rf ϭ 0.33 (Et2O/PE, 1:3). tr (HP
specificity. M.p. 105 °C (CHCl3). tr (DEX β-6-TBDM, 120 °C) ϭ 1) ϭ 13.3 min; tr (HP 1701) ϭ 17.9 min. 1H NMR (300 MHz,
121/126 min. [α]2D0 ϭ ϩ149 [c ϭ 2.00, CHCl3, at 77% ee (e.r. ϭ
88.5:11.5)].
CDCl3): δ ϭ 1.15 [d, 3J ϭ 6.7 Hz, 6 H, iPr(CH3)2]; 1.62Ϫ1.73,
1.78Ϫ1.86, 1.96Ϫ2.07 (each m, 2 H ϩ 1 H ϩ 3 H, 4CH2/5CH2/
2980
Eur. J. Org. Chem. 2002, 2970Ϫ2988

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
6CH2); 4.04 (br. s, 1 H, iPrCH); 5.06 (br. s, 1 H, NH); 5.67 (dt, 15 mL). The combined organic layers were washed with brine
4
3
3J2,3 ϭ 9.9, J2,4 ϭ 2.0 Hz, 1 H, 2CH); 5.81 (dt, J3,4 ϭ 3.6 Hz, 1 (20 mL), dried with MgSO4, filtered, and concentrated in vacuo to
H, 3CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 19.7 (5CH2); 24.8 afford a yellowish oil, which was subjected to FCC (110 mL SiO2;
(4CH2); 22.9 [iPr(CH3)2]; 30.1 (6CH2); 40.8 (iPrCH); 43.6 (t,
gradient Et2O/PE, 1:50 Ǟ 1:15). Thiocarbamates (ϩ)-(S)-20d
1J1CD ϭ 12 Hz, 1CD); 126.8 (2CH); 130.6 (3CH) ppm. IR (KBr): (19 mg, 66 µmol, 7%) and (ϩ)-(S)-21d (172 mg, 0.594 mmol, 59%)
ν˜ ϭ 3276 s [ν(NϪH)], 3030 m, 2968 s, 2924 s, 2870 w, 2855 w, 1642
s [ν(CϭO)], 1626 s, 1533 s [δ(NϪH)], 1455 m, 1385 w, 1367 m,
were isolated, both as colorless crystals, and each formed with 92%
ee (e.r. ϭ 96:4), 96% stereospecificity.
1230 s, 1222 s, 1204 s, 867 s, 815 s, 751 m, 724 m, 638 m cmϪ1
.
S-(1-Methylcyclohex-2-enyl) N-Isopropylmonothiocarbamate (20b):
Methylations followed General Procedure C; yields and stereospec-
ificities are given in Table 3. M.p. 103 °C (Et2O/PE for rac-20b);
m.p. 103 °C [EE/cyclohexane for (R)-20b at 87% ee (e.r. ϭ
93.5:6.5)]. Rf ϭ 0.54 (Et2O/PE, 1:3). tr (HP 1) ϭ 13.3 min; tr (HP
1701) ϭ 17.6 min; tr (DEX β-120, 115 °C) ϭ 221/226 min; tr (DEX
α-120, 107 °C) ϭ 243/249 min. (R)-20b: [α]2D0 ϭ ϩ159 [c ϭ 0.62,
GC-MS (EI [80 eV]): m/z (%)
ϭ
200 (32) [Mϩ]; 120 (20)
[HS(COH)NH-iPrϩ]; 115 (11) [{M Ϫ iPrNCO}ϩ]; 86 (6) [CONH-
iPrϩ]; 82 (100) [{M Ϫ S(CO)NH-iPr}ϩ]; 80 (39) [{M Ϫ S(CO)NH-
iPr Ϫ H2}ϩ]; 70 (13); 58 (9) [CONH-iPrϩ]; 54 (10) [retro-
DielsϪAlder {M Ϫ S(CO)NH-iPr Ϫ C2H4}ϩ]; 43 (33) [iPrϩ]. MS
(ESI {MeOH/CHCl3}, [1.31 kV, 33 V], ESϩ): m/z (%) ϭ 223 (100)
[M
ϩ ϩ
Naϩ]; 201 (22) [M Hϩ]. HR-MS (EI [70 eV]):
1
CHCl3, at 87% ee (e.r. ϭ 93.5:6.5)]. H NMR (400 MHz, CDCl3):
C10H16DNOS (200.31): calcd. 200.10936; found 200.11979.
δ ϭ 1.11 [d, 3J ϭ 6.4 Hz, 6 H, iPr(CH3)2]; 1.60, 1.60Ϫ1.68 (s ϩ m,
3 H ϩ 2 H, 1-CH3 ϩ 5CH2); 1.76Ϫ1.87, 1.91Ϫ2.07, 2.26Ϫ2.32
(each m, 1 H ϩ 2 H ϩ 1 H, 4CH2/6CH2); 3.98 (ψ-oct, 1 H, iPrCH);
5.17 (br. s, 1 H, NH); 5.70Ϫ5.76 (m, 2 H, 2CH/3CH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 19.4 (5CH2); 22.8/22.9 [iPr(CH3)2];
24.7 (4CH2); 29.0 (1-CH3); 35.8 (6CH2); 43.1 (iPrCH); 50.5 (1C);
128.6, 132.5 (2CH/3CH); 165.8 (CϭO) ppm. IR (KBr): ν˜ ϭ 3289
s (ν NϪH), 3019 m, 2973 s, 2927 s, 2880 w, 2855 w, 1644 s [ν(Cϭ
O)], 1525 s [δ(NϪH)], 1453 m, 1368 m, 1223 s, 1170 m, 1131 m,
1091 w, 874 m, 815 s, 736 m, 630 m cmϪ1. MS (EI [70 eV]): m/z
(%) ϭ 213 (34) [Mϩ]; 155 (1) [{M Ϫ iPrNH}ϩ]; 120 (24)
[HS(COH)NH-iPrϩ]; 95 (100) [{M Ϫ S(CO)NH-iPr}ϩ]; 79 (19)
[{M Ϫ HS(CO)NH-iPr Ϫ CH3}ϩ]; 77 (9) [Phϩ]; 67 (6) [retro
rac-S-(3-Deuteriocyclohex-1-enyl) N-Isopropylmonothiocarbamate
(rac-21a): M.p. 102 °C (Et2O/PE). Rf ϭ 0.25 (Et2O/PE, 1:3). tr (HP
1) ϭ 13.4 min; tr (HP 1701) ϭ 18.4 min. 1H NMR (300 MHz,
CDCl3): δ ϭ 1.12 [d, 3J ϭ 6.7 Hz, 6 H, iPr(CH3)2]; 1.53Ϫ1.63,
1.65Ϫ1.76 (each m, 2 H ϩ 2 H, 4CH2/5CH2); 2.09Ϫ2.20 (m, 1 H,
3 CHD); 2.26Ϫ2.34 (m, 2 H, 6CH2); 3.99 (ψ-oct, 1 H, iPrCH); 5.22
(br. s, 1 H, NH); 6.19Ϫ6.21 (m, 1 H, 2CH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 21.1, 23.6 (4CH2/5CH2); 22.8 [iPr(CH3)2];
1
26.7 (t, J3CD ϭ 19 Hz, 3CHD); 32.2 (6CH2); 43.6 (iPrCH); 128.7
(1C); 139.7 (2CH); 165.6 (CϭO) ppm. IR (KBr): ν˜ ϭ 3284 s
[ν(NϪH)], 3022 m, 2968 s, 2957 s, 2942 s, 2925 s, 2882 s, 1647 s
[ν(CϭO)], 1622 s, 1524 s [δ(NϪH)], 1448 m, 1386 w, 1365 w, 1317
m, 1220 s, 870 m, 812 s, 702 w, 613 m cmϪ1. GC-MS (EI [80 eV]):
m/z (%) ϭ 200 (4) [Mϩ]; 115 (92) [{M Ϫ iPrNCO}ϩ]; 86 (8)
[CONH-iPrϩ]; 82 (100) [{M Ϫ S(CO)NH-iPr}ϩ]; 70 (35); 58 (5)
[CONH-iPrϩ]; 54 (8) [retro DielsϪAlder {M Ϫ S(CO)NH-iPr Ϫ
C2H4}ϩ]; 43 (37) [iPrϩ]. MS (ESI {MeOH/CHCl3}, [1.31 kV, 33 V],
ESϩ): m/z (%) ϭ 239 (52) [M ϩ Kϩ]; 223 (50) [M ϩ Naϩ]; 201
(100) [M ϩ Hϩ]. HR-MS (EI [70 eV]): C10H16DNOS (200.31):
calcd. 200.10936; found 200.11521.
DielsϪAlder {M
(213.34): calcd. C 61.93, H 8.98, N 6.57; found C 61.97, H 9.19,
N 6.49.
Ϫ S(CO)NH-iPr Ϫ
C2H4}ϩ]. C11H19NOS
S-(3-Methylcyclohex-1-enyl) N-Isopropylmonothiocarbamate (21b):
Methylations followed General Procedure C; yields and stereospec-
ificities are given in Table 3. M.p. 79 °C (Et2O/PE for rac-21b); m.p.
79 °C [EE/cyclohexane for (R)-21b at 71% ee (e.r. ϭ 85.5:14.5)].
Rf ϭ 0.42 (Et2O/PE, 1:3). tr (HP 1701) ϭ 18.6 min; tr (DEX β-120,
115 °C) ϭ 221/226 min. (R)-21b: [α]2D0 ϭ ϩ5.6 [c ϭ 0.97, CHCl3,
at 71% ee (e.r. ϭ 85.5:14.5)]. 1H NMR (400 MHz, CDCl3): δ ϭ
Alkylations. General Procedure C: Alkylations were performed un-
der standard deprotonation conditions (General Procedure B); the
ratio of sBuLi and electrophile Ϫ the alkyl halide Ϫ was crucial
here for optimum yields. The optimum molar amount of employed
electrophile is given by the total molar amount of sBuLi minus the
molar amount of thiocarbamate (the molar amount of thiocarba-
mate must not be multiplied by the number of the acidic protons
Ϫ it has to be substracted one time). If lower amounts were used,
conversions were lower, if higher amounts were used, additional N-
alkylation occurred, resulting in reduced yields of the more readily
purified and crystallizable N-monoalkylthiocarbamates. Represent-
ative procedure: Thiocarbamate (S)-14b (200 mg, 1.00 mmol, 96%
ee, e.r. ϭ 98:2) and TMEDA (291 mg, 2.51 mmol, 2.51 equiv.) were
dissolved in THF (5.0 mL) in a flask equipped with a rubber sep-
tum. The flask was cooled to Ϫ78 °C in a dry ice/acetone bath,
and sBuLi (1.32 mL, 1.32  solution, 2.51 mmol, 2.51 equiv.) was
added dropwise over a period of 5 min through a precooled needle.
The yellow reaction mixture was stirred for an additional 10 min,
and benzyl bromide (1.55 mL, 1.0  solution in THF, 1.55 mmol,
1.55 equiv.) was added dropwise over a period of 3 min through a
precooled needle. The flask was sealed with Parafilm and, after
the mixture had stirred for an additional 15.5 h, HOAc/Et2O
(2.51 mL, 1.0  solution in Et2O, 2.51 mmol, 2.50 equiv.) was ad-
ded. The reaction mixture was allowed to warm to approx. 0 °C,
and saturated NaHCO3 solution (5 mL) was added. The phases
were separated, and the aqueous layer was extracted with EE (3 ϫ
3
3
1.00 (d, J ϭ 7.2 Hz, 3 H, 3-CH3); 1.14, 1.13Ϫ1.18 (d ϩ m, J ϭ
6.4 Hz, 6 H ϩ 1 H, iPr(CH3)2 ϩ CHHЈ); 1.57Ϫ1.68, 1.73Ϫ1.84,
2.19Ϫ2.39 (each m, 1 H ϩ 2 H ϩ 3 H, 3CH/4CH2/5CH2/6CH2);
3.99 (ψ-oct, 1 H, iPrCH); 5.24 (br. s, 1 H, NH); 6.06Ϫ6.08 (m, 1
1
3
H, 2CH). H NMR (300 MHz, C6D6): δ ϭ 0.84 (d, J ϭ 6.4 Hz, 3
H, iPrCH3); 0.85 (d, 3J ϭ 6.4 Hz, 3 H, iPrCH3Ј); 0.94 (d, 3J ϭ
7.1 Hz, 3 H, 3-CH3); 1.03Ϫ1.18, 1.56Ϫ1.80, 2.13Ϫ2.27, 2.49Ϫ2.71
(each m, 1 H ϩ 3 H ϩ 1 H ϩ 2 H, 3CH/4CH2/5CH2/6CH2); 4.01
(ψ-oct, 1 H, iPrCH); 4.79 (br. s, 1 H, NH); 6.23Ϫ6.26 (m, 1 H,
2CH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 21.0 (3-CH3); 22.5
(4CH2); 22.8 [iPr(CH3)2]; 29.9, 32.1 (5CH2/6CH2); 32.3 (3CH); 43.6
(iPrCH); 127.7 (1C); 145.5 (2CH); 165.5 (CϭO) ppm. IR (KBr):
ν˜ ϭ 3302 s [ν(NϪH)], 3026 m, 2968 s, 2958 s, 2942 s, 2927 s, 2868
m, 2848 m, 1657 s [ν(CϭO)], 1622 s, 1528 s [δ(NϪH)], 1453 m,
1367 w, 1315 m, 1222 s, 1131 m, 867 m, 815 m, 696 w, 611 m cmϪ1
.
MS (EI [70 eV]): m/z (%) ϭ 213 (2) [Mϩ]; 170 (0.5) [{M Ϫ iPr}ϩ];
155 (1) [{M Ϫ iPrNH}ϩ]; 128 (39) [McLafferty {M Ϫ iPrNCO}ϩ];
113 (18) [{M Ϫ iPrNCO Ϫ Me}ϩ]; 95 (100) [{M Ϫ S(CO)NH-
iPr}ϩ]; 85 (7) [{M Ϫ iPrNCO Ϫ n-Pr}ϩ]; 79 (10) [{M Ϫ S(CO)NH-
iPr Ϫ CH4}ϩ]; 77 (6) [Phϩ]; 67 (7) [retro DielsϪAlder {M Ϫ
S(CO)NH-iPr Ϫ C2H4}ϩ]. C11H19NOS (213.34): calcd. C 61.93, H
8.98, N 6.57; found C 62.09, H 9.01, N 6.42.
Warming Experiments: Dilithiated species (R)-9 was prepared from
thiocarbamate (R)-14b by General Procedure B. The flask with spe-
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2981

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
cies (R)-9 was kept Ϫ after the injection of sBuLi was completed cyclohexane for rac-19b); m.p. 77Ϫ78 °C [EE/cyclohexane for (ϩ)-
FULL PAPER
Ϫ for 10 min in the dry ice/acetone bath, and it was then set in a
cooling bath of indicated temperature (Ϫ50 °C or Ϫ26 °C or 0
°C) for 15 min while stirring was continued. The flask was quickly
transferred back into the dry ice/acetone cooling bath and after an
additional 15 min of stirring the MeI solution was added. Further
operative steps followed General Procedure C.
(R)-19b at 57% ee (e.r. ϭ 78.5:21.5)]. Rf ϭ 0.34 (EE/cyclohexane,
1:2). tr (HP 1) ϭ 13.2 min; tr (HP 1701) ϭ 18.3 min; tr (DEX β-
225, 155 °C) ϭ 48/51 min. (R)-19b: [α]2D0 ϭ ϩ3.0 [c ϭ 0.51, CHCl3,
at 57% ee (e.r. ϭ 78.5:21.5)]. 1H NMR (300 MHz, CDCl3): δ ϭ 1.00
(d, 3J ϭ 7.1 Hz, 3 H, 3-CH3); 1.10Ϫ1.23, 1.55Ϫ1.69, 1.71Ϫ1.85,
2.18Ϫ2.40 (each m, 1 H ϩ 1 H ϩ 2 H ϩ 3 H, 3CH/4CH2/5CH2/
3
6CH2); 2.83 (d, J ϭ 4.9 Hz, 3 H, NϪCH3); 5.43 (br. s, 1 H, NH);
N-Isopropyl-3-(methylsulfanyl)cyclohex-2-enecarboxamide
(24):
6.05Ϫ6.08 (m, 1 H, 2CH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
21.0 (3-CH3); 22.4 (4CH2); 27.8 (NϪCH3); 29.9, 32.1 (5CH2/
6CH2); 32.3 (3CH); 127.4 (1C); 145.5 (2CH) ppm. IR (KBr): ν˜ ϭ
3308 s [ν(NϪH)], 3024 w, 2955 s, 2929 s, 2914 m, 2871 m, 2860 m,
2848 m, 1656 s [ν(CϭO)], 1517 s [δ(NϪH)], 1452 w, 1411 m, 1319
w, 1225 s, 1160 m, 1124 m, 1006 m, 969 w, 872 w, 812 m, 631 m
cmϪ1. MS (EI [70 eV]): m/z (%) ϭ 185 (4) [Mϩ]; 95 (100) [{M Ϫ
S(CO)NHMe}ϩ]; 79 (21) [{M Ϫ HS(CO)NHMe Ϫ CH3}ϩ]; 77 (12)
[Phϩ]; 67 (26) [retro-DielsϪAlder {M Ϫ S(CO)NHMe Ϫ C2H4}ϩ];
57 (7) [MeNCOϩ]. C9H15NOS (185.29): calcd. C 58.34, H 8.16, N
7.56; found C 58.59, H 8.38, N 7.55.
Rf ϭ 0.47 (EE). tr (HP 1701) ϭ 20.5 min. 1H NMR (300 MHz,
CDCl3): δ ϭ 1.11 (d, 3J ϭ 6.6 Hz, 3 H, iPrCH3); 1.12 (d, 3J ϭ
6.6 Hz, 3 H, iPrCH3Ј); 1.56Ϫ1.91, 2.11Ϫ2.18 (each m, 4 H ϩ 2 H,
4CH2/5CH2/6CH2); 2.22 (s, 3 H, SϪCH3); 2.93Ϫ3.00 (m, 1 H,
1CH); 4.04 (dsept, 3J ϭ 8.1 Hz, 1H iPrCH); 5.27Ϫ5.30 (m, 1 H,
2CH); 5.41 (br. s, 1 H, NH) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 14.0 (SϪCH3); 21.2 (5CH2); 22.7, 22.8 [iPr(CH3)2/iPr(CH3Ј)2];
26.4, 29.6 (4CH2/6CH2); 41.3, 44.2 (iPrCH/1CH); 114.9 (2CH);
139.2 (3C); 173.3 (CϭO) ppm. IR (KBr): ν˜ ϭ 3303 s [ν(NϪH)],
3059 w, 2972 s, 2939 s, 2916 s, 2877 m, 1637 s [ν(CϭO)], 1541 s
[δ(NϪH)], 1469 w, 1450 m, 1428 m, 1380 w, 1365 w, 1334 w, 1301
w, 1225 s, 1172 w, 1127 w, 1041 m, 908 m, 803 m, 667 m cmϪ1. MS
(EI [70 eV]): m/z (%) ϭ 213 (17) [Mϩ]; 199 (7) [{M Ϫ MeS}ϩ]; 155
(1) [{M Ϫ iPrNH}ϩ]; 127 (100) [{M Ϫ CONH-iPr}ϩ]; 113 (23); 79
(78) [{M Ϫ H(CO)NH-iPr Ϫ SCH3}ϩ]; 77 (27) [Phϩ]. C11H19NOS
(213.34): calcd. C 61.93, H 8.98, N 6.57; found C 61.67, H 8.93,
N 6.39.
S-[1-(Prop-2-enyl)cyclohex-2-enyl] N-Isopropylmonothiocarbamate
(20c): Allylations followed General Procedure C; yields and stereo-
specificities are given in Table 5. M.p. 59 °C (EE/cyclohexane for
rac-20c); m.p. 56 °C [EE/cyclohexane for (ϩ)-(S)-20c at 92% ee
(e.r. ϭ 96:4)]. Rf ϭ 0.43 (Et2O/PE, 1:3); Rf ϭ 0.16 (EE/cyclohexane,
1:10). tr (HP 1) ϭ 15.2 min; tr (HP 1701) ϭ 19.5 min; tr (DEX β-
6-TBDM, 122 °C) ϭ 174/178 min. (S)-20c: [α]2D0 ϭ ϩ133 [c ϭ 0.90,
CHCl3, at 92% ee (e.r. ϭ 96:4)]. 1H NMR (300 MHz, CDCl3): δ ϭ
1.12 [d, 3J ϭ 6.6 Hz, 6 H, iPr(CH3)2]; 1.58Ϫ1.77, 1.79Ϫ1.92,
1.94Ϫ2.09, 2.13Ϫ2.22 (each m, 2 H ϩ 1 H ϩ 2 H ϩ 1 H, 4CH2/
5CH2/6CH2); 2.67Ϫ2.82 (m, 2 H, 1CH2); 3.97 (ψ-oct, 1 H, iPrCH);
5.02Ϫ5.04, 5.06Ϫ5.10 (each m, 1 H ϩ 1 H, 3ЈCH2); 5.13 (br. s, 1
H, NH); 5.72Ϫ5.91 (m, 3 H, 2ЈCH/2CH/3CH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 19.0 (5CH2); 22.7/22.8 [iPr(CH3)2]; 24.7
(4CH2); 33.1 (6CH2); 43.1 (iPrCH); 44.6 (1ЈCH2); 53.4 (1C); 117.7
(3ЈCH2); 129.6 (3CH); 130.5 (2CH); 134.3 (2ЈCH); 165.9 (CϭO)
ppm. IR (KBr): ν˜ ϭ 3292 s [ν(NϪH)], 3073 w, 3021 m, 2974 s,
2932 s, 2876 w, 2835 w, 1642 s [ν(CϭO)], 1520 s [δ(NϪH)], 1444
m, 1367 m, 1216 s, 1164 m, 1129 w, 1059 w, 949 m, 912 m, 871 m,
814 s, 739 m, 627 m cmϪ1. GC-MS (EI [70 eV]): m/z (%) ϭ 239 (8)
[Mϩ]; 198 (2) [{M Ϫ allyl}ϩ]; 154 (5) [{M Ϫ iPrNCO}ϩ]; 121 (71)
[{M Ϫ S(CO)NH-iPr}ϩ]; 120 (72) [HS(COH)NH-iPrϩ ϩ McLaf-
ferty {M Ϫ HOCSNH-iPr}ϩ]; 113 (44); 105 (27); 92 (30) [McLaf-
ferty {M Ϫ HOCSNH-iPr Ϫ C2H3}ϩ]; 93 (35) [McLafferty {M Ϫ
HOCSNH-iPr Ϫ C2H4}ϩ]; 91 (54) [McLafferty {M Ϫ HOCSNH-
iPr Ϫ C2H5}ϩ]; 79 (100) {M Ϫ HSCONH-iPr Ϫ allyl}ϩ]; 77 (39)
[Phϩ]; 70 (67); 67 (38); 41 (34). C13H21NOS (239.38): calcd. C
65.23, H 8.84, N 5.85; found C 65.20, H 8.62, N 5.72.
Methylations of thiocarbamate 14a were performed according to
General Procedure C. Yields and stereospecificities are given in
Table 4. In one case (Table 4, Entry 5), TMEDA was replaced by
5.0 equiv. HMPT. Dry lithium chloride (7.1 equiv.) was dissolved
in THF at room temp. with the aid of an ultrasonic bath (Table 4,
Entry 6). In situ N-silylation (Table 4, Entry 7) was performed by
dropwise addition of 1.1 equiv. of a 1.0  solution of TMSOTf in
THF to the solution of thiocarbamate (S)-14a and TMEDA in
THF at 0 °C. The reaction mixture was stirred for 30 min at room
temp., cooled to Ϫ78 °C in a dry ice/acetone bath, and sub-
sequently treated with 2.51 equiv. of sBuLi and 1.51 equiv. of MeI/
THF according to General Procedure C.
S-(1-Methylcyclohex-2-enyl) N-Methylmonothiocarbamate (18b):
Yields and stereospecificities are given in Table 4. M.p. 57 °C (EE/
cyclohexane for rac-18b); m.p. 64Ϫ65 °C [EE/cyclohexane for (ϩ)-
(R)-18b at 67% ee (e.r. ϭ 83.5:16.5)]. Rf ϭ 0.43 (EE/cyclohexane,
1:2). tr (HP 1) ϭ 12.5 min; tr (HP 1701) ϭ 17.2 min; tr (DEX β-
120, 120 °C) ϭ 198/202 min. (R)-18b: [α]2D0 ϭ ϩ117 [c ϭ 1.08,
CHCl3, at 58% ee (e.r. ϭ 79:21)]. 1H NMR (400 MHz, CDCl3): δ ϭ
1.58, 1.58Ϫ1.66 (s ϩ m, 3 H ϩ 2 H, 1-CH3 ϩ 5CH2); 1.75Ϫ1.86,
1.89Ϫ2.06, 2.25Ϫ2.33 (each m, 1 H ϩ 2 H ϩ 1 H, 4CH2/6CH2);
2.77 (d, 3J ϭ 4.8 Hz, 3 H, NϪCH3); 5.36 (br. s, 1 H, NH);
5.69Ϫ5.72 (m, 2 H, 2CH/3CH) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 19.3 (5CH2); 24.7 (4CH2); 27.2 (NϪCH3); 29.1 (1-
CH3); 35.6 (6CH2); 50.5 (1C); 128.6 (3CH); 132.2 (2CH); 167.6
(CϭO) ppm. IR (KBr): ν˜ ϭ 3305 s [ν(NϪH)], 3021 m, 2958 s, 2932
s, 2863 m, 2832 m, 1642 s [ν(CϭO)], 1526 s [δ(NϪH)], 1443 w,
1410 m, 1362 w, 1225 s, 1169 m, 1086 w, 1004 w, 869 w, 825 m, 788
m, 729 m, 619 m cmϪ1. MS (EI [70 eV]): m/z (%) ϭ 185 (9) [Mϩ];
95 (100) [{M Ϫ S(CO)NH-Me}ϩ]; 79 (29) [{M Ϫ HS(CO)NHMe
Ϫ CH3}ϩ]; 77 (23) [Phϩ]; 67 (6) [retro DielsϪAlder {M Ϫ
S-[3-(Prop-2-enyl)cyclohex-1-enyl] N-Isopropylmonothiocarbamate
(21c): Allylations followed General Procedure C; yields and stereo-
specificities are given in Table 5. M.p. 65 °C (EE/cyclohexane for
rac-21c); m.p. 66 °C [EE/cyclohexane for (ϩ)-(S)-21c at 86% ee
(e.r. ϭ 93:7)]. Rf ϭ 0.28 (Et2O/PE, 1:3); Rf ϭ 0.10 (EE/cyclohexane,
1:10). tr (HP 1) ϭ 16.1 min; tr (HP 1701) ϭ 20.7 min; tr (DEX β-
225, 150 °C) ϭ 110/118 min. (S)-21c: [α]2D0 ϭ ϩ2.95 [c ϭ 0.95,
CHCl3, at 86% ee (e.r. ϭ 93:7)]. 1H NMR (300 MHz, CDCl3): δ ϭ
1.14 [d, 3J ϭ 6.6 Hz, 6 H, iPr(CH3)2]; 1.18Ϫ1.28, 1.56Ϫ1.86,
2.03Ϫ2.12, 2.18Ϫ2.37 (each m, 1 H ϩ 3 H ϩ 2 H ϩ 3 H, 3CH/
4CH2/5CH2/6CH2/1ЈCH2); 3.98 (ψ-oct, 1 H, iPrCH); 4.98Ϫ5.00,
5.01Ϫ5.05 (each m, 1 H ϩ 1 H, 3ЈCH2); 5.26 (br. s, 1 H, NH);
5.67Ϫ5.83 (m, 1 H, 2ЈCH); 6.09Ϫ6.12 (m, 1 H, 2CH) ppm. 13C
NMR (75 MHz, CDCl3): δ ϭ 22.4 (5CH2); 22.7 [iPr(CH3)2]; 27.5,
S(CO)NHMe
Ϫ
C2H4}ϩ]; 57 (44) [MeNCOϩ]. C9H15NOS
(185.29): calcd. C 58.34, H 8.16, N 7.56; found C 58.51, H 8.03,
N 7.44.
S-(3-Methylcyclohex-1-enyl) N-Methylmonothiocarbamate (19b):
Yields and stereospecificities are given in Table 4. M.p. 87 °C (EE/ 32.3 (4CH2/6CH2); 37.2 (3CH); 39.8 (1ЈCH2); 43.6 (iPrCH); 116.5
2982 Eur. J. Org. Chem. 2002, 2970Ϫ2988

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
(3ЈCH2); 126.6 (1C); 136.2 (2ЈCH); 143.3 (2CH); 165.4 (CϭO)
Ϫ PhCH3}ϩ]; 70 (66); 42 (27). C17H23NOS (289.44): calcd. C 70.55,
ppm. IR (KBr): ν˜ ϭ 3288 s [ν(NϪH)], 3079 m, 3024 m, 2978 s, H 8.01, N 4.84; found C 70.63, H 8.10, N 4.75.
2967 s, 2928 s, 2862 m, 2847 m, 1648 s [ν(CϭO)], 1620 s, 1523 s
Thiocarbamate rac-15 was methylated on
a 100-mg scale
[δ(NϪH)], 1467 m, 1437 s, 1386 m, 1365 m, 1317 m, 1218 s, 1125
(0.47 mmol) according to General Procedure C; yields are given in
Table 6. Performance of the reaction with (S)-15 (100 mg,
0.47 mmol, 91% ee, e.r. ϭ 95.5:4.5) in THF furnished (ϩ)-(R)-26
(22 mg, 97 µmol, 21%) with 87% ee (e.r. ϭ 93.5:6.5; 96% stereospec-
ificity) and thiocarbamate (ϩ)-(R)-27 (52 mg, 0.23 mmol, 49%)
with 88% ee (e.r. ϭ 94:6; 97% stereospecificity) both as colorless
crystals.
m, 994 m, 913 s, 869 s, 812 s, 699 w, 611 m cmϪ1. GC-MS (EI
[70 eV]): m/z (%) ϭ 239 (1) [Mϩ]; 198 (2) [{M Ϫ allyl}ϩ]; 154 (12)
[{M Ϫ iPrNCO}ϩ]; 121 (9) [{M Ϫ S(CO)NH-iPr}ϩ]; 113 (100)
[McLafferty {M Ϫ iPrNCO Ϫ allyl}ϩ]; 79 (51) [{M Ϫ S(CO)NH-
iPr Ϫ propene}ϩ]; 77 (12) [Phϩ]; 70 (56); 42 (22); 41 (21).
C13H21NOS (239.38): calcd. C 65.23, H 8.84, N 5.85; found C
65.25, H 8.97, N 5.82.
S-(1-Methylcyclohept-2-enyl) N-Isopropylmonothiocarbamate (26):
M.p. 95 °C (Et2O/PE for rac-26); m.p. 96 °C [EE/cyclohexane for
(ϩ)-(R)-26 at 87% ee (e.r. ϭ 93.5:6.5)]. Rf ϭ 0.36 (Et2O/PE, 1:3).
tr (HP 1701) ϭ 18.9 min; tr (DEX γ-225, 93 °C) ϭ 888/894 min.
(R)-26: [α]2D0 ϭ ϩ170 [c ϭ 1.22, CHCl3, at 87% ee (e.r. ϭ 93.5:6.5)].
1H NMR (400 MHz, CDCl3): δ ϭ 1.13 [d, 3J ϭ 6.6 Hz, 6 H,
iPr(CH3)2]; 1.66 (s, 3 H, 1-CH3); 1.38Ϫ1.50, 1.67Ϫ1.81, 1.82Ϫ1.94,
2.07Ϫ2.17, 2.20Ϫ2.30, 2.32Ϫ2.40 (each m, 1 H ϩ 3 H ϩ 1 H ϩ 1
H ϩ 1 H ϩ 1 H, 4CH2/5CH2/6CH2/7CH2); 3.99 (ψ-oct, 1 H,
S-(1-Benzylcyclohex-2-enyl) N-Isopropylmonothiocarbamate (20d):
Benzylations were carried out by General Procedure C; yields and
stereospecificities are given in Table 5. M.p. 106 °C (EE/cyclohex-
ane for rac-20d); m.p. 99 °C [Et2O/PE for (ϩ)-(S)-20d at 92% ee
(e.r. ϭ 96:4)]. Rf ϭ 0.37 (Et2O/PE, 1:3); Rf ϭ 0.66 (EE/cyclohexane,
1:3). tr (HP 1) ϭ 20.0 min; tr (ChiraGrohm 1 (2 ϫ 60 mm), iPrOH/
nhexane, 1:200, 0.10 mL/min) ϭ 9/11 min. (S)-20d: [α]2D0 ϭ ϩ81
[c ϭ 0.43, CHCl3, at 92% ee (e.r. ϭ 96:4)]. 1H NMR (300 MHz,
CDCl3): δ ϭ 1.17 (d, 3J ϭ 6.6 Hz, 3 H, iPrCH3); 1.18 (d, 3J ϭ
6.6 Hz, 3 H, iPrCH3Ј); 1.54Ϫ1.67, 1.73Ϫ2.08, 2.16Ϫ2.24 (each m,
1 H ϩ 4 H ϩ 1 H, 4CH2/5CH2/6CH2); 3.34 (s, 2 H, 1ЈCH2); 4.04
(ψ-oct, 3J ϭ 6.5 Hz, 1 H, iPrCH); 5.16 (br. d, 1 H, NH); 5.78 (dψ-
3
iPrCH); 5.12 (br. s, 1 H, NH); 5.62 (d, J ϭ 11.6 Hz, 1 H, 2CH);
3
3
5.73 (ddd, J3,4CH ϭ 6.8, J3,4CHЈ ϭ 5.1 Hz, 1 H, 3CH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 22.9 [iPr(CH3)2]; 26.0, 27.4, 27.9
(5CH2/6CH2/7CH2); 30.8 (1-CH3); 38.8 (4CH2); 43.1 (iPrCH); 55.8
(1C); 132.5 (2CH); 137.0 (3CH) ppm. IR (KBr): ν˜ ϭ 3297 s
[ν(NϪH)], 3014 w, 2968 s, 2927 s, 2874 m, 2856 m, 1644 s [ν(Cϭ
O)], 1522 s [δ(NϪH)], 1453 m, 1385 w, 1367 w, 1316 w, 1212 s,
1167 m, 1227 w, 1102 w, 951 w, 871 m, 814 s, 778 w, 706 w, 688 w,
610 m cmϪ1. GC-MS (EI [70 eV]): m/z (%) ϭ 227 (3) [Mϩ]; 142 (5)
[{M Ϫ iPrNCO}ϩ]; 120 (11) [HS(COH)NH-iPrϩ]; 109 (100) [{M
Ϫ S(CO)NH-iPr}ϩ]; 92 (12); 79 (10); 67 (46). C12H21NOS (227.37):
calcd. C 63.39, H 9.31, N 6.16; found C 63.44, H 9.35, N 5.97.
3
3
t, J2,3 ϭ 10.0, J3,4 ϭ 3 Hz, 1 H, 3CH); 5.86 (dm, 1 H, 2CH);
7.16Ϫ7.31 (m, 5 H, PhCH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
19.0 (5CH2); 22.8, 22.9 (iPrCH3/iPrCH3Ј); 24.7 (4CH2); 33.1
(6CH2); 43.2 (iPrCH); 45.9 (1ЈCH2); 54.6 (1C); 126.4 (pPhCH);
127.6 (mPhCH); 129.7 (3 CH); 130.6 (2CH); 131.1 (oPhCH); 137.5
(PhC) ppm. IR (KBr): ν˜ ϭ 3315 s [ν(NϪH)], 3028 m, 2971 s, 2932
s, 2874 w, 2860 w, 1641 s [ν(CϭO)], 1623 m, 1516 s [δ(NϪH)], 1455
m, 1366 w, 1214 s, 1162 m, 1126 w, 919 w, 899 w, 876 m, 813 s, 765
m, 730 m, 707 s, 630 m cmϪ1. MS (EI [70 eV]): m/z (%) ϭ 289 (16)
[Mϩ]; 204 (4) [{M Ϫ iPrNCO}ϩ]; 198 (12) [{M Ϫ Bn}ϩ]; 171 (68)
[{M Ϫ S(CO)NH-iPr}ϩ]; 170 (46) [{M Ϫ HS(CO)NH-iPr}ϩ]; 155
(6); 141 (9); 129 (21); 113 (86) [{M Ϫ iPrNCO Ϫ Bn}ϩ]; 91 (100)
S-(3-Methylcyclohept-1-enyl) N-Isopropylmonothiocarbamate (27):
M.p. 85 °C (Et2O/PE for rac-27); m.p. 81 °C [EE/cyclohexane for
(ϩ)-(R)-27 at 88% ee (e.r. ϭ 94:6)]. Rf ϭ 0.25 (Et2O/PE, 1:3). tr
(HP 1701) ϭ 19.9 min; tr (DEX β-225, 135 °C) ϭ 170/177 min. (R)-
27: [α]2D0 ϭ ϩ15.5 [c ϭ 0.97, CHCl3, at 88% ee (e.r. ϭ 94:6)]. 1H
ϩ
[C7H7 (tropylium)]; 79 (37) [{M Ϫ HS(CO)NH-iPr Ϫ Bn}ϩ]; 77
(13) [Phϩ]; 70 (15). HR-MS (EI [70 eV]): C17H23NOS (289.44):
calcd. 289.15002; found 289.14911.
3
NMR (400 MHz, CDCl3): δ ϭ 1.04 (d, J ϭ 7.1 Hz, 3 H, 3-CH3);
1.14 [d, 3J ϭ 6.5 Hz, 6 H, iPr(CH3)2]; 1.25Ϫ1.38, 1.44Ϫ1.64,
1.68Ϫ1.77, 1.87Ϫ1.96, 2.37Ϫ2.49, 2.55Ϫ2.64 (each m, 1 H ϩ 3 H
ϩ 1 H ϩ 1 H ϩ 2 H ϩ 1 H, 3CH/4CH2/5CH2/6CH2/7CH2); 4.01
(br. s, 1 H, iPrCH); 5.22 (br. s, 1 H, NH); 6.03Ϫ6.06 (m, 1 H,
2CH) ppm. 13C NMR (90 MHz, CDCl3): δ ϭ 22.7, 22.8 [3-CH3/
iPr(CH3)2]; 26.4, 30.3, 35.0 (4CH2/5CH2/6CH2); 35.4 (3CH); 37.7
(7CH2); 43.6 (iPrCH); 131.8 (1C); 149.9 (2CH) ppm. IR (KBr):
ν˜ ϭ 3305 s [ν(NϪH)], 2976 m, 2957 m, 2920 s, 2874 w, 2848 m,
1652 s [ν(CϭO)], 1620 w, 1516 s [δ(NϪH)], 1455 m, 1383 w, 1361
w, 1337 w, 1331 w, 1208 s, 1167 m, 1150 w, 1135 w, 966 w, 869 m,
809 s, 704 w, 622 m cmϪ1. MS (EI [70 eV]): m/z (%) ϭ 227 (6) [Mϩ];
142 (63) [McLafferty {M Ϫ iPrNCO}ϩ]; 127 (14) [McLafferty {M
Ϫ iPrNCO Ϫ CH3}ϩ]; 109 (100) [{M Ϫ S(CO)NH-iPr}ϩ]; 92 (18);
79 (26); 67 (49); 57 (56); 55 (44). C12H21NOS (227.37): calcd. C
63.39, H 9.31, N 6.16; found C 63.17, H 9.10, N 6.01.
S-(3-Benzylcyclohex-1-enyl) N-Isopropylmonothiocarbamate (21d):
Benzylations were carried out by General Procedure C; yields and
stereospecificities are given in Table 5. M.p. 93 °C (EE/cyclohexane
for rac-21d); m.p. 105 °C [Et2O/PE for (ϩ)-(S)-21d at 92% ee (e.r. ϭ
96:4)]. Rf ϭ 0.24 (Et2O/PE, 1:3); Rf ϭ 0.57 (EE/cyclohexane, 1:3).
tr (HP 1) ϭ 21.0 min; tr (ChiraGrohm 4 (2 ϫ 60 mm), iPrOH/nhex-
ane, 1:200, 0.10 mL/min) ϭ 14/19 min. (S)-21d: [α]2D0 ϭ ϩ22.1 [c ϭ
1.08, CHCl3, at 92% ee (e.r. ϭ 96:4)]. 1H NMR (300 MHz, CDCl3):
3
δ ϭ 1.16 [d, J ϭ 6.6 Hz, 6 H, iPr(CH3)2]; 1.19Ϫ1.32, 1.55Ϫ1.89,
2.24Ϫ2.38, 2.50Ϫ2.72 (each m, 1 H ϩ 3 H ϩ 2 H ϩ 3 H, 3CH/
3
4CH2/5CH2/6CH2/1ЈCH2); 4.01 (ψ-oct, J ϭ 6.5 Hz, 1 H, iPrCH);
5.23 (br. d, 1 H, NH); 7.09Ϫ7.23 (m, 1 H, 2CH); 7.16Ϫ7.31 (m, 3
H, oPhCH/pPhCH); 7.28 (ψ-t, 2 H, mPhCH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 22.4 (5CH2); 22.7 [iPr(CH3)2]; 27.7, 32.4
(4CH2/6CH2); 39.3 (3CH); 41.9 (1ЈCH2); 43.6 (iPrCH); 126.0
(pPhCH); 128.3 (mPhCH); 128.7 (1C); 129.1 (oPhCH); 140.0
(PhC); 143.0 (2CH); 165.4 (CϭO) ppm. IR (KBr): ν˜ ϭ 3289 s
[ν(NϪH)], 3023 m, 2973 s, 2933 s, 2908 s, 2860 m, 2848 m, 1657 s
[ν(CϭO)], 1624 s, 1600 m, 1524 s [δ(NϪH)], 1500 s, 1453 m, 1445
m, 1367 m, 1315 m, 1216 s, 1172 m, 1156 m, 1134 m, 874 s, 814 s,
Hydroxyalkylations. General Procedure D: Addition to aldehydes
and ketones basically followed General Procedure C, but an excess
of carbonyl compound (1.5Ϫ25 equiv.) was employed as elec-
trophile.
rac-S-[3-(1-Hydroxybenzyl)cyclohex-1-enyl]
N-Isopropylmonothi-
742 s, 696 s, 624 s cmϪ1. GC-MS (EI [70 eV]): m/z (%) ϭ 289 (0.5) ocarbamate (rac-21e): Addition to 1.5 equiv. of benzaldehyde for
[Mϩ]; 204 (10) [{M Ϫ iPrNCO}ϩ]; 198 (3) [{M Ϫ Bn}ϩ]; 171 (2)
19 h at Ϫ78 °C by General Procedure D produced a viscous oil,
[{M Ϫ S(CO)NH-iPr}ϩ]; 130 (26); 113 (100) [{M Ϫ iPrNCO Ϫ which was subjected to FCC (SiO2, gradient Et2O/PE). Separation
Bn}ϩ]; 91 (43) [C7H7 (tropylium)]; 79 (49) [{M Ϫ S(CO)NH-iPr of diastereomeric adducts syn-rac-21e and anti-rac-21e by simple
ϩ
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2983

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
FULL PAPER
FCC was insufficient, the isolated mixture of diastereomers showed
d.r. ϭ 55:45 (1.23:1; syn/anti). HPLC provided a sample of almost
diastereomerically pure syn-rac-21e.
(3) [{M Ϫ iPr}ϩ]; 199 (71) [McLafferty {M Ϫ iPr-CHO}ϩ]; 413
(8); 120 (33) [HS(COH)NH-iPrϩ]; 114 (94); 113 (81); 81 (100)
[McLafferty {M Ϫ iPrϪCHO Ϫ S(CO)NH-iPr }ϩ]; 79 (59) [{M Ϫ
iPrϪCH2OH Ϫ S(CO)NH-iPr}ϩ]; 77 (12) [Phϩ]; 55 (26). MS (ESI
{MeOH/CHCl3}, [1.33 kV, 42 V], ESϩ): m/z (%) ϭ 294 (100) [M
ϩ Naϩ]; 272 (20) [M ϩ Hϩ]. HR-MS (ESI [MeOH/CHCl3], ESϩ):
C14H25NO2S (271.42): [M ϩ Hϩ] calcd. 272.1684; found 272.1661;
[M ϩ Naϩ] calcd. 294.1504; found 294.1494.
Adduct syn-21e: Rf ϭ 0.25 (Et2O/PE, 1:1). 1H NMR (400 MHz,
CDCl3): δ ϭ 1.16 [d, 3J ϭ 6.5 Hz, 6 H, iPr(CH3)2]; 1.43Ϫ1.62,
1.80Ϫ1.89, 2.22Ϫ2.29, 2.67Ϫ2.75 (each m, 3 H ϩ 1 H ϩ 2 H ϩ 1
H, 3CH/4CH2/5CH2/6CH2); 2.65 (br. s, 1 H, OH); 4.03 (ψ-oct, 1
3
H, iPrCH); 4.78 (d, J3,1Ј ϭ 5.0 Hz, 1 H, 1ЈCH); 5.43 (br. s, 1 H,
NH); 6.07 (s, 1 H, 2CH); 7.24Ϫ7.30, 7.34Ϫ7.38 (each m, 1 H ϩ 4 Adduct anti-21f: Rf ϭ 0.26 (Et2O/PE, 1:1). 1H NMR (300 MHz,
H, PhCH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 21.7, 22.3 CDCl3): δ ϭ 0.82 (d, 3J ϭ 8.8 Hz, 3 H, 3ЈCH3); 0.94 (d, 3J ϭ
(4CH2/5CH2); 22.7/22.8 [iPr(CH3)2]; 32.7 (6CH2); 43.9 (iPrCH);
8.7 Hz, 3 H, 2Ј-CH3); 1.12/1.13 [d, 3J ϭ 6.6 Hz, 6 H, iPr(CH3)2];
45.2 (3CH); 76.2 (1ЈCH); 126.2 (PhCH); 127.4 (pPhCH); 128.2 1.41Ϫ1.94, 2.22Ϫ2.29 (each m, 6 H ϩ 2 H, OH/4CH2/5CH2/6CH2/
(PhCH); 131.0 (1C); 141.6 (2CH); 142.3 (PhC); 165.4 (CϭO) ppm. 2ЈCH); 2.44Ϫ2.55 (m, 1 H, 3 CH); 3.13 (dψ-t, 3J1Ј,2Ј ϭ 6.7, 3J1Ј,3 ϭ
IR (KBr): ν˜ ϭ 3494 s [ν(OϪH)], 3316 s [ν(NϪH)], 3062 w, 3030 w, 4.9 Hz, 1 H, 1ЈCH); 4.00 (ψ-oct, 1 H, iPrCH); 5.58 (br. s, 1 H,
3
2972 s, 2933 s, 2867 m, 1653 s [ν(CϭO)], 1525 s [δ(NϪH)], 1497 s, NH); 6.27 (d, J ϭ 1.9 Hz, 1 H, 2CH) ppm. 13C NMR (100 MHz,
1453 s, 1388 w, 1369 w, 1319 w, 1207 s, 1168 m, 1190 w, 1068 m,
CDCl3): δ ϭ 17.6 (3ЈCH3); 19.6 (2Ј-CH3); 22.7 [iPr(CH3)2]; 22.8,
1047 m, 1027 m, 1005 m, 871 m, 811 m, 763 m, 702 s cmϪ1. MS 25.7 (4CH2/5CH2); 31.0 (2ЈCH); 32.6 (6CH2); 40.3 (3CH); 43.7
(EI [70 eV]): m/z (%) ϭ 287 (0.5) [{M Ϫ H2O}ϩ]; 244 (0.5) [{M Ϫ (iPrCH); 80.1 (1ЈC); 130.7 (1C); 140.3 (2CH); 165.6 (CϭO).
H2O Ϫ iPr}ϩ]; 220 (3) [McLafferty {M Ϫ iPrNCO}ϩ]; 199 (80)
C14H25NO2S (271.42): calcd. C 61.95, H 9.28, N 5.16; found C
[McLafferty {M Ϫ PhϪCHO}ϩ]; 120 (24) [HS(COH)NH-iPrϩ]; 61.85, H 9.34, N 5.08.
114 (49); 113 (100); 107 (55) [PhϪCHOHϩ]; 81 (47) [McLafferty
S-[3-(1-Hydroxy-1-methylethyl)cyclohex-1-enyl] N-Isopropylmono-
{M Ϫ PhϪCHO Ϫ S(CO)NH-iPr}ϩ]; 79 (84) [{M Ϫ BnOH Ϫ
S(CO)NH-iPr}ϩ]; 77 (35) [Phϩ]; 60 (22). HR-MS (ESI [MeOH/
CHCl3], ESϩ): C17H23NO2S (305.44): [M ϩ Hϩ] calcd. 306.1528;
found 306.1527; [M ϩ Naϩ] calcd. 328.1347; found 328.1379.
thiocarbamate (21g): Hydroxyalkylations were carried out accord-
ing to General Procedure D; yields and stereospecificities are given
in Table 8. M.p. 86 °C (EE/cyclohexane for rac-21g); (Ϫ)-(R)-21g
was isolated as a resin-like compound. Rf ϭ 0.17 (Et2O/PE, 2:1);
Adduct anti-21e:[66] Rf ϭ 0.23 (Et2O/PE, 1:1). 1H NMR (300 MHz, Rf ϭ 0.30 (EE/cyclohexane, 1:1). tr (HP 1) ϭ 17.7 min; tr (DEX β-
CDCl3): δ ϭ 1.17/1.18 [d, 3J ϭ 6.6 Hz, 6 H, iPr(CH3)2]; 1.42Ϫ1.70,
1.82Ϫ1.93, 2.17Ϫ2.35, 2.60Ϫ2.77 (each m, 3 H ϩ 1 H ϩ 2 H ϩ 2
225, 160 °C) ϭ 156/161 min. (R)-21g: [α]2D0 ϭ Ϫ16.0 [c ϭ 0.775,
CHCl3, at 73% ee (e.r. ϭ 86.5:13.5)]. 1H NMR (300 MHz, CDCl3):
3
H, OH/3CH/4CH2/5CH2/6CH2); 4.03 (ψ-oct, 1 H, iPrCH); 4.59 (d, δ ϭ 1.12 [d, J ϭ 6.6 Hz, 6 H, iPr(CH3)2]; 1.16 (s, 3 H, 1Ј-CH3);
3J ϭ 5.5 Hz, 1 H, 1ЈCH); 5.49 (br. s, 1 H, NH); 6.28 (d, 3J ϭ 1.22 (s, 3 H, 2ЈCH3); 1.26Ϫ1.39, 1.50Ϫ1.65, 1.75Ϫ1.93, 2.20Ϫ2.34
2.0 Hz, 1 H, 2CH); 7.23Ϫ7.39 (m, 5 H, PhCH) ppm. 13C NMR
(each m, 1 H ϩ 1 H ϩ 3 H ϩ 3 H, OH/3CH/4CH2/5CH2/6CH2);
(75 MHz, CDCl3): δ ϭ 22.6 (4CH2); 22.7 [iPr(CH3)2]; 25.4 (5CH2); 3.98 (ψ-oct, 1 H, iPrCH); 5.46 (br. d, 1 H, NH); 6.30 (br. s, 1 H,
1
3
32.6 (6CH2); 43.8 (iPrCH); 45.0 (3CH); 77.1 (1ЈCH); 126.0 (PhCH); 2CH). H NMR (300 MHz, C6D6); δ ϭ 0.84 (d, J ϭ 6.5 Hz, 3 H,
127.3 (pPhCH); 128.3 (PhCH); 130.8 (1C); 139.7 (2CH); 143.3
(PhC); 165.5 (CϭO).
iPrCH3); 0.85 (d, 3J ϭ 6.5 Hz, 3 H, iPrCH3Ј); 1.13 (s, 3 H, 1Ј-CH3);
1.14 (s, 3 H, 2ЈCH3); 1.42 (br. s, 1 H, OH); 1.24Ϫ1.37, 1.51Ϫ1.68,
1.75Ϫ1.85, 2.14Ϫ2.22, 2.40Ϫ2.59 (each m, 1 H ϩ 2 H ϩ 1 H ϩ 1
H ϩ 2 H, 3CH/4CH2/5CH2/6CH2); 4.01 (ψ-oct, 1 H, iPrCH); 4.91
(br. s, 1 H, NH); 6.60Ϫ6.63 (m, 1 H, 2CH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 22.8 [iPr(CH3)2]; 23.1, 23.3 (4CH2/5CH2);
26.5 (1Ј-CH3); 28.4 (2ЈCH3); 32.3 (6CH2); 43.7 (iPrCH); 48.7
(3CH); 72.8 (1ЈC); 130.4 (1C); 140.6 (2CH); 165.6 (CϭO) ppm. IR
(KBr): ν˜ ϭ 3404 s [ν(OϪH)], 3257 s [ν(NϪH)], 3040 w, 2972 s,
2948 s, 2935 s, 2877 w, 2855 m, 1646 s [ν(CϭO)], 1620 m, 1532 s
[δ(NϪH)], 1456 m, 1379 m, 1368 m, 1268 w, 1215 s, 1135 m, 932
w, 906 m, 874 m, 812 m, 640 m cmϪ1. MS (EI [70 eV]): m/z (%) ϭ
242 (2) [{M Ϫ CH3}ϩ]; 211 (1) [{M Ϫ iPr}ϩ]; 199 (59) [McLafferty
{M Ϫ acetone}ϩ]; 172 (2) [{M Ϫ iPrNCO}ϩ]; 171 (2) [{M Ϫ
CONH-iPr}ϩ]; 157 (7) [{M Ϫ iPrNCO Ϫ CH3}ϩ]; 139 (5) [{M Ϫ
S(CO)NH-iPr}ϩ]; 120 (36) [HS(COH)NH-iPrϩ]; 114 (53); 81 (95)
[McLafferty {M Ϫ acetone Ϫ S(CO)NH-iPr}ϩ]; 79 (41) [{M Ϫ
CH3CHOHCH3 Ϫ S(CO)NH-iPr }ϩ]; 59 (100) [CH3COHCH3ϩ].
MS (ESI {MeOH/CHCl3}, ESϩ): m/z (%) ϭ 537 (30) [{2 ϫ M ϩ
Na}ϩ]; 280 (100) [M ϩ Naϩ]; 258 (12) [M ϩ Hϩ]. C13H23NO2S
(257.39): calcd. C 60.66, H 9.01, N 5.44; found C 60.81, H 8.93,
N 5.34.
rac-S-[3-(1-Hydroxy-2-methylpropyl)cyclohex-1-enyl] N-Isopropyl-
monothiocarbamate (rac-21f): Addition to 1.5 equiv. of 2-methyl-
propanal for 14 h at Ϫ78 °C according to General Procedure D
produced a viscous syrup. Diastereomeric adducts syn-rac-21f and
anti-rac-21f were separated by FCC (SiO2, gradient Et2O/PE)
yielding crystallizing, resin-like compounds. 1H NMR on the crude
product established d.r. ϭ 55:45 (1.20:1; syn/anti), in good agree-
ment with the ratio of 54:46 (1.16:1; syn/anti) of the isolated ad-
ducts. Crystals of the adduct syn-rac-21f suitable for X-ray struc-
ture analysis were grown by diffusion of PE into a solution of syn-
rac-21f in Et2O.
Adduct syn-21f: M.p. 123 °C (Et2O/PE). Rf ϭ 0.33 (Et2O/PE, 1:1).
1H NMR (300 MHz, CDCl3): δ ϭ 0.87 (d, 3J ϭ 6.7 Hz, 3 H,
3ЈCH3); 0.99 (d, 3J ϭ 6.6 Hz, 3 H, 2Ј-CH3); 1.12/1.13 [d, 3J ϭ
6.6 Hz, 6 H, iPr(CH3)2]; 1.44Ϫ1.92, 2.16Ϫ2.32 (each m, 5 H ϩ 3
H, OH/4CH2/5CH2/6CH2/2ЈCH); 2.49Ϫ2.58 (m, 1 H, 3CH); 3.25
3
3
(dψ-t, J1Ј,2Ј ϭ 8.3, J1Ј,3 ϭ 3.7 Hz, 1 H, 1ЈCH); 4.00 (ψ-oct, 1 H,
iPrCH); 5.48 (br. s, 1 H, NH); 6.00Ϫ6.03 (m, 1 H, 2CH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 18.9 (3ЈCH3); 19.1 (2Ј-CH3); 20.3,
22.5 (4CH2/5CH2); 22.7 [iPr(CH3)2]; 30.4 (2ЈCH); 32.7 (6CH2); 40.7
(3CH); 43.8 (iPrCH); 79.3 (1ЈC); 130.3 (1C); 143.3 (2CH); 165.5
(CϭO) ppm. IR (KBr): ν˜ ϭ 3436 s [ν(OϪH)], 3244 s [ν(NϪH)],
3035 w, 2973 s, 2955 s, 2939 s, 1930 s, 2871 m, 1653 s [ν(CϭO)],
1534 s [δ(NϪH)], 1467 m, 1455 m, 1443 m, 1391 m, 1366 m, 1323
Acetone Adducts of Thiocarbamate 14a: Hydroxyalkylations were
carried out according to General Procedure D; yields and stereo-
specificities are given in Table 8.
S-[1-(1-Hydroxy-1-methylethyl)cyclohex-2-enyl]
N-Methylmono-
w, 1217 s, 1168 m, 1130 m, 1072 m, 1004 m, 984 m, 891 m, 813 m, thiocarbamate (18g): M.p. 146 °C (Et2O/PE for rac-18g). Rf ϭ 0.25
1
642 w, 533 w cmϪ1. MS (EI [70 eV]): m/z (%) ϭ 271 (1) [Mϩ]; 228
(EE/cyclohexane, 1:1). H NMR (300 MHz, CDCl3): δ ϭ 1.20 (s,
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2984

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
3 H, 1Ј-CH3); 1.37 (s, 3 H, 2ЈCH3); 1.63Ϫ1.80, 1.83Ϫ2.21 (each m,
2 H ϩ 5 H, OH/4CH2/5CH2/6CH2); 2.81 (d, 3J ϭ 4.9 Hz, 3 H,
iPrCH3Ј); 1.11Ϫ1.88, 2.16Ϫ2.25, 2.44Ϫ2.52 (each m, 15 H ϩ 1 H
ϩ 2 H, OH/3CH/4CH2/5CH2/6CH2/2ЈCH2/3ЈCH2/4ЈCH2/5ЈCH2/
6ЈCH2); 4.01 (ψ-oct, 1 H, iPrCH); 4.96 (br. d, 1 H, NH); 6.56Ϫ6.59
3
4
NϪCH3); 5.89 (br. s, 1 H, NH); 5.64 (dd, J2,3 ϭ 10.1, J2,4
ϭ
2.0 Hz, 1 H, 2CH); 5.82Ϫ5.88 (dm, 1 H, 3CH) ppm. 13C NMR (m, 1 H, 2CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 21.93, 21.96,
(75 MHz, CDCl3): δ ϭ 19.1 (1Ј-CH3/2ЈCH3); 24.8, 26.3 (4CH2/ 22.2 (3ЈCH2/4ЈCH2/5ЈCH2); 22.7 [iPr(CH3)2]; 23.1, 25.7 (4CH2/
5CH2); 27.7 (NϪCH3); 29.2 (6CH2); 65.3 (1C); 76.6 (1ЈC); 126.7 5CH2); 32.5 (6CH2); 34.2, 35.7 (2ЈCH2/6ЈCH2); 43.6 (iPrCH); 47.2
(2CH); 131.1 (3CH); 167.2 (CϭO) ppm. IR (KBr): ν˜ ϭ 3352 s
(3CH); 73.2 (1ЈC); 130.5 (1C); 140.6 (2CH); 165.5 (CϭO) ppm. IR
[ν(OϪH)], 3291 s [ν(NϪH)], 2979 s, 2958 m, 2940 s, 2861 w, 2856 (KBr): ν˜ ϭ 3458 s [ν(OϪH)], 3270 s [ν(NϪH)], 2970 m, 2929 s,
w, 1629 s [ν(CϭO)], 1504 s [δ(NϪH)], 1462 m, 1437 m, 1409 m, 2856 m, 1654 s [ν(CϭO)], 1524 s [δ(NϪH)], 1447 m, 1419 w, 1386
1382 w, 1366 w, 1218 s, 1164 m, 1064 m, 1064 w, 1006 w, 963 m, w, 1365 w, 1319 w, 1279 w, 1215 s, 1167 w, 1129 w, 957 m, 874 w,
920 w, 890 m, 825 m, 791 m, 735 w, 679 m, 592 m cmϪ1. MS (EI
813 w, 539 w cmϪ1. MS (EI [70 eV]): m/z (%) ϭ 199 (27) [McLaf-
[70 eV]): m/z (%) ϭ 229 (2) [Mϩ]; 211 (6) [{M Ϫ H2O}ϩ]; 171 (73) ferty {M Ϫ cyclohexanone}ϩ]; 171 (3) [McLafferty ϩ retro
[McLafferty {M DielsϪAlder {M cyclohexanone
acetone}ϩ]; 154 (12); 139 (28) [{M C2H4}ϩ]; 120 (34)
SCONHMe}ϩ]; 114 (26); 113 (28); 92 (94) [HS(HO)CNHMeϩ]; 81 [HS(COH)NH-iPrϩ]; 114 (36); 99 (51) [cC6H10OHϩ]; 81 (100)
Ϫ
Ϫ
Ϫ
Ϫ
(100) [McLafferty {M Ϫ acetone Ϫ S(CO)NHMe}ϩ]; 79 (57) [{M [McLafferty {M Ϫ cyclohexanone Ϫ S(CO)NH-iPr }ϩ]; 79 (44)
Ϫ CH3CHOHCH3 Ϫ S(CO)NHMe}ϩ]; 59 (63) [CH3COHCH3ϩ]. [{M Ϫ cC6H11OH Ϫ S(CO)NH-iPr}ϩ]; 77 (12) [Phϩ]; 55 (26). MS
MS (ESI {MeOH/CHCl3}, [1.31 kV, 34 V], ESϩ): m/z (%) ϭ 252
(ESI {MeOH/CHCl3}, [1.32 kV, 33 V], ESϩ): m/z (%) ϭ 320 (100)
(100) [M ϩ Naϩ]; 230 (12) [M ϩ Hϩ] Ǟ {230 (105); 212 (100) [{M [M ϩ Naϩ]; 298 (8) [M ϩ Hϩ]. HR-MS (ESI [MeOH/CHCl3],
Ϫ H2O} ϩ Naϩ]; 155 (20); 139 (20); 92 (18) [HS(HO)CNHMeϩ]}.
ESϩ): C16H27NO2S (297.46): [M ϩ Hϩ]: calcd. 298.1841; found
HR-MS (ESI [MeOH/CHCl3], ESϩ): C11H19NO2S (229.34) [{2 ϫ 298.1829; [M ϩ Naϩ]: calcd. 320.1660; found 320.1674.
M} ϩ Hϩ]: calcd. 459.2351; found 459.2316; [{2 ϫ M} ϩ Naϩ]:
S-[3-(1-Hydroxy-1-phenylbenzyl)cyclohex-1-enyl] N-Isopropylmono-
thiocarbamate (21i): Hydroxyalkylations were carried out according
to General Procedure D; yields and stereospecificities are given in
calcd. 481.2171; found 481.2155 (both Coulomb dimers).
S-[3-(1-Hydroxy-1-methylethyl)cyclohex-1-enyl] N-Methylmono-
thiocarbamate (19g): Isolated as a resin-like compound. Rf ϭ 0.17 Table 8. M.p. 130 °C (Et2O/PE for rac-21i); m.p. 129 °C [Et2O/PE
(EE/cyclohexane, 1:1). tr (DEX β-225, 170 °C) ϭ 100/107 min. (S)- for (S)-21i at 23% ee (e.r. ϭ 61.5:38.5)]. Rf ϭ 0.14 (Et2O/PE, 1:3).
19g: [α]2D0 ϭ ϩ9.2 [c ϭ 1.0, CHCl3, at 63% ee (e.r. ϭ 81.5:18.5)]. tr [ChiraGrohm 2 (2 ϫ 250 mm), iPrOH/nhexane, 3:97, 0.30 mL/
1H NMR (300 MHz, CDCl3): δ ϭ 1.18 (s, 3 H, 1Ј-CH3); 1.25 (s, 3 min] ϭ 6/9 min. (S)-21i: [α]2D0 ϭ ϩ21.7 [c ϭ 1.39, CHCl3, at 23%
H, 2ЈCH3); 1.27Ϫ1.41, 1.52Ϫ1.68, 1.77Ϫ1.95, 2.22Ϫ2.36 (each m, ee (e.r. ϭ 61.5:38.5)]. 1H NMR (300 MHz, CDCl3): δ ϭ 1.13 (d,
1 H ϩ 2 H ϩ 2 H ϩ 3 H, OH/3CH/4CH2/5CH2/6CH2); 2.82 (d,
3J ϭ 6.7 Hz, 3 H, iPrCH3); 1.15 (d, 3J ϭ 7.1 Hz, 3 H, iPrCH3Ј);
1.40Ϫ1.50, 1.52Ϫ1.65, 1.78Ϫ1.89, 2.17Ϫ2.26 (each m, 2 H ϩ 1 H
3J ϭ 4.9 Hz, 3 H, NϪCH3); 5.62 (br. s, 1 H, NH); 6.32 (br. s, 1 H,
2CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 23.1, 23.3 (4CH2/ ϩ 1 H ϩ 2 H, 4CH2/5CH2/6CH2); 3.60Ϫ3.69 (m, 1 H, 3CH); 3.67
5CH2); 26.5 (1Ј-CH3); 27.9 (NϪCH3); 28.4 (2ЈCH3); 32.4 (6CH2); (s, 1 H, OH); 3.92Ϫ4.09 (m, 1 H, iPrCH); 5.21 (d, J ϭ 7.6 Hz, 1
48.6 (3CH); 72.8 (1ЈC); 130.3 (1C); 140.7 (2CH); 167.2 (CϭO)
3
3
H, NH); 5.94Ϫ5.96 (m, 1 H, 2CH); 7.13 (tt, JmPh,pPh ϭ 6.6,
ppm. IR (KBr): ν˜ ϭ 3423 s [ν(OϪH)], 3278 s [ν(NϪH)], 2981 s, 4JoPh,pPh ϭ 1.3 Hz, 1 H, pPhCH); 7.17 (tt, 1 H, pPhЈCH);
2975 s, 3952 s, 2947 s, 2861 w, 1655 s [ν(CϭO)], 1534 s [δ(NϪH)], 7.22Ϫ7.33 (m, 4 H, mPhCH/mPhЈCH); 7.51 (dm, 2 H, oPhCH);
1452 m, 1407 m, 1379 m, 1223 s, 1178 w, 1153 w, 1128 m, 1006 w, 7.62 (dm, 2 H, oPhЈCH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
932 w, 906 m, 847 w, 815 m, 624 m cmϪ1. MS (EI [70 eV]): m/z
22.7 [iPr(CH3)2]; 22.8, 22.9, 33.1 (4CH2/5CH2/6CH2); 44.1
(%) ϭ 229 (0.2) [Mϩ]; 214 (1) [{M Ϫ CH3}ϩ]; 171 (46) [McLafferty (iPrCH); 45.8 (3CH); 79.4 (1ЈCH); 125.5, 125.9 (mPhCH/
{M Ϫ acetone}ϩ]; 157 (5) [{M Ϫ MeNCO Ϫ CH3}ϩ]; 113 (23); 92
mPhЈCH); 126.2, 126.5 (pPhCH/pPhЈCH); 128.0 128.3 (oPhCH/
(61) [HS(HO)CNHMeϩ]; 81 (83) [McLafferty {M Ϫ acetone Ϫ oPhЈCH); 132.7 (1C); 140.4 (2CH); 145.5, 146.9 (PhC/PhЈC); 165.4
S(CO)NHMe}ϩ]; 79 (37) [{M
CH3CHOHCH3 (CϭO) ppm. IR (KBr): ν˜ ϭ 3451 s [ν(OϪH)], 3291 s [ν(NϪH)],
S(CO)NHMe}ϩ]; 59 (100) [CH3COHCH3ϩ]. MS (ESI {MeOH/ 3059 m, 3029 m, 2971 s, 2933 s, 2873 m, 2832 m, 1655 s [ν(CϭO)],
CHCl3}, [1.32 kV, 29 V], ESϩ): m/z (%) ϭ 268 (12) [M ϩ Kϩ]; 252
1638 s [ν(CϭCPh)], 1528 s [δ(NϪH)], 1493 s [ν(CϭCPh)], 1447 m,
Ϫ
Ϫ
(100) [M ϩ Naϩ]; 230 (22) [M ϩ Hϩ] Ǟ {230 (35); 212 (100) [{M 1388 w, 1366 w, 1321 w, 1216 s, 1168 w, 1007 m, 974 w, 909 s, 869
Ϫ H2O} ϩ Naϩ]; 155 (28); 139 (95)}. C11H19NO2S (229.34): calcd.
C 57.61, H 8.35, N 6.11; found C 57.69, H 8.23, N 6.55. HR-MS
(ESI [MeOH/CHCl3], ESϩ): [M ϩ NH4ϩ]: calcd. 247.1480; found
247.1522; [M ϩ Naϩ]: calcd. 252.1034; found 252.1072.
w, 810 m, 743 s, 728 s, 701 s, 655 w, 638 w, 539 w cmϪ1. MS (EI
[70 eV]): m/z (%) ϭ 318 (0.2) [Mϩ]; 199 (56) [McLafferty {M Ϫ
benzophenone}ϩ];
183
(100)
[PhCOHPhϩ];
120
(26)
[HS(COH)NH-iPrϩ]; 105 (95) [PhCOϩ from benzophenone]; 81
(38) [McLafferty {M Ϫ benzophenone Ϫ S(CO)NH-iPr }ϩ]; 79
(18) [{M Ϫ Ph2CHOH Ϫ S(CO)NH-iPr}ϩ]; 77 (43) [Phϩ]; 55 (26).
C23H23NO2S (381.35): calcd. C 72.40, H 7.13, N 3.67; found C
72.12, H 7.01, N 3.33.
S-[3-(1-Hydroxycyclohexyl)cyclohex-1-enyl] N-Isopropylmonothio-
carbamate (21h): Hydroxyalkylations were carried out according to
General Procedure D; yields and stereospecificities are given in
Table 8. M.p. 153 °C (Et2O/PE for rac-21h); m.p. 141 °C [Et2O/PE
for (ϩ)-(S)-21h at 90% ee (e.r. ϭ 95:5)]. Rf ϭ 0.12 (Et2O/PE, 1:1). Ni0-Catalyzed Cross-Coupling Providing Isoterpineol 28: Toluene
tr [ZWE-805 (4 ϫ 250 mm), H2O/THF/n-hexane, 1:1000:4000, (3 mL) was added to [1,2-bis(diphenylphosphanyl)ethane]nickel(II)
0.50 mL/min] ϭ 12/14 min. (S)-21h: [α]2D0 ϭ ϩ11.4 [c ϭ 1.82,
CHCl3, at 90% ee (e.r. ϭ 95:5)]. 1H NMR (300 MHz, CDCl3): δ ϭ
chloride (30 mg, 57 µmol, 15 mol %) and thiocarbamate (ϩ)-19g
(87 mg, 0.38 mmol, 63% ee, e.r. ϭ 81.5:18.5) in a Schlenk tube.
1.12 [d, 3J ϭ 6.6 Hz, 6 H, iPr(CH3)2]; 1.15Ϫ1.27, 1.30Ϫ1.65, After careful addition of methylmagnesium bromide solution
1.65Ϫ1.81, 1.83Ϫ1.94, 2.17Ϫ2.26, 2.28Ϫ2.38 (each m, 1 H ϩ 11 H (0.78 mL 2.9  in Et2O, 2.3 mmol, 6.0 equiv.) at room temp., the
ϩ 2 H ϩ 1 H ϩ 2 H ϩ 1 H, OH/3CH/4CH2/5CH2/6CH2/2ЈCH2/ gray, cloudy reaction mixture was heated to 90 °C in an oil bath
3ЈCH2/4ЈCH2/5ЈCH2/6ЈCH2); 3.99 (ψ-oct, 1 H, iPrCH); 5.56 (br. s,
for 18 h with stirring. Ether (15 mL) and aqueous HCl (7 mL, 2.0
1 H, NH); 6.30 (br. s, 1 H, 2CH). 1H NMR (300 MHz, C6D6): δ ϭ ) were added at room temp., the phases were separated, and the
0.84 (d, 3J ϭ 6.6 Hz, 3 H, iPrCH3); 0.85 (d, 3J ϭ 6.6 Hz, 3 H,
aqueous layer was extracted with ether (2 ϫ 10 mL). The combined
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2985

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
FULL PAPER
Table 9. Details of X-ray crystallographic studies
(ϩ)-(R)-14c
(Ϫ)-(S)-20b
(Ϫ)-(S)-21b
(ϩ)-(S)-21d
21g
Empirical formula
Molecular mass
Temperature
C11H19NOS
213.33
C11H19NOS
213.33
C11H19NOS
213.33
C17H23NOS
289.42
C13H23NO2S
257.38
223(2) K
223(2) K
223(2) K
223(2) K
223(2) K
˚
˚
˚
˚
˚
Wavelength
1.54178 A
1.54178 A
1.54178 A
1.54178 A
1.54184 A
¯
Crystal system,
space group
orthorhombic,
P21 (no. 4)
triclinic, P1 (no. 1)
orthorhombic,
triclinic, P1 (no. 2)
P212121 (no. 19)
P212121 (no.19)
˚
˚
˚
˚
˚
Unit cell dimensions
a ϭ 9.685(2) A
a ϭ 5.985(4) A
a ϭ 6.510(1) A, α ϭ 86.60(2)° a ϭ 9.892(6) A
a ϭ 9.891(2) A, α ϭ 83.18(1)°
˚
˚
˚
˚
˚
b ϭ 12.590(1) A
b ϭ 22.318(9) A, β ϭ 98.90(4)° b ϭ 9.076(1) A, β ϭ 88.21(2)° b ϭ 11.864(3) A
b ϭ 12.242(2) A, β ϭ 69.66(2)°
c ϭ 13.659(2) A, γ ϭ 74.94(1)°
˚
˚
˚
˚
˚
c ϭ 20.348(3) A
c ϭ 9.231(4) A
c ϭ 11.169(3) A, γ ϭ 75.08(1)° c ϭ 13.674(2) A
3
3
3
3
3
˚
˚
˚
˚
˚
Volume
2481.1(7) A
1218.2(11) A
4, 1.163 Mg/m3
2.117 mmϪ1
464
636.5(2) A
1604.8(11) A
1496.8(4) A
Z, calculated density
Absorption coefficient
F(000)
8, 1.142 Mg/m3
2.079 mmϪ1
928
2, 1.113 Mg/m3
2.026 mmϪ1
4, 1.198 Mg/m3
1.742 mmϪ1
4, 1.142 Mg/m3
1.853 mmϪ1
560
232
624
Crystal size
0.60 ϫ 0.50 ϫ 0.30 mm
0.25 ϫ 0.20 ϫ 0.20 mm
3.96Ϫ74.39°
0.50 ϫ 0.15 ϫ 0.10 mm
3.97Ϫ74.21°
0.40 ϫ 0.08 ϫ 0.05 mm
4.93Ϫ74.20°
0.45 ϫ 0.10 ϫ 0.05 mm
3.45Ϫ66.49°
θ range for data collection 4.13Ϫ74.16°
Limiting indices
Ϫ12 Յ h Յ 0, 0 Յ k Յ 15, 0 Յ h Յ 7, 0 Յ k Յ 27,
Ϫ7 Յ h Յ 8, 0 Յ k Յ 11,
Ϫ13 Յ l Յ 13
2758/2758
0 Յ h Յ 12, Ϫ14 Յ k Յ 0, Ϫ11 Յ h Յ 11, Ϫ14 Յ k Յ 14,
Ϫ25 Յ l Յ 0
2856/2856
Ϫ11 Յ l Յ 11
2811/2569
0 Յ l Յ 17
0 Յ l Յ 16
Reflections collected/
unique/observed
Max./min.
1875/1875
5528/5286
[R(int) ϭ 0.00]/2538
0.574/0.369
[R(int) ϭ 0.015]/2330
0.677/0.620
[R(int) ϭ 0.000]/2297
0.823/0.431
[R(int) ϭ 0.000]/1299
0.918/0.542
[R(int) ϭ 0.047]/2172
0.913/0.489
transmission
Refinement method
Full-matrix,
least squares on F2
Full-matrix,
least squares on F2
Full-matrix,
least squares on F2
Full-matrix,
least squares on F2
Full-matrix,
least squares on F2
Data/restraints/
parameters
2856/0/266
2569/1/266
2758/3/266
1875/0/187
5286/0/323
Goodness-of-fit on F2
Final R indices [I Ͼ 2σ(I)] R1 ϭ 0.054, wR2 ϭ 0.147 R1 ϭ 0.047, wR2 ϭ 0.123
1.062
1.039
1.086
1.007
1.023
R1 ϭ 0.050, wR2 ϭ 0.141
R1 ϭ 0.045, wR2 ϭ 0.098 R1 ϭ 0.062, wR2 ϭ 0.103
Absolute structure
parameter
0.05(4)
0.02(3)
Ϫ0.01(3)
Ϫ0.01(4)
Ϫ
Extinction coefficient
Largest diff. peak/hole
0.0020(4)
0.007(1)
0.013(2)
Ϫ
Ϫ
Ϫ3
Ϫ3
Ϫ3
Ϫ3
Ϫ3
˚
˚
˚
˚
˚
0.35/Ϫ0.33 e A
0.26/Ϫ0.33 e A
0.25/Ϫ0.27 e A
0.26/Ϫ0.39 e A
0.25/Ϫ0.31 e A
organic layers were dried with MgSO4, filtered, and concentrated
in vacuo. Subsequent FCC (47 mL SiO2; Et2O/PE, 1:3) yielded iso-
terpineol (ϩ)-28 (53 mg, 0.34 mmol, 91%) as a colorless liquid. Ab
listed in Table 9. Crystallographic data (excluding structure factors)
for the structures reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
initio calculations [aug-SV(p)/BH-LYP and others] indicated the publication no. CCDC-141924 [(ϩ)-(R)-14c], -143289 [(Ϫ)-(S)-
(S) absolute configuration for isoterpineol (ϩ)-28. Rf ϭ 0.37 (Et2O/
PE, 1:1). tr (HP 5) ϭ 7.75 min; tr (HP 1701) ϭ 10.3 min. (ϩ)-(S)-
28: [α]2D0 ϭ ϩ24.1 [c ϭ 1.10, CHCl3, (ee nd)]. 1H NMR (400 MHz,
20b], -143290 [(Ϫ)-(S)-21b], -141448 [(ϩ)-(S)-21d], and -141081
(21g). Copies of the data can be obtained free of charge on applica-
tion to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax:
CDCl3): δ ϭ 1.14 (s, 3 H, 2CH3); 1.16Ϫ1.24, 1.18 (m ϩ s, 1 H ϩ (internat.) ϩ 44-1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
3 H, nCHHЈ ϩ 1-CH3);* 1.26 (s, 1 H, OH); 1.38Ϫ1.54 (m, 1 H,
Acknowledgments
Generous support by the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie (stipend for F. M.) is grate-
fully acknowledged.
mCHHЈ);* 1.67 (s, 3 H, 3Ј-CH3); 1.72Ϫ1.98 (m, 4 H, 4ЈCH2/5ЈCH2/
6ЈCH2);* 2.05Ϫ2.16 (m, 1 H, 1ЈCH); 5.44 (br. s, 1 H, 2ЈCH); *
a definitive assignment of the position is not possible. 13C NMR
(100 MHz, CDCl3): δ ϭ 22.6, 24.3 (5ЈCH2/6ЈCH2); 24.2 (3Ј-CH3);
26.2, 27.9 (2CH3/1-CH3); 30.0 (4ЈCH2); 47.2 (1ЈCH); 73.0 (1C);
121.4 (2ЈCH); 136.9 (3ЈC). MS (EI [70 eV]): m/z (%) ϭ 154 (3)
[Mϩ]; 139 (6) [{M Ϫ CH3}ϩ]; 136 (3) [{M Ϫ H2O}ϩ]; 96 (78) [retro
ene {M Ϫ acetone}ϩ]; 81 (69) [retro ene {M Ϫ acetone Ϫ CH3}ϩ];
68 (18); 67 (16); 59 (100) [CH3COHCH3ϩ]. GC-HR-MS (EI
[70 eV]): C10H18O (154.25): [M Ϫ CH3]: calcd. 139.1123; found
139.1115; [M Ϫ H2O]: calcd. 136.1252; found 136.1287; [M Ϫ CH3
Ϫ H2O]: calcd. 121.1017; found 121.1037.
[1]
[1a]
Reviews:
2376; Angew. Chem. Int. Ed. Engl. 1997, 36, 2282.
A. Basu, D. J. Gallagher, J. S. Park, S. Thayumanavan, Acc.
D. Hoppe, T. Hense, Angew. Chem. 1997, 109,
[1b]
P. Beak,
[1c]
Chem. Res. 1996, 29, 552.
V. K. Aggarwal, Angew. Chem.
1994, 106, 185; Angew. Chem. Int. Ed. Engl. 1994, 33, 175.
W. C. Still, C. Sreekumar, J. Am. Chem. Soc. 1980, 102, 1201.
D. Hoppe, F. Hintze, P. Tebben, Angew. Chem. 1990, 102, 1457;
Angew. Chem. Int. Ed. Engl. 1990, 29, 1424.
[2]
[3]
[4]
Highly enantioenriched carbanionic species 1b, 2, and 3 are
accessible by deprotonation of the corresponding prochiral pre-
cursors with butyllithium in the presence of the enantiopure
natural diamine (Ϫ)-sparteine; see ref.[1aϪ1b]
X-ray Crystallographic Study: Data sets were collected with an
EnrafϪNonius CAD4 diffractometer. Programs used: data collec-
tion EXPRESS (Nonius B.V., 1994), data reduction MolEN (K.
Fair, EnrafϪNonius B.V., 1990), structure solution SHELXS-86
and SHELXS-97 (G. M. Sheldrick, Acta Crystallogr. 1990, A46,
467Ϫ473), structure refinement SHELXL-97 (G. M. Sheldrick,
Univ. of Göttingen, 1997), graphics MoPict 4 (M. Brüggemann,
Westfälische Wilhelms-Universität Münster, 2001). Details are
[5] [5a]
D. Hoppe, A. Carstens, T. Krämer, Angew. Chem. 1990,
[5b]
102, 1455; Angew. Chem. Int. Ed. Engl. 1990, 29, 1422.
C.
Derwing, H. Frank, D. Hoppe, Eur. J. Org. Chem. 1999, 3519.
D. Hoppe, T. Krämer, Angew. Chem. 1986, 98, 171; Angew.
Chem. Int. Ed. Engl. 1986, 25, 160.
[6]
2986
Eur. J. Org. Chem. 2002, 2970Ϫ2988

Enantioenriched α-Thioallyllithium Compounds
FULL PAPER
thiol was assigned on the basis of the order of elution of its
acetate during chromatography on cellulose triacetate; the as-
signment was made by analogy with the chromatographic
properties of substituted five- and six-membered-ring lactones.
T. Fukazawa, T. Hashimoto, Tetrahedron: Asymmetry
T. Fukazawa, Y. Shimoji, T. Hashimoto,
Tetrahedron: Asymmetry 1996, 6, 1649.
[7]
L represents a donor ligand at the lithium cation; the structures
of these ligands are omitted for the sake of clarity.
[8]
P. Beak, S. T. Kerrick, S. Wu, J. Chu, J. Am. Chem. Soc. 1994,
116, 8616.
[27] [27a]
[9a] G. A. Weissenburger, P. Beak, J. Am. Chem. Soc. 1996, 118,
[9]
[27b]
[9b]
1993, 4, 2323.
12218.
D. J. Pippel, G. A. Weissenburger, N. C. Faibish, P.
Beak, J. Am. Chem. Soc. 2001, 123, 4919.
[28] [28a]
[10]
M. Asami, T. Ishizaki, S. Inoue, Tetrahedron: Asymmetry
High configurational stability is found for N-alkyl-2-lithiopyr-
rolidines, which cannot be formed by direct deprotonation; see:
R. E. Gawley, Q. Zhang, J. Am. Chem. Soc. 1993, 115, 7515.
[28b]
1994, 5, 793.
D. Bhuniya, A. DattaGupta, V. K. Singh, J.
Org. Chem. 1996, 61, 6108. [28c] M. J. Södergren, P. G. Anders-
son, J. Am. Chem. Soc. 1998, 120, 10760.
[11] [11a] R. W. Hoffmann, T. Rühl, J. Harbach, Liebigs Ann. Chem.
[11b]
[29] [29a]
1992, 725.
H. Ahlbrecht, J. Harbach, R. W. Hoffmann, T.
K. B. Sharpless, T. R. Verhoeven, Aldrichim. Acta 1979,
[29b]
Ruhland, Liebigs Ann. 1995, 211. [11c] R. K. Dress, T. Rölle, R.
W. Hoffmann, Chem. Ber. 1995, 128, 673. [11d] R. W. Hoffmann,
R. K. Dress, T. Ruhland, A. Wenzel, Chem. Ber. 1995, 128, 861.
12, 63.
1980, 102, 5974.
T. Katsuki, K. B. Sharpless, J. Am. Chem. Soc.
[29c]
V. S. Martin, S. S. Woodard, T. Karsuki,
Y. Yamada, M. Ikeda, K. B. Sharpless, J. Am. Chem. Soc. 1981,
103, 6237.
[12] [12a] H. J. Reich, R. R. Dykstra, Angew. Chem. 1993, 105, 1489;
[12b]
[30]
Angew. Chem. Int. Ed. Engl. 1993, 32, 1469.
R. R. Dykstra, J. Am. Chem. Soc. 1993, 115, 7041.
H. J. Reich,
The maximum chirality transfer is achieved if the rearrange-
ment of enantioenriched O-ester 12b proceeds exclusively
through a cyclic transition state. We tried to impose a cyclic
transition state on the rearrangement by addition of PdII salts
in different solvents; this should produce a cationic bicyclic
transition state of the rearrangement through electrophilic ad-
dition of Pd2ϩ onto the double bond and subsequent nucleo-
philic attack of the sulfur atom on the generated carbocation.
However, a marked loss of enantioenrichment was observed,
which may result from thiocarbamate-induced reduction of
PdII to Pd0, which is known to catalyze the rearrangement
through a dissociative reaction pathway involving a stabilized
allylic cation.[21b]
[12c]
H. J.
[12d]
Reich, K. J. Kulicke, J. Am. Chem. Soc. 1995, 117, 6621.
H. J. Reich, K. J. Kulicke, J. Am. Chem. Soc. 1996, 118, 273.
R. W. Hoffmann, M. Julius, F. Chemla, T. Ruhland, G.
Frenzen, Tetrahedron 1994, 50, 6049.
[13]
[14]
W. Klute, M. Krüger, R. W. Hoffmann, Chem. Ber. 1996,
129, 633.
[15] [15a] R. W. Hoffmann, M. Julius, K. Oltmann, Tetrahedron Lett.
[15b]
1990, 31, 7419.
R. W. Hoffmann, M. Bewersdorf, Liebigs
[15c]
Ann. Chem. 1992, 643.
T. Ruhland, R. Dress, R. W.
Hoffmann, Angew. Chem. 1993, 105, 1487; Angew. Chem. Int.
[15d]
Ed. Engl. 1993, 32, 1467.
See refs.[11a,11b,11d,12a]
[31]
[32]
[16]
By General Procedure B, as given in the Exp. Sect. The same
lithiation conditions were employed for alkylations in General
Procedure C.
α-Thio- and α-seleno-substituted Grignard reagents sometimes
show markedly higher configurational stability; for example
see: α-thio: P. G. Nell, New J. Chem. 1999, 973; α-seleno; see:
ref.[14]
The given stereospecificity refers to the transmission of enanti-
oenrichment for the overall process of lithiation and elec-
trophilic substitution. We expect that lithiation should proceed
with absolute stereospecificity, in consequence the given ste-
reospecificity should result from a combination of the config-
urational stability of dilithiated species and the enantiospecific-
ity of the electrophilic substitution step.
[17] [17a] J.-M. Lehn, G. Wipff, J. Demuynck, Helv. Chim. Acta 1977,
[17b]
60, 1239.
P. v. R. Schleyer, T. Clark, A. J. Kos, G. W.
Spitznagel, C. Rohde, D. Arad, K. N. Houk, N. G. Rondan, J.
[17c]
Am. Chem. Soc. 1984, 106, 6467.
W. Zarges, M. Marsch,
K. Harms, W. Koch, G. Frenking, G. Boche, Chem. Ber. 1991,
[17d]
121, 543.
K. B. Wiberg, H. Castejon, J. Am. Chem. Soc.
For methylation of dianion 9, other Meϩ sources such as
F3CSO3Me were not applicable.
[33]
[34]
[35]
1994, 116, 10489. [17e] A. M. Elnahas, P. v. R. Schleyer, J. Com-
put. Chem. 1994, 15, 596.
[18]
This property of thiocarbamate 21b might be used to prepare
larger quantities (Ͼ 1 mmol) of high enantiomeric purity.
This can be regarded as additional evidence that inversion of
the carbanionic center in 16 (or 9 and 17) is not the rate-deter-
mining step of racemization, because the presence of an excess
of Liϩ should facilitate the inversion by an associative process
(SE2 process).
This procedure turned out to be extremely efficient for the or-
tho-lithiation of aromatic N-isopropylcarbamates, see: M.
Kauch, D. Hoppe, Can. J. Chem. 2001, 79, 1736Ϫ1746.
The absolute configurations were assigned in analogy with
methylation of cyclohexenyllithium compounds (R)-9 and (S)-
16.
B. Kaiser, D. Hoppe, Angew. Chem. 1995, 107, 344, Angew.
Chem. Int. Ed. Engl. 1995, 34, 323.
[19] [19a]
D. Hoppe, B. Kaiser, O. Stratmann, R. Fröhlich, Angew.
Chem. 1997, 109, 24, 2872; Angew. Chem. Int. Ed. Engl. 1997,
[19b]
36, 2784.
O. Stratmann, D. Hoppe, R. Fröhlich, J. Prakt.
[19c]
Chem. 2000, 342, 828.
O. Stratmann, B. Kaiser, R.
Fröhlich, O. Meyer, D. Hoppe, Chem. Eur. J. 2001, 7, 423.
F. Marr, R. Fröhlich, D. Hoppe, Org. Lett. 1999, 1, 2081.
[36]
[37]
[38]
[20]
[21] [21a]
H. Harayama, T. Kozera, M. Kimura, S. Tanaka, Y. Tam-
[21b]
aru, Chem. Lett. 1996, 543.
H. Harayama, T. Nagahama,
T. Kozera, M. Kimura, K. Fugami, S. Tanaka, Y. Tamaru,
Bull. Chem. Soc. Jpn. 1997, 70, 445.
N-Methylmonothiocarbamates are easily accessible by addition
of allylic alcohols to solid MeNCS in this way, whereas a thiol-
based synthesis would require the use of hazardous, volatile
MeNCO.
[22]
F. Marr, Dissertation, Westfälische Wilhelms-Universität
Münster, 2001, p. 91, 242.
[39] [39a]
T. Hayashi, N. Fujitaka, T. Oishi, T. Takeshima, Tetrahed-
[23] [23a]
[23b]
R. E. Hackler, T. W. Balko, J. Org. Chem. 1973, 38, 2106.
ron Lett. 1980, 21, 303. [39b] D. Hoppe, R. Hanko, A. Brönneke,
F. Lichtenberg, E. v. Hülsen, Chem. Ber. 1985, 118, 2822.
H. E. Zimmermann, M. D. Traxler, J. Am. Chem. Soc. 1957,
[23c]
T. Hayashi, Tetrahedron Lett. 1974, 15, 339.
T. Nakai,
H. Shiono, M. Okawara, Tetrahedron Lett. 1974, 15, 3625. [23d]
T. Nakai, A. Ari-Izumi, Tetrahedron Lett. 1976, 17, 2355.
Harayama reported low des for the thermal activated re-
arrangement of O-6-carvyl N-methylthiocarbamates, see
ref.[21b]
[40]
[41]
79, 1920.
[24]
[41a]
For the same reaction with carbamates (O for S) see:
D.
Hoppe, T. Krämer, Angew. Chem. 1986, 98, 171; Angew. Chem.
[41b]
Int. Ed. Engl. 1986, 25, 160.
T. Krämer, D. Hoppe, Tetra-
[25] [25a]
R. Oehrlein, R. Jeschke, B. Ernst, D. Bellus, Tetrahedron
hedron Lett. 1987, 28, 5149. [41c] D. Hoppe, O. Zschage, Angew.
Chem. 1989, 101, 67; Angew. Chem. Int. Ed. Engl. 1989, 28, 67;
correction of configuration in: O. Zschage, D. Hoppe, Tetra-
hedron 1992, 48, 5657.
[25b]
Lett. 1989, 3517.
bemeyer, R. Oehrlein, D. Bellus, Helv. Chim. Acta 1997, 80,
B. Ernst, J. Gonda, R. Jeschke, U. Nub-
[25c]
876.
10, 2511.
A. Böhme, H.-J. Gais, Tetrahedron: Asymmetry 1999,
[42]
Recent investigations employing acyclic thiocarbamates have
found a different synthetic approach to aldehyde adducts with
In refs.[25a,25b] the absolute configuration of cyclohex-2-ene-1-
[26]
Eur. J. Org. Chem. 2002, 2970Ϫ2988
2987

F. Marr, R. Fröhlich, B. Wibbeling, C. Diedrich, D. Hoppe
FULL PAPER
good diastereomeric purity; results will be published in due
course.
M. Kattannek, C. Kölmel, M. Kollwitz, K. May, C. Ochsen-
feld, H. Öhm, A. Schäfer, U. Schneider, O. Treutler, M. von
Arnim, F. Weigend, P. Weis, H. Weiss, Universität Karlsruhe,
2000.
[43]
Addition of acetone to thiobenzyllithium compound (S)-8 pro-
ceeds with only 61% stereospecificity; see ref.[19c]
H. Yamataka, Y. Kawafuji, K. Negareda, N. Miyano, T.
[52] [52a] A. D. Becke, Phys. Rev. A 1988, 38, 3098. [52b] J. P. Perdew,
Phys. Rev. B 1986, 33, 8822.
[44] [44a]
[44b]
Hanafusa, J. Org. Chem. 1989, 54, 4701.
K. S. Rein, Z.-H.
[53]
Chen, P. T. Perumal, L. Echegoyen, R. E. Gawley, Tetrahedron
Lett. 1991, 32, 1941. [44c] J. J. Eisch, Res. Chem. Intermed. 1996,
22, 145.
Similar hydrogen bonds are found in the crystals of 21b, be-
tween the NH protons and the carbonyl oxygen atoms of a
pair of molecules.
A. Schäfer, H. Horn, R. Ahlrichs, J. Chem. Phys. 1992, 97,
2571.
K. Eichkorn, O. Treutler, H. Öhm, M. Häser, R. Ahlrichs,
[54]
[45]
[46]
Chem. Phys. Lett. 1995, 240, 283.
[55]
R. Bauernschmitt, R. Ahlrichs, Chem. Phys. Lett. 1996, 256,
454.
[56]
These conditions, invented independently by Kumada and by
A. D. Becke, J. Chem. Phys. 1993, 98, 1372.
[46a]
[57]
Corriu, were applied to thiocarbamates for the first time.
F. Weigend, M. Häser, Theor. Chem. Acc. 1997, 97, 331.
[58]
K. Tamao, K. Sumitani, M. Kumada, J. Am. Chem. Soc. 1972,
94, 4374. [46b] R. J. P. Corriu, J. P. Masse, J. Chem. Soc., Chem.
Commun. 1972, 144.
((AUTHOR: The meaning of this sentence is unclear! Can it be
rephrased?))The determined experimental [α] values have been
corrected to 100% ee by assumption of a complete conservation
of enantioenrichment by derivatization of 19g with 63% ee to-
wards 28, the ee of the latter could not be detected.
[47]
[48]
For cross-coupling of primary vinyl carbamates (O for S) see:
[47a] P. Kocienski, N. Dixon, Synlett 1989, 52. [47b] P. Kocienski,
C. Barber, Pure Appl. Chem. 1990, 62, 1933.
[59] [59a]
H. Gilman, A. H. Haubein, J. Am. Chem. Soc. 1944, 66,
[59b]
The absolute configuration of sylveterpineol (ϩ)-28 was not
1515.
H. Gilman, F. K. Cartledge, J. Organomet. Chem.
known previously. [48a] J. L. Simonsen, J. Chem. Soc. 1920, 117,
1964, 2, 447. [59c] D. J. Wakefield, Organolithium Methods, Aca-
demic Press, San Diego, 1988.
[48b]
570.
J. L. Simonsen, The Terpenes, 2nd ed., Cambridge
[60]
[61]
University Press, Cambridge, 1953, vol. I.
S. C. Watson, J. F. Eastham, J. Organomet. Chem. 1967, 9, 165.
rac-Cyclohept-2-en-1-ol (rac-11) was synthesized by 1,2-reduc-
tion of cyclohept-2-en-1-one with NaBH4/CeCl3·7H2O in
MeOH at 0 °C in 71Ϫ73% yield (after FCC).
Synthesized by kinetic resolution of rac-11 with 0.6 equiv. of
(ϩ)-(2R,3R)-DIPT/TIPT/TBHP,[29] at Ϫ30 °C/6 d. The (ϩ)-
(2R,3R)-DIPT used showed Ͼ 99% op.
Determined by CPGC; tr (DEX β-120, 80 °C) ϭ 82/87 min;
the minor enantiomer was not observed for enantioenriched
(R)-11.
Rearrangement of crude O-ester (S)-12b of 68% ee (e.r. ϭ
84:16) up to 79% ee (e.r. ϭ 89.5:10.5) from carbamoylation of
(S)-10 on a 1-g scale furnished thiocarbamate (R)-14b in
77Ϫ79% yield (FCC) over two steps, showing m.p. 93 °C
(Et2O/PE).
Carbamoylation of rac-cyclohept-2-en-1-ol (rac-11, 1.22 g, 10.0
mmol) according to General Procedure A, followed by re-
arrangement of the crude carbamoylation product rac-13 by
heating for 5 h to 105Ϫ110 °C and an additional 2 h to 110
°C, produced O-ester rac-13 (90 mg, 0.41 mmol, 3.9%) and S-
ester rac-15 (1.73 g, 8.11 mmol, 81%), isolated by FCC in good
yields over two steps.
[49] [49a]
[49b]
S. Grimme, Chem. Phys. Lett. 2001, 339, 380.
P. J.
Stephens, F. J. Devlin, J. R. Cheeseman, M. J. Frisch, J. Phys.
Chem. A 2001, 105, 5356.
[50]
[62]
[63]
[64]
All quantum chemical calculations were performed with the
TURBOMOLE suite of programs.[51] The structures of the iso-
terpineol 28 were fully optimized at the density functional
(DFT) level, by employing the BP86 functional,[52] a Gaussian
AO basis of valence-triple-zeta quality including polarization
functions (TZVP),[53] and the RI-approximation for the two-
electron integrals.[54] The structures were used in subsequent
calculations of the frequency-dependent optical rotatory dis-
persion ([α]) at different radiation wavelengths. These calcula-
tions were performed in the time-dependent DFT[55] frame-
work, described in detail in ref.[49] In the TDDFT approach,
polarized split-valence basis sets [SV(P)][53] augmented with
diffuse basis functions (C, O: [1s1p1d], H: [1s1p]) and the
BHLYP hybrid density functional[56] were used. Single-point
energy calculations for three conformers of 28 were performed
at the RIMP2 level[57] of theory to assess their Boltzmann
population at room temperature, by use of aug-TZVP AO as
basis and the DFT-optimized geometries.
[65]
[51]
[66]
TURBOMOLE (Vers. 5.3): R. Ahlrichs, M. Bär, H.-P. Baron,
R. Bauernschmitt, S. Böcker, M. Ehrig, K. Eichkorn, S. Elliott,
F. Furche, F. Haase, M. Häser, H. Horn, C. Huber, U. Huniar,
Data extracted from spectra of the mixture syn-anti-21e.
Received February 6, 2002
[O02077]
2988
Eur. J. Org. Chem. 2002, 2970Ϫ2988