Palladium(0) catalyzed enantioselective rearrangement of O-allylic thiocarbamates to S-allylic thiocarbamates: Asymmetric synthesis of allylic thiols

Article abstract of DOI:10.1016/S0957-4166(99)00263-3

The Pd(0) catalyzed rearrangement of the O-allylic thiocarbamates rac- 2a, rac-2b and rac-4 in the presence of the chiral bisphosphane 5 proceeded quantitatively and gave the S-allylic thiocarbamates 6a, 6b and 7, respectively, with 91, 92 and 97% ee, res

Full text of DOI:10.1016/S0957-4166(99)00263-3

Pergamon
Tetrahedron: Asymmetry 10 (1999) 2511–2514
Palladium(0) catalyzed enantioselective rearrangement of
O-allylic thiocarbamates to S-allylic thiocarbamates:
asymmetric synthesis of allylic thiols
Achim Böhme and Hans-Joachim Gais ∗
Institut für Organische Chemie der Rheinisch-Westfälischen Technischen Hochschule Aachen, Professor-Pirlet-Straße 1,
D-52056 Aachen, Germany
Received 1 June 1999; accepted 23 June 1999
Abstract
The Pd(0) catalyzed rearrangement of the O-allylic thiocarbamates rac-2a, rac-2b and rac-4 in the presence of
the chiral bisphosphane 5 proceeded quantitatively and gave the S-allylic thiocarbamates 6a, 6b and 7, respectively,
with 91, 92 and 97% ee, respectively, in high yields. Saponification of the S-allylic thiocarbamate 7 furnished the
allylic thiol 9 with 97% ee. © 1999 Elsevier Science Ltd. All rights reserved.
The Pd(0) catalyzed allylic alkylation of sulfinates in the presence of chiral phosphanes provides an
effective means for the asymmetric synthesis of allylic aryl as well as alkyl sulfones.1–6 We have recently
described the utilization of this method for the asymmetric synthesis of allylic heteroaryl sulfides from
the corresponding thiols.7 Unfortunately, however, all attempts to extend the Pd(0) catalyzed allylation to
alkyl thiols were unsuccessful. The low reactivity of alkyl thiols in the Pd(0) catalyzed allylic alkylation
seems to be a general phenomenon.8–15 Because of the ready alkylation,16,17 arylation,18–20 heteroaryla-
tion (vide infra),16,17 and further functionalization of thiols at the S-atom,16,17 chiral allylic thiols would
be ideal starting materials for the synthesis of a broad range of chiral allylic sulfides provided that an
asymmetric synthesis of the former were available. The results of previous studies of the Pd(0)/PPh3
catalyzed rearrangement of O-allylic phosphorothionates,21 phosphonothionates,21 thioesters9,10 and
thiocarbamates18 suggested a perhaps facile asymmetric synthesis of allylic thiols by using as the
key step an enantioselective Pd(0) catalyzed rearrangement of racemic O-allylic phosphorothionates,
phosphonothionates, thioesters, or thiocarbamates to the corresponding enantiomerically enriched S-
allylic isomers.
Herein, we describe the successful realization of this concept in the case of O-allylic thiocarbamates
having a symmetrical carbon skeleton.
∗
Corresponding author. E-mail: gais@rwth-aachen.de
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00263-3

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The racemic O-allylic thiocarbamates rac-2a, rac-2b and rac-4 were synthesized in nonoptimized
yields of 73, 51 and 66%, respectively, from the racemic allylic alcohols rac-1a, rac-1b and rac-3,
respectively, and methyl isothiocyanate18 (Scheme 1).
Scheme 1.
Because of the high enantioselectivities recorded in the Pd(0) catalyzed allylic substitution of the
racemic carbonates derived from rac-1a, rac-1b and rac-3 with heteroaromatic thiols and sulfinates by
using the bisphosphane 5,2–7 we have chosen this ligand for the Pd(0) catalyzed rearrangement of rac-2a,
rac-2b and rac-4 (Scheme 2). Treatment of the O-allylic thiocarbamate rac-2a with Pd2(dba)3·CHCl3
(dba=dibenzylideneacetone) and 5 in methylene chloride at room temperature led to a quantitative
rearrangement and gave the S-allylic thiocarbamate 6a with an ee-value of 91% in 92% yield (Table 1,
entry 1). The rearrangement of rac-2b under the same conditions furnished 6b with 92% ee in 94% yield
(Table 1, entry 2).
Scheme 2.
This highly enantioselective rearrangement is not restricted to acyclic substrates. Treatment of the
cyclic thiocarbamate rac-4 with Pd2(dba)3·CHCl3 and 5 in methylene chloride after a reaction time of
3 h at room temperature delivered the S-allylic thiocarbamate 7 with an ee-value of 97% in 94% yield

A. Böhme, H.-J. Gais / Tetrahedron: Asymmetry 10 (1999) 2511–2514
2513
Table 1
Pd(0) catalyzed rearrangement of O-allylic thiocarbamates
(Table 1, entry 3). In the case of rac-4 the rearrangement could be accomplished by using 1.25 mol% of
Pd and 1.5 mol% of 5.
The ee-values of 6a, 6b and 7 were determined by GC analysis on an octakis-(2,6-di-O-pentyl-3-O-
butyryl)-γ-cyclodextrin column [rac-6a: tR (6a)=48.9 min, tR (ent-6a)=48.8 min; rac-6b: tR (6b)=50.1
min, tR (ent-6b)=49.9 min] and on an octakis-(2,3-O-dipentyl-6-O-methyl)-γ-cyclodextrin column [rac-
7: tR (7)=103.3 min, tR (ent-7)=103.2 min]. Determination of the absolute configuration of 6a was made
by chemical correlation with the sulfide (+)-(R)-87 of known absolute configuration (Scheme 3). Thus,
(+)-6a was treated with 2-chloropyrimidine in the presence of potassium hydroxide in THF at reflux to
give (+)-8 in 95% yield. Since 6a and 6b have the same sign of optical rotation the (R) configuration was
also assigned to 6b.
Scheme 3.
The feasibility of the synthesis of enantiomerically highly enriched allylic thiols from the corre-
sponding S-allylic thiocarbamates under basic conditions was demonstrated by the saponification of
7 with sodium hydroxide in aqueous solution which furnished the allylic thiol 9,22 having the (S)
configuration, with 97% ee [α]D20 −271.3 (c 0.8, CHCl3)) in a nonoptimized yield of 63%. The ee-value
of 9 was determined by GC analysis on an octakis-(2,6-di-O-pentyl-3-O-butyryl)-γ-cyclodextrin column
[tR (9)=6.7 min, tR (ent-9)=6.5 min]. The above-described Pd(0) catalyzed enantioselective synthesis of
allylic thiols is synthetically especially attractive because it uses racemic allylic alcohols as the starting
materials and renders the use of an external nucleophile superfluous. In the cases investigated the thermal
rearrangement of the O-allylic thiocarbamates18 posed no problem.
The stereochemical course of the Pd(0) catalyzed rearrangement of rac-2a, rac-2b and rac-4 in the
presence of the bisphosphane 5 is the same as observed in the case of the Pd(0) catalyzed allylic
substitution of the carbonates of rac-1a, rac-1b and rac-3 with heteroaromatic thiols and sulfinates by
using this ligand. This observation in combination with the results of previous mechanistic studies of the
Pd(0)/PPh3 catalyzed rearrangement of O-allylic thiocarbamates18 suggests that 6a, 6b and 7 are formed

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A. Böhme, H.-J. Gais / Tetrahedron: Asymmetry 10 (1999) 2511–2514
by an external attack of the nucleophile N-methyl thiocarbamate on the corresponding chiral Pd(II)-π-
allylic complexes derived from rac-2a, rac-2b and rac-4, respectively.23
Acknowledgements
Financial support of this work by the Deutsche Forschungsgemeinschaft (SFB 380) is gratefully
acknowledged.
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