Published on the web September 5, 2011
959
Synthesis of Acylsilanes by Palladium-catalyzed Cross-coupling Reaction
of Thiol Esters and Silylzinc Chlorides
Hiroki Azuma, Kentaro Okano, and Hidetoshi Tokuyama*
Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578
(Received May 23, 2011; CL-110431; E-mail: tokuyama@mail.pharm.tohoku.ac.jp)
An acylsilane synthesis by a Pd-catalyzed cross-coupling
reaction of thiol esters and silylzinc chlorides was developed.
S-Phenyl thiol esters with a variety of functional groups were
converted to corresponding acylsilanes.
Et–ZnI
cat. [PdCl2(PPh3)2]
O
O
SEt
Et
toluene
rt, 5 min
MeO
MeO
91%
Since acylsilanes possess a variety of unique reactivities,1
their synthesis has been an important research topic in organic
chemistry.1p-1r,2-4 Brook2a and Corey2b independently reported
representative methods to prepare acylsilanes by silylation of a
lithiated dithiane followed by removal of dithiane. Acylsilanes
are also synthesized by 1,2-addition of silyllithium to aldehydes
followed by oxidation according to a procedure of Reich.5
However, both methods have only limited functional group
compatibility since they use strong bases such as n-BuLi. To
circumvent these problems, palladium-catalyzed cross-coupling
of acid chlorides with disilane4a-4d or stannylsilane4e has
recently been reported. These methods, however, are unsatis-
factory because they require harsh conditions such as heating at
high temperature without solvent. On the other hand, thiol esters
are a suitable substrate for cross-coupling reactions based on
oxidative addition of a transition-metal catalyst to the C-S
bond.6,7 Under this background, we initiated a study of the
transformation of thiol esters to acylsilanes. Herein, we report
a mild synthesis of acylsilanes by palladium-catalyzed cross-
coupling of thiol esters and silylzinc chlorides.
O
O
O
R
Et
R
R
SEt
Pd
Pd0
O
SEt
Et
R
Pd
Et–ZnI
EtS–ZnI
Scheme 1. Palladium-catalyzed ketone synthesis.
O
O
R
SiR3
R
R
SEt
Pd
Pd0
O
O
SEt
SiR3
R
Pd
Based on the proposed reaction mechanism for the
palladium-catalyzed cross-coupling reaction of thiol esters with
organozinc reagent (Scheme 1), we considered a working
hypothesis for transformation of thiol esters to acylsilanes as
shown in Scheme 2. Oxidative addition of palladium(0) to the
C-S bond of the thiol ester gives acyl palladium species which
should be transformed to the acylsilane via transmetalation with
a silyl metal reagent followed by reductive elimination with
regeneration of Pd(0).
R3Si–Metal
EtS–Metal
Scheme 2. Working hypothesis for acylsilane formation.
PhMe2Si–ZnCl
(3 equiv)
[PdCl2(PPh3)2]
(5 mol%)
O
O
With this idea in mind, we explored a suitable silyl metal
reagent for the expected cross-coupling reaction. Using thiol
ester 1a as the model substrate, various silyl metal reagents4,8
were tested for ketone synthesis using [PdCl2(PPh3)2]. However,
silylating reagents, which act as silyl anion sources, did not
provide the desired acylsilane (Scheme 3). Eventually, we found
that the cross-coupling reaction proceeded when using PhMe2-
Si-ZnCl9,10 although the yield was low.
SEt
SiMe2Ph
THF-Et2O
rt, 10 h
MeO
MeO
2a
1a
33%
4a-4d
Me3Si–SiMe3 4e
Me3Si–SnBu3
PhMe2Si–Bpin8
These silyl reagents did not give acylsilane 2a.
This promising result prompted us to optimize the process
regarding thiol ester substrate, ligand, and catalyst. First, we
observed a significant structure effect on the reaction rate in a
comparison of thiol esters 1a, 1b, and 1c (Table 1). Thus, the
reaction of 1a or 1b using a combination of [Pd(dba)2] and Ph3P
provided the desired acylsilane 2a in 33-34% yield with
recovery of a substantial amount of thiol esters (Entries 1 and 2).
In contrast, the use of thiol ester 1c derived from benzenethiol
Scheme 3. Reaction using various silyl metal reagents.
resulted in rapid conversion (Entry 3).11 Then we carried out
ligand screening using 1c as a substrate. Yield of acylsilane 2a
strongly depended on the choice of ligand. Thus, the reaction
using tricyclohexylphosphane gave the best yield (Entries 3-6).
The bulky and electron-rich trialkylphosphane ligand would
Chem. Lett. 2011, 40, 959-961
© 2011 The Chemical Society of Japan