Angewandte
Communications
Chemie
Asymmetric Catalysis
Regio- and Enantioselective Cobalt-Catalyzed Sequential
Hydrosilylation/Hydrogenation of Terminal Alkynes
Abstract: A highly regio- and enantioselective cobalt-cata-
lyzed sequential hydrosilylation/hydrogenation of alkynes was
developed to afford chiral silanes. This one-pot method is
operationally simple and atom economic. It makes use of
relatively simple and readily available starting materials,
namely alkynes, silanes, and hydrogen gas, to construct more
valuable chiral silanes. Primary mechanistic studies demon-
strated that highly regioselective hydrosilylation of alkynes
with silanes occurred as a first step, and the subsequent cobalt-
catalyzed asymmetric hydrogenation of the resulting vinyl-
silanes showed good enantioselectivity.
C
hiral organosilanes are important synthetic intermedi-
Scheme 1. Transition-metal-catalyzed asymmetric hydrogenation for
the synthesis of chiral silanes.
ates[1] for chiral catalysts[2] and silasubstitution in medicinal
chemistry.[3] Although several methods have been generally
developed to prepare chiral organosilanes, such as asymmet-
ric hydrosilylation of double bonds,[4] desymmetrization of
silanes,[5] and asymmetric silicon–hydride bond insertions,[6]
the development of new strategies to efficiently construct
chiral organosilanes is still highly desirable. Asymmetric
hydrogenation of unsaturated carbon–carbon bonds[7] is
a useful reaction that has been widely used in organic
synthesis, as well as in the chemical industry. Owing to the
difficulty in differentiating the two enantiotopic faces in
prochiral substrates,[8] direct highly enantioselective hydro-
genation of 1,1-disubtituted vinyl silanes has not so far been
reported. In 2006, Andersson and co-workers[9] reported an
iridium-catalyzed asymmetric hydrogenation of vinyl silanes,
however, only one example of asymmetric hydrogenation of
1,1-disubstituted vinyl silane was demonstrated, with 58% ee.
Sequential reactions are one of the most powerful
synthetic methodologies, and they show unique step-economy
features, decrease the cost of purifications, and improve the
efficiency of synthesis.[10] Inspired by previously reported
work on the hydrosilylation of alkynes[11] and asymmetric
hydrogenation of alkenes,[12] we developed a one-pot cobalt-
catalyzed regio- and enantioselective sequential hydrosilyla-
tion/hydrogenation reaction of terminal alkynes to prepare
chiral organosilanes (Scheme 1).
through asymmetric cobalt catalysis affords vinyl silane 3a in
38% yield, as well as the side product 4a in 35% yield with
68% ee [Eq. (1)]. This initial result strongly encouraged us to
optimize the reaction conditions for this unexpected chiral
silane.
At the beginning of the optimization, hydrogen gas was
selected as a more atom-economic hydrogenation reagent
than hydrosilane. The reaction of 1a with Ph2SiH2 in the
[13]
presence of 5 mol% of cobalt precatalyst L1a·CoCl2 and
15 mol% of NaBHEt3 as a reductant in a solution of Et2O
(0.5m) at room temperature using a balloon of hydrogen gas
afforded the hydrosilylation product in 44% yield (Table 1,
entry 1) and a mixture of the branched and linear hydro-
genation products 4a and 5a in 37% yields with a 60:40 ratio
of regioisomers (rr). When we changed the group on the
oxazoline to an isopropyl group, hydrosilylation/hydrogena-
tion products were afforded in 32% yield with 93:7 rr
(entry 2). When using less steric bulky 2,6-dimethyl imine
(L1c), a significant improvement was observed, and the
reaction afforded 4a in 83% yield with > 99:1 rr and 80% ee
(entry 3). When 2,4,6-trimethyl imine was used, the enantio-
selectivity of the reaction to give 4a was increased to 88%
without any vinyl silanes (L1d, entry 4). The reaction with
a ligand with a less sterically bulky methyl group on the
oxazoline moiety afforded 4a in 91% yield and 88% ee
(entry 5). Various cobalt precatalysts, as well as reductants
and solvents, were screened, but no better results were
During our previous studies,[11e] we found that the reaction
of phenylacetylene 1a with 3 equivalents of diphenylsilane
[*] J. Guo, X. Shen, Prof. Z. Lu
Department of Chemistry, Zhejiang University
Hangzhou, Zhejiang 310058 (China)
E-mail: luzhan@zju.edu.cn
Supporting information and the ORCID identification number(s) for
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!