Angewandte
Communications
Chemie
Table 1: Evaluation of reaction conditions.
phenylcyclopropyl)methanol (1a). The dehydrogenative cou-
pling of 1a with diethylsilane catalyzed by [{Ir(cod)Cl}2] or
[{Ir(cod)OMe}2] under conditions we reported previously for
the dehydrogenative silylation of alcohols and amines[24,26–28]
led to a mixture of hydrosilyl ether 2a and dialkoxysilane 4
[Eq. (1)]. In contrast, the same reaction catalyzed by
0.2 mol% [Ru(PPh3)3Cl2] at 508C delivered 2a exclusively.
Entry
Ligand
Hydrogen acceptor
Yield [%][a]
ee [%][b]
1
L1
L2
L3
L4
L5
L6
L7
L1
L1
L1
cyclohexene
cyclohexene
cyclohexene
cyclohexene
cyclohexene
cyclohexene
cyclohexene
norbornene
none
93
9
83
nd
nd
À11
À39
À45
À36
84
2[c]
3[c]
4[c]
5[c]
6
25
35
55
60
48
81
54
90
7
8
The ruthenium complex did not catalyze the silylation of
alcohol 1a with the silyl ether 2a.[27,29] Silyl ether 2a formed
by the Ru-catalyzed process was used without further
9[c]
10[d]
70
87
cyclohexene
À
purification for the silylation of a cyclopropyl C H bond
[a] Determined by GC analysis with dodecane as the internal standard.
[b] Determined by SFC analysis on a chiral stationary phase. A negative
ee value indicates ent-3a was formed as the major enantiomer. nd=not
determined. [c] 12 h. [d] 508C, 24 h.
after removal of the solvent and remaining diethylsilane.
Having identified a simple synthesis of 2a, we sought
conditions for this asymmetric, intramolecular silylation
(Table 1). Based on previous reports of Rh-catalyzed silyla-
tions of C H bonds,[9–12] we examined the Rh catalyst derived
À
from [{Rh(cod)Cl}2] and (S)-DTBM-SEGPHOS (L1) with
cyclohexene as a hydrogen acceptor[30] at 808C (entry 1). The
À
functionalization of the cyclopropyl C H bond occurred in
2 hours under these conditions, yielding the cyclized product
3a in 93% yield and 83% ee. Other SEGPHOS derivatives,
such as (S)-SEGPHOS (L2), (R)-DM-SEGPHOS (L3), and
(R)-DMM-SEGPHOS (L4), formed catalysts with lower
reactivity and enantioselectivity toward the silylation than
did (S)-DTBM-SEGPHOS (L1) (entries 2–4). These results
suggest that bulky substituents on the ligand are important for
achieving both high reactivity and high selectivity. Complexes
generated from related bisphosphine ligands, such as (R)-
DTBM-BINAP (L5), (R)-DTBM-MeOBIPHEP (L6), and
(R)-DTBM-GARPHOS (L7) (entries 5–7), were less selec-
tive catalysts.
The presence of a hydrogen acceptor in the reaction and
the proper identity of this acceptor were critical to achieve
high yield and good enantioselectivity, and the temperature
substantially affected the enantioselectivity. In the absence of
a hydrogen acceptor, competing processes occurred, including
the disproportionation of 2a to form 4 (entry 9), and low yield
and ee of the silylcyclopropane were observed. The reaction
with norbornene instead of cyclohexene as hydrogen acceptor
also occurred in lower yield, due to the hydrosilylation and
dehydrogenative silylation of norbornene (entry 8). Reac-
tions run at 508C occurred with higher enantioselectivity than
those run at 808C, and high conversion was maintained
(entry 10).
Having established conditions for the enantioselective
silylation of cyclopropane 2a, we investigated the scope of the
reaction. Table 2 shows yields of isolated products and
representative yields determined by gas chromatography
1
(GC) or H NMR spectroscopy.[34] In general, the enantiose-
lectivity of the reaction correlated with the steric properties of
the aryl ring in the substrate. The enantioselectivities for
reactions of substrates containing meta (1b,c) or ortho (1d)
substituents on the aryl rings were higher than the enantio-
selectivities for substrates lacking any substituents (1a) or
those of substrates containing only para (1g) substituents on
the aryl ring. A similar correlation between enantioselectivity
and steric properties was observed for the reactions of
cyclopropylmethanols substituted with naphthyl groups. For
example, the enantioselectivity of the reaction of (1-naph-
thylcyclopropyl)methanol (1 f) was higher than that of the
reaction of the less sterically demanding (2-naphthylcyclo-
propyl)methanol (1e).
With cyclohexene as hydrogen acceptor, L1 as ligand, and
508C as the reaction temperature (entry 10), the competing
processes were suppressed. For example, products from the
À
silylation of aryl C H bonds were not observed, although the
conditions we developed are similar to those used for the
Further reactions probed the functional-group tolerance
of the silylation process. Aryl halides (1g,h) and a trifluoro-
methylarene (1i) were both compatible with the reaction
conditions. Oxygen-based functional groups, such as methoxy
(1j), benzyloxy (1k), siloxy (1l), and alkoxycarbonyl (1m)
[11]
À
silylation of aryl C H bonds. In addition, ring opening of
the cyclopropane by the hydrosilyl group was not observed.
Opening of a cyclopropane ring by a hydrosilane in the
presence of Rh catalysts has been reported previously.[31–33]
2
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
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