Angewandte
Chemie
selective reaction,[13] leading to enantioenriched a-chiral
allylsilanes.
3,3’-bis(diphenylmethyl) analogue (R)-17 f gave 13aa in 71%
yield and 81% ee (entry 11). Finally, (R)-17g[15e] was found to
be the most effective ligand, with 13aa being produced in
71% yield and 97% ee (entry 12).[16]
To study the feasibility of a three-component coupling of
1,3-dienes, aldehydes, and a silylborane, we first investigated
the reaction using achiral ligands. Thus, the reaction of 1,3-
diene 6a, benzaldehyde (7a), and PhMe2SiB(pin) (12) was
carried out in the presence of 10 mol% of [Ni(cod)2] and
10 mol% of PPh3 in DMF at room temperature for 3 hours
(Scheme 3). As a result, the coupling product 13aa was
With optimized conditions in hand, we explored the scope
of the enantioselective coupling (Table 2). Reaction of 6a
with 7b and 7c, bearing an electron-donating group on the
aromatic ring, afforded the corresponding products 13ab and
13ac in high yield and enantiopurity (entries 1 and 2). When
1,3-diene 6a was reacted with p-trifluorobenzaldehyde (7d),
the yield of 13ad decreased to 29%, although the ee remained
high (entry 3). Coupling reactions of bicyclic aromatic
aldehydes 7e and 7 f with 6a also proceeded to afford the
corresponding products 13ae and 13af in high yield and
enantiopurity (entries 4 and 5). Aliphatic aldehydes 7g–7i
were also suitable for coupling with 6a, giving allylsilanes
13ag–13ai in a highly enantioselective manner (entries 6–8).
The coupling of siladiene 6b with 7a gave 13ba in 80% yield
and 82% ee (entry 9). Also, alkyl substituted diene 6c was
coupled with 7a and the corresponding product 13ca was
obtained in moderate yield and enantiopurity as a single
diastereomer (entry 10). Next, the asymmetric coupling
reaction of internal dienes with 7a was investigated
(entries 11 and 12). When the reaction of unsymmetrical
diene 6d and 7a was carried out under optimized conditions,
the corresponding coupling product 13da was obtained in
Scheme 3. Three-component coupling of 1,3-diene 6a, benzaldehyde
(2a), and silylborane 12 and determination of product stereochemistry
at C1 and C3. cod=1,5-cyclooctadiene, pin=pinacolato, MOM=me-
thoxymethyl, PPTS= pyridinium p-toluenesulfonate.
Table 1: Screening of chiral ligands.[a]
obtained in 94% yield as a single diastereomer. The relative
stereochemistries of the hydroxy group at the C1 position and
the PhMe2Si group at the C3 position of 13aa were
1
determined by H NMR spectroscopy and NOESY experi-
ments on 14 (derived from 13aa) to be 1,3-syn orientation.
This result indicated that the reaction of oxanickelacycle 8
with silylborane 12 proceeded to give the cross-coupling
product 11aa exclusively, as expected, from which 13aa was
produced by hydrolysis of the boron–oxygen bond.[14]
Entry
Ligand
t [h]
Yield [%]
ee [%]
1
2
3
4
5
6
7
8
(R)-BnO-MOP
NMDPP
(R,R)-15
(R,R)-16
24
3
54
57
26
37
70
29
51
56
59
57
71
71
12[b]
1[b]
24
16
24
26
18
13
18
26
24
22
6[b]
2[b]
Encouraged by this result, we set out to conduct a screen
of various chiral ligands for the realization of an enantiose-
lective version of the 1,3-diene and aldehyde coupling
(Table 1). The coupling reaction of 6a, 7a, and 12 using
chiral phosphine ligands, (R)-BnO-MOP,[15a] NMDPP, (R,R)-
15,[15b] or phosphoroamidite ligand (R,R)-16,[15c] gave 13aa in
moderate yield and low ee (entries 1–4). However, the use of
(R)-MonoPhos provided 13aa in 70% yield, although the
enantioselectivity was still low (entry 5). Based on these
results, MonoPhos seemed to be a good starting point, so we
decided to modify it and apply its analogues to the coupling
reaction (entries 6–11). When N,N-diisopropyl and N,N-
dibenzyl analogues (R)-17a and (R)-17b[15d] were employed,
both the yield and ee of 13aa decreased (entries 6 and 7). On
the other hand, modification of the 3,3’ positions of the
binaphthyl skeleton was found to be effective for improving
the enantioselectivity (entries 8–12). Introduction of a methyl
group ((R)-17c)[15d] and a phenyl group ((R)-17d)[15d] at the
3,3’-positions increased the ee of 13aa to 52% and 58%,
respectively (entries 8 and 9). The reaction using 3,3’-dime-
sityl derivative (R)-17e provided the coupling product 13aa in
57% yield and 94% ee (entry 10). The coupling reaction using
(R)-MonoPhos
À19[c]
À4[c]
À9[c]
À52[c]
À58[c]
94[b]
81[b]
97[b]
(R)-17a (R1 =H, R2 =iPr)
(R)-17b (R1 =H, R2 =Bn)
(R)-17c (R1 =R2 =Me)
(R)-17d (R1 =Ph, R2 =Me)
(R)-17e (R1 =mesityl, R2 =Me)
(R)-17 f (R1 =CHPh2, R2 =Me)
(R)-17g (R1 =CHPh2, R2 =Bn)
9
10
11
12
[a] cod=1,5-cyclooctadiene, MOM=methoxymethyl. [b] (1S,3R)-13aa
was formed as the major enantiomer. [c] (1R,3S)-13aa was formed as the
major enantiomer. The absolute configuration of 13aa was determined
by transformation to a known compound. For details, see the Supporting
Information.
Angew. Chem. Int. Ed. 2012, 51, 1228 –1231
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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