Palladium-catalyzed asymmetric silaborative C-C cleavage of meso-methylenecyclopropanes

Article abstract of DOI:10.1021/ja0703170

An enantioselective silaborative C-C cleavage of meso-methylenecyclopropanes (meso-MCPs) was achieved by using a palladium catalyst bearing a chiral monodentate phosphine ligand. The (R)-2-bis(3,5-dimethylphenyl)phosphino-1,1′-binaphthyl gave the highest

Full text of DOI:10.1021/ja0703170

Published on Web 03/06/2007
Palladium-Catalyzed Asymmetric Silaborative C-C Cleavage of
meso-Methylenecyclopropanes
Toshimichi Ohmura, Hiroki Taniguchi, Yoshiyuki Kondo, and Michinori Suginome*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Katsura, Kyoto 615-8510, Japan
Received January 16, 2007; E-mail: suginome@sbchem.kyoto-u.ac.jp
Scheme 1. Asymmetric Ring Opening via C-C Bond Cleavage
Desymmetrization of cyclic compounds via asymmetric ring-
opening reactions has been recognized as an important strategy for
catalytic asymmetric synthesis. In these reactions, relatively reactive
carbon-heteroatom bonds, such as C-O bonds in epoxides, acid
anhydrides, and oxabicyclic alkenes, and C-N bonds in aziridines,
are cleaved in the presence of chiral catalysts, including enzymes.1
In view of the high synthetic utility of this method, it is highly
desirable to expand the method to other cyclic systems by taking
advantage of the rapid advances in catalyses involving the activation
of unreactive bonds. A general scheme of desymmetrization of
carbocycles via C-C bond cleavage is depicted in Scheme 1.
Achiral carbocycles are converted into acyclic carbochains via
selective cleavage of one of the two enantiotopic C-C σ-bonds.
Despite the potential usefulness, this type of desymmetrization has
only been realized in Rh-catalyzed hydrogenative C-C cleavage
of cyclobutanones2 and Pd-catalyzed arylative ring opening of
cyclobutanols,3 to the best of our knowledge.4
As a part of our silaboration study,5 we have developed transition-
metal-catalyzed silaborative C-C bond cleavage of methylenecy-
clopropanes (MCPs), which exhibits distinctive reaction pathways
that depend critically on the catalysts used and the structure of the
MCPs.6,7 An example is shown by the reaction of 7-methylenebi-
cyclo[4.1.0]heptane (2), whose proximal C-C bond cleavage is
accompanied by regioselective introduction of a silyl and a boryl
groups at the cleaved C-C bond. Herein, we describe a new
asymmetric desymmetrization system utilizing silaborative C-C
cleavage of meso-MCPs, which are easily prepared from cis-
alkenes,8 using a palladium catalyst bearing an optically active
monodentate phosphorus ligand.
Table 1. Optimization of Reaction Conditions for Pd-Catalyzed
Asymmetric Silaborative C-C Cleavage of 2 with 1a
entry
Si−B
ligand
time (h)
yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1b
1c
(+)-NMDPP
(S)-MONOPHOS
(R,R)-4
(S)-QUINAP
(S)-MOP
(R)-5a
(R)-5b
(R)-5b
(R)-5b
72
72
72
120
120
120
120
48
65
91
71
41
68
80
85
87
n.r.
26d
27
61d
1
16
71
87
90
120
a 1 (0.40 mmol), 2 (0.60 mmol), Pd(dba)2 (8.0 µmol), and ligand (9.6
µmol) were stirred in toluene (0.2 mL) at 50 °C unless otherwise noted.
b Isolated yield. c Determined after conversion to the corresponding â-silyl
ketones (see eq 1) that were analyzed by HPLC with a chiral stationary
phase column. d (1R,2R)-3a was formed as major isomer.
After brief screening of the catalysts, we decided to employ
palladium-phosphine catalysts with a Pd/P ratio of 1/1 as these
exhibit high catalyst activity in the silaboration of allenes.5a The
original palladium catalyst bearing an isocyanide ligand6 seemed
unfavorable for the asymmetric induction because of the require-
ment for a relatively high reaction temperature (110 °C) and less
flexibility in the design of chiral isocyanides.9 We found that the
palladium-phosphine catalyst showed high catalyst activity in the
reaction of Me2PhSiB(pin) (1a) with 2; the reaction proceeded even
at 50 °C in the presence of Pd(dba)2 (2.0 mol %) with PPh3 (2.4
mol %), giving 2-(1-borylethenyl)-1-silylcyclohexane 3a in 64%
yield after 24 h. The catalyst activity was found to be highly
dependent upon the Pd/P ratio. The reaction slowed down signifi-
cantly in the absence of the phosphine ligand or in the presence of
increased amounts of the ligand (Pd/P ratio of 1/2.4) (4 and 0%
yield, respectively, under otherwise identical reaction conditions).10
With the modified reaction conditions, we examined asymmetric
silaborative C-C cleavage of 2 with 1a in the presence of palladium
catalysts bearing various optically active monodentate phosphorus
ligands (entries 1-6, Table 1). The reactions gave nonracemic 3a
at 50 °C in 41-91% yield after 72-120 h. Poor enantioselectivities
were observed in the reactions using (+)-NMDPP, (S)-MONO-
PHOS, (S)-QUINAP, and (S)-MOP (entries 1, 2, 4, and 5), whereas
(R,R)-4 and (R)-5a gave 3a with much better enantiomeric excesses
(ee’s) (61 and 71% ee, entries 3 and 6). To improve enantioselec-
tivity, we carried out reactions using derivatives of 5 that have
varied diarylphosphino groups on the 1,1′-binaphthyl skeleton.11
We found that the highest enantioselectivity was attained with 2-bis-
(3,5-dimethylphenyl)phosphino-1,1′-binaphthyl [(R)-5b],12 which
afforded 3a with 87% ee (entry 7).
Further improvement of enantioselectivity was achieved when
MePh2SiB(pin) (1b) was used, resulting in 90% ee for the formation
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J. AM. CHEM. SOC. 2007, 129, 3518-3519
10.1021/ja0703170 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Asymmetric Silaborative C-C Cleavage of MCPsa
Table 3. Diastereoselective Conversion of 3b, 11, 12, and 14 via
Homologation-Allylborationa
entry
substrate
R3CHO
product
yield (%)b
drc
1
2
3
4
5
6
3b
3b
3b
11
EtCHO
i-PrCHO
PhCHO
PhCHO
PhCHO
PhCHO
16a
16b
16c
17
18 (91% ee)
19
78
80
70
63
69
71
94:6d
94:6
97:3
93:7
97:3
93:7
12 (91% ee)
14
a In THF (0.23 mL), 3b, 11, 12, or 14 (0.17 mmol) was reacted with
ClCH2Li (0.26 mmol), and then the resulting mixture was treated with
aldehydes (0.34 mmol). b Isolated yield. c Determined by HPLC analysis.
1
d Determined by H NMR.
the six-membered cyclic transition state.14 As expected, enantioen-
riched 12 afforded 18 without a drop in ee (entry 5).
In conclusion, we developed Pd-catalyzed asymmetric silabo-
rative C-C cleavage of meso-MCPs, affording synthetically useful
2-boryl-4-silyl-1-butene derivatives with high ee’s.
a 1b (0.40 mmol), MCP (0.60 mmol), Pd(dba)2 (8.0 µmol), and (R)-5b
(9.6 µmol) were stirred in toluene (0.2 ml) at 50 °C unless otherwise noted.
b Isolated yield. c Determined after conversion to the corresponding â-silyl
ketones (see eq 1) that were analyzed by HPLC with a chiral stationary
phase column. d Pd(dba)2 (3.0 mol %), (R)-5b (3.6 mol %), and MCP (2.0
equiv) were used. e Yield after conversion to the corresponding â-silyl
ketones. f Pd(dba)2 (4.0 mol %) and (R)-5b (4.8 mol %) were used.
Acknowledgment. This paper is dedicated to the memory of
the late Professor Emeritus Yoshihiko Ito. This work is supported
inpartbyGrant-in-AidforYoungScientists(B)fromMEXT(toT.O.).
Supporting Information Available: Experimental details and
characterization data of the products. This material is available free of
charge via Internet at http://pubs.acs.org.
of 3b (entry 8). The more sterically demanding triphenylsilyl
derivative 1c, however, did not react at all under the same reaction
conditions (entry 9). It is interesting to note that the optimized
reaction conditions using silylborane 1b and Pd/(R)-5b catalyst are
identical to those for the enantioselective silaboration of allenes
reported recently,5d indicating mechanistic similarity in the asym-
metric induction step.
Various meso-MCPs were subjected to asymmetric silaborative
C-C cleavage under the optimized conditions using silylborane
1b and Pd/(R)-5b catalyst (Table 2). The reaction of bicyclic MCPs
6-8 that have fused five-, seven-, and eight-membered carbocycles
gave 11-13 in high yield with high enantioselectivities (90-91%
ee, entries 1-3). On the other hand, non-fused 9 afforded 14 with
lower ee (81% ee, entry 4). We also carried out the reaction of
cyclic acetal 10, giving 15 with 89% ee, although the yield was
modest (entry 5).
References
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Oxidation of 3b and 11-15 by treatment with H2O2 under basic
conditions afforded the corresponding optically active â-silyl
ketones in high yields with no epimerization.
Their synthetic utility was also demonstrated by a diastereose-
lective homologation-allylboration sequence (Table 3). Reaction
of 3b with ClCH2Li and treatment with EtCHO gave homoallylic
alcohol 16a in 78% yield with high diastereomeric ratio (94:6, entry
1). High diastereoselectivities were observed not only in the reaction
of 3b with i-PrCHO and PhCHO (entries 2 and 3) but also in the
reactions of 11, 12, and 14 with PhCHO (entries 4-6). These
reactions indicate that the stereochemistry of the â-substituent on
allylic boronates efficiently controls the diastereoface selection in
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