Rhodium-catalyzed asymmetric conjugate addition of organoboronic acids to nitroalkenes [7]

Full text of DOI:10.1021/ja002805c

10716
J. Am. Chem. Soc. 2000, 122, 10716-10717
Scheme 1
Rhodium-Catalyzed Asymmetric Conjugate Addition
of Organoboronic Acids to Nitroalkenes
Tamio Hayashi,* Taichi Senda, and Masamichi Ogasawara
Department of Chemistry
Graduate School of Science, Kyoto UniVersity
Sakyo, Kyoto 606-8502, Japan
ReceiVed July 31, 2000
The conjugate addition of organometallic reagents to electron
deficient olefins is an important method for the construction of
new carbon-carbon bonds1 and its enantioselective version using
asymmetric catalysis has recently been an active field of research.2
Although some successful results have been achieved on the
asymmetric addition to R,â-unsaturated carbonyl compounds,
there have been very few reports on the asymmetric addition to
1-nitroalkenes,3-5 despite the wide applicability of nitro com-
pounds to organic transformations.6 In our previous studies on
rhodium-catalyzed asymmetric 1,4-addition of organoboron re-
agents to electron-deficient olefins including R,â-unsaturated
ketones, esters, and phosphonates,7 the substrates we have
employed are limited to those lacking the R-substituents due to
their low reactivity toward the asymmetric addition, and as a
result, no information on the relative stereochemistry at R and â
positions has been obtained. Here we wish to report that
1-nitroalkenes containing R-substituents are good substrates for
the rhodium-catalyzed asymmetric 1,4-addition and the reaction
of 1-nitrocyclohexene proceeds with high diastereoselectivity
giving thermodynamically less stable cis isomer preferentially
(Scheme 1).
We chose 1-nitrocyclohexene (1a), which is a commercially
available 1-nitroalkene, as a substrate for the asymmetric addition
of phenylboronic acid (2m) and examined several reaction
conditions for high chemical yield and high stereoselectivity. It
was found that the asymmetric phenylation takes place with high
enantioselectivity under the reaction conditions used for the
reaction of R,â-unsaturated ketones.7a Thus, a mixture of 1a, 2m
(5 equiv to 1a), and 3 mol % of the rhodium catalyst Rh(acac)-
(C2H4)2/(S)-binap (1/1.1) in dioxane/H2O (10/1) was heated at
100 °C for 3 h. Aqueous workup followed by silica gel
chromatography gave 79% yield of 2-phenyl-1-nitrocyclohexane
(3am). It turned out that the main phenylation product 3am is a
cis isomer (cis/trans ) 87/13) and both of the cis and trans
isomers are 98.3% enantiomerically pure (HPLC analysis with a
chiral stationary phase column) (entry 2 in Table 1). Treatment
of the cis-rich mixture with sodium bicarbonate in refluxing
ethanol caused cis-trans equilibration giving thermodynamically
more stable trans isomer (trans/cis ) 97/3).8 The enantiomeric
purity was kept 98.3% ee after the equilibration, indicating that
the cis and trans isomers have the same absolute configuration
at 2 position and the opposite configuration at 1 position. Their
absolute configurations were assigned to be (1S,2S) for cis isomer
and (1R,2S) for trans isomer by correlation with known com-
pounds (vide infra). It should be noted that the rhodium-catalyzed
asymmetric phenylation produced thermodynamically less stable
cis isomer of high enantiomeric purity and it can be isomerized,
if one wishes, into trans isomer without loss of its enantiomeric
purity. The isomers were readily separated pure by preparative
TLC on silica gel or by a preparative GPC. The preferential
formation of cis-3am in the catalytic phenylation may indicate
the protonation of a rhodium nitronate intermediate9 in the
catalytic cycle (Scheme 2).
(1) For a review on 1,4-addition reactions: Perlmutter, P. Conjugate
Addition Reactions in Organic Synthesis; Pergamon Press: Oxford, 1992.
(2) For a pertinent review on asymmetric conjugate addition of organo-
metallic reagents: Tomioka, K.; Nagaoka, Y. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
1999; Vol. 3, Chapter 31.1.
(3) Very recently, high enantioselectivity has been reported by Ji and Barnes
on the addition of 1,3-dicarbonyl compounds to nitroalkenes: Ji, J.; Barnes,
D. M.; Zhang, J.; King, S. A.; Wittenberger, S. J.; Morton, H. E. J. Am. Chem.
Soc. 1999, 121, 10215.
The chemical yield, cis-selectivity, and enantioselectivity in
forming (1S,2S)-3am were dependent to some extent on the
amount of the boronic acid 2m, the reaction temperature, and
the solvent used. The yield was higher (89%) with 10 equiv of
2m (entry 1). The highest cis-selectivity (89/11) and the highest
enantioselectivity (99.3% ee) was observed in the reactions carried
out at 80 °C (entry 3) and in DMA/H2O (entry 6), respectively.
(4) For examples of noncatalytic asymmetric 1,4-addition to nitroalkenes,
see: (a) Juaristi, E.; Beck, A. K.; Hansen, J.; Matt, T.; Mukhopadhyay, T.;
Simson, M.; Seebach, D. Synthesis 1993, 1271. (b) Scha¨fer, H.; Seebach, D.
Tetrahedron 1995, 51, 2305.
(5) For examples of catalytic asymmetric 1,4-addition to nitroalkenes, see
(a) Brunner, H.; Kimel, B. Monatsh. Chem. 1996, 127, 1063. (b) Sewald, N.;
Wendisch, V. Tetrahedron: Asymmetry 1998, 9, 1341.
(6) For reviews: (a) Askani, R.; Taber, D. F. In ComprehensiVe Organic
Synthesis; Trost, B, M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 6,
Chapter 1.4. (b) Tamura, R.; Kamimura, A.; Ono, N. Synthesis 1991, 423. (c)
Fuji, K.; Node, M. Synlett 1991, 603.
(7) (a) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N. J.
Am. Chem. Soc. 1998, 120, 5579. (b) Takaya, Y.; Ogasawara, M.; Hayashi,
T. Tetrahedron Lett. 1998, 39, 8479. (c) Takaya, Y.; Senda, T.; Kurushima,
H.; Ogasawara, M.; Hayashi, T. Tetrahedron: Asymmetry 1999, 10, 4047.
(d) Takaya, Y.; Ogasawara, M.; Hayashi, T. Tetrahedron Lett. 1999, 40, 6957.
(e) Hayashi, T.; Senda, T.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc.
1999, 121, 11591.
Under similar reaction conditions, 1-nitrocyclohexene (1a)
underwent asymmetric addition of some other arylboronic acids
(2n-2q) in good yields with high enantioselectivity (entries
9-12). The corresponding cis-2-aryl-1-nitrocyclohexanes (3an-
3aq) were produced with over 85% cis-selectivity and with the
enantioselectivity ranging between 97.6 and 99.0% ee. The
enantioselectivity in the addition of alkenylboronic acid (2r) was
low compared with that of arylboronic acids, but it was improved
by use of DMA/H2O as a solvent (entries 13 and 14). The
(8) The equilibration of 3am from cis to trans has been reported: Bordwell,
F. G.; Yee, K. C. J. Am. Chem. Soc. 1970, 92, 5933.
(9) The preference for the formation of the less stable cis isomer has been
reported on protonation of 2-substituted cyclohexane nitronate ions: Bordwell,
F. G.; Yee, K. C. J. Am. Chem. Soc. 1970, 92, 5939.
10.1021/ja002805c CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/14/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 43, 2000 10717
Table 1. Asymmetric Conjugate Addition of Boronic Acids 2 to Nitroalkenes 1 Catalyzed by (S)-BINAP-Rhodium(I)a
entry
nitroalkene 1
RB(OH)2 2 (equiv to 1)
solvent (10/1)
yieldb (%) of 3
cis/transc
% eed
after equiv cis/transc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1c
1c
1d
2m (10)
2m (5)
2m (5)
2m (5)
2m (5)
2m (5)
2m (5)
2m (5)
2n (10)
2o (5)
2p (5)
2q (10)
2r (5)
2r (10)
2m (10)
2m (5)
2m (5)
2m (10)
2m (10)
dioxane/H2O
dioxane/H2O
dioxane/H2Oe
dioxane/H2Of
DMF/H2O
89 (3am)
79 (3am)
54 (3am)
<5 (3am)
73 (3am)
42 (3am)
83 (3am)
18 (3am)
89 (3an)
88 (3ao)
89 (3ap)
84 (3aq)
71 (3ar)
90 (3ar)
45 (3bm)
73 (3bm)
81 (3cm)
93 (3cm)
33 (3dm)
87/13
87/13
89/11
-
98.5
98.3
98.7
-
3/97
81/19
83/17
84/16
81/19
88/12
85/15
85/15
85/15
77/23
75/25
26/74
17/83
44/56
40/60
39/61g
99.0
99.3
93.7
91.8
97.6
99.0
99.0
98.0
60.7
82.9
78.7
90.6
37.6
73.0
96.8
DMA/H2O
1-propanol/H2O
toluene/H2O
dioxane/H2O
dioxane/H2O
dioxane/H2O
dioxane/H2O
dioxane/H2O
DMA/H2O
dioxane/H2O
DMF/H2O
dioxane/H2O
DMA/H2O
3/97
3/97
4/96
2/98
10/90
8/92
13/87
dioxane/H2O
36/64g
a The reaction was carried out with nitroalkene 1 (0.40 or 0.20 mmol), boronic acid 2 (2.0 mmol) in a given solvent (1.1 mL) at 100 °C for 3
h in the presence of 3 mol % of the catalyst generated from Rh(acac)(C2H4)2 and (S)-BINAP (1/1.1) unless otherwise noted. b Isolated yield by
1
silica gel chromatography. c Determined by H NMR. d Determined by HPLC analysis with chiral stationary phase columns (Daicel Chiralcel OJ,
OD-H, or Chiralpak AD) except for 3ar whose % ee was determined by GLC analysis with CP-Cyclodex â236M. e At 80 °C. f At 60 °C. g Ratio
of diastereomeric isomers.
Scheme 2
Scheme 3
asymmetric addition of phenylboronic acid was also successful
for other cyclic nitroalkenes, 1-nitrocycloheptene (1b) and 1-ni-
trocyclopentene (1c), and for a linear nitroalkene 1d, which gave
the corresponding phenylation products with high enantioselec-
tivity, though the diastereoselectivity is not so high (entries 16,
18, and 19).10
The optically active nitroalkanes obtained by the present
rhodium-catalyzed asymmetric addition are useful chiral building
blocks which can be readily converted into a wide variety of
optically active compounds by taking advantage of the versatile
reactivity of nitro compounds (Scheme 3). Thus, for example,
exposure of 3am (98% ee) to the Nef reaction conditions gave
(S)-2-phenylcyclohexanone (4)11 of 90% ee.12 The reaction was
accompanied by a slight loss of enantiomeric purity probably due
to the presence of an acidic hydrogen at the stereogenic carbon
center which is bonded to carbonyl and phenyl groups. Reduction
of the nitro group in cis-3am (>99% cis) and trans-3am (>99%
trans) by hydrogenation catalyzed by palladium on charcoal gave
the corresponding optically active 2-phenyl-1-aminocyclohex-
anes,13 cis-5 and trans-5, respectively, without cis/trans isomer-
ization or loss of their enantiomeric purity. Their % ee’s (98%
ee) were confirmed by an HPLC analysis of the acetamides 6.
Nitro compounds containing acidic hydrogen(s) are known to be
good nucleophiles applicable to further carbon-carbon bond
forming reactions. As an example, Michael addition of (2S)-3am,
which is a mixture of cis and trans isomers in an 85/15 ratio, to
methyl acrylate14 followed by reduction of the nitro group in 7
gave spiro amide 815 as a single isomer in a high yield.
Acknowledgment. This work was supported by “Research for the
Future” Program, the Japan Society for the Promotion of Science and a
Grant-in-Aid for Scientific Research, the Ministry of Education, Japan.
(10) The asymmetric addition to the nitroalkenes which lack the R-sub-
stituent is also possible, though the yield or enantioselectivity is not so high
as that for the cyclic nitroalkenes. For examples, the reaction (100 °C, 3 h in
dioxane/H2O (10/1)) of phenylboronic acid (2a) with (E)-1-nitro-3-methyl-
butene and (E)-1-nitro-3,3-dimethylbutene gave the corresponding phenylation
products in 88% yield; 63% ee and 5% yield; 99.5% ee, respectively.
Supporting Information Available: Experimental procedures, spec-
troscopic and analytical data for the substrates and products (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
(11) [R]20 -97 (c 0.78, benzene). The reported value for (S)-2-phenyl-
D
cyclohexanone is [R]24 -114 (c 0.60, benzene): Berti, G.; Macchia, B.;
Macchia, F.; Monti, L. DJ. Chem. Soc. (C) 1971, 3371.
JA002805C
(12) The enantiomeric purity was determined by HPLC analysis with
Chiralcel OD-H (hexane/2-propanol ) 9/1).
(14) Moffett, R. B. Organic Syntheses; Wiley: New York, 1963; Collect.
Vol. 4, p 652.
(15) The enantiomeric purities of 7 and 8 were determined to be 98% ee
by HPLC analysis with chiral stationary phase columns (Chiralcel OJ for 7
and Chiralcel OD-H for 8 (hexane/2-propanol ) 4/1)).
(13) cis-5: [R]20 +63 (c 0.42, MeOH). trans-5: [R]20 -36 (c 0.84,
D
D
MeOH). The specific rotations of (1S, 2S)-5 and (1R,2S)-5 have been reported
to be [R]27 +59 (c 0.26, MeOH) and [R]27 -45 (c 0.074, MeOH),
D
respectivelyD: Verbit, L.; Price, H. C. J. Am. Chem. Soc. 1972, 94, 5143.