Rhodium-catalyzed asymmetric 1,4-addition of aryl- and alkenylboronic acids to enones

Full text of DOI:10.1021/ja980666h

J. Am. Chem. Soc. 1998, 120, 5579-5580
5579
proceeds with high enantioselectivity in the presence of a chiral
phosphine-rhodium catalyst.7
Rhodium-Catalyzed Asymmetric 1,4-Addition of
Aryl- and Alkenylboronic Acids to Enones
Our initial studies were focused on the development of reaction
conditions including reaction temperature, solvent, rhodium
precursor, and chiral ligand for the asymmetric addition of
phenylboronic acid (2m) to 2-cyclohexenone (1a) producing
3-phenylcyclohexanone (3am). Under the conditions reported
Yoshiaki Takaya, Masamichi Ogasawara, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science
Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Masaaki Sakai and Norio Miyaura*
DiVision of Molecular Chemistry
Graduate School of Engineering
Hokkaido UniVersity, Sapporo 060-8628, Japan
previously,5 that is, in the presence of rhodium catalyst generated
from Rh(acac)(CO)2 and a phosphine ligand at 50 °C for 16 h,
the reaction is very slow with any chiral ligands examined,8 giving
only <2% yield of 3am. It was found that the reaction is
efficiently catalyzed by a rhodium complex generated in situ by
mixing Rh(acac)(C2H4)2 with 1 equiv of (S)-binap in an aqueous
solvent at 100 °C (eq 1). Thus, a mixture of 1a (39 mg, 0.40
mmol), 2m (68 mg, 0.56 mmol, 1.4 equiv), Rh(acac)(C2H4)2 (3.1
mg, 0.012 mmol, 3 mol %), and (S)-binap (7.5 mg, 0.012 mmol)
in dioxane/H2O (1.0 mL/0.1 mL) was heated at 100 °C for 5 h.
After aqueous workup, silica gel chromatography (hexane/EtOAc
) 5/1) gave 44 mg (64% yield) of (S)-3-phenylcyclohexanone
(3am) whose enantiomeric excess is 97% (entry 1 in Table 1).
The absolute configuration of (S) was determined by comparison
ReceiVed March 2, 1998
The 1,4-conjugate addition of organometallic reagents to enones
is widely used process for carbon-carbon bond formation giving
â-substituted carbonyl compounds which are versatile synthons
to further organic transformations. Although considerable efforts
have been made to develop efficient chiral catalytic systems for
asymmetric 1,4-addition, the successful examples are rare in terms
of enantioselectivity, catalytic activity, and generality.1-4 Very
recently, a part of the authors discovered the rhodium-catalyzed
1,4-conjugate addition of aryl- and alkenylboronic acids to
enones.5 This new catalytic reaction has several advantages over
other 1,4-addition reactions. (1) The organoboronic acids used
in this reaction are stable to oxygen and moisture, permitting us
to run the reaction in protic media or even in an aqueous solution.
(2) The organoboronic acids are much less reactive toward enones
in the absence of a rhodium catalyst than the organometallic
reagents so far used, such as organomagnesium or -lithium
reagents, and no 1,2-addition to enones takes place in the presence
or absence of the catalyst. (3) The reaction is catalyzed by
transition-metal complexes coordinated with phosphine ligands.
Since chiral phosphine ligands are the chiral auxiliaries most
extensively studied for transition-metal-catalyzed asymmetric
reactions,6 one can use the accumulated knowledge of the chiral
phosphine ligands for the asymmetric reaction. Here we report
asymmetric 1,4-addition of aryl- and alkenylboronic acids which
of the specific rotation ([R]20 -21 (c 0.96, chloroform)) with
D
that reported for (R)-3am,9 and the enantiomeric excess was
determined by HPLC analysis using a chiral stationary phase
column (Chiralcel OD-H, hexane/2-propanol ) 98/2). Use of
Rh(acac)(CO)2 in place of Rh(acac)(C2H4)2 as a catalyst precursor
significantly lowered both catalytic activity and enantioselectivity
(entry 2). 1H and 31P NMR studies revealed that Rh(acac)(C2H4)2
reacts immediately with 1 equiv of (S)-binap in C6D6 to give Rh-
(acac)[(S)-binap] quantitatively.10 The isolated Rh(acac)[(S)-
binap] complex showed essentially the same catalytic activity and
stereoselectivity (entry 3) as the in situ catalyst generated from
Rh(acac)(C2H4)2 and (S)-binap, indicating that Rh(acac)[(S)-binap]
is a catalytically active species or a key precursor. In contrast,
addition of (S)-binap to Rh(acac)(CO)2 in the same solvent gave
a complex mixture consisting of two main species, Rh(acac)[(S)-
binap] and an unidentified species. The lower selectivity of the
catalyst generated from Rh(acac)(CO)2 is attributed to the
formation of the complex mixture.
(1) For reviews, see: (a) Schmalz, H.-G. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4,
Chapter 1.5. (b) Rossiter, B. E.; Swingle, N. M. Chem. ReV. 1992, 92, 771.
(c) Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley and
Sons: New York, 1994; pp 207-212. (d) No´gra´di, M. StereoselectiVe
Synthesis; VCH Publishers: New York, 1995; pp 213-224. (e) Seyden-Penne,
J. Chiral Auxiliaries and Ligands in Asymmetric Synthesis; John Wiley and
Sons: New York, 1995.
(2) For recent examples for asymmetric addition of organozinc or
magnesium reagents in the presence of nickel or copper catalysts, see: (a)
Feringa, B. L.; Pineschi, M.; Arnold, L. A.; Imbos, R.; de Vries, A. H. M.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2620. (b) Kno¨bel, A. K. H.; Escher,
I. H.; Pfaltz, A. Synlett 1997, 1429. (c) Alexakis, A.; Burton, J.; Vastra, J.;
Mangeney, P. Tetrahedron: Asymmetry 1997, 8, 3987. (d) De Vries, A. H.
M.; Imbos, R.; Feringa, B. L. Tetrahedron: Asymmetry 1997, 8, 1467. (e) De
Vries, A. H. M.; Meetsma, A.; Feringa, B. L. Angew. Chem., Int. Ed. Engl.
1996, 35, 2374. (f) Kanai, M.; Tomioka, K. Tetrahedron Lett. 1995, 36, 4275.
(g) Van Klaveren, M.; Lambert, F.; Eijkelkamp, D. J. F. M.; Grove, D. M.;
van Koten, G. Tetrahedron Lett. 1994, 35, 6135. (h) Asami, M.; Usui, K.;
Higuchi, S.; Inoue, S. Chem. Lett. 1994, 297. (i) Soai, K.; Okudo, M.;
Okamoto, M. Tetrahedron Lett. 1991, 32, 95. (j) Bolm, C. Tetrahedron:
Asymmetry 1991, 2, 701.
It was found that phenylboronic acid (2m) undergoes hydrolysis
giving benzene as a competing reaction under the reaction
(7) Asymmetric Michael addition forming a chiral carbon center on the
nucleophile has been reported to be catalyzed by a chiral bis(phosphine)-
rhodium complex: (a) Sawamura, M.; Hamashima, H.; Ito, Y. J. Am. Chem.
Soc. 1992, 114, 8295. (b) Sawamura, M.; Hamashima, H.; Ito, Y. Tetrahedron
1994, 50, 4439.
(8) The following chiral ligands were examined: 2,2′-bis(diphenylphos-
phino)-1,1′-binaphthyl (binap), 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis-
(diphenylphosphino)butane (diop), 2,3-bis(diphenylphosphino)butane (chira-
phos), 2,2′-bis[4-(isopropyl)oxazolyl]-1,1′-binaphthyl (boxax), 2-[2-(diphenyl-
phosphino)phenyl]-4-(isopropyl)oxazoline (phox), 2-diphenylphosphino-2′-
methoxy-1,1′-binaphthyl (mop).
(9) The specific rotation of (R)-3-phenylcyclohexanone (3am, 98.7% ee)
has been reported to be [R]20 +20.5 (c 0.58, chloroform): Schultz, A. G.;
Harrington, R. E. J. Am. CheDm. Soc. 1991, 113, 4926.
(3) Asymmetric addition of aryllithiums catalyzed by a chiral ligand has
been reported: Tomioka, K.; Shindo, M.; Koga, K. Tetrahedron Lett. 1993,
34, 681.
(4) For recent examples for catalytic asymmetric Michael addition of
malonate esters, see: (a) Yamaguchi, M.; Shiraishi, T.; Hirama, M. J. Org.
Chem. 1996, 61, 3520. (b) Arai, T.; Sasai, H.; Aoe, K.; Okamura, K.; Date,
T.; Shibasaki, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 104 and references
therein.
(10) Rh(acac)[(S)-binap]: 1H NMR (C6D6, 23 °C) δ 1.54 (s, 6H, MeCO),
5.35 (s, 1H, COCHCO), 6.45 (br, 4H), 6.52 (t, J ) 7.2 Hz, 2H), 6.65-6.68
(m, 2H), 6.72 (d, J ) 8.3 Hz, 2H), 6.97-7.00 (m, 2H), 7.15-7.20 (m, 9H),
7.23 (d, J ) 8.1 Hz, 2H), 7.64 (quint, J ) 4.3 Hz, 2H), 8.03 (br, 4H), 8.21
(br, 3H); 31P{1H} NMR (C6D6, 23 °C) δ 55.3 (d, JRh-P ) 193 Hz). Anal.
Calcd for RhC49H39O2P2: C, 71.36; H, 4.77. Found: C, 71.07; H, 4.76. It has
been reported that the addition of a bisphosphine to Rh(acac)(cod) forms
Rh(acac)(bisphosphine): Fennis, P. J.; Budzelaar, P. H. M.; Frijns, J. H. G.;
Orpen, A. G. J. Organomet. Chem. 1990, 393, 287.
(5) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16, 4229.
(6) For a review, see: Ojima, I. Catalytic Asymmetric Synthesis; VCH
Publishers: New York, 1993.
S0002-7863(98)00666-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/19/1998

5580 J. Am. Chem. Soc., Vol. 120, No. 22, 1998
Communications to the Editor
Table 1. Asymmetric 1,4-Addition of Boronic Acids 2 to Enones
1 Catalyzed by (S)-binap-Rhodium(I)a
Scheme 1
RB(OH)2 2 temp
entry enone 1 (equiv to 1) (°C) (%) of 3 % eec (c in CHCl3)
yieldb
[R]20
D
1
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1c
1d
1e
2m (1.4) 100
2m (1.4) 100
2m (1.4) 100
2m (2.5) 100
2m (5.0) 100 >99 (3am) 97 (S)
2m (5.0) 100 >99 (3am) 96 (S)
64 (3am) 97 (S) -21 (0.96)
15 (3am) 43 (S)
62 (3am) 97 (S)
2d
3e
4
93 (3am) 97 (S)
5
6f
7
2m (1.4)
2m (1.4)
2m (1.4)
40
60
80
<2 (3am) 97 (S)
3 (3am) 97 (S)
42 (3am) 97 (S)
59 (3am) 97 (S)
8
9
10
2m (1.4) 120g
11
12h
13
14
15
16
17
18
19
20
21
2n (5.0)
2o (2.5)
2p (5.0)
2q (5.0)
2r (2.5)
2s (5.0)
100 >99 (3an) 97
-17 (0.95)
-11 (0.97)
-13 (0.91)
-9.5 (1.13)
-12 (0.88)
-19 (0.86)
100
100
100
100
100
70 (3ao) 99
97 (3ap) 96
94 (3aq) 96
88 (3ar) 94
76 (3as) 91
Scheme 2a
2m (1.4) 100
2r (2.5) 100
2m (1.4) 100
2m (5.0) 100
2m (2.5) 100
93 (3bm) 97 (S) -92 (0.82)
64 (3br) 96
51 (3cm) 93
82 (3dm) 97
88 (3em) 92
-79 (0.45)
-58 (0.75)
-33 (1.12)
-17 (1.26)
a The reaction was carried out in dioxane/H2O (10/1) for 5 h in the
presence of 3 mol % of the catalyst generated from Rh(acac)(C2H4)2
and (S)-binap unless otherwise noted. b Isolated yield by silica gel
chromatography. c Determined by HPLC analysis with chiral stationary
phase columns: Daicel Chiralcel OD-H (3am, 3ao, 3ap, 3cm, 3dm,
3em), AD (3an, 3aq), OB-H (3bm) (eluent, hexane/2-propanol ) 98/
2), and AS (3ar, 3as, 3br) (eluent, hexane/2-propanol ) 90/10).
d Rh(acac)(CO)2 was used in place of Rh(acac)(C2H4)2. e Isolated
Rh(acac)[(S)-binap] was used as a catalyst. f In the presence of 1 mol
% of the catalyst. g In a pressure-resistant reactor. h Reaction in
1-propanol/H2O (10/1).
a The binaphthylene moiety in (S)-binap is omitted for clarity.
conditions. The yield of the addition product 3am was greatly
improved by use of a large excess of the boronic acid (entries 4
and 5). With 5 times excess of phenylboronic acid (2m), a
quantitative yield of 3am was obtained even in the presence of 1
mol % of the catalyst without loss of enantioselectivity (entry
6). The reaction temperature is also important for the high
chemical yield (entries 7-10). At 60 °C or lower, the 1,4-addition
was very slow giving 3am in not higher than 3% yield. The
highest yield was achieved at 100 °C. Interestingly, the enantio-
selectivity was kept constant at the reaction temperature ranging
between 40 and 120 °C.11
The scope of the present catalytic asymmetric addition is broad
(Scheme 1). Aryl groups substituted with either electron-donating
or -withdrawing groups, 4-MeC6H4, 4-CF3C6H4, 3-MeOC6H4, and
3-ClC6H4, were introduced onto 2-cyclohexenone with high
enantioselectivity by the reaction with the corresponding boronic
acids 2n-q (entries 11-14). Asymmetric addition of 1-alkenyl-
boronic acids was also successful, (E)-1-heptenylboronic acid (2r)
and (E)-3,3-dimethyl-1-butenylboronic acid (2s) giving the cor-
responding products of over 90% ee (entries 15 and 16).
Cyclopentenone (1b) also underwent the asymmetric addition of
phenyl- and 1-heptenylboronic acids with high enantioselectivity
under similar reaction conditions to give the corresponding
3-substituted cyclopentanones, 3bm12 (97% ee (S)) and 3br (96%
ee), respectively, in high yields (entries 17 and 18). High
enantioselectivity was also observed in the reaction of linear
enones 1d and 1e which have trans olefin geometry (entries 20
and 21). Thus, the present catalytic asymmetric 1,4-addition
proceeds with high enantioselectivity for both cyclic and linear
R,â-unsaturated ketones with a variety of aryl- and alkenylboronic
acids.
The catalytic cycle has been proposed to involve the insertion
of carbon-carbon double bond of enone into aryl-rhodium bond
as a key step.5 Scheme 2 shows the stereochemical pathway
forming the products of (S) configuration, which is exemplified
by the reaction of 2-cyclohexenone. According to the highly
skewed structure known for transition-metal complexes coordi-
nated with a binap ligand,13 (S)-binap-rhodium intermediate A
should have an open space at the lower part of the vacant
coordination site, the upper part being blocked by one of the
phenyl rings of the binap ligand. The olefinic double bond of
2-cyclohexenone coordinates to rhodium with its 2si face forming
B rather than with its 2re face, which undergoes migratory
insertion to form a stereogenic carbon center whose absolute
configuration is (S). All the 1,4-addition products 3 obtained here
are expected to have the absolute configuration resulting from
the attack of 2si face of enones.
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.
Supporting Information Available: Experimental procedures and
spectroscopic and analytical data for the products (3 pages, print/PDF).
See any current masthead page for ordering information and Web access
instructions.
(11) For some other substrates, the higher enantioselectvity was observed
at the higher reaction temperature.
JA980666H
(12) The specific rotation of (S)-3-phenylcyclopentanone (3bm, 70% ee)
has been reported to be [R]RT -67.7 (c 1.0, chloroform): Barnhart, R. W.;
D
Wang, X.; Noheda, P.; Bergens, S. H.; Whelan, J.; Bosnich, B. J. Am. Chem.
Soc. 1994, 116, 1821.
(13) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T. Organometallics
1993, 12, 4188 and references therein.