Asymmetric conjugate 1,4-addition of arylboronic acids to α,β-unsaturated esters catalyzed by rhodium(I)/(S)-binap

Article abstract of DOI:10.1021/jo0002184

Arylboronic acids underwent the conjugate 1,4-addition to α,β-unsaturated esters to give β-aryl esters in high yields in the presence of a rhodium(I) catalyst. The addition of arylboronic acids to isopropyl crotonate resulted in high yields and high enantioselectivity exceeding 90% ee in the presence of 3 mol % of Rh(acac)(C₂H₄)₂ and (S)-binap at 100 °C. The rhodium/(S)-binap complex provided (R)-3-phenylbutanoate in the addition of phenylboronic acid to benzyl crotonate. The effects on the enantioselectivity of chiral phosphine ligands, rhodium precursors, and substituents on α,β-unsaturated esters are discussed, as well as the mechanistic aspect of the catalytic cycle.

Full text of DOI:10.1021/jo0002184

J . Org. Chem. 2000, 65, 5951-5955
5951
Asym m etr ic Con ju ga te 1,4-Ad d ition of Ar ylbor on ic Acid s to
r,â-Un sa tu r a ted Ester s Ca ta lyzed by Rh od iu m (I)/(S)-bin a p
Satoshi Sakuma, Masaaki Sakai, Ryoh Itooka, and Norio Miyaura*
Division of Molecular Chemistry, Faculty of Engineering, Hokkaido University, Sapporo 060-8628, J apan
miyaura@org-mc.eng.hokudai.ac.jp
Received February 15, 2000
Arylboronic acids underwent the conjugate 1,4-addition to R,â-unsaturated esters to give â-aryl
esters in high yields in the presence of a rhodium(I) catalyst. The addition of arylboronic acids to
isopropyl crotonate resulted in high yields and high enantioselectivity exceeding 90% ee in the
presence of 3 mol % of Rh(acac)(C2H4)2 and (S)-binap at 100 °C. The rhodium/(S)-binap complex
provided (R)-3-phenylbutanoate in the addition of phenylboronic acid to benzyl crotonate. The effects
on the enantioselectivity of chiral phosphine ligands, rhodium precursors, and substituents on R,â-
unsaturated esters are discussed, as well as the mechanistic aspect of the catalytic cycle.
Conjugate 1,4-addition reactions by rhodium-,1
nickel-,2 ruthenium-,3 or copper4 complexes are of great
value in asymmetric synthesis since various chiral aux-
iliaries are now available for the metal-catalyzed reac-
tions.5 We have recently reported the rhodium-catalyzed
1,4-conjugate addition reactions of aryl- and 1-alkenyl-
boronic acids to enones in an aqueous solvent, which
proceeds through a sequence of boron-rhodium trans-
metalation, yielding an organorhodium(I) species and its
addition to enones.6 Hayashi7 and the joint research with
them8 demonstrated asymmetric variants by using a
rhodium(I)-chiral phosphine complex. Among the chiral
phosphines examined, the binap ligand9 developed by
Noyori for asymmetric hydrogenation of alkenes was
found to be the best chiral auxiliary, achieving over 90%
ee for cyclic and acyclic enones. The efficiency of trans-
metalation from boron to rhodium was also demonstrated
in catalytic 1,2-additions of organoboronic acids to alde-
hydes10 and N-sulfonyl imines.11 The utility of potassium
organotrifluoroborates (RBF3K) as the nucleophile for
both rhodium-catalyzed 1,4- and 1,2-additions was re-
cently reported by Batey.12
Here, we report a conjugate 1,4-addition of arylboronic
acids (2) to R,â-unsaturated esters (1) yielding optically
active â-aryl esters (3) in the presence of a rhodium(I)-
binap catalyst (eq 1).13
(1) (a) Sawamura, M.; Hamashima, H.; Ito, Y. J . Am. Chem. Soc.
1992, 114, 8295-8296. (b) Sawamura, M.; Hamashima, H.; Ito, Y.
Tetrahedron 1994, 50, 4439-4454.
(2) (a) Ikeda, S.; Cui, D.-M.; Sato, Y. J . Am. Chem. Soc. 1999, 121,
4712-4713. (b) Bolm, C. Tetrahedron: Asymmetry 1991, 2, 701-704.
(c) Soai, K.; Hayasaka, T.; Ugajin, S. J . Chem. Soc., Chem. Commun.
1989, 516-517. (d) Petrier, C.; Barbosa, J . C. S.; Dupuy, C.; Luche,
J .-L. J . Org. Chem. 1985, 50, 5761-5765. (e) Cacchi, S.; Palmieri, G.
J . Organomet. Chem. 1985, 282, C3-6. (f) Greene, A. E.; Lansard,
J .-P.; Luche. J .-L.; Petrier, C. J . Org. Chem. 1984, 49, 931-932.
(g) Dayrit, F. M.; Gladkowski, D. E.; Schwartz, J . Ibid. 1980, 102,
3976-3978.
(3) (a) Murahashi, S.-I.; Naota, T.; Taki, H.; Mizuno, M.; Takaya,
H.; Komiya, S.; Mizuho, Y.; Oyasato, N.; Hiraoka, M.; Hirano, M.;
Fukuoka, A. J . Am. Chem. Soc. 1995, 117, 12436-12451. (b) Mitsudo,
T.; Nakagawa, Y.; Watanabe, K.; Hori, Y.; Misawa, H.; Watanabe, H.;
Watanabe, Y. J . Org. Chem. 1985, 50, 565-571. (c) Trost, B. M. Angew.
Chem., Int. Ed. Engl. 1995, 34, 259-281.
(4) (a) Alexakis, A. In Transition Metals for Organic Synthesis;
Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998; Vol. 1,
Chapter 3.10. (b) Lipshutz, B. H. In Organometallics in Synthesis;
Schlosser, M., Ed.; Wiley: New York, 1994; p 283.
(5) For reviews, see: (a) Schmalz, H.-G. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, C1991;
Vol. 4, Chapter l.5. (b) Rossiter, B. E.; Swingle, N. M. Chem. Rev. 1992,
92, 771-806. (c) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
J ohn Wiley and Sons: NewYork, 1994; pp 207-212. (d) Seyden-Penne.
Chiral Auxiliaries and Ligands in Asymmetric Synthesis; J ohn Wiley
and Sons: NewYork, 1995. (e) Tomioka, K.; Nagaoka, Y.; Yamaguchi,
M. In Comprehensive Asymmetric Catalysis I-III; J acobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. 3, Chapter
31.
Rea ction Con d ition s
The 1,4-addition reactions of phenylboronic acid to
the representative R,â-unsaturated esters in the presence
of [Rh(cod)(MeCN)2]BF4 (3 mol %) are summarized in
Table 1.
The reaction was highly dependent on the substituent
(R1 in 1), which may affect the rate of insertion of 1 into
a rhodium-carbon bond. Thus, the additions to both
dimethyl fumarate and diethyl maleate smoothly pro-
ceeded at room temperature (entries 1 and 2), whereas
the additions to cinnamate, acrylate, and crotonate were
heated to 50, 80, and 100 °C to complete the reactions
(9) 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl. See: Noyori, R.;
Takaya, H. Acc. Chem. Res. 1990, 23, 345-350.
(10) Sakai, M.; Ueda, M.; Miyaura, N. Angew. Chem., Int. Ed. Engl.
1998, 37, 3279-3280. Ueda, M.; Miyaura, N. J . Org. Chem. 2000, 65,
4450-4452.
(11) Ueda, M.; Miyaura, N. J . Organomet. Chem. 2000, 595, 31-
35.
(6) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16,
4229-4231.
(12) Batey, R. A.; Thadani, A. N.; Smil, D. V. Org. Lett. 1999, 1,
1683-1686.
(13) Preliminary results were discussed in The Xth International
Conference on Boron Chemistry; Durham, J uly 11-15, 1999 and
Symposium on Organic and Inorganic Syntheses via Boranes in
American Chemical Society 218th Meeting; New Orleans, Aug 22-
25, 1999.
(7) (a) Hayashi, T.; Senda, T.; Takaya, Y.; Ogasawara, M. J . Am.
Chem. Soc. 1999, 121, 11591-11592. (b) Takaya, Y.; Ogasawara, M.;
Hayashi, T.; Tetrahedron Lett. 1998, 39, 8479-8482.
(8) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura,
N. J . Am. Chem. Soc. 1998, 120, 5579-5580.
10.1021/jo0002184 CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/23/2000

5952 J . Org. Chem., Vol. 65, No. 19, 2000
Sakuma et al.
Ta ble 2. Effect of Rh od iu m P r ecu r sor on th e
Ta ble 1. Ad d ition of P h en ylbor on ic Acid to
r,â-Un sa tu r a ted Ester s w ith [Rh (cod )(MeCN)2]BF 4
a
Asym m etr ic Ad d ition of P h en ylbor on ic Acid to Ben zyl
Cr oton a tea
entry
R,â-unsaturated ester
T/°C
yieldb/%
entry
ligand
T/°C time/h yieldb/% % ee
1
2
3
4
5
6
7
8
9
(E)-MeO2CCHdCHCO2Me
(Z)-EtO2CCHdCHCO2Et
(E)-PhCHdCHCO2Me
(E)-4-NO2C6H4CHdCHCO2Me
CH2dCHCO2Me
(E)-MeCHdCHCO2Me
MeCHdC(CO2Et)2
MeCHdC(CO2Et)2
25
25
50
50
80
100
100
70
84
79
87
97
60c,d
82d
9d
c
1
2
3
4
5
6
7
8
[Rh(cod)(MeCN)2]BF4
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
Rh(acac)(C2H4)2
100
100
100
60
100
100
100
60
16
16
2
24
16
16
16
24
90
98
99
48
98
98
99
64
85
86
87
88
86
86
87
33
d
Rh(acac)(coe)2
Rh(acac)(CO)2
[RhCl(cod)]2
[RhCl(cod)]2
76e
traced
(Z)-EtO2CCHdC(Me)CO2Et
100
a
a
A mixture of benzyl crotonate (1 mmol) and phenylboronic acid
(2 mmol) in aqueous dioxane was stirred in the presence of a
A mixture of R,â-unsaturated ester (1 mmol) and phenyl-
boronic acid (2 mmol) in aqueous MeOH (6/1) was stirred for 16 h
b
b
rhodium complex (3 mol %) and (S)-binap (4.5 mol %). Isolated
in the presence of [Rh(cod)(MeCN)2]BF4 (3 mol %). Isolated
yields. c cod ) 1,5-cyclooctadiene. coe ) cyclooctene.
d
yields. c The reaction was accompanied with methyl 3,3-diphenyl-
propionate (7%). In aqueous dioxane (6/1). e The reaction was
d
carried out in aqueous EtOH (5/2) at 70 °C for 24 in the presence
of phenylboronic acid (4 mmol).
phenylboronic acid to benzyl crotonate to reveal the
effects of rhodium precursors on yields and enantiose-
lectivities (Table 2).15
(entries 3-6). The relative reactivity is parallel to the
order of rhodium/alkene complex stability or the insertion
rate, which can be estimated by the LUMO energy level
of alkenes.14 However, the addition to trisubstituted
alkenes was very slow, even at 100 °C, due to their large
steric hindrance on the coordination to the rhodium metal
center (entries 7 and 9). The prolongation of reaction time
to 1 day improved the yield to 76% in the presence of 4
equiv of phenylboronic acid (entry 8). Similar to the
results obtained in the addition to enones, aqueous
solvents combining water and a weak donor solvent such
as alcohols, dimethoxyethane (DME), or dioxane afforded
good results. J udging from the recovery of the products,
the saponification of the esters was very slow even at
100 °C.
The addition of phenylboronic acid to methyl acrylate
(entry 5) was accompanied by 3,3-diphenylpropanoate
(7%), which was derived from â-hydride elimination,
giving ethyl cinnamate (eqs 2 and 3). A cinnamate
intermediate was not detected in the reaction mixture
since it is more reactive than the parent acrylate (entries
3 and 5).
All of the cationic and neutral rhodium complexes
examined, such as [Rh(cod)(CH3CN)2]BF4, Rh(acac)(CH2d
CH2)2, Rh(acac)(coe)2, Rh(acac)(CO)2, and [Rh(cod)Cl]2,
were highly effective at 100 °C (entries 1-8). There were
no large differences in yields or enantioselectivities (% ee)
between cationic and neutral rhodium complexes, but
neutral complexes were superior to cationic rhodiums
because a combination of Rh(acac)(CH2dCH2)2/(S)-binap
revealed higher enantioselectivity (1-3% ee) than [Rh-
(cod)(CH3CN)2]BF4/(S)-binap (entry 1). The reaction was
completed within 2 h at 100 °C and overnight at 60 °C
(entries 2 and 3). The enatioselectivity was not affected
by the reaction temperatures or by the reaction times,
although the RhCl complex resulted in significantly low
enantioselectivity at 60 °C (entry 8). The isolated Rh-
(acac)[(S)-binap]15 showed essentially the same enatio-
selectivity as that of the in situ preparation.
The enatiomeric excess (% ee) was determined by
HPLC analysis using a chiral stationary column (Dicel
Chiralcel OD-H or OB-H). The addition of PhB(OH)2 to
benzyl crotonate with a cationic rhodium/(S)-binap cata-
lyst (entry 1) provided benzyl 3-phenylbutanoate ([R]D
-14.5 (c 1.02, CHCl3), whose saponification with H2 (1.5
atm, 10% Pd/C in EtOH at room temperature for 3 h)
gave 3-phenylbutanoic acid ([R]D -42.6 (c 0.77, benzene)
(eq 4). Thus, the absolute configuration of the ester (7)
obtained from (S)-binap was established to be (R) by the
specific rotation reported for (R)-3-phenylbutanoic acid
([R]D -45.8 (c 0.77, benzene).16
The formation of a Heck-type product suggests the
presence of a mechanism involving a rhodium species
bound to the R-carbon (6). However, such byproducts
were not observed, or were only observed in negligibly
small amounts, in other substrates shown in entries 1-9.
The effects of commercially available chiral ligands
on the enantioselectivity in the addition of 3-methoxy-
phenylboronic acid to isopropyl crotonate are summarized
in Table 3 and Figure 1.
Asym m etr ic Ad d ition
The in situ preparation of a catalyst from rhodium
complexes and (S)-binap was followed by the addition of
(15) The reaction of Rh(acac)(cod) with bisphosphine (P-P) yields
a Rh(acac)(P-P) complex: Fennis, P. J .; Budzelaar, P. H. M.; Frijns,
J . H. G.; Orpen, A. G. J . Organomet. Chem. 1990, 393, 287-298. For
Rh(acac)[(S)-binap] complex, see ref 7.
(16) Suzuki, I.; Kin, H.; Yamamoto, Y. J . Am. Chem. Soc. 1993, 115,
10139-10147.
(14) (a) Slexander, J . J . In The Chemistry of the Metal-Carbon Bond;
Hartley, F. R., Patai, S., Eds.; J ohn Wiley & Sons: New York, 1985;
Vol. 2, Chapter 5. (b) Yamamoto, A. Organotransition Metal Chemistry-
Fundemental Concepts and Applications; Wiley: New York, 1986.

Conjugate 1,4-Addition of Arylboronic Acids
J . Org. Chem., Vol. 65, No. 19, 2000 5953
selectivity, though both reactions were very slow, even
in the presence of a large excess of boronic acid (entries
10 and 11). The o-methoxy group in Rh(2-MeOC6H4)-
(PMe3)3 coordinates to the rhodium metal center,18 but
it is not obvious at present whether the significant effect
of an o-methoxy group is derived not only from steric
interaction but also from intramolecular chelation.
Together with the effect of the ester group (R2), the
â-substitution (R1) significantly affected the yields and
enantioselectivities. The enantioselectivity improved to
97% ee in the â-isopropyl derivative (entry 12), but the
increase in steric interaction significantly reduced the
chemical yield, which was not improved in the presence
of a large excess of arylboronic acids or by prolongation
of the reaction time. More flexible chiraphos was better
ligand for improving the chemical yield, but the enanti-
oselectivity was not sufficient for practical purposes
(entry 13). Although bulky â-alkyl groups caused an
increase in the enantioselectivity, all attempts at high-
enantioselective addition to â-aryl derivatives such as
cinnamate were unsuccessful (entries 14 and 15).
F igu r e 1. Chiral ligands.
Ta ble 3. Effect of Liga n d on th e Asym m etr ic Ad d ition of
3-Meth oxyp h en ylbor on ic Acid to Isop r op yl Cr oton a tea
Under similar reaction conditions, arylboronic esters
8 and 9 also underwent the conjugate addition (eq 5).
entry
ligand
(S)-binap
(S)-tol-binap
(R,R)-diop
(R,R)-chiraphos
(S,R)-bppfa
(S,S)-Me-duphos
(S)-MeO-mop
yieldb/%
% ee
1
2
3
4
5
6
7
91
43
45
97
9
91
91
7
75
0
92
trace
29
a
A mixture of isopropyl crotonate (1 mmol) and 3-methoxy-
phenylboronic acid (2 mmol) in aqueous dioxane was stirred for
16 h at 100 °C in the presence of Rh(acac)(C2H4)2 (3 mol %) and
b
ligand (4.5 mol %). Isolated yields.
The pinacol ester 9 resulted in a slightly lower yield,
but the enantioselectivity thus obtained was the same
as that of phenylboronic acid (entry 3). Various arylbor-
onic pinacol esters are now accessible by the palladium-
catalyzed cross-coupling reaction of bis(pinacolato)-
diboron with aryl halides or triflates or by a similar
coupling reaction of pinacolborane with aryl halides in
the presence of triethylamine.19 Thus, the stepwise bond-
forming reactions catalyzed by palladium and rhodium
may allow one-pot synthesis of â-aryl esters.
The complexes in situ obtained from binap, chiraphos,
and Me-duphos afforded high yields of the addition
product (entries 1, 4, and 6), but binap was again found
to be the best ligand giving both high yields and high
asymmetric induction, similar to those obtained by the
1,4-addition to enones (entry 1). Other bidentate ligands
resulted in low yields or low enantioselectivities (entries
2, 3, and 5). The chiral monodentate ligand MeO-mop,
reported in asymmetric hydrosilylation,17 did not catalyze
the reaction (entry 7).
The results of 1,4-addition of representative arylboronic
acids to R,â-unsaturated esters in the presence of Rh-
(acac)(C2H4)/(S)-binap are summarized in Table 4.
Mech a n ism
Although work on mechanistic details is still in progress,
it is thought that the present transformation may have
resulted from a catalytic cycle that involves the trans-
metalation of arylboronic acid to a rhodium(I) species 10
to give an arylrhodium(I) complex 11, the coordination
of an unsaturated ester to rhodium followed by insertion
into the Rh-C bond to afford an equilibrium mixture of
12 and 13 and, finally, the hydrolysis of the rhodium
enolate 13 with water to provide 14 and 10 (Figure 2).
The arylrhodium(I)/arylphosphine complexes are un-
stable, making isolation in pure form impossible, but they
3-Methoxyphenylboronic acid was added to a series of
crotonates to reveal the effect of the ester group (R2 in 1)
(entries 1-6). The bulkiness of the ester group improved
the enantioselectivity in the order of ethyl ∼ isobutyl ∼
benzyl < isopropyl ∼ cyclohexyl < tert-butyl, thus sug-
gesting the superiority of secondary and tertiary alkyl
esters, whereas the reaction was very slow for the tert-
butyl ester (entry 6). Various arylboronic acids having
ortho, meta, and para substituents smoothly underwent
the addition to isopropyl crotonate with high enantio-
selectivity exceeding 90% ee (entries 4 and 7-12). There
was no appreciable difference in yields or enantio-
selectivity between meta- and para-functionalized aryl-
boronic acids (entries 4 and 7-9). However, ortho-
substitution caused a significant increase in the enantio-
(18) J ones, R. A.; Wilkinson, G. J . Chem. Soc., Dalton Trans. 1979,
472-477.
(19) Th coupling between bis(pinacolato)diboron with aryl halides
or triflates, see: (a) Ishiyama, T.; Murata, M.; Miyaura, N. J . Org.
Chem. 1995, 60, 7508-7510. (b) Ishiyama, T.; Itoh, Y.; Kitano, T.;
Miyaura, N. Tetrahedron. Lett. 1997, 38, 3447-3450. The coupling of
haloarenes with pinacolborane: (c) Murata, M.; Watanabe, S.; Masuda,
Y. J . Org. Chem. 1999, 62, 6458-6459. (d) Murata, M.; Oyama, T.;
Watanabe, S.; Masuda, Y. J . Org. Chem. 2000, 65, 164-168.
(17) Uozumi, Y.; Hayashi, T. J . Am. Chem. Soc. 1991, 113, 9887-
9888.

5954 J . Org. Chem., Vol. 65, No. 19, 2000
Ta ble 4. Asym m etr ic Ad d ition of Ar ylbor on ic Acid s to r,â-Un sa tu r a ted Ester sa
Sakuma et al.
entry
R,â-unsaturated ester
ArB(OH)2
yieldb/%
% ee
[R]20 (c in CHCl3)
D
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
(E)-CH3CHdCHCO2C2H5
3-MeOC6H4B(OH)2
3-MeOC6H4B(OH)2
3-MeOC6H4B(OH)2
3-MeOC6H4B(OH)2
3-MeOC6H4B(OH)2
3-MeOC6H4B(OH)2
4-MeC6H4B(OH)2
4-MeOC6H4B(OH)2
4-MeOC6H4B(OH)2
2-MeC6H4B(OH)2
2-MeOC6H4B(OH)2
3-MeOC6H4B(OH)2
3-MeOC6H4B(OH)2
4-MeC6H4B(OH)2
4-MeC6H4B(OH)2
81
98
97
91
97
54
89
55
87
88
87
91
91
92
92
92
92
94
98
97
77
77
78
-20.3 (1.01)
-21.7 (1.01)
-12.3 (1.00)
-21.2 (1.02)
-18.4 (1.01)
-19.5 (1.01)
-23.5 (1.01)
(E)-CH3CHdCHCO2CH2CH(CH3)2
(E)-CH3CHdCHCO2CH2Ph
(E)-CH3CHdCHCO2i-C3H7
(E)-CH3CHdCHCO2cyclo-C6H11
(E)-CH3CHdCHCO2t-C4H9
(E)-CH3CHdCHCO2i-C3H7
(E)-CH3CHdCHCO2i-C3H7
(E)-CH3CHdCHCO2i-C3H7
(E)-CH3CHdCHCO2i-C3H7
(E)-CH3CHdCHCO2i-C3H7
(E)-(CH3)2CHCHdCHCO2i-C3H7
(E)-(CH3)2CHCHdCHCO2i-C3H7
(E)-PhCHdCHCO2i-C3H7
82c
35c
43c
26
-21.6 (0.99)
-8.5 (1.00)
-2.0 (1.00)
-17.5 (1.02)
92d
28
(E)-PhCHdCHCO2i-C3H7
37c
+2.9 (0.99)
a
A mixture of R,â-unsaturated ester (1 mmol) and arylboronic acid (2 mmol) in aqueous dioxane was stirred for 16 h at 100 °C in
the presence of Rh(acac)(C2H4)2 (3 mol %) and (S)-binap (4.5 mol %). Isolated yields by chromatography over silica gel. c Arylboronic
acid (5 mmol) was used. (R,R)-Chiraphos was used in place of (S)-binap.
b
d
Heathcock.22 The η1 oxygen-bound rhodium enolate com-
plexes, synthesized from RhCl(CO)(PMe3)2 and potassium
enolates or silyl enolates, exhibit a dynamic equilibrium
between the O-bound and the C-bound forms, which are
sufficiently nucleophilic to condense with carbonyl com-
pounds. Thus, the hydrolysis of the rhodium enolate 13
with water lead to 14, which avoids the â-hydride
elimination from 12 giving the Heck-coupling product
(eq 3) or Aldol-type condensation of 13. Although there
is no clear evidence that (hydroxo)rhodium(I)24 exists as
an active species for transmetalation (10 f 11), results
of present study implied that there is a mechanism that
involves transmetalation as a crucial step in the catalytic
cycle. The high oxophilicity of the boron center and the
basicity of transition metal hydroxides would induce
transmetalation, which can be rationalized by the related
catalyzed reactions by palladium and platinum complexes
F igu r e 2. Proposed catalytic cycle.
whereby organic groups on the boron atom readily
transfer to Pd(acac)2,25 [η3-C3H5PdOAc]2,26 η3-C3H5Pd-
(acac),26 RPd(OR)L2 (R ) H, Me, Ac)26,27,28 and [Pt(OR)(S)-
are key intermediates for carrying out various coupling
L2]+ (R ) H, Me)29 under neutral conditions. The reaction
of phenylboronic acid with benzyl crotonate with the Rh-
(acac)/(S)-binap complex (entry 2 in Table 2) was retarded
completely by the addition of a 3 mol % of acid such as
HBF4, AcOH, or HCl, thus suggesting that neutralization
of the (hydroxo)rhodium species inhibits transmetalation.
reactions with organic halides20 and additions to alkenes
and alkynes.21 Preliminary results suggested a sequence
of the formation of the ArRh(I) species and its addition
to unsaturated esters because the Michael adduct was
obtained when the in situ preparation of phenylrhodium-
(I) (15) from a Vaska complex was followed by the
addition to methyl vinyl ketone (eq 6). The sequence
involves insertion of the alkene double bond into the
Rh-C bond and hydrolysis of the rhodium intermediate
(11 f 14).
The stereochemical pathway in the insertion of the
C-C double bond of 1 into the Rh-aryl bond can be
explained by a mechanism similar to that of the 1,4-
addition to enones.6 The binap ligand was originally
(22) The reaction of (PPh3)3RhCl with PhMgBr or trans-RhCl(CO)-
(PPh3)2 with PhLi yields the phenylrhodium(I) complexes: Keim, W.
J . Organomet. Chem. 1968, 14, 179-184. Hegedus, L. S.; Lo, S. M.;
Bloss, D. E. J . Am. Chem. Soc. 1973, 95, 3040-3042.
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The synthesis of rhodium enolate and its applications
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1989, 8, 2659-2664.

Conjugate 1,4-Addition of Arylboronic Acids
J . Org. Chem., Vol. 65, No. 19, 2000 5955
Exp er im en ta l Section
Rh(acac)(CH2dCH2)2, Rh(acac)(CO)2, and [Rh(cod)Cl]2 are
commercially available. [Rh(cod)(CH3CN)2]BF431 and Rh(acac)-
32
(coe)2 were synthesized by the reported procedures. HPLC
analysis was directly performed with a chiral stationary phase
column, Chiralcel OD-H and OB-H, purchased from Dicel Co.,
Ltd.
Gen er a l P r oced u r e. Rhodium complex (0.03 mmol), ligand
(0.045 mmol), and arylboronic acid (2 or 5 mmol) were added
to a flask containing a magnetic stirring bar, a septum inlet,
and a reflux condenser. The flask was flashed with argon and
charged with 1,4-dioxane (6 mL) and water (1 mL). After being
stirred for 30 min, R,â-unsaturated ester (1.0 mmol) was
added. The mixture was then stirred for 16 h at the temper-
ature shown in Tables 1-4. The product was extracted with
benzene, washed with brine, and dried over MgSO4. Chroma-
tography over silica gel gave the desired product.
(R)-3-P h en ylbu ta n oic Acid (Eq 4). (acac)Rh(C2H4)2 (0.03
mmol), (S)-binap (0.045 mmol), and phenylboronic acid (2
mmol) were placed in a flask. The flask was flashed with argon
and then charged with 1,4-dioxane (6 mL) and water (1 mL).
After being stirred for 30 min, benzyl crotonate was added.
The mixture was then stirred for 16 h at 100 °C. Chromatog-
raphy over silica gel yielded benzyl 3-phenylbutanoate: yield
0.252 g (99%); 86% ee (HPLC, OD-H; hexane/2-propanol )
98:2).
To a glass pressure bottle containing a magnetic stirring
bar and 10% Pd-C (10 mg) were added EtOH (3 mL) and
benzyl 3-phenylbutanoate (1 mmol). The resulting mixture was
stirred for 3 h at room temperature under 1.5 atmospheres of
hydrogen. The catalyst was removed by filtration through
Celite, and the acid was then extracted with 1 M NaOH (50
mL). The aqueous phase was treated with 1 M HCl (100 mL),
and the product was then extracted with diethyl ether.
Evaporation of solvent yielded 3-phenylbutanoic acid: yield
0.118 g (72%); [R]D -42.6 (c 0.77, benzene).
Ad d ition of P h en ylr h od iu m (I) Com p lex to Meth yl
Vin yl Keton e (Eq 6). To a solution of Vaska complex RhCl-
(CO)(PPh3)2 (0.03 mmol) in THF (0.5 mL) was added phenyl-
lithium (0.832 M in diethyl ether, 0.3 mmol) at -78 °C. After
the misture was stirred for 1.5 h at -78 °C, DMF (6 mL), H2O
(1 mL) and methyl vinyl ketone (1 mmol) were added. The
resulting mixture was stirred overnight at room temperature.
GC analysis revealed the formation of 4-phenyl-2-butanone in
72% yield based on the Vaska complex.
F igu r e 3. Transition state.
designed for asymmetric hydrogenation, but it also works
well in the Heck reaction30 and the conjugate addition
because those reactions involve a similar molecular
recognition mechanism. The configuration of a speculated
intermediate of the rhodium-(S)-binap30 and R,â-unsat-
urated ester coordinated is shown in Figure 3.
The coordination of 1 with its 2re face to a vacant
orbital of the rhodium-(S)-binap complex provides (R)-3
(Ar ) Ph, R ) Me, R′ ) CH2Ph) on the migratory inser-
tion of the C-C double bond into the rhodium-carbon
bond (eq 4). A comparison of a series of crotonic esters
(entries 1-6 in Table 4) revealed the superiority of bulky
R2, which may interact with the upper phenyl group of
the binap ligand at the coordination from its 2 si face.
In addition to our previous reports6 on 1,4-additions
of aryl- and 1-alkenylboronic acids to enones, the reaction
with R,â-unsaturated esters was found to be efficiently
catalyzed by a rhodium-binap catalyst. Because of the
simple experimental procedure using a catalytic amount
of a rhodium-binap complex, we anticipate the feasibility
of conjugate additions to other Michael acceptors. Pre-
liminary results for the addition of phenylboronic acid
to N-benzyl crotonamide are shown in eq 7. Under
reaction conditions similar to those used for the esters,
various amides showed a higher enantioselectivity than
that of the corresponding ester derivatives, the results
of which will be reported elsewhere (eq 7).13
Su p p or tin g In for m a tion Ava ila ble: Text describing
experimental details and spectral and/or analytical data of the
products. This material is available free of charge via Internet
at http://pubs.acs.org.
J O0002184
(31) Green, M.; Kuc, T. A.; Taylor, S. H. J . Chem. Soc. A 1971, 2334-
2337.
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