Rhodium-catalyzed asymmetric 1,4-addition of sodium tetraarylborates to β,β-disubstituted α,β-unsaturated esters

Article abstract of DOI:10.1021/ol102674z

A rhodium-catalyzed 1,4-addition of sodium tetraarylborates to β,β-disubstituted α,β-unsaturated esters has been developed. Highly efficient asymmetric catalysis has also been described to create quaternary carbon stereocenters at the β-position of esters by tuning the ester group of substrates and employing a readily available chiral diene ligand.

Full text of DOI:10.1021/ol102674z

ORGANIC
LETTERS
2011
Vol. 13, No. 2
350-352
Rhodium-Catalyzed Asymmetric
1,4-Addition of Sodium Tetraarylborates
to ꢀ,ꢀ-Disubstituted r,ꢀ-Unsaturated
Esters
Ryo Shintani* and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo, Kyoto 606-8502, Japan
shintani@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Received November 4, 2010
ABSTRACT
A rhodium-catalyzed 1,4-addition of sodium tetraarylborates to ꢀ,ꢀ-disubstituted r,ꢀ-unsaturated esters has been developed. Highly efficient
asymmetric catalysis has also been described to create quaternary carbon stereocenters at the ꢀ-position of esters by tuning the ester group
of substrates and employing a readily available chiral diene ligand.
Catalytic asymmetric 1,4-addition of organometallic reagents
to ꢀ,ꢀ-disubstituted R,ꢀ-unsaturated compounds has been
extensively investigated in the past few years for the efficient
construction of all-carbon quaternary stereocenters.1 Most
widely employed substrates in this regard are R,ꢀ-unsaturated
ketones under copper2 or rhodium3 catalysis, and several
other reactive substrates such as nitroalkenes,4 R,ꢀ-unsatur-
ated pyridyl sulfones,5 and 3-substituted maleimides6 have
also been utilized. In contrast, although ꢀ-chiral esters would
be synthetically more useful, the use of ꢀ,ꢀ-disubstituted R,ꢀ-
unsaturated esters has been much less explored, presumably
because of their inherently lower reactivity as electrophiles.
As a consequence, only alkylidene Meldrum’s acids, highly
activated diesters, have been successfully employed to date.7
In this context, herein we describe the development of
rhodium-catalyzed 1,4-addition of air-stable sodium tet-
raarylborates to ꢀ,ꢀ-disubstituted R,ꢀ-unsaturated esters,
(1) For reviews on quaternary stereocenters, see: (a) Trost, B. M.; Jiang,
C. Synthesis 2006, 369. (b) Christoffers, J.; Baro, A. AdV. Synth. Catal.
2005, 347, 1473. (c) Douglas, C. J.; Overman, L. E. Proc. Natl. Acad. Sci.
U.S.A. 2004, 101, 5363. (d) Denissova, I.; Barriault, L. Tetrahedron 2003,
59, 10105.
(2) (a) d’Augustin, M.; Palais, L.; Alexakis, A. Angew. Chem., Int. Ed.
2005, 44, 1376. (b) Fuchs, N.; d’Augustin, M.; Humam, M.; Alexakis, A.;
Taras, R.; Gladiali, S. Tetrahedron: Asymmetry 2005, 16, 3143. (c) Martin,
D.; Kehrli, S.; d’Augustin, M.; Clavier, H.; Mauduit, M.; Alexakis, A. J. Am.
Chem. Soc. 2006, 128, 8416. (d) Vuagnoux-d’Augustin, M.; Alexakis, A.
Chem.sEur. J. 2007, 13, 9647. (e) Hawner, C.; Li, K.; Cirriez, V.; Alexakis,
A. Angew. Chem., Int. Ed. 2008, 47, 8211. (f) He´non, H.; Mauduit, M.;
Alexakis, A. Angew. Chem., Int. Ed. 2008, 47, 9122. (g) Palais, L.; Alexakis,
A. Chem.sEur. J. 2009, 15, 10473. (h) Hird, A. W.; Hoveyda, A. H. J. Am.
Chem. Soc. 2005, 127, 14988. (i) Lee, K.; Brown, M. K.; Hird, A. W.;
Hoveyda, A. H. J. Am. Chem. Soc. 2006, 128, 7182. (j) Brown, M. K.;
May, T. L.; Baxter, C. A.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2007,
46, 1097. (k) Matsumoto, Y.; Yamada, K.; Tomioka, K. J. Org. Chem.
2008, 73, 4578.
(3) (a) Shintani, R.; Tsutsumi, Y.; Nagaosa, M.; Nishimura, T.; Hayashi,
T. J. Am. Chem. Soc. 2009, 131, 13588. (b) Shintani, R.; Takeda, M.;
Nishimura, T.; Hayashi, T. Angew. Chem., Int. Ed. 2010, 49, 3969. (c)
Hawner, C.; Mu¨ller, D.; Gremaud, L.; Felouat, A.; Woodward, S.; Alexakis,
A. Angew. Chem., Int. Ed. 2010, 49, 7769.
(4) Wu, J.; Mampreian, D. M.; Hoveyda, A. H. J. Am. Chem. Soc. 2005,
127, 4584.
(5) Mauleo´n, P.; Carretero, J. C. Chem. Commun. 2005, 4961.
(6) Shintani, R.; Duan, W.-L.; Hayashi, T. J. Am. Chem. Soc. 2006,
128, 5628.
(7) (a) Fillion, E.; Wilsily, A. J. Am. Chem. Soc. 2006, 128, 2774. (b)
Wilsily, A.; Fillion, E. Org. Lett. 2008, 10, 2801. (c) Wilsily, A.; Lou, T.;
Fillion, E. Synthesis 2009, 2066. (d) Wilsily, A.; Fillion, E. J. Org. Chem.
2009, 74, 8583.
10.1021/ol102674z  2011 American Chemical Society
Published on Web 12/03/2010

where high enantioselectivity can be achieved by employing
a readily available chiral diene ligand.
Table 1. Rhodium-Catalyzed 1,4-Addition of Sodium
Tetraphenylborate to (E)-3-Methyl-5-phenyl-2-pentenoates:
Effect of Ester and Ligand
Recently, we described that sodium tetraarylborates can
function as effective nucleophiles for the rhodium/diene-
catalyzed 1,4-addition reactions to ꢀ,ꢀ-disubstituted R,ꢀ-
unsaturated ketones, where other typical organoboron nu-
cleophiles such as arylboronic acids completely fail.3a To
assess the reactivity difference between ꢀ,ꢀ-disubstituted
unsaturated ketones and esters, we initially conducted a
control experiment by employing enone (E)-1a (1.0 equiv)
and enoate (E)-1b (1.0 equiv) in the rhodium/cod-catalyzed
1,4-addition of sodium tetraphenylborate (1.0 equiv) in
methanolic dioxane at 60 °C (eq 1). Under these conditions,
ketone product 2a and ester product 2b were obtained in
55% and 25% yield, respectively, indicating that ꢀ,ꢀ-
disubstituted enoate 1b is significantly lower in reactivity
than enone 1a.
yield ee
product (%)a (%)b
entry
substrate (R)
diene*
1
2
3
4
5
6
7
(E)-1b (Me)
cod
(R)-L1
(R)-L1
2b
2b
2c
2d
2d
2d
2d
60c
79
84
93
93
91
94
(E)-1b
76
89
97
99
97
98
(E)-1c (t-Bu)
(E)-1d (2,6-Me2C6H3) (R)-L1
(E)-1d
(E)-1d
(E)-1d
(R)-L2
(R,R)-Bn-bod*
(R,R)-Ph-bod*
a Isolated yield. b Determined by chiral HPLC on a Chiralcel OD-H
column with hexane/2-propanol ) 100/1. c Determined by 1H NMR of the
crude material.
bod*12 and (R,R)-Ph-bod*12,13 also exhibited similarly high
efficiency (91-94% yield, 97-98% ee; entries 6 and 7).14
Under the conditions using [RhCl((R)-L2)]2, the reaction of
(E)-1d also proceeded well with only 1.0 equiv of sodium
tetraphenylborate to give 2d in acceptable yield of 79% with
the same enantioselectivity (Table 2, entry 2). It is worth noting
that the use of (Z)-1d as a substrate produced the opposite
Keeping this result in mind, we examined several reaction
conditions using (E)-1b and sodium tetraphenylborate and
found that a reaction with 3.0 equiv of sodium tetraphe-
nylborate under the catalysis of [RhCl(cod)]2 (5 mol % Rh)
in the presence of 3.0 equiv of MeOH in dioxane proceeded
at 60 °C with moderate efficiency to give 1,4-adduct 2b in
60% yield (Table 1, entry 1).8 In contrast, product 2b was
9
not obtained at all in the presence of [RhCl(binap)]2 as a
catalyst or by the use of other typical phenylboron nucleo-
philes such as phenylboronic acid, phenylboroxine, phenyl-
boronic acid neopentylglycol ester, and potassium phenyl-
trifluoroborate.
Table 2. Rhodium-Catalyzed Asymmetric 1,4-Addition of
Sodium Tetraarylborates to ꢀ,ꢀ-Disubstituted R,ꢀ-Unsaturated
Esters 1: Scope
Fortunately, while developing an asymmetric variant of
this process, we discovered that a rhodium complex coor-
dinated with ester-attached chiral diene (R)-L110 displayed
activity higher than that of [RhCl(cod)]2, giving 2b in 79%
yield with 76% ee (entry 2). In the presence of [RhCl((R)-
L1)]2, both yield and ee were further improved by changing
the substrate to tert-butyl ester (E)-1c (84% yield, 89% ee;
entry 3) and to 2,6-dimethylphenyl ester (E)-1d (93% yield,
97% ee; entry 4).11 We subsequently found that even higher
enantioselectivity could be achieved through modification
of the chiral diene ligand to (R)-L210 (99% ee; entry 5).
Conventional C2-symmetric chiral dienes such as (R,R)-Bn-
yield ee
entry
1 (R, R′)
Ar
product (%)a (%)b
1
(E)-1d ((CH2)2Ph, Me)
(E)-1d
(Z)-1d (Me, (CH2)2Ph)
(E)-1e ((CH2)2Ph, Et)
(Z)-1e (Et, (CH2)2Ph)
Ph
Ph
Ph
Ph
Ph
(S)-2d 93
(S)-2d 79
(R)-2d 95
99
99
99
99
99
2c
3
4d
5d
6
(S)-2e
(R)-2e
(S)-2f
(S)-2g
90
89
(E)-1f ((CH2)2CHdCMe2, Me) Ph
92e 97
7
(E)-1g (4-ClC6H4, Me)
(E)-1h (SiMe2Ph, Me)
(E)-1d
Ph
Ph
93
99
96
98
98
98
96
98
8
(S)-2h 84
9f
4-MeOC6H4 (S)-2i
4-MeC6H4 (S)-2j
90
89
10f (E)-1d
(8) Attempts to improve the yield of 2b under the catalysis of
[RhCl(cod)]2 were not successful by further changing the stoichiometry,
reaction temperature, etc.
11
(E)-1d
4-ClC6H4
3-MeOC6H4 (S)-2l
3-MeC6H4 (S)-2m 96
(S)-2k 85
12d,f (E)-1d
64
(9) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem.
Soc. 2002, 124, 5052.
13f (E)-1d
a Isolated yield. b Determined by chiral HPLC with hexane/2-propanol.
c The reaction was conducted using 1.0 equiv of Ph4BNa and 1.0 equiv of
MeOH at 0.40 M substrate concentration. d The reaction was conducted
with 8 mol % of catalyst. e The product was obtained as a mixture of olefin
isomers [(R ) (CH2)2CHdCMe2)/(R ) (CH2)3C(Me))CH2) ) 93/7]. f The
reaction was conducted in THF.
(10) Okamoto, K.; Hayashi, T.; Rawal, V. H. Chem. Commun. 2009,
4815.
(11) (a) Sakuma, S.; Sakai, M.; Itooka, R.; Miyaura, N. J. Org. Chem.
2000, 65, 5951. (b) Takaya, Y.; Senda, T.; Kurushima, H.; Ogasawara, M.;
Hayashi, T. Tetrahedron: Asymmetry 1999, 10, 4047. (c) Nishimura, T.;
Wang, J.; Nagaosa, M.; Okamoto, K.; Shintani, R.; Kwong, F.; Yu, W.;
Chan, A. S. C.; Hayashi, T. J. Am. Chem. Soc. 2010, 132, 464.
Org. Lett., Vol. 13, No. 2, 2011
351

3.16,17 The formation of 5 rather than the simple 1,4-addition
product (2b) can be explained as follows. Thus, insertion of
the olefin of 1b into a phenylrhodium species provides
intermediate A. As a result of the aprotic reaction conditions,
this intermediate does not undergo protonolysis, and instead,
alkyl-to-aryl 1,4-rhodium migration preferentially takes place
to give arylrhodium intermediate B.18 Successive intramo-
lecular insertion of ester carbonyl into this arylrhodium
species,19 followed by ꢀ-oxygen elimination from intermedi-
ate C, leads to the formation of indanone 5.
Figure 1. Proposed stereochemical pathway for the Rh/(R)-L2-
catalyzed 1,4-addition of sodium tetraphenylborate to (E)-1d.
enantiomer of 2d with 99% ee (entry 3), indicating that the
catalyst efficiently recognizes the olefin geometry of the
substrates. The same results were obtained for substrate 1e
having sterically very similar ethyl and 2-phenylethyl groups
at the ꢀ-position (entries 4 and 5). In addition to alkyl groups,
aryl and silyl groups are also tolerated at the ꢀ-position of
substrates to give the corresponding 1,4-adducts in high yield
with excellent enantioselectivity (entries 6-8). The present
catalysis is not limited to these acyclic enoates and is applicable
to cyclic substrates as well. For example, phenylation of R,ꢀ-
unsaturated lactone 3 smoothly proceeds under similar condi-
tions to give compound 4 in 98% yield with 99% ee (eq 2).
With regard to the nucleophilic component, several other aryl
groups can be effectively added to (E)-1d with uniformly high
enantiomeric excesses (entries 9-13).
In summary, we have developed a rhodium/diene-catalyzed
1,4-addition of sodium tetraarylborates to ꢀ,ꢀ-disubstituted
R,ꢀ-unsaturated esters. Highly efficient asymmetric catalysis
has also been described to create quaternary carbon stereo-
centers at the ꢀ-position of esters by tuning the ester group
of substrates and employing chiral diene (R)-L2 as the ligand.
In addition, a new way of constructing 3,3-disubstituted
1-indanones has also been discovered by conducting the
arylation reactions under aprotic conditions.
Acknowledgment. Support has been provided in part by a
Grant-in-Aid for Scientific Research (S) (19105002), the
Ministry of Education, Culture, Sports, Science and Technology,
Japan.
The stereochemical outcome in the reaction of (E)-1d with
sodium tetraphenylborate under the catalysis of Rh/(R)-L2
can be rationalized as shown in Figure 1. To minimize the
unfavorable steric interaction between the ester group of (E)-
1d and the substituent on the olefin of (R)-L2,10 (E)-1d
coordinates to phenylrhodium species with its R-re face,
thereby leading to the formation of 2d with S configuration.15
This model can also well explain the formation of (R)-2d
from (Z)-1d as demonstrated in Table 2, entry 3.
It is worth noting that the course of the present catalysis
significantly changes by employing aprotic reaction condi-
tions. For example, a reaction of (E)-1b with sodium
tetraphenylborate in the absence of MeOH selectively gave
3,3-disubstituted 1-indanone 5 in 72% yield as shown in eq
Supporting Information Available: Experimental pro-
cedures and compound characterization data. This material
is available free of charge via the Internet at http://
pubs.acs.org.
OL102674Z
(16) (a) Almost no reaction took place with 2,6-dimethylphenyl ester
(E)-1d. (b) The use of other chiral diene ligands resulted in lower yield
and ee (e.g., (R)-L1: 31% yield, 61% ee. (R)-L2: 33% yield, 60% ee. (R,R)-
Ph-bod*: 61% yield, 60% ee). (c) When the reaction of (E)-1b was
conducted using Rh/(R,R)-Bn-bod* catalyst in the presence of MeOH, 1,4-
adduct 2b was obtained in 62% yield with 75% ee. Somewhat lower ee
value of 5 in eq 3 is probably due to the partial isomerization of substrate
(E)-1b to (Z)-1b under the reaction conditions, which was confirmed in the
remaining 1b after the reaction.
(17) For examples of rhodium-catalyzed synthesis of 3,3-disubstituted
1-indanones, see: (a) Matsuda, T.; Shigeno, M.; Makino, M.; Murakami,
M. Org. Lett. 2006, 8, 3379. (b) Shintani, R.; Hayashi, T. Org. Lett. 2005,
7, 2071. (c) Shintani, R.; Takatsu, K.; Hayashi, T. Angew. Chem., Int. Ed.
2007, 46, 3735. (d) Shintani, R.; Takatsu, K.; Katoh, T.; Nishimura, T.;
(12) Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem.
2005, 70, 2503.
(13) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani,
R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.
(14) For reviews on chiral diene ligands, see: (a) Shintani, R.; Hayashi,
T. Aldrichimica Acta 2009, 42, 31. (b) Defieber, C.; Gru¨tzmacher, H.;
Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482. For early examples
of chiral diene ligands in asymmetric catalysis, see: (c) Hayashi, T.; Ueyama,
K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508. (d)
Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. M. J. Am. Chem. Soc.
2004, 126, 1628.
Hayashi, T. Angew. Chem., Int. Ed. 2008, 47, 1447
.
(18) (a) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem.
Soc. 2000, 122, 10464. (b) Matsuda, T.; Shigeno, M.; Murakami, M. J. Am.
Chem. Soc. 2007, 129, 12086. (c) Shigeno, M.; Yamamoto, T.; Murakami,
M. Chem.sEur. J. 2009, 15, 12929. (d) Seiser, T.; Roth, O. A.; Cramer,
N. Angew. Chem., Int. Ed. 2009, 48, 6320.
(19) (a) Miura, T.; Sasaki, T.; Nakazawa, H.; Murakami, M. J. Am.
Chem. Soc. 2005, 127, 1390. (b) Shintani, R.; Okamoto, K.; Otomaru, Y.;
Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54.
(15) See Supporting Information for the assignment of the absolute
configuration.
352
Org. Lett., Vol. 13, No. 2, 2011