Sodium tetraarylborates as effective nucleophiles in rhodium/diene- catalyzed 1,4-addition to β,β-disubstituted α,β-unsaturated ketones: Catalytic asymmetric construction of quaternary carbon stereocenters

Article abstract of DOI:10.1021/ja905432x

(Chemical Equation Presented) A rhodium-catalyzed 1,4-addition of sodium tetraarylborates to β,β-disubstituted α,β-unsaturated ketones is described. Highly efficient asymmetric catalysis has also been achieved by employing a readily available chiral diene

Full text of DOI:10.1021/ja905432x

Published on Web 09/03/2009
Sodium Tetraarylborates as Effective Nucleophiles in Rhodium/
Diene-Catalyzed 1,4-Addition to ꢀ,ꢀ-Disubstituted r,ꢀ-Unsaturated Ketones:
Catalytic Asymmetric Construction of Quaternary Carbon Stereocenters
Ryo Shintani,* Yosuke Tsutsumi, Makoto Nagaosa, Takahiro Nishimura, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Received July 2, 2009; E-mail: shintani@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Table 1. Rhodium-Catalyzed 1,4-Addition of Phenylboron
Reagents to 3-Methyl-2-cyclohexen-1-one (1a)
Catalytic asymmetric construction of all-carbon quaternary stereocenters
is a subject of great importance in synthetic organic chemistry,1 and 1,4-
addition of organometallic reagents to ꢀ,ꢀ-disubstituted R,ꢀ-unsaturated
compounds represents a powerful method for creating such stereocenters.
In this context, some effective examples have appeared in the copper-
catalyzed asymmetric 1,4-addition of highly reactive nucleophiles such
as diorganozincs,2 Grignard reagents,3 and triorganoaluminums.4 In
contrast, the use of air-stable, easily handled organoboron nucleophiles
such as organoboronic acids has been limited to the reactions of R,ꢀ-
unsaturated pyridyl sulfones5 and 3-substituted maleimides6 under rhodium
catalysis. In this communication, we show that air-stable sodium tet-
raarylborates can function as effective nucleophiles in rhodium/diene-
catalyzed 1,4-addition to ꢀ,ꢀ-disubstituted R,ꢀ-unsaturated ketones and
that highly efficient asymmetric catalysis can be achieved by employing
a readily available chiral diene ligand.
entry
Rh catalyst
Ph-B
additive
yield (%)a
1
2
3
4
5
6
[Rh(OH)(cod)]2
[Rh(OH)(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(binap)]2
PhB(OH)2
H2O
none
H2O
MeOH
MeOH
MeOH
0
20
73c
76c
0
b
PhB(OR)2
Ph4BNa
Ph4BNa
PhBF3K
Ph4BNa
0
a Determined by 1H NMR analysis against an internal standard.
b (OR)2 ) OCH2CMe2CH2O. c Isolated yield.
Rhodium-catalyzed 1,4-addition of organoboronic acids to ꢀ-mono-
substituted R,ꢀ-unsaturated compounds has been extensively investigated
during the past decade,7 and [Rh(OH)(cod)]2 is one of the most active
catalysts known to date.8 Unfortunately, however, our initial attempt to
apply this catalyst system to the reaction of 3-methyl-2-cyclohexen-1-
one (1a), a ꢀ,ꢀ-disubstituted R,ꢀ-enone, with phenylboronic acid resulted
in no formation of 1,4-adduct 2aa but instead led to full consumption of
the nucleophile by hydrolysis (Table 1, entry 1). Suppression of hydrolysis
of the nucleophile by employing a phenylboronic acid ester under aprotic
conditions did produce 2aa, but in only 20% yield (entry 2). These results
indicate that the insertion step of the enone into a phenylrhodium
intermediate had to be accelerated by properly tuning the reaction system.9
In this regard, we were able to find that sodium tetraphenylborate10 can
be used as an effective nucleophile to generate the desired 1,4-adduct 2aa
in significantly higher yield (73-76% yield; entries 3 and 4). It is worth
noting that the use of potassium phenyltrifluoroborate11 as the nucleophile
or a rhodium/bisphosphine complex such as [RhCl(binap)]2 as the catalyst
(entries 5 and 6) did not give 2aa under conditions otherwise identical to
those of entry 4.
On the basis of the above consideration, a proposed catalytic
cycle for the present catalysis is illustrated in Figure 1. Complex
3, initially formed by the reaction of [RhCl(cod)]2 with sodium
tetraphenylborate, undergoes transmetalation to give a phenyl-
rhodium species and triphenylborane. Subsequent insertion of enone
1a into the phenyl-rhodium bond with the aid of Lewis acidic
triphenylborane, followed by protonolysis, produces 1,4-adduct 2aa
along with the formation of an alkoxorhodium intermediate. Ligand
exchange of this intermediate with sodium tetraphenylborate then
regenerates complex 3 to complete the cycle.
Because this reaction is effectively catalyzed by a rhodium/diene
complex, the use of a chiral diene ligand14,15 would lead to the
development of its asymmetric variant. As shown in eq 2, we found
that employing our conventional chiral dienes such as (R,R)-Bn-
bod* and (R,R)-Ph-bod*16 in the reaction of 1a with sodium
tetraphenylborate induced excellent enantioselectivity of g98%, but
the chemical yield of 2aa turned out to be only moderate (48-65%
yield). The use of chiral diene (R)-4, which can be rapidly prepared
To gain some insight into the high activity of sodium tetraphenylborate
under the Rh/cod catalyst system, we conducted a stoichiometric reaction
using Rh(cod)(η6-C6H5)BPh3 (3), which can be readily prepared from
[RhCl(cod)]2 and sodium tetraphenylborate at room temperature.12 As
shown in eq 1, reaction of complex 3 with 1a proceeded smoothly at 60
°C to give 2aa in 63% yield after aqueous workup. This outcome, along
with the results in Table 1, entries 1 and 2, indicates that triphenylborane,
which is generated by transmetalation of the phenyl group from boron to
rhodium in complex 3, might act as an effective Lewis acid13 to assist in
the insertion of 1a into the phenyl-rhodium bond.
Figure 1. Proposed catalytic cycle for the rhodium-catalyzed 1,4-addition
of sodium tetraphenylborate to 1a {[Rh] ) Rh(cod)}.
9
13588 J. AM. CHEM. SOC. 2009, 131, 13588–13589
10.1021/ja905432x CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
in an enantiopure form by a stereoselective [4 + 2] cycloaddition
between commercially available (R)-R-phellandrene and 2-naphthyl
propiolate,17 significantly improved the chemical yield of 2aa while
retaining the high enantioselectivity (85% yield, 98% ee). This high
activity of Rh/(R)-4 can presumably be attributed to the acceleration
of both the transmetalation18 and insertion19 steps due to the
electron-withdrawing nature of (R)-4.
Acknowledgment. Support was provided in part by a Grant-
in-Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan [(S) (19105002),
the Global COE Program “Integrated Materials Science” of Kyoto
University].
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
via the Internet at http://pubs.acs.org.
References
(1) (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) Wu, J.; Mampreian, D. M.; Hoveyda, A. H. J. Am. Chem. Soc. 2005,
127, 4584. (b) Hird, A. W.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127,
14988. (c) Fillion, E.; Wilsily, A. J. Am. Chem. Soc. 2006, 128, 2774. (d)
Lee, K.-s.; Brown, M. K.; Hird, A. W.; Hoveyda, A. H. J. Am. Chem. Soc.
2006, 128, 7182. (e) Brown, M. K.; May, T. L.; Baxter, C. A.; Hoveyda,
A. H. Angew. Chem., Int. Ed. 2007, 46, 1097.
(3) (a) Martin, D.; Kehrli, S.; d’Augustin, M.; Clavier, H.; Mauduit, M.;
Alexakis, A. J. Am. Chem. Soc. 2006, 128, 8416. (b) He´non, H.; Mauduit,
M.; Alexakis, A. Angew. Chem., Int. Ed. 2008, 47, 9122.
(4) (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) Vuagnoux-
d’Augustin, M.; Alexakis, A. Chem.sEur. J. 2007, 13, 9647. (d) May,
T. L.; Brown, M. K.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2008, 47,
7358. (e) Hawner, C.; Li, K.; Cirriez, V.; Alexakis, A. Angew. Chem., Int.
Ed. 2008, 47, 8211.
(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) Christoffers, J.; Koripelly, G.; Rosiak, A.; Ro¨ssle, M. Synthesis 2007,
1279. (b) Hayashi, T. Bull. Chem. Soc. Jpn. 2004, 77, 13. (c) Hayashi, T.;
Yamasaki, K. Chem. ReV. 2003, 103, 2829. (d) Fagnou, K.; Lautens, M.
Chem. ReV. 2003, 103, 169. (e) Bolm, C.; Hildebrand, J. P.; Mun˜iz, K.;
Hermanns, N. Angew. Chem., Int. Ed. 2001, 40, 3284.
(8) Itooka, R.; Iguchi, Y.; Miyaura, N. J. Org. Chem. 2003, 68, 6000.
(9) For the mechanism of the rhodium-catalyzed 1,4-addition reactions, see:
Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc.
2002, 124, 5052.
(10) For examples of the use of sodium tetraarylborates in the rhodium-catalyzed
addition reactions, see: (a) Ueda, M.; Miyaura, N. J. Organomet. Chem.
2000, 595, 31. (b) Ueura, K.; Miyamura, S.; Satoh, T.; Miura, M. J.
Organomet. Chem. 2006, 691, 2821.
(11) (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Org. Lett. 1999, 1, 1683. (b)
Pucheault, M.; Darses, S.; Genet, J.-P. Tetrahedron Lett. 2002, 43, 6155.
(12) (a) Schrock, R. R.; Osborn, J. A. Inorg. Chem. 1970, 9, 2339. Also see:
(b) Oro, L. A.; Pinilla, E.; Tenajas, M. L. J. Organomet. Chem. 1978, 148,
81. (c) Aresta, M.; Quaranta, E.; Albinati, A. Organometallics 1993, 12,
2032.
Under the catalysis of Rh/(R)-4, several cyclic enone substrates
effectively undergo ꢀ-phenylation to give the corresponding ketones
with a quaternary carbon stereocenter in high yield and enantiose-
lectivity (75-83% yield, 89-98% ee; Table 2, entries 1-4). For
acyclic enones, (R,R)-Bn-bod* induces better enantioselectivity
(92-94% yield, 78-91% ee; entries 5 and 6),20 and it is noteworthy
that E and Z substrates gave the opposite enantiomers enriched with
each other. With regard to the nucleophilic component, not only
phenyl but also some other aryl groups can be added to enone 1a
with high efficiency (62-84% yield, 91-97% ee; entries 7-10).
In summary, we have developed a rhodium-catalyzed 1,4-addition
of tetraarylborates to ꢀ,ꢀ-disubstituted R,ꢀ-unsaturated ketones.
Highly efficient asymmetric catalysis to create quaternary carbon
stereocenters by employing a readily available chiral diene ligand
[(R)-4] has also been described.
Table 2. Rhodium-Catalyzed Asymmetric 1,4-Addition of Sodium
Tetraarylborates to 1
(13) (a) Tolman, C. A.; Seidel, W. C.; Druliner, J. D.; Domaille, P. J.
Organometallics 1984, 3, 33. (b) Brunkan, N. M.; Brestensky, D. M.; Jones,
W. D. J. Am. Chem. Soc. 2004, 126, 3627. (c) Nakao, Y.; Yada, A.; Ebata,
S.; Hiyama, T. J. Am. Chem. Soc. 2007, 129, 2428. (d) Yamashita, Y.;
Gopalarathnam, A.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 7508.
(14) For reviews, see: (a) Johnson, J. B.; Rovis, T. Angew. Chem., Int. Ed. 2008,
47, 840. (b) Defieber, C.; Gru¨tzmacher, H.; Carreira, E. M. Angew. Chem.,
Int. Ed. 2008, 47, 4482. For early reports, 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.
(15) (a) Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005,
7, 307. (b) Wang, Z.-Q.; Feng, C.-G.; Xu, M.-H.; Lin, G.-Q. J. Am. Chem.
Soc. 2007, 129, 5336. (c) Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira,
E. M. Org. Lett. 2004, 6, 3873. (d) La¨ng, F.; Breher, F.; Stein, D.;
Gru¨tzmacher, H. Organometallics 2005, 24, 2997. (e) Gendrineau, T.;
Chuzel, O.; Eijsberg, H.; Genet, J.-P.; Darses, S. Angew. Chem., Int. Ed.
2008, 47, 7669.
(16) (a) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.;
Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584. (b) Otomaru, Y.;
Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503.
(17) (a) Okamoto, K.; Hayashi, T.; Rawal, V. H. Chem. Commun. 2009, 4815.
Also see:(b) Okamoto, K.; Hayashi, T.; Rawal, V. H. Org. Lett. 2008, 10,
4387.
(18) Clarke, M. L.; Heydt, M. Organometallics 2005, 24, 6475.
(19) Chen, Q.; Lin, B.-L.; Fu, Y.; Liu, L.; Guo, Q.-X. Res. Chem. Intermed.
2005, 31, 759.
(20) In the presence of (R)-4, (E)-1e gave (S)-2ea with 66% ee and (Z)-1e gave
(R)-2ea with 72% ee.
entry
1
Ar
time (h)
product
yield (%)a
ee (%)b
1
2
3
1a
1b
1c
1d
Ph
Ph
Ph
Ph
Ph
Ph
24
24
24
48
60
60
48
60
24
48
(R)-2aa
(R)-2ba
(S)-2ca
(R)-2da
(S)-2ea
(R)-2ea
(R)-2ab
(R)-2ac
(R)-2ad
(R)-2ae
83
79
80
75
92
94
73
62
84
65
98
98
98
89
78
91
91
91
95
97
4
5c
6c
7d
8
(E)-1e
(Z)-1e
1a
4-MeC6H4
4-FC6H4
3-MeC6H4
3-ClC6H4
1a
1a
1a
9
10e
a Isolated yield. b Determined by chiral HPLC with hexane/
2-propanol. c (R,R)-Bn-bod* was used as the ligand. d The reaction was
conducted in THF. e The reaction was conducted at 90 °C with 10 mol
% rhodium catalyst.
JA905432X
9
J. AM. CHEM. SOC. VOL. 131, NO. 38, 2009 13589