Catalytic asymmetric allylation of prochiral nucleophiles, α-acetamido- β-ketoesters [10]

Full text of DOI:10.1021/ja9900104

3236
J. Am. Chem. Soc. 1999, 121, 3236-3237
Table 1. Asymmetric Allylation of R-Acetamido-â-ketoesters 1a
Catalytic Asymmetric Allylation of Prochiral
Nucleophiles, r-Acetamido-â-ketoesters
entry
R1 (1)
R2 (2) time, h product yield, %b ee, %c
1
2
3
4
5
6
7
8
9
Me (1b)
Ph (1c)
Me (1b)
Ph (1c)
Et (1a)
Me (1b)
Ph (1c)
H (2a)
H (2a)
Pr (2b)
Pr (2b)
Ph (2c)
Ph (2c)
Ph (2c)
24
24
24
48
4
2
48
2
3b
3c
3d
3e
3f
3g
3h
3i
84
92
96
40
87
87
71
86
85
76
80
87
89
91
94
95
92
91
Ryoichi Kuwano and Yoshihiko Ito*
Department of Synthetic Chemistry and
Biological Chemistry, Graduate School of Engineering
Kyoto UniVersity, Sakyo-ku, Kyoto 606-8501, Japan
i-Bu (1d) Ph (2c)
i-Pr (1e) Ph (2c)
ReceiVed January 4, 1999
4
3j
a All reactions were carried out in toluene (0.2 M) at -30 °C. The
ratio of 1:2:t-BuOK:[Pd(π-allyl)Cl]2:(R)-BINAP was 100:150:120:1:
1.05 unless otherwise noted. b Isolated yield by PTLC. c Determined
by HPLC analysis with chiral stationary-phase column.
Catalytic asymmetric allylation through a chiral π-allylpalla-
dium(II) complex has been intensively studied.1 Most of the
successful examples introduce a chiral center on an allylic sub-
strate.2 The enantioselective electrophilic attack of a π-allyl-
palladium(II) to a stabilized prochiral nucleophile is not facile to
be controlled by a chiral ligand on the palladium atom,3,4 which
is at the opposite side of the π-allyl carbon structure from the
approaching nucleophile (Figure 1).5 Some devices have led to
The first attempt for asymmetric allylation of methyl 2-(N-
acetylamino)-3-oxopentanoate (1a) with allyl methyl carbonate
was carried out in THF at 0 °C in the presence of the palladium
catalyst generated from Pd2(dba)3‚CHCl3 and (R)-BINAP.9 The
reaction was completed in 5 h to give the corresponding allylation
product (3a) with 45% ee in 97% yield.10,11 The enantioselectivity
was improved up to 72% ee by the use of allyl acetate and t-BuOK
in toluene at -30 °C for 30 h in the presence of the palladium
complex catalyst generated from [Pd(π-allyl)Cl]2 and (R)-BINAP,
giving 3a in 76% yield (Scheme 1).
Figure 1.
the high enantioselective allylation of carbon nucleophiles, for
example, (i) by the use of a bimetallic catalyst system for
allylation with chiral rhodium(I) enolate of R-cyanopropionates,6
(ii) by the use of a chiral bidentate ligand with wide bite angle
for asymmetric allylation of cyclic â-ketoesters,7 which may
induce effective transmission of the ligand chirality.
Scheme 1
Herein, we wish to report a highly enantioselective allylation
(up to 95% ee) of prochiral nucleophiles, R-acetamido-â-
ketoesters 1, catalyzed by the chiral BINAP-palladium complex.
The R-acetamido-â-ketoesters are new carbon nucleophiles, which
undergo palladium-catalyzed allylations to furnish R-allyl-R-
acetamido-â-ketoesters 3 having a quaternary stereogenic center
at the R-carbon.8
(1) For reviews, see: (a) Hayashi, T. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; VCH Publishers: New York, 1994; pp 325-365. (b) Trost, B.
M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395-422. (c) Williams, J. M.
J. Synlett 1996, 705-710. (d) Lu¨bbers, T.; Metz, P. In StereoselectiVe
Synthesis; Helmchen, G., Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.;
Thieme: Stuttgart, 1996; Vol. 4, pp 2371-2473.
(2) For recent examples, see: (a) Trost, B. M. Acc. Chem. Res. 1996, 29,
355-364. (b) von Matt, P.; Pfalz, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
566-568. (c) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.;
Tijani, A. J. Am. Chem. Soc. 1994, 116, 4062-4066. (d) Kudis, S.; Helmchen,
G. Angew. Chem., Int. Ed. Engl. 1998, 37, 3047-3050.
(3) (a) Fiaud, J.-C.; De Gournay, A. H.; Lacheve´que, M.; Kagan, H. B. J.
Organomet. Chem. 1978, 154, 175-185. (b) Hayashi, T.; Kanehira, K.;
Tsuchiya, H.; Kumada, M. J. Chem. Soc., Chem. Commun. 1982, 1162-
1164. (c) Ito, Y.; Sawamura, M.; Matsuoka, M.; Matsumoto, Y.; Hayashi, T.
Tetrahedron Lett. 1987, 28, 4849-4852. (d) Hayashi, T.; Kanehira, K.;
Hagihara, T.; Kumada, M. J. Org. Chem. 1988, 53, 113-120. (e) Sawamura,
M.; Nagata, H.; Sakamoto, H.; Ito, Y. J. Am. Chem. Soc. 1992, 114, 2586-
2592. (f) Sawamura, M.; Nakayama, Y.; Tang, W.-M.; Ito, Y. J. Org. Chem.
1996, 61, 9090-9096. (g) Genet, J.-P.; Ferroud, D.; Juge, S.; Montes, J. R.
Tetrahedron Lett. 1986, 27, 4573-4576. (h) Genet, J.-P.; Juge, S.; Montes,
J. R.; Gaudin, J. M. J. Chem. Soc., Chem. Commun. 1988, 718-719. (i) Genet,
J.-P.; Juge, S.; Achi, S.; Mallart, S.; Montes, J. R.; Levif, G. Tetrahedron
1988, 44, 5263-5275.
The allylations of R-acetamido-â-ketoesters 1 with some allylic
substrates 2 in toluene at -30 °C were examined, as summarized
in Table 1. Various optically active allylation products 3b-j were
obtained with 77-95% ee in high yields by the use of the (R)-
BINAP-palladium catalyst. Noteworthy is that the allylation of
1 with γ-substituted allylic substrates 2b and 2c provided
selectively the corresponding 3d-j without being accompanied
by the regio- and (Z)-geometrical isomers. The enantioselectivities
depended significantly upon substituent at the γ-carbon of 2,
(8) For catalytic asymmetric syntheses of R-alkylated R-amino acids with
high enantiomeric excess, see: (a) Ito, Y.; Sawamura, M.; Shirakawa, E.;
Hayashizaki, K.; Hayashi, T. Tetrahedron 1988, 44, 5253-5262. (b) Ruble,
J. C.; Fu, G. C. J. Am. Chem. Soc. 1998, 120, 11532-11533 and ref 4b.
(9) (R)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl: Miyashita, A.; Ya-
suda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J. Am. Chem.
Soc. 1980, 102, 7932-7934.
(10) Representative results with other chiral ligands in THF were as
follows: (+)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)-
butane (DIOP: 2% ee), (2S,3S)-2,3-bis(diphenylphosphino)butane (CHIRA-
PHOS: 1% ee), (R)-N,N-dimethyl-1-[(S)-1′,2-bis(diphenylphosphino)ferrocenyl]-
ethylamine (BPPFA: 13% ee), (R,R)-2,2′′-bis[(S)-1-(diphenylphosphino)ethyl]-
1,1′′-biferrocene (PhTRAP: 21% ee), (1R,2R)-bis[N-(2′-diphenylphosphino)-
benzoylamino]cyclohexane (no reaction), (S)-2-[2-(diphenylphosphino)phenyl]-
4-(phenyl)oxazoline (1% ee).
(4) (a) Baldwin, I. C.; Williams, J. M. J. Tetrahedron: Asymmetry 1995,
6, 679-682. (b) Trost, B. M.; Ariza, X. Angew. Chem., Int. Ed. Engl. 1997,
36, 2635-2637.
(5) (a) Trost, B. M.; Weber, L.; Strege, P. E.; Fullerton, T. J.; Dietsche, T.
J. J. Am. Chem. Soc. 1978, 100, 3416-3426. (b) Hayashi, T.; Konishi, M.;
Kumada, M. J. Chem. Soc., Chem. Commun. 1984, 107-108. (c) Hayashi,
T.; Yamamoto, A.; Ito, Y. J. Organomet. Chem. 1988, 338, 261-264.
(6) Sawamura, M.; Sudoh, M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309-
3310.
(11) Toluene was superior to THF, giving 56% ee of 3a. The enantiose-
lectivities of 3a in some other solvents were as follows: Et2O (47% ee), CH2-
Cl2 (31% ee), i-PrOH (40% ee).
(7) Trost, B. M.; Radinov, R.; Grenzer, E. M. J. Am. Chem. Soc. 1997,
119, 7879-7880.
10.1021/ja9900104 CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/19/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 13, 1999 3237
giving higher enantioselectivities with increasing steric bulkiness
of the γ-substituents. In general, the allylation of 1 with cinnamyl
acetate (2c) proceeded well at -30 °C to afford the corresponding
3f-j with 91-95% ee (entries 5-9). On the other hand, the acyl
substituent R1 of 1 affected the enantioselectivities of the allylation
reaction slightly.
The allylation of 1b with either (Z)-2b or 4 afforded (R)-3d
with nearly identical enantioselectivity (85-86% ee) without the
formation of its regio- and geometrical isomers, suggesting that
the nucleophilic attack of an enolate of 1 may be slow as com-
pared with any possible π-σ-π isomerization of the π-allyl-
palladium complex initially generated (Scheme 2).12
Figure 2. X-ray crystal structure of [Pd(π-allyl){(R)-BINAP}]ClO4‚(CH3-
COCH3). (a) ORTEP drawing (50% probability level). Hydrogen atoms,
perchlorate anion, and acetone are omitted for clarity. (b) Space filling
model. Black atoms indicate the carbon atoms of the π-allyl ligand.
Scheme 2
Optically active (R)-2-(N-acetylamino)-3-oxocarboxylates 3
thus obtained were readily converted into various R-alkylated
R-amino acid derivatives (Scheme 3). Reductions of 3 with
Scheme 3
Although the mechanism for the enantioface-selection of the
enolate of 1 has not been made clear yet, the phenyl groups of
BINAP ligand may be crucially important for the control of
stereoselectivity. As seen from the X-ray crystal structure of [Pd-
(π-allyl){(R)-BINAP}]ClO4 (Figure 2),13 two equatorial14 phenyls
on the phosphorus stretch out over the π-allyl ligand on the
palladium atom. Consequently, the phenyl groups of BINAP may
interact with the prochiral nucleophile approaching the π-allyl
carbon structure from the opposite face.
L-Selectride15 gave the corresponding (2R,3S)-R-alkyl-â-hydroxy-
R-amino acid derivatives 5 with high diastereoselectivities (>96%
de).16 The absolute configurations of 3 were assigned to be R by
NMR studies of the MTPA esters of 5.17 Oxidative cleavage of
the olefin of 3g with NaIO4 and a catalytic amount of RuO2 (2
mol %) followed by treatment with diazomethane gave a protected
R-acetylaspartic acid 6 in 82% yield without the loss of the
enantiopurity.18
We succeeded in highly enantioselective allylation of prochiral
nucleophile 1 by a BINAP-palladium catalyst, providing optically
active R-allyl-R-acetamido-â-ketoesters 3, which are versatile
precursors for the synthesis of â-hydroxy-R-alkyl-R-amino acids.
Further mechanistic studies are in progress.
(12) (a) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1980, 102, 4730-
4743. (b) Mackenzie, P. B.; Whelan, J.; Bosnich, B. J. Am. Chem. Soc. 1985,
107, 2046-2054. (c) Hayashi, T.; Yamamoto, A.; Hagihara, T. J. Org. Chem.
1986, 51, 723-727.
(13) For crystal structures of BINAP-palladium complexes with a di- or
trisubstituted π-allyl ligand, see: (a) Pregosin, P. S.; Ru¨egger, H.; Salzmann,
R.; Albinati, A.; Lianza, F.; Kunz, R. W. Organometallics 1994, 13, 83-90.
(b) Pregosin, P. S.; Ru¨egger, H.; Salzmann, R.; Albinati, A.; Lianza, F.; Kunz,
R. W. Organometallics 1994, 13, 5040-5048. (c) Drommi, D.; Nesper, R.;
Pregosin, P. S.; Trabesinger, G.; Zu¨rcher, F. Organometallics 1997, 16, 4268-
4275. (d) Yamaguchi, M.; Yabuki, M.; Yamagishi, T.; Sakai, K.; Tsubomura,
T. Chem. Lett. 1996, 241-242.
(14) Equatorial orientation of phenyl group in BINAP-metal complex was
defined in the following references: (a) Noyori, R. Science 1990, 248, 1194-
1199. (b) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T.; Nishioka, E.;
Yanagi, K.; Moriguchi, K.-i. Organometallics 1993, 12, 4188-4196.
(15) Brown, H. C.; Krishnamurthy, S. J. Am. Chem. Soc. 1972, 94, 7159-
7161.
(16) The relative stereochemisty between the 2- and 3-position was
determined by the X-ray crystal structure of racemic 5 (R ) H). See Supporting
Information.
Acknowledgment. This work was supported by a Grant-in-Aid for
Scientific Research on Priority Areas, No. 706: Dynamic Control of
Stereochemistry, from Monbusho.
Supporting Information Available: Experimental procedures, com-
pound characterization data, and X-ray crystal structure data (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
(17) Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem.
Soc. 1991, 113, 4092-4096.
(18) Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org.
Chem. 1981, 46, 3936-3938.
JA9900104