9090
J. Org. Chem. 1996, 61, 9090-9096
Enantioselective Allylation of Nitro Group-Stabilized Carbanions Catalyzed by Chiral Crown Ether Phosphine-Palladium Complexes Masaya Sawamura,*,† Yuki Nakayama,‡ Wen-Ming Tang,‡,§ and Yoshihiko Ito*,‡ Department of Chemistry, School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan, and Department of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering, Kyoto University, Kyoto 606-01, Japan Received July 15, 1996X
Enantioselective allylations of R-nitro ketones (3) and R-nitro esters (15) with allyl acetate were carried out in the presence of 2 equiv of alkali metal fluorides (KF, RbF, CsF) and 1 mol % of palladium catalysts prepared in situ from Pd2(dba)3‚CHCl3 and chiral phosphine ligands. Moderate enantioselectivities were observed in the reaction of nitro ketones 3, giving products 4 (4a, 49% ee; 4b, 58% ee; 4c, 44% ee) when rubidium fluoride and ferrocenylphosphine ligands bearing monoaza15-crown-5 (1b) or monoaza-18-crown-6 (1c) moieties were used as a base and a chiral ligand, respectively. Optically active allylation product 4a was converted into 1-methyl-1-azaspiro[4.5]decan-10-amine (13), a precursor to opioid receptor binding agents. Enantioselectivity in the reaction of nitro esters 15 increased in accord with increasing steric demand of the ester alkyl group (Me < Et < t-Bu). The highest selectivity (80% ee) for the reaction of tert-butyl ester 15c was observed when the reaction was carried out at -40 °C in the presence of the palladium catalyst with the ligand (1c) bearing a monoaza-18-crown-6 moiety, RbF (2 equiv), and RbClO4 (1 equiv). The pronounced effect of the crown ether moiety for both enantioselection and rate acceleration can be explained by assuming the formation of a ternary complex involving the crown ether, rubidium cation, and enolate anion at the stereodifferentiating transition state. Optically active nitro ester (R)-16c was converted into (R)-R-methylglutamic acid (20). Introduction Stereocontrol by a chiral catalyst in the palladiumcatalyzed enantioselective allylation of prochiral stabilized carbanions is an extremely difficult task because a chiral ligand is located far from the prochiral nucleophile attacking the π-allyl carbon of the (π-allyl)palladium(II) intermediate and the nucleophile does not interact with the palladium atom directly at the stereodifferentiating transition state.1,2 We have previously reported that reasonably high enantioselectivity can be obtained in the allylation of β-diketone enolates by employing properly designed chiral phosphines bearing an aza crown ether moiety as ligands of the palladium catalysts.3,4 The crown ether phosphines were designed so as to have a secondary interaction with the reacting substrate5,6 by forming a crown ether-metal enolate inclusion complex. However, the mechanism of stereocontrol remains to be clarified. In order to gain a deeper insight into the stereocontrol by means of the secondary ligand-substrate interaction, it is important not only to expand the scope †
The University of Tokyo. Kyoto University. On leave from Department of Chemistry, Guizhou Teachers University, China. X Abstract published in Advance ACS Abstracts, November 15, 1996. (1) (a) Fiaud, J.-C.; Hibon De Gournary, A.; Larcheveque, M. Kagan, H. B. J. Organomet. Chem. 1978, 154, 175. (b) Hayashi, T.; Kanehira, K.; Tsuchiya, H.; Kumada, M. J. Chem. Soc., Chem. Commun. 1982, 1162. (c) Hayashi, T.; Kanehira, K.; Hagihara, T.; Kumada, M. J. Org. Chem. 1988, 53, 113. (d) Ito, Y.; Sawamura, M.; Matsuoka, M.; Matsumoto, Y.; Hayashi, T. Tetrahedron Lett. 1987, 28, 4849. (e) Genet, J.-P.; Ferroud, D.; Juge, S.; Montes, J. R. Tetrahedron Lett. 1986, 27, 4573. (f) Genet, J.-P.; Juge, S.; Montes, J. R.; Gaudin, J. M. J. Chem. Soc., Chem. Commun. 1988, 718. (g) Genet, J.-P.; Juge, S.; Achi, S.; Mallart, S.; Montes, J. R.; Levif, G. Tetrahedron 1988, 44, 5263. (2) Exceptionally high selectivities have been reported in the enantioselective allylation of 2-cyanopropionate promoted by a palladiumrhodium two-component catalyst system: Sawamura, M.; Sudoh, M.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3309. ‡ §
S0022-3263(96)01343-6 CCC: $12.00
and limitations of this type of reaction but also to achieve the highest enantioselectivity possible. In this context, we examined several nitro compounds such as R-nitro ketones (3a-c) and R-nitro esters (15a-c) as a new class of substrates for the enantioselective palladium-catalyzed allylation.7 Since the nitro group can be easily converted (3) Sawamura, M.; Nagata, H.; Sakamoto, H.; Ito, Y. J. Am. Chem. Soc. 1992, 114, 2586. (4) Reexamination of the enantiomeric excesses of the allylation product of 2-acetylcyclohexanone by GLC analysis with Chiraldex G-TA (0.25 mm × 30 m, 120 °C, base-line separation) revealed that the reported ee values in refs 1c and 3, which had been determined by 1H NMR analyses with a chiral shift reagent and by optical rotations of the allylation product, respectively, had been overestimated by aproximately 15%. The highest ee values for this allylation product reported in ref 1c (81% ee) and ref 3 (75% ee) should be revised to 70% ee and 65% ee, respectively. The ee value (65% ee) for the allylation product of 2-acetylcyclopentanone reported in ref 3, which had been determined by 1H NMR analysis with a chiral shift reagent, was confirmed to be correct by GLC analysis with Chiraldex G-TA (120 °C, base-line separation). Separation of the allylation product of 2-methyl-1-phenylbutane-1,3-dione by chiral GLC was not successful. (5) For a review, see: Sawamura, M.; Ito, Y. Chem. Rev. 1992, 92, 857. (6) For recent papers in accord with this concept, see: (a) Sawamura, M.; Kitayama, K.; Ito, Y. Tetrahedron: Asymmetry 1993, 4, 1829. (b) Ward, J.; Bo¨rner, A.; Kagan, H. B. Tetrahedron: Asymmetry 1992, 3, 849. (c) Bo¨rner, A.; Holz, J.; Kless, A.; Heller, D.; Berens, U. Tetrahedron Lett. 1994, 35, 6071. (d) Bo¨rner, A.; Ward, J.; Ruth, W.; Holz, J.; Kless, A.; Heller, D.; Kagan, H. B. Tetrahedron 1994, 50, 10419. (e) Holz, J.; Bo¨rner, A.; Kless, A.; Borns, S.; Trinkhaus, S.; Selke, R.; Heller, D. Tetrahedron: Asymmetry 1995, 6, 1973. (f) Bo¨rner, A.; Kless, A.; Kempe, R.; Heller, D.; Holz, J.; Baumann, W. Chem. Ber. 1995, 128, 767. (g) Bo¨rner, A.; Holz, J.; Ward, J.; Kagan, H. B. J. Org. Chem. 1993, 58, 6814. (h) Bo¨rner, A.; Kless, A.; Holz, J.; Baumann, W.; Tillack, A.; Kadyrov, R. J. Organomet. Chem. 1995, 490, 213. (i) Kless, A.; Kadyrov, R.; Bo¨rner, A.; Holz, J.; Kagan, H. B. Tetrahedron Lett. 1995, 36, 4601. (j) Fields, L. B.; Jacobsen, E. N. Tetrahedron: Asymmetry 1993, 4, 2229. (k) Yamazaki, A.; Morimoto, T.; Achiwa, K. Tetrahedron: Asymmetry 1993, 4, 2287. (l) Yamazaki, A.; Achiwa, K. Tetrahedron: Asymmetry 1995, 6, 51. (m) Spencer, J.; Gramlich, V.; Ha¨usel, R.; Togni, A. Tetrahedron: Asymmetry 1996, 7, 41. (n) MacFarland, D. K.; Landis, C. R. Organometallics 1996, 15, 483. (o) Sasai, H.; Arai, T.; Satow, Y.; Houk, K. N.; Shibasaki, M. J. Am. Chem. Soc. 1995, 117, 6194. (p) Kimmich, B. F. M.; Landis, C. R.; Powell, D. R. Organometallics 1996, 15, 4141.
© 1996 American Chemical Society
Allylation of Nitro Group-Stabilized Carbanions Scheme 1
J. Org. Chem., Vol. 61, No. 26, 1996 9091 Table 1. Enantioselective Allylation of 2-Nitrocyclohexanone (3a) with Allyl Acetate in the Presence of Pd-(S)-(R)-1c Catalysta entry
base
solvent
3a concn, M
yield,b %
4a ee,c % (confign)
1 2 3 4 5 6 7 8
KF KF KF KF RbF RbF RbF CsF
mesitylene toluene THF CH2Cl2 THF CH2Cl2 CH2Cl2 CH2Cl2
1.0 1.0 1.0 1.0 1.0 1.0 0.5 1.0
40 47 66 33 50 57 28 31
14 (R) 19 (R) 25 (R) 25 (R) 29 (R) 38 (R) 42 (R) 31 (R)
a Reaction was carried out in 2 mL of solvent at -25 °C for 40 h. 3a (1 mmol):allyl acetate:base:Pd2(dba)3‚CHCl3:(S)-(R)-1c ) 1:1.5:2.0:0.005:0.0105. b Isolated yield by PTLC. c Determined by GLC analysis of 4a with Chiraldex G-TA (150 °C, base-line separation).
Table 2. Ligand Effect in the Palladium-Catalyzed Enantioselective Allylation of 2-Nitrocyclohexanone (3a) with Allyl Acetatea
into an amino group, these reactions may be regarded as equivalents of enantioselective allylations of R-amino ketones and R-amino esters (acids), respectively.8 Results and Discussion Enantioselective Allylation of r-Nitro Ketones (Scheme 1, Tables 1-3). The reaction of 2-nitrocyclohexanone (3a) with allyl acetate was carried out at -25 °C in the presence of alkali metal fluorides (MF, 2 equiv; M ) K, Rb, Cs) and the palladium catalysts (1 mol %) prepared in situ from Pd2(dba)3‚CHCl3 and chiral phosphine ligands.
Table 1 summarizes the results with the ferrocenylphosphine ligand tethered to monoaza-18-crown-6 with dimethylene group 1c. The reaction was quenched (7) For the palladium-catalyzed allylic alkylations of nitro groupstabilized carbanions, see the following. For R-nitro ketones: (a) Ognyanov, V.; Hesse, M. Synthesis 1985, 645. For R-nitro esters: (b) Genet, J. P.; Ferroud, D. Tetrahedron Lett. 1984, 25, 3579. (c) Genet, J. P.; Grisoni, S. Tetrahedron Lett. 1986, 27, 4165. (d) Lalonde, J. J.; Bergbreiter, D. E.; Wong, C.-H. J. Org. Chem. 1988, 53, 2323. For nitroalkanes: (e) Tsuji, J.; Shimizu, I.; Minami, I.; Ohashi, Y.; Sugiura, T.; Takahashi, K. J. Org. Chem. 1985, 50, 1523. (f) Deardorff, D. R.; Savin, K. A.; Justman, C. J.; Karanjawala, Z. E.; Sheppeck, J. E., II; Hager, D. C.; Aydin, N. J. Org. Chem. 1996, 61, 3616. (8) For the use of 2-nitropropionates for the preparation of Rmethylated R-amino acids, see: Robinson, B.; Shepherd, D. M. J. Chem. Soc. 1961, 5037. See also ref 7d.
entry
chiral ligand
1 2 3 4 5 6 7 8 9 10 11 12
(S)-(R)-1a (S)-(R)-1b (S)-(R)-1c (S)-(R)-1d (S)-(R)-1e (S)-(R)-1f (S)-(R)-2a (S)-(R)-2b (S)-(R)-2c (R)-BINAP (S,S)-CHIRAPHOS (R)-DIOP
4a 3a concn, M yield,b % ee,c % (confign) 0.5 0.5 0.5 0.5 1.0 0.5 0.7 0.7 0.7 0.5 0.5 0.5
9 27 28 48 40 11 8 22 17 18 2 14
4 (R) 41 (R) 42 (R) 39 (R) 17 (R) 31 (R) 2 (R) 2 (S) 6 (R) 15 (R)
