Practical enantioselective synthesis of β-substituted-β-amino esters

被引:34
作者
Awasthi, AK [1 ]
Boys, ML [1 ]
Cain-Janicki, KJ [1 ]
Colson, PJ [1 ]
Doubleday, WW [1 ]
Duran, JE [1 ]
Farid, PN [1 ]
机构
[1] Pfizer Inc, Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA
关键词
D O I
10.1021/jo050177h
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A practical, large-scale synthesis of a P-amino ester 1 was developed. A chiral imine derived from (S)-phenylglycinol and 3-trimethylsilylpropanal was coupled with the Reformatsky reagent 3 with high diastereoselectivity (de > 98%) to give (SS)-4a as the major isomer. The amino alcohol residue of the coupling product 4 was oxidatively cleaved with sodium periodate in the presence of methylamine. An unusual selective oxidative cleavage of the (SS)-isomer was observed and the imine 6 was obtained with ee > 99% while the (RS)-4b isomer was not cleaved. Reaction with p-toluenesulfonic acid monohydrate allowed for the hydrolysis of the imine and the isolation of the amine as its salt. The title compound I was then obtained by transesterification, desilylation, and hydrochloride salt formation in a one-pot process. The method was successfully applied toward the synthesis of a wide variety of P-amino esters.
引用
收藏
页码:5387 / 5397
页数:11
相关论文
共 48 条
  • [41] ADDITION OF A REFORMATSKY REAGENT TO N-ANTHRACENE-9-SULFONYL AND RELATED IMINES - SYNTHESIS OF PROTECTED BETA-AMINO ACIDS
    ROBINSON, AJ
    WYATT, PB
    [J]. TETRAHEDRON, 1993, 49 (48) : 11329 - 11340
  • [42] Asymmetric synthesis of β-amino acid derivatives incorporating a broad range of substitution patterns by enolate additions to tert-butanesulfinyl imines
    Tang, TP
    Ellman, JA
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (22) : 7819 - 7832
  • [43] Use of enzyme penicillin acylase in selective amidation/amide hydrolysis to resolve ethyl 3-amino-4-pentynoate isomers
    Topgi, RS
    Ng, JS
    Landis, B
    Wang, P
    Behling, JR
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 1999, 7 (10) : 2221 - 2229
  • [44] ENANTIOSELECTIVE SYNTHESIS OF 3-AMINO-2-AZETIDINONES VIA THE ESTER ENOLATE IMINE CONDENSATION
    VANDERSTEEN, FH
    KLEIJN, H
    BRITOVSEK, GJP
    JASTRZEBSKI, JTBH
    VANKOTEN, G
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (14) : 3906 - 3916
  • [45] ASYMMETRIC-SYNTHESIS OF BETA-LACTAMS VIA THE ZINC-MEDIATED GLYCINE ESTER ENOLATE IMINE CONDENSATION REACTION USING ALPHA-AMINO ESTERS AS THE CHIRAL AUXILIARY
    VANMAANEN, HL
    KLEIJN, H
    JASTRZEBSKI, JTBH
    VERWEIJ, J
    KIEBOOM, APG
    VANKOTEN, G
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (14) : 4331 - 4338
  • [46] VANMAANEN HL, 1994, RECL TRAV CHIM PAY B, V113, P567
  • [47] WU MJ, 1990, SYNLETT, P636
  • [48] POTENT IN-VITRO AND IN-VIVO INHIBITORS OF PLATELET-AGGREGATION BASED UPON THE ARG-GLY-ASP SEQUENCE OF FIBRINOGEN - (AMINOBENZAMIDINO)SUCCINYL (ABAS) SERIES OF ORALLY-ACTIVE FIBRINOGEN RECEPTOR ANTAGONISTS
    ZABLOCKI, JA
    RICO, JG
    GARLAND, RB
    ROGERS, TE
    WILLIAMS, K
    SCHRETZMAN, LA
    RAO, SA
    BOVY, PR
    TJOENG, FS
    LINDMARK, RJ
    TOTH, MV
    ZUPEC, ME
    MCMACKINS, DE
    ADAMS, SP
    MIYANO, M
    MARKOS, CS
    MILTON, MN
    PAULSON, S
    HERIN, M
    JACQMIN, P
    NICHOLSON, NS
    PANZERKNODLE, SG
    HAAS, NF
    PAGE, JD
    SZALONY, JA
    TAITE, BB
    SALYERS, AK
    KING, LW
    CAMPION, JG
    FEIGEN, LP
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (13) : 2378 - 2394