Asymmetric formation of quaternary centers through aza-annulation of chiral β-enamino amides with acrylate derivatives

被引:60
作者
Benovsky, P
Stephenson, GA
Stille, JR [1 ]
机构
[1] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA
[2] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA
关键词
D O I
10.1021/ja9729591
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The stereoselective formation of six-membered nitrogen heterocycles that contain an asymmetric quaternary carbon center was achieved through aza-annulation of beta-enamino amide substrates with activated acrylate derivatives. Condensation of a racemic beta-keto amide with an optically active primary amine, either (R)-alpha-methylbenzylamine or alpha-amino esters, generated the corresponding optically active tetrasubstituted secondary enamine, in which the enamine tautomer was stabilized through conjugation with an amide carbonyl. Treatment of the intermediate enamine with acryloyl chloride, acrylic anhydride, or sodium acrylate/ethyl chloroformate resulted in aza-annulation to give the corresponding delta-lactam with high diastereoselectivity (>96% de). For the variety of different beta-enamino amide substrate classes examined in this reaction, the optimum method for activation of the acrylate derivative was the use of EtO2CCl. When aza-annulation was performed with an alpha-acetamido-substituted acrylate derivative, the stereoselective formation of the quaternary carbon center was accompanied by poor selectivity for generation of the center alpha to the lactam carbonyl. Crystallographic analysis of one alpha-amido aza-annulation product was performed to identify the key structural features of these molecules.
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页码:2493 / 2500
页数:8
相关论文
共 53 条
  • [1] [Anonymous], INT TABLES XRAY CRYS
  • [2] [Anonymous], 1994, Aldrichimica Acta
  • [3] Arrieta A., 1981, TETRAHEDRON LETT, V22, P1729
  • [4] AN APPARATUS FOR THE EFFICIENT REMOVAL OF H2O FROM REACTION MIXTURES
    BARTA, NS
    PAULVANNAN, K
    SCHWARZ, JB
    STILLE, JR
    [J]. SYNTHETIC COMMUNICATIONS, 1994, 24 (04) : 583 - 590
  • [5] ASYMMETRIC FORMATION OF QUATERNARY CENTERS THROUGH AZA-ANNULATION OF CHIRAL BETA-ENAMINO ESTERS WITH ACRYLATE DERIVATIVES
    BARTA, NS
    BRODE, A
    STILLE, JR
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (14) : 6201 - 6206
  • [6] Formation of dihydropyridone- and pyridone-based peptide analogs through aza-annulation of beta-enamino ester and amide substrates with alpha-amido acrylate derivatives
    Beholz, LG
    Benovsky, P
    Ward, DL
    Barta, NS
    Stille, JR
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (04) : 1033 - 1042
  • [7] SYNTHESIS OF BICYCLIC PYRIDONE AND DIHYDROPYRIDONE ANALOGS OF BETA-LACTAM ANTIBIOTICS
    CAPPS, NK
    DAVIES, GM
    LOAKES, D
    MCCABE, RW
    YOUNG, DW
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1991, (12): : 3077 - 3086
  • [8] Stereochemical aspects in the asymmetric Michael addition of chiral imines to substituted electrophilic alkenes
    Cave, C
    Desmaele, D
    dAngelo, J
    Riche, C
    Chiaroni, A
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (13) : 4361 - 4368
  • [9] CHIBA T, 1985, CHEM PHARM BULL, V33, P4002
  • [10] CHIBA T, 1985, CHEM PHARM BULL, V33, P2731