SYNTHESIS OF ALPHA-SUBSTITUTED ALPHA-AMINO-ACIDS VIA CATIONIC INTERMEDIATES

被引:38
作者
ROOS, EC
LOPEZ, MC
BROOK, MA
HIEMSTRA, H
SPECKAMP, WN
KAPTEIN, B
KAMPHUIS, J
SCHOEMAKER, HE
机构
[1] UNIV AMSTERDAM,DEPT ORGAN CHEM,NIEUWE ACHTERGRACHT 129,1018 WS AMSTERDAM,NETHERLANDS
[2] DSM RES & PATENTS,DEPT BIOORGAN CHEM,6160 MD GELEEN,NETHERLANDS
关键词
D O I
10.1021/jo00064a011
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A novel synthetic approach to racemic alpha-substituted alpha-amino acids is described. The key intermediates of this methodology are highly electrophilic iminium ions, bearing carbonyl substituents at both the iminium carbon and nitrogen atom. The preparation of precursors 8, 10a-c, and 12 includes electrochemical oxidation techniques according to literature procedures. When an alpha-methyl precursor (8 or 10a) was used, reactions with allylsilanes and silyl enol ethers led to the desired products, but elimination to dehydroalanine derivatives appeared to be an important side reaction. A major improvement in the yields of the desired products could be effected by using longer reaction times. In this way, efficient syntheses of protected alpha-methyl-alpha-amino acids could be developed. The elimination process appeared to be a more serious problem in the alpha-benzyl (10b) and alpha-allyl (10c) cases. On the other hand, the alpha-phenyl precursor 12 appeared to be highly useful, because the elimination is impossible in this case. High yields of alpha-phenyl-alpha-amino acid derivatives were obtained upon reaction of 12 with silicon-activated pi-nucleophiles. Deprotection led to various types of free alpha-substituted alpha-amino acids.
引用
收藏
页码:3259 / 3268
页数:10
相关论文
共 76 条
  • [11] NEW SYNTHESES OF ALPHA-AMINO-ACIDS BASED ON N-ACYLIMINO ACETATES
    BRETSCHNEIDER, T
    MILTZ, W
    MUNSTER, P
    STEGLICH, W
    [J]. TETRAHEDRON, 1988, 44 (17) : 5403 - 5414
  • [12] CATIVIELA C, 1992, SYNLETT, P121
  • [13] REACTIONS OF FLUOROBENZENE TRICARBONYLCHROMIUM COMPLEXES WITH ANIONS FROM SCHIFF-BASES OF ALPHA-AMINO ESTERS - ENANTIOSELECTIVE SYNTHESIS OF ALPHA-ARYL AMINO-ACIDS
    CHAARI, M
    JENHI, A
    LAVERGNE, JP
    VIALLEFONT, P
    [J]. TETRAHEDRON, 1991, 47 (26) : 4619 - 4630
  • [14] MECHANISM OF HYDROLYSIS OF CHLOROSILANES - NUCLEOPHILIC CATALYSIS - KINETIC STUDIES AND EVIDENCE FOR A HEXACOORDINATE INTERMEDIATE
    CORRIU, RJP
    DABOSI, G
    MARTINEAU, M
    [J]. JOURNAL OF ORGANOMETALLIC CHEMISTRY, 1978, 150 (01) : 27 - 38
  • [15] A STEREOSELECTIVE SYNTHESIS OF N-BOC-ALPHA-AMINO ALCOHOLS AND ALPHA-AMINO-ACIDS
    ERMERT, P
    MEYER, J
    STUCKI, C
    SCHNEEBELI, J
    OBRECHT, JP
    [J]. TETRAHEDRON LETTERS, 1988, 29 (11) : 1265 - 1268
  • [16] ALPHA-ALKYLATION OF ACYCLIC AMINO-ACIDS WITH SELF-REPRODUCTION OF THE CENTER OF CHIRALITY - A NEW ROUTE TO (S)-(+)-ALPHA-ALKYLATED ASPARTIC ACIDS
    FADEL, A
    SALAUN, J
    [J]. TETRAHEDRON LETTERS, 1987, 28 (20) : 2243 - 2246
  • [17] INDIRECT ELECTROCHEMICAL ALPHA-METHOXYLATION OF N-ACYL AND N-CARBOALKOXY ALPHA-AMINO-ACID ESTERS AND APPLICATION AS CATIONIC GLYCINE EQUIVALENTS
    GINZEL, KD
    BRUNGS, P
    STECKHAN, E
    [J]. TETRAHEDRON, 1989, 45 (06) : 1691 - 1701
  • [19] Greenstein J. P., 1984, CHEM AMINO ACIDS, V1-3
  • [20] ACYCLIC STEREOSELECTION IN ALPHA-AMIDOALKYLATION REACTIONS
    HARDING, KE
    DAVIS, CS
    [J]. TETRAHEDRON LETTERS, 1988, 29 (16) : 1891 - 1894