Enantioselective carbon-hydrogen insertion is an effective and efficient methodology for the synthesis of (R)-(-)-baclofen

被引：29

作者：

Doyle, MP ^{[1
]}

Hu, WH ^{[1
]}

机构：

[1] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA

来源：

CHIRALITY | 2002年 / 14卷 / 2-3期

关键词：

chiral dirhodium(II) carboxamidates; metal carbene reactions; catalytic enantioselective synthesis; diazoacetate;

D O I：

10.1002/chir.10060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A highly enantioselective methodology for the synthesis of the GABA(B) receptor agonist (R)-(-)-baclofen is described. This synthesis begins with p-chlorophenethyl alcohol and involves a catalytic carbon-hydrogen insertion reaction of a chiral dirhodium(II) carboxamidate with the corresponding diazoacetate (81% yield, 95% ee). Subsequent steps convert the intermediate gamma-lactone to (R)(-)-baclofen in a 60% overall yield. The amount of catalyst required for the C-H insertion transformation is only 0.5 mol%. (C) 2002 Wiley-Liss, Inc.

引用

收藏

页码：169 / 172

页数：4

相关论文

共 16 条

[1] Enantioselective synthesis of 4-substituted 2-pyrrolidinones by site-selective C-H insertion of α-methoxycarbonyl-α-diazoacetanilides catalyzed by dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate] [J].

Anada, M ;

Hashimoto, S .

TETRAHEDRON LETTERS, 1998, 39 (1-2) :79-82

[2] Michael addition of nitromethane to non-racemic chiral Cr(CO)3 complexes of ethyl cinnamate derivatives:: stereoselective synthesis of (R)-(-)-baclofen [J].

Baldoli, C ;

Maiorana, S ;

Licandro, E ;

Perdicchia, D ;

Vandoni, B .

TETRAHEDRON-ASYMMETRY, 2000, 11 (09) :2007-2014

[3] 3-THIENYLAMINOBUTYRIC AND 3-FURYLAMINOBUTYRIC ACIDS - SYNTHESIS AND BINDING GABA-B RECEPTOR STUDIES [J].

BERTHELOT, P ;

VACCHER, C ;

FLOUQUET, N ;

DEBAERT, M ;

LUYCKX, M ;

BRUNET, C .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (08) :2557-2560

[4] Intramolecular regioselective insertion into unactivated prochiral carbon-hydrogen bonds with diazoacetates of primary alcohols catalyzed by chiral dirhodium(II) carboxamidates. Highly enantioselective total synthesis of natural lignan lactones [J].

Bode, JW ;

Doyle, MP ;

Protopopova, MN ;

Zhou, QL .

JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (26) :9146-9155

[5] REACTIONS OF SODIUM PHENYLACETYLIDE AND SODIUM ALKOXIDE WITH TOSYL AND MESYL AZIDES [J].

BOYER, JH ;

MACK, CH ;

GOEBEL, N ;

MORGAN, LR .

JOURNAL OF ORGANIC CHEMISTRY, 1958, 23 (07) :1051-1053

[6] Enantioselective synthesis of beta-substituted butyric acid derivatives via orthoester Claisen rearrangement of enzymatically resolved allylic alcohols: application to the synthesis of (R)-(-)-baclofen [J].

Brenna, E ;

Caraccia, N ;

Fuganti, C ;

Fuganti, D ;

Grasselli, P .

TETRAHEDRON-ASYMMETRY, 1997, 8 (22) :3801-3805

[7] Enantioselective Michael addition of nitromethane to α,β-enones catalyzed by chiral quaternary ammonium salts.: A simple synthesis of (R)-baclofen [J].

Corey, EJ ;

Zhang, FY .

ORGANIC LETTERS, 2000, 2 (26) :4257-4259

[8]

Doyle M. P., 1998, Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides

[9] Recent advances in asymmetric catalytic metal carbene transformations [J].

Doyle, MP ;

Forbes, DC .

CHEMICAL REVIEWS, 1998, 98 (02) :911-935

[10] ASYMMETRIC-SYNTHESIS OF LACTONES WITH HIGH ENANTIOSELECTIVITY BY INTRAMOLECULAR CARBON HYDROGEN INSERTION REACTIONS OF ALKYL DIAZOACETATES CATALYZED BY CHIRAL RHODIUM(II) CARBOXAMIDES [J].

DOYLE, MP ;

VANOEVEREN, A ;

WESTRUM, LJ ;

PROTOPOPOVA, MN ;

CLAYTON, TW .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (23) :8982-8984