Efficient stereoselective synthesis of enantiopure cis- and trans-1 2,4-trisubstituted piperidines

被引：12

作者：

Etayo, Pablo ^{[1
]}

Badorrey, Ramon ^{[1
]}

Diaz-de-Villegas, Maria D. ^{[1
]}

Galvez, Jose A. ^{[1
]}

机构：

[1] Univ Zaragoza CSIC, Inst Univ Catalisis Homogenea, Inst Ciencia Mat Aragon, Dept Quim Organ, E-50009 Zaragoza, Spain

来源：

TETRAHEDRON-ASYMMETRY | 2007年 / 18卷 / 23期

关键词：

D O I：

10.1016/j.tetasy.2007.10.042

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

Enantionterically pure (2R,4S)- and (2 R,4R)-2-[(S)-1, 2-dibenzy] oxyethyl]-4-[2-(diphenylmethoxy)ethyl]-1-[(S)-1-phenylethyl]piperidines eis-1 and trans-1 have been synthesised from N-[(S)-1-phenylethyl]-(S)-2,3-di-O-benzylglyceraldimine in six steps in 31% and 18% overall yields, respectively. The efficiency of the synthetic strategy developed for the synthesis of these compounds relies on: (a) the totally diastereoselective tandem Mannich-Michael reaction between Danishefsky's diene and the starting glyceraldimine, (b) the high yielding Wadsworth-Emmons reaction of the 4-piperidone intermediate and (c) the diastereodivergent reduction of the exocyclic C-C double bond at C-4 of the piperidine ring. These transformations led to 1, 2,4-trisubstituted piperidines with two new stereogenic centres with excellent stereo se lectivity. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2812 / 2819

页数：8

共 29 条

[1] Naturally occurring iminosugars and related compounds: Structure, distribution, and biological activity [J].

Asano, N .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2003, 3 (05) :471-484

[2] Highly convergent stereoselective synthesis of chiral key intermediates in the synthesis of Palinavir from imines derived from L-glyceraldehyde [J].

Badorrey, R ;

Cativiela, C ;

Díaz-de-Villegas, MD ;

Gálvez, JA .

TETRAHEDRON, 2002, 58 (02) :341-354

[3] Study of the reaction of imines derived from (R)-glyceraldehyde with Danishefsky's diene. [J].

Badorrey, R ;

Cativiela, C ;

Díaz-de-Villegas, MD ;

Gálvez, JA .

TETRAHEDRON, 1999, 55 (24) :7601-7612

[4] Asymmetric hetero Diels-Alder reaction of N-benzylimines derived from R-glyceraldehyde: A new approach to homochiral piperidine building blocks and its application to the synthesis of (2R)-4-oxopipecolic acid [J].

Badorrey, R ;

Cativiela, C ;

DiazdeVillegas, MD ;

Galvez, JA .

TETRAHEDRON LETTERS, 1997, 38 (14) :2547-2550

[5] Structure-activity relationships of substituted N-benzyl piperidines in the GBR series:: Synthesis of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl) piperidine, an allosteric modulator of the serotonin transporter [J].

Boos, Terrence L. ;

Greiner, Elisabeth ;

Calhoun, W. Jason ;

Prisinzano, Thomas E. ;

Nightingale, Barbara ;

Dersch, Christina M. ;

Rothman, Richard B. ;

Jacobson, Arthur E. ;

Rice, Kenner C. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (11) :3967-3973

[6] Synthesis of piperidines [J].

Buffat, MGP .

TETRAHEDRON, 2004, 60 (08) :1701-1729

[7] PREPARATION OF 1-(TERT-BUTOXYCARBONYL)-2,6-DIALKYL-2,3-DIHYDRO-4-PYRIDONES - A STEREOCONTROLLED SYNTHESIS OF (+/-)-MYRTINE [J].

COMINS, DL ;

LAMUNYON, DH .

TETRAHEDRON LETTERS, 1989, 30 (38) :5053-5056

[8] IRIDIUM COMPOUNDS IN CATALYSIS [J].

CRABTREE, R .

ACCOUNTS OF CHEMICAL RESEARCH, 1979, 12 (09) :331-338

[9] CATIONIC IRIDIUM DIOLEFIN COMPLEXES AS ALKENE HYDROGENATION CATALYSTS AND ISOLATION OF SOME RELATED HYDRIDO COMPLEXES [J].

CRABTREE, RH ;

FELKIN, H ;

MORRIS, GE .

JOURNAL OF ORGANOMETALLIC CHEMISTRY, 1977, 141 (02) :205-215

[10] Alkaloids from amphibian skin: A tabulation of over eight-hundred compounds [J].

Daly, JW ;

Spande, TF ;

Garraffo, HM .

JOURNAL OF NATURAL PRODUCTS, 2005, 68 (10) :1556-1575

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