Diastereoselective One-Pot Knoevenagel Condensation/Corey-Chaykovsky Cyclopropanation

被引：16

作者：

Clemens, Jeremy J. ^{[1
]}

Asgian, Juliana L. ^{[1
]}

Busch, Brett B. ^{[1
]}

Coon, Timothy ^{[1
]}

Ernst, Justin ^{[1
]}

Kaljevic, Leonard ^{[1
]}

Krenitsky, Paul J. ^{[1
]}

Neubert, Timothy D. ^{[1
]}

Schweiger, Edwin J. ^{[1
]}

Termin, Andreas ^{[1
]}

Stamos, Dean ^{[1
]}

机构：

[1] Vertex Pharmaceut, Dept Drug Innovat, San Diego, CA 92121 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2013年 / 78卷 / 02期

关键词：

FERROELECTRIC LIQUID-CRYSTALS; STEREOSELECTIVE-SYNTHESIS; DILITHIATED NITRILES; CYANOCYCLOPROPANES; EPIBROMOHYDRIN; SELECTIVITY; CYCLIZATION; EPOXIDATION; DOPANTS;

D O I：

10.1021/jo302443k

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Efforts to substitute the cyclopropane ring in a series of aryl cyclopropylnitriles led to the discovery of an operationally simple one-pot method for Knoevenagel condensation and subsequent Corey-Chaykovsky cyclopropanation giving diastereomerically pure products as a racemic mixture of enantiomers. Method development and results for variably substituted aryl acetonitriles and aldehydes in the reaction are reported. A concise synthesis of (+/-)-bicifadine in two steps is provided to demonstrate the utility of the method.

引用

页码：780 / 785

页数：6

共 25 条

[1] REACTION OF VINYL SULFONE WITH ALPHA-METALLATED NITRILES [J].

AGAWA, T ;

YOSHIDA, Y ;

KOMATSU, M ;

OHSHIRO, Y .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1981, (03) :751-755

[2] Catalytic, asymmetric sulfur ylide-mediated epoxidation of carbonyl compounds: Scope, selectivity, and applications in synthesis [J].

Aggarwal, VK ;

Winn, CL .

ACCOUNTS OF CHEMICAL RESEARCH, 2004, 37 (08) :611-620

[3] One-pot cyclization of dilithiated nitriles with isothiocyanates and epibromohydrin. Synthesis of 2-cyano-1-(hydroxymethyl)cyclopropanes and 2-cyanomethylidene-4-(hydroxymethyl)thiazolidines [J].

Albrecht, Uwe ;

Freifeld, Ilia ;

Reinke, Helmut ;

Langer, Peter .

TETRAHEDRON, 2006, 62 (24) :5775-5786

[4]

Bryson T., 1992, SYNLETT, P723

[5] Efficient and practical syntheses of a stable labelled form of the non-narcotic analgesic, bicifadine and its metabolites [J].

Chen, Zhengming ;

Yang, Ji ;

Little, Gillian ;

Keats, Andrew .

JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2007, 50 (1-2) :97-104

[6] Stereoselective construction of nitrile-substituted cyclopropanes [J].

Denton, Justin R. ;

Cheng, Kevin ;

Davies, Huw M. L. .

CHEMICAL COMMUNICATIONS, 2008, (10) :1238-1240

[7] 1-ARYL-3-AZABICYCLO[3.1.0]HEXANES, A NEW SERIES OF NON-NARCOTIC ANALGESIC AGENTS [J].

EPSTEIN, JW ;

BRABANDER, HJ ;

FANSHAWE, WJ ;

HOFMANN, CM ;

MCKENZIE, TC ;

SAFIR, SR ;

OSTERBERG, AC ;

COSULICH, DB ;

LOVELL, FM .

JOURNAL OF MEDICINAL CHEMISTRY, 1981, 24 (05) :481-490

[8] STEREOSELECTIVE SYNTHESIS OF VINYLCYCLOPROPANES FROM 2-PHENYLSULFONYL-1,3-CYCLOHEXADIENES AND KETONE ENOLATES OR NITRILE ANION [J].

ERICSSON, AM ;

PLOBECK, NA ;

BACKVALL, JE .

ACTA CHEMICA SCANDINAVICA, 1994, 48 (03) :252-257

[9] 25 YEARS OF DIMETHYLSULFOXONIUM METHYLIDE (COREYS REAGENT) [J].

GOLOLOBOV, YG ;

NESMEYANOV, AN ;

LYSENKO, VP ;

BOLDESKUL, IE .

TETRAHEDRON, 1987, 43 (12) :2609-2651

[10] SYNTHESIS AND REACTIONS OF A STABLE 2-SELENANAPHTHALENE, 1-CYANO-2-METHYL-2-SELENANAPHTHALENE [J].

HORI, M ;

KATAOKA, T ;

SHIMIZU, H ;

TSUTSUMI, K ;

YOSHIMATSU, M .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (08) :2458-2463

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