Aluminum(III)-Catalyzed, Formal Homo-Nazarov-Type Ring-Opening Cyclizations toward the Synthesis of Functionalized Tetrahydroindolizines

被引：13

作者：

Cavitt, Marchello A. ^{[1
]}

France, Stefan ^{[1
,2
]}

机构：

[1] Georgia Inst Technol, Sch Chem & Biochem, 901 Atlantic Dr, Atlanta, GA 30332 USA

[2] Georgia Inst Technol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA

来源：

SYNTHESIS-STUTTGART | 2016年 / 48卷 / 12期

基金：

美国国家科学基金会;

关键词：

heterocycles; fused-ring systems; ring-opening cyclizations; tetrahydroindolizines; formal homo-Nazarov cyclization; donor-acceptor cyclopropanes; 1,3-DIPOLAR CYCLOADDITIONS; 1,3-DICARBONYL COMPOUNDS; EFFICIENT ACCESS; ALKALOIDS; 5,6,7,8-TETRAHYDROINDOLIZINES; RHAZINILAM; INDOLIZINES; ALKYLATION; CMV423; KOPSIA;

D O I：

10.1055/s-0035-1561621

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A general approach to functionalized 5,6,7,8-tetrahydroindolizines (THIs) is disclosed. The THIs are directly formed from Al(OTf)(3)-catalyzed, formal homo-Nazarov-type ring-opening cyclizations of N-pyrrolyl cyclopropyl malonamides. The THI products were stable to silica gel chromatography and isolated in up to 97% yield with diastereomeric ratios up to 4.0:1. The cyclization demonstrates good substrate scope as aryl, heteroaryl, gem-dialkyl, heteroatomic, and silylmethyl donor groups on the cyclopropane are tolerated. Moreover, the protocol is both pharmaceutically relevant and environmentally friendly as a cheap, earth-abundant metal catalyst is used along with acetonitrile as a greener solvent.

引用

页码：1910 / 1919

页数：10

共 50 条

[1] Photochromism of tetrahydroindolizines. Part XIV: synthesis of cis-fixed conjugated photochromic pyridazinopyrrolo [1,2-b]isoquinolines incorporating carbon-rich linkers [J].

Ahmed, Saleh A. ;

Khairou, Khalid S. ;

Asghar, Basim H. ;

Muathen, Hussni A. ;

Nahas, Nariman M. A. ;

Alshareef, Hossa F. .

TETRAHEDRON LETTERS, 2014, 55 (14) :2190-2196

[2]

[Anonymous], 2011, Int. J. Pharm. Sci. Rev. Res

[3]

Apodaca R., 2002, PCT Int. Appl., Patent No. [2002024695, WO 2002024695 A2]

[4] A Tandem, Bicatalytic Continuous Flow Cyclopropanation-Homo-Nazarov-Type Cyclization [J].

Aponte-Guzman, Joel ;

Shenje, Raynold ;

Huang, Yong ;

Woodham, Wesley H. ;

Saunders, Steven R. ;

Mostaghimi, Sina M. ;

Flack, Kyle R. ;

Pollet, Pamela ;

Eckert, Charles A. ;

Liotta, Charles L. ;

France, Stefan .

INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, 2015, 54 (39) :9550-9558

[5] Tetrahydroindolizinone NK1 antagonists [J].

Bao, Jianming ;

Lu, Huagang ;

Morriello, Gregori J. ;

Carlson, Emma J. ;

Wheeldon, Alan ;

Chicchi, Gary G. ;

Kurtz, Marc M. ;

Tsao, Kwei-Lan C. ;

Zheng, Song ;

Tong, Xinchun ;

Mills, Sander G. ;

DeVita, Robert J. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (07) :2354-2358

[6]

Bertin L., 2011, PCT Int. Appl, Patent No. [WO 2011027081 A2, 2011027081]

[7] Catalytic One-Pot Synthesis of 1-Substituted 5,6,7,8-Tetrahydroindolizine Derivatives [J].

Biletzki, Tobias ;

Imhof, Wolfgang .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2012, 2012 (33) :6513-6516

[8] In vitro metabolism and drug interaction potential of a new highly potent anti-cytomegalovirus molecule, CMV423 (2-chloro 3-pyridine 3-yl 5,6,7,8-tetrahydroindolizine 1-carboxamide) [J].

Bournique, B ;

Lambert, N ;

Boukaiba, R ;

Martinet, M .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2001, 52 (01) :53-63

[9] Single-Step Synthesis of 5,6,7,8-Tetrahydroindolizines via Annulation of 2-Formylpiperidine and 1,3-Dicarbonyl Compounds [J].

Capomolla, Simona S. ;

Lim, Ngiap-Kie ;

Zhang, Haiming .

ORGANIC LETTERS, 2015, 17 (14) :3564-3567

[10] New efficient access to fused (Het)Aryltetrahydroindolizinones via N-acyl iminium intermediates [J].

Chiurato, Matteo ;

Boulahjar, Rajaa ;

Routier, Sylvain ;

Troin, Yves ;

Guillaumet, Gerald .

TETRAHEDRON, 2010, 66 (25) :4647-4653

← 1 2 3 4 5 →