Synlett 2012; 23(20): 2880-2893
DOI: 10.1055/s-0032-1317414
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© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Cyanation of Nonactivated Alkynes; Development of Cyanopalladation and Its Application to Cyclization and Cycloaddition Reactions

Shigeru Arai*
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, 260-8675 Chiba, Japan   Fax: +81(43)2262942   Email: arai@p.chiba-u.ac.jp
,
Atsushi Nishida
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, 260-8675 Chiba, Japan   Fax: +81(43)2262942   Email: arai@p.chiba-u.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 09 August 2012

Accepted after revision: 18 September 2012

Publication Date:
14 November 2012 (online)


Abstract

This account describes the cyanopalladation of simple and nonactivated alkynes and their application to various cyclization and cycloaddition protocols. A unique feature of cyanopalladation is the direct nucleophilic cyanation with an external CN source such as TMSCN of simple alkynes, which can be effectively activated by Pd(II) under molecular oxygen. There are two possible pathways: syn- and anti-cyanopalladation, which are strongly influenced by the structure of the substrates. The former is usually the major pathway because nucleophilic cyanation is favored to occur at the less hindered alkynyl carbon. The latter could be controlled by the Markovnikov rule, with cyanide directly attacking the π-complex of alkynyl carbons from the site opposite Pd(II). Once the cyanoalkenyl Pd(II) species are formed by cyanopalladation, these intermediates act as useful precursors for sequential carbon–carbon bond-forming reactions, such as 5-exo and 6-endo cyclizations and [4+2] cycloaddition. Cyclization is triggered by regio- and stereoselective cyanopalladation, and [4+2] cycloaddition gives up to five stereogenic centers through the formation of four C–C bonds in a single operation. The reaction pathways and the origin of stereochemistry are also described.

1 Introduction

2 Catalytic 1,2-Dicyanation

2.1 Terminal Alkynes

2.2 Internal Alkynes

2.3 Synthetic Applications

3 Dicyanative Cyclization

3.1 5-exo Cyclization

3.2 Diyne Cyclization

3.2.1 Terminal Diynes

3.2.2 Internal Diynes

3.3 6-endo Cyclization

4 Dicyanative [4+2] Cycloaddition

5 Conclusion

 
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