In Search of an Atom-Economical Synthesis of Chiral Ynamides

Jason A. Mulder; Kimberly C. M. Kurtz; Richard P. Hsung

doi:10.1055/s-2003-40817

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Synlett 2003(10): 1379-1390
DOI: 10.1055/s-2003-40817

ACCOUNT

In Search of an Atom-Economical Synthesis of Chiral Ynamides

Jason A. Mulder, Kimberly C. M. Kurtz, Richard P. Hsung*
Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
e-Mail: hsung@chem.umn.edu;

Further Information

Publication History

Received 10 March 2003
Publication Date:
24 July 2003 (online)

Abstract
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Abstract

Failed attempts and successes in searching for an atom-economical and efficient synthesis of chiral ynamides are described in this account. These events are illustrated in chronological order, and comparisons are made along the way to reflect other elegant methods known for preparations of ynamides and other electron deficient ynamines. The purpose of this account is to facilitate and revitalize interest in the chemistry of ynamines within the synthetic community.

1 Introduction
2 Failed Attempts in Achieving Direct Approaches
2.1 Palladium Catalyzed Cross-Coupling
2.2 Alkynyl Iodonium Salts
2.3 Base-Promoted Isomerization
3 Elimination Protocols
3.1 Lithium-Halogen Exchange
3.2 The Viehe Sequence
4 The Isomerization Protocol with Limitations
5 A Cu-Salt Catalyzed Cross-Coupling
6 Summary
7 Outlook

Key words

Ynamines - electron deficient ynamines - ynamides - base-promoted isomerization of propargyl amides - copper catalyzed cross-couplings of amides - alkynyl halides

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9

The unfortunate and premature loss of Professor J. Ficini is one critical reason for lack of advancement in the field.

10

No real attempt is being made in this account to truly distinguish or classify various different electron deficient ynamines 1-9 in Figure [2] , however, for certain level of structural clarity and convenience we have regarded compounds 1-5 as electron deficient ynamines whereas compounds 6-9 in which the nitrogen atom is directly attached to an electron-withdrawing carbonyl or sulfonyl group as ynamides.