Catalyst-Enabled Site-Divergent Stereoselective Michael Reactions: Overriding Intrinsic Reactivity of Enynyl Carbonyl Acceptors

Daisuke Uraguchi; Ryo Shibazaki; Naoya Tanaka; Kohei Yamada; Ken Yoshioka; Takashi Ooi

doi:10.1002/anie.201800057

Catalyst-Enabled Site-Divergent Stereoselective Michael Reactions: Overriding Intrinsic Reactivity of Enynyl Carbonyl Acceptors

Angew Chem Int Ed Engl. 2018 Apr 16;57(17):4732-4736. doi: 10.1002/anie.201800057. Epub 2018 Mar 9.

Authors

Daisuke Uraguchi¹, Ryo Shibazaki¹, Naoya Tanaka¹, Kohei Yamada¹, Ken Yoshioka¹, Takashi Ooi^{1

2}

Affiliations

¹ Institute of Transformative Bio-Molecules (WPI-ITbM) and Department of Molecular and Macromolecular Chemistry, Graduate School of Engineering, Nagoya University, Nagoya, 464-8601, Japan.
² CREST, Japan Science and Technology Agency (JST), Nagoya University, Nagoya, 464-8601, Japan.

PMID: 29436085
DOI: 10.1002/anie.201800057

Abstract

A site-divergent stereoselective Michael reaction system is developed based on the identification of two distinct catalysts. Cinchonidine-derived thiourea catalyzes the 1,4-addition of prochiral azlactone enolates to enynyl N-acyl pyrazoles in a highly diastereo- and enantioselective manner to give stereochemically defined alkynes, while P-spiro chiral triaminoiminophosphorane catalytically controls the stereoselective 1,6-addition and the consecutive γ-protonation of the vinylogous enolate intermediate to afford Z,E-configured conjugated dienes. This 1,6-adduct serves as a valuable precursor for the synthesis of a 2-amino-2-deoxy sugar.

Keywords: Michael addition; alkynes; amino acids; carbohydrates; organocatalysis.

Publication types

Research Support, Non-U.S. Gov't