Site-Selective Conjugate Addition Through Catalytic Generation of Ion-Pairing Intermediates

Abstract

Site-selectivity in conjugate addition reactions is tightly associated with the principle of vinylogy. Various vinylogous nucleophiles and electrophiles have been applied to stereoselective conjugate additions directed by chiral small-molecule catalysts. This chapter focuses on the systems that control site- and stereoselectivity via chiral ion-pairing intermediates under organocatalytic conditions and describes individual vinylogous substrates in a separate section. Although site-selectivity originates largely from the intrinsic stereoelectronic nature of individual substrates, catalyst-controlled site-selectivity can be attained in certain cases.

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…During the 2010–2018 period considered here, a considerable number of authoritative reviews, accounts, and highlights appeared in the literature that focused on particular aspects of vinylogy . Many of them accounted for specific HOMO-raising catalytic activation modalities of pronucleophiles (amino-organocatalysis, − NHC-organocatalysis, , noncovalent organocatalysis); − some dealt with selected classes of vinylogous functional groups (aldehydes, , nitriles, , alkylidene carbo- or heterocycles , ), while others were focused on either specific reaction types (Michael additions, , Mukaiyama-type C–C bond forming reactions, organocascade reactions) or selected target categories (polyketides, γ-butenolides , ).…”

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

“…When this regiochemical consideration is coupled with a stereochemical issue in a general synthetic context, simultaneous dictation of both the selectivities poses a more profound challenge, particularly in catalytically directing the bond‐forming reactions that involve multiple stereoselectivity factors . One of the synthetically relevant carbon–carbon bond formations that are associated with this innate selectivity problem is the Michael addition of prochiral enolates to extended conjugate systems, such as dienyl carbonyl compounds.…”

Vinylogous and Arylogous Stereoselective Base-Promoted Phase-Transfer Catalysis

“…Since it is well known that ionpairing plays a key role in the mechanism of phase-transfer catalyzed processes, the regioand stereoselectivity under such conditions are expected to be governed by interactions between the cation catalyst and the vinylogous enolate-type anion (II, VI, IX, XII, XV in Scheme 1) [37][38][39][40]. In fact, although site-selectivity of vinylogous reactions is often affected by intrinsic stereoelectronic features of reagents, the role played by the catalyst's control in processes involving ion-pair intermediates has been demonstrated in many cases [41].…”