Catalytic Enantioselective Desymmetrization Reactions to All-Carbon Quaternary Stereocenters

Abstract

This Review summarizes the advances in the construction of all-carbon quaternary stereocenters via catalytic enantioselective desymmetrization of prochiral and meso-compounds, highlights the power and potential of this strategy in the total synthesis of natural products and biologically active compounds, and outlines the synthetic opportunities still available.

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…140–144 Such desymmetrization reactions have the advantage that creation of the quaternary center and the induction of chirality occur in separate events. While numerous desymmetrizing cyclizations have been developed, 144 the formation of acyclic quaternary carbon stereocenters through transition-metal catalyzed desymmetrization remains uncommon.…”

Forging Fluorine‐Containing Quaternary Stereocenters by a Light‐Driven Organocatalytic Aldol Desymmetrization Process

“…The resulting symmetry‐breaking process generates two stereocenters simultaneously, and forges a C−F stereogenic unit far from the reaction site. The desymmetrization of centrosymmetric or meso compounds by chiral catalysts is a powerful method for making chiral molecules,7 and has been used extensively to synthesize natural compounds and biologically relevant molecules 7a. However, this strategy has never yet been used to install quaternary fluorine‐containing stereocenters 8…”

“…Since the pioneering work of Hajos and Parrish,13 symmetric 1,3‐diketones of type 1 have been used extensively to design new desymmetric aldol processes. However, these have proceeded through intramolecular manifolds exclusively 7a, 13…”

“…This type of scaffold belongs to a class of valuable chiral intermediates which are useful for synthesizing biologically relevant compounds and natural products 7a, 13, 17. The organocatalytic desymmetrization of 2‐fluoro‐2‐(3‐oxobutyl) cyclopentane 1,3‐dione ( 1 v ), which transiently affords the enantioenriched fluorinated 3‐hydroxyketone 3 v , was followed by an enamine‐mediated cyclization upon addition of pyrrolidine (50 mol %) to the same reaction flask.…”

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

“…Desymmetrization has become a well-developed strategy for the construction of complex molecular frameworks [1–6]. Cyclohexadienones are multipurpose synthetic building blocks that have found a central role in desymmetrization methodologies.…”