Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

Abstract

Whereas numerous asymmetric methods for formation of quaternary carbon stereocenters in cyclic systems have been documented, the construction of acyclic quaternary carbon stereocenters with control of absolute stereochemistry remains a formidable challenge. This review summarizes enantioselective methods for the construction of acyclic quaternary carbon stereocenters from achiral or chiral racemic reactants via transition metal catalysis.

Catalyst‐Dependent Chemoselective Formal Insertion of Diazo Compounds into C−C or C−H Bonds of 1,3‐Dicarbonyl Compounds

“…In contrast, the use of Sc(OTf) 3 as the catalyst led to as witch in chemoselectivity,n ow effecting af ormal C À Hi nsertion and leading to products of 1,3-dicarbonyl alkylation. In contrast, the use of Sc(OTf) 3 as the catalyst led to as witch in chemoselectivity,n ow effecting af ormal C À Hi nsertion and leading to products of 1,3-dicarbonyl alkylation.…”

“…In the complementary scandium-catalyzed CÀHinsertion, protonation of the diazo compound 1 by HOTfcould yield the diazonium ion B' ',w hich displays carbocation-like reactivity, [23] undergoing facile nucleophilic attack by the scandium enolate A' ' to give complex C' '.The CÀHinsertion product 4 is then released, with regeneration of Sc(OTf) 3 .I nt he absence of this chelate A' ' (Scheme 4), direct reaction on the more reactive enolate oxygen atom may instead by possible (to give 5c). Thed ivergent reactivity of the diazo compounds under different modes of catalysis is therefore rationalized by the putative formation of an electrophilic silver carbenoid species in the presence of AgOTf,w hereas in the presence of Sc(OTf) 3 ,t he diazo compound behaves as ac arbocation source.…”

Quaternary stereocentres via an enantioconvergent catalytic SN1 reaction

“…Their construction has long been recognized as an important challenge to the field of chemical synthesis, and several distinct catalytic, enantioselective approaches have been developed in response. 1,2,3,4 Notable examples include cycloadditions, 5 α and β-alkylation and arylation of carbonyls, 6–8 3,3′-additions, 9 S N 2′ reactions, 10 and Heck-type cross-couplings. 11 Each of these very powerful methods relies on enantiofacial addition across a prochiral substrate (Figure 1a) and therefore requires the preparation of stereochemically well-defined starting materials (such as trisubstituted olefins), and subsequent enantioselective bond formation.…”

Feedstock Reagents in Metal‐Catalyzed Carbonyl Reductive Coupling: Minimizing Preactivation for Efficiency in Target‐Oriented Synthesis

“…[47c] In an effort to extend the concepts of hydrogen-autotransfer-mediated carbonyl addition to the synthesis of terpenoid natural products,c atalytic couplings of alcohols with isoprene oxide were developed. [51] No stoichiometric byproducts are generated, as each atom in the reactants is integrated in the reaction product. [51] No stoichiometric byproducts are generated, as each atom in the reactants is integrated in the reaction product.…”