Copper‐Catalyzed Radical Enantioselective Carbo‐Esterification of Styrenes Enabled by a Perfluoroalkylated‐PyBox Ligand

Abstract

Chiral lactones are found in many natural products. The reaction of simple alkenes with iodoacetic acid is a powerful method to build lactones, but the enantioselective version of this reaction has not been implemented to date. Herein, we report the efficient catalytic radical enantioselective carbo-esterification of styrenes enabled by a newly developed Cu I -perfluoroalkylated PyBox system. Simple styrenes have been converted to useful chiral lactones, whose synthetic applications are showcased. Mechanistic studies reveal that this reaction is a rare example of an efficient liganddecelerated system, in which the ligand decelerates the reaction, but the reaction is still efficient with reduced amounts of ligand. This uncommon catalytic system may inspire further consideration of the effect of ligands in asymmetric catalysis.

Copper‐Catalyzed Radical Difluoromethylation‐Peroxidation of Alkenes: Synthesis of β‐Difluoromethyl Peroxides

“…The coupling of B and C affords the alkyl Cu(III) intermediate D , which undergoes reductive elimination to generate the desired β ‐difluoromethyl peroxide 4 , as well as releases the Cu(I) catalyst. Alternatively, the group transfer or radical substitution mechanism which undergoes Cu(I)/Cu(II) catalytic cycle could not be excluded at the current stage [25] …”

“…Alternatively, the group transfer or radical substitution mechanism which undergoes Cu(I)/Cu(II) catalytic cycle could not be excluded at the current stage. [25] In summary, we have developed a copper-catalyzed difluoromethylation-peroxidation reaction of alkenes with CF 2 HSO 2 Na and t BuOOH. This three-component difunctionaliza-tion protocol enables the convenient synthesis of a variety of βdifluoromethyl peroxides in moderate to good yields under mild conditions.…”

Radical transformations for allene synthesis

“…The group of Bao discovered that alkyl peroxides actually is a type of masked trifunctional reagents: oxidants, radical initiators, and functional-group releasing agents. 16 Later in 2018, Bao, Zhang, and coworkers disclosed that with alkyl diacyl peroxides as the trifunctional reagents, the copper-catalyzed intermolecular 1,4-carbocyanation of 1,3-enynes under mild conditions is a versatile method for the generation of tetrasubstituted allenes 5 and 6 ( Scheme 3 ). 17 Not only generic alkyl groups but also functionalized alkyl groups can be used as the carbon sources.…”

Copper-Catalyzed Three-Component Photo-ATRA-Type Reaction for Asymmetric Intermolecular C-O Coupling

“…Notably, the Bao group further developed an elegant ligand-decelerated strategy for copper-catalyzed asymmetric two-component ATRA-type reaction of styrenes and iodoacetic acid, wherein the C-O radical coupling was shifted to an intramolecular fashion after addition of the initially formed acetic carbon radical to alkene. 17 Though these breakthroughs have reinvigorated the C-O radical coupling-based ATRA-type reactions, the very useful catalytic enantioselective three-component variants remain a formidable challenge. Drawing inspiration from these studies 11-17 and coppercatalyzed asymmetric allylic substitution chemistry that involves [σ + π]-allylcopper(III) and π-allylcopper(III) complexes as the key intermediates, 18 we envisioned that a similar formal allyl-copper(III) complex might be formed if one πbond of aryl ring could engage in coordination toward copper (Figure 1B).…”