Copper-catalyzed Asymmetric Functionalization Of Tertiary Carbon Radicals

Quaternary carbon stereocenters are widely found in natural products and drug molecules,and the construction of optically pure quaternary carbon center is still a huge challenge in organic synthesis.Among them,the transition metal-catalyzed asymmetric radical reactions attracts extensive attentions due to its high efficiency and diversity of bond-formation.This dissertation mainly focuses on the copper-catalyzed asymmetric transformations of tertiary carbon radical,and the iron-catalyzed asymmetric trifluoromethylcyanation of alkenes is also preliminarily studied.A copper-catalyzed asymmetric trifluoromethylalkynylation of acrylamides was achieved,which involves the asymmetric alkynylation of tertiary alkyl radicals.A bulky chiral ligand is employed in this reaction,which provides a direct and efficient method for construction of all-carbon quaternary carbon center bearing an alkynyl substituent in good yields and enantioselectivities.An unprecedented copper-catalyzed asymmetric atom transfer radical addition（ATRA）was disclosed,which remains a grand challenge since the discovery of the first racemic ATRA in the 1940s.This reaction undergoes an enantioselective radical chlorination of alkenes,which affords chlorinated carbon-centred quaternary compounds in good yield with excellent enantioselectivity.Notably,the well-designed bulky chiral ligand plays a key role in the successful enantioselective radical chlorination process.Mechanism studies indicated that fort the final asymmetric radical chlorination process,the carbon-centred radical was selectively trapped by chiral copper（II）chloride species,which is much faster than radical chain chlorination.DFT calculation also indicated energy profile of the radical attack to chlorine atom of another molecule is much higher than the radical atom transfer at（L3-4）CuCl₂,resulting in the observed excellent enantioselectivity.An iron-catalyzed asymmetric trifluoromethylcyanation of styrenes was preliminarily studied,which provides chiral benzylic nitrile compounds with a low yield and excellent enantioselectivity.Preliminary experimental mechanism investigations indication that L*Fe^III（CN）₄ construction of C-CN bond with benzylic radicals was not efficient,resulting in side reaction of benzylic radicals.