摘要：

ConspectusThe catalytic, asymmetric synthesis of complex molecules has beena core focus of our research program for some time because developmentsin the area can have an immediate impact on the identification ofnovel strategies for the synthesis of value-added molecules. In concertwith this central interest, we have emphasized the design of ligandscaffolds as a tactic to discover and develop novel chemistry andovercome well-recognized synthetic challenges. Based on our group'swork on chiral pool-derived diolefin ligands, we designed and implementeda class of hybrid (phosphoramidite,olefin) ligands, which combinesthe properties of both phosphoramidite and olefin motifs to impact,fine-tune, and even override the inherent reactivity of the metalcenter. Specifically, we have utilized these unique modifying ligandsto address several recognized limitations in the field of iridium-catalyzed,asymmetric allylic substitution. The methods we have documented typicallyemploy branched, unprotected allylic alcohols as substrates and obviatethe need for rigorous exclusion of air and moisture.FollowingTakeuchi's seminal report demonstrating the highaptitude of Ir­(I)-phosphite catalysts for  branch-selective allylicsubstitution, concerted efforts from numerous research laboratorieshave led to a broadening of the synthetic utility of this reactionclass. The first section of this Account outlines the process leadingto our discovery of an unprecedented (phosphoramidite,olefin) ligandand its validation in the first iridium-catalyzed amination of branched,unprotected allylic alcohols. This section continues with our workinvolving heteroatom-based nucleophiles within inter- and intramolecularetherification, thioetherification and spiroketalization processes.The second section highlights the use of readily available carbonnucleophiles possessing sp, sp², and sp³ hybridizationin a series of enantioselective carbon–carbon bond-formingreactions. We describe how alkylzinc, allylsilane, and several classesof organotrifluoroborate nucleophiles can be coupled enantioselectivelyto enable construction of several key motifs including 1,5-dienes,1,4-dienes, and 1,4-enynes. Since the unique electronic and stericproperties of this class of ligands renders the (η³-allyl)-Ir­(III) intermediate highly electrophilic, even weak nucleophilessuch as alkyl olefins can be used. We also show that more nucleophilicalkene motifs such as enamines and -tetrahydrocannabinol.This Account concludes with an overview of our organometallic mechanisticstudies regarding relevant intermediates within the catalytic cycleof this class of allylic substitution. These studies have allowedus to better understand the origin of the unique characteristics exhibitedby this catalyst in comparison to related systems.

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