Iridium-Catalyzed Enantioselective Allylation of Alkenyl Boronates

Organoboronic esters are highly functionalizable synthetic intermediates owing to their unique reactivity that allows for pre-complexation with organometallic reagents to form boronates, which can then engage in bimolecular reactions. Furthermore, incorporation of boronic esters into their corresponding products allows for subsequent diversification through a wide variety of synthetically useful transformations. Some of the most valuable transformations of organoboronic esters involve 1,2-metalate shifts from anionic "ate" complexes. First described are select methodologies that showcase the use of this 1,2-metalate rearrangement from organoboron compounds over the past several decades. This includes 1,2-metalate shifts onto sp3 and sp2-hybridized adjacent carbons through intramolecular expulsion of the leaving group, as well as stoichiometric use of external electrophiles. Select catalyst-promoted 1,2-metalate rearrangements will be discussed that engage alkenyl boronates and in some cases render the migration stereoselective. Additionally, select examples of iridium-catalyzed nucleophilic substitution reactions will be examined. The second chapter describes the reaction of alkenyl boronates with allylic carbonates to generate tertiary bis-homoallyl boronic esters with high enantioselectivity and 1,3-diastereocontrol. The three-component coupling features an Ir(phosphoramidite) complex, which catalyzes a kinetic resolution of secondary allylic carbonates. Alkenyl boronate addition to an Ir(π-allyl) intermediate and a 1,2-metalate shift provides the observed products. Synthetic transformations of the tertiary boronic ester provide access to quaternary stereocenters in a diastereoselective manner. An extension to trisubstituted olefins sets three-contiguous stereocenters and provides initial insights into the diastereoselectivity of the reaction through a conserved syn-addition pathway. The final chapter provides detailed mechanistic investigations that outline the overall catalytic cycle and reveal trends in reactivity and selectivity. Analysis of relative stereochemistry in a variety of 1,1-disubtituted alkenyl boronates provides insight into the transition state of the addition and indicates a concerted pathway. Kinetic analysis of the reaction revealed the kinetic order dependence in boronate, catalyst, and both the slow- and fast-reacting enantiomer of allylic carbonate as well as the turnover-limiting step of the reaction. Hammett studies explored substituent effects in both aryl-derived alkenyl boronates and aryl carbonates. Nucleophile-specific parameters N and sN for the alkenyl boronate complex were determined and compared to other classes of compounds. Initial investigations into the migratory selectivity of the 1,2-metalate shift were also examined using (bis)alkenyl boronates.