Research Projects

Compared to the well-established asymmetric allylic substitution under transition metal catalysis (e.g., Tsuji-Trost reaction), the related allenylic substitution reactions are much less explored. The initial developments under palladium catalysis led to a diverse outcome (linear/branched allenylic substitution vs dienylation) depending on the nature of substrates, ligands and nucleophiles, which makes synthetic planning difficult. More importantly, the scope of nucleophiles in Pd-catalyzed allenylic substitution remains severely limited to amine and active methylene class of compounds. In this context, the emergence of iridium-catalyzed allenylic substitution is noteworthy both from the mechanistic and application perspectives. In the past few years, we have made notable contributions in this area. Our work has expanded the scope of Ir-catalyzed asymmetric allenylic substitutions to include C(sp3)-H nucleophiles [amide/ketone enolate surrogates, (bis)vinylogous dienol and trienol silanes] and C(sp2)-H nucleophiles [hydroxynaphthoquinone, (hetero)arenes for Friedel-Crafts allenylation, pyridine meta-allenylation through oxazinopyridines]. In addition, we uncovered the mechanistic understanding of the core as well as peripheral pathways. As a part of this research program, we now aim to delve into the uncharted territories of Ir-catalyzed asymmetric allenylic substitution. The first part of this objective entails the unexplored class of nucleophiles such as C(sp)-H nucleophile (e.g., terminal alkynes), heterocycles and carbonyl-derivatives with unconventional site-selectivity (e.g., pyrrole C3-allenylation, pyridine C2-allenylation, beta-allenylation of acrylonitrile etc.), alpha-allenylation of amines in cooperation with aldehyde catalysis, value added nucleophiles for post-catalytic functionalization (e.g., bis-boryl methane) and heteroatom-nucleophiles (e.g., thiols). Besides, we would investigate the possibility of the creation of vicinal all-carbon quaternary stereocenters using tertiary allenylic alcohols with α-substituted cyanoesters as nucleophile. This reaction would have the potential to offer stereodivergency through its merger with copper-catalysis under judicious combinations of ligands on Ir and Cu. Despite its versatility, asymmetric allenylic substitution under Ir-catalysis is not devoid of limitations. Due to the putative intermediacy of η2-Ir(I)-bound allenylic carbocation, the electrophilic scope is limited to aryl-substituted allenylic alcohols. Moreover, only monosubstituted allene unit in allenylic electrophile is compatible with the commonly employed Ir(I)/(P,olefin) catalyst. These constraints provide opportunities for the development of new catalysts. We would like to explore rhodium-complexes as catalysts for asymmetric allenylic substitution reactions. Our preliminary experiments with a Rh(I)/(P,olefin) complex showed promising outcomes: With certain classes of nucleophiles, this unprecedented catalyst system appears to be compatible with both aromatic and aliphatic allenylic alcohols, furnishing the allenylic substitution products with good yield, excellent branched-selectivity and good enantioselectivity (up to 94:6 er). Besides transition metal catalysis, we would also like to explore the possibility of organocatalytic enantioselective allenylic substitution reactions. More specifically, Morita-Baylis-Hillman-type allenylic esters and carbonates would be employed as electrophiles under Lewis base catalysis. This class of allenylic electrophiles, owing to their electron-deficient nature, are known to be incompatible with Ir-catalysis. Similarly, some nucleophiles (e.g., nitroalkanes, deconjugated butenolides, photoenolizable carbonyls, phosphites etc.) are also known to be unreactive in Ir-catalyzed allenylic substitution. Organocatalysis could provide a complementary approach to tackle these problems and access hitherto unexplored chemical spaces under transition metal catalysis.