α-Azaaryl carbonyl derivatives in stereodivergent catalytic reactions

Abstract

The catalytic synthesis of chiral azaarenes has become a focal point of research due to their signifi`1cant applications across various fields, including medicinal chemistry and materials science. α-Azaaryl carbonyl compounds, featuring both an electron-withdrawing C=N moiety within an azaarene core and a carbonyl functional group, have proven to be versatile precursors in the synthesis of stereochemically intricate azaaryl molecules. In particular, the generation of chiral α-azaaryl enolate intermediates, catalyzed by chiral Lewis acids, has enabled the precise construction of α-stereogenic chiral azaarenes. This review explores recent advances in the stereodivergent transformations of α-azaaryl carbonyl derivatives with an array of carbon electrophiles, emphasizing the efficiency of catalytic systems involving chiral copper Lewis acids combined with Ir, Pd, Ni, amine, or Ru catalysts. These strategies offer precise control over the stereochemical outcome, facilitating access to all stereoisomers of multi-stereogenic chiral azaarenes. Additionally, we discuss a sequence-dependent approach that allows for controlled stereodivergence in reactions with α-azaaryl carbonyl derivatives. Through a detailed exploration of recent advancements, mechanistic insights, and practical applications, this review underscores the potential of stereodivergent catalytic reactions to unlock new avenues in the synthesis of azaaryl compounds. By presenting diverse strategies and expanding opportunities for controlling stereochemistry, it fosters further development in the design of structurally and stereochemically complex azaarene-based frameworks.