A Facile Enantioselective Alkynylation of Chromones

Abstract

The first catalytic enantioselective alkynylation of chromones is reported. In this process, chromones are silylated to form silyloxybenzopyrylium ions that lead to silyl enol ethers after Cu‐catalyzed alkyne addition using StackPhos as a ligand. The outcome of the reaction is impacted by distal ligand substituents with differing electronic character and it was found that successful reactions could be achieved with different ligand congeners by using different solvents. This sequence enables access to different products by protonation or further functionalization, thus increasing complexity in a divergent manner. The transformation is high yielding over a broad scope to provide a variety of useful chromanones in high enantioselectivity.

Lactone Synthesis by Enantioselective Orthogonal Tandem Catalysis

“…With the goal of developing a method to couple these alkyne reactivities in an efficient one‐pot transformation, it was recognized that both reaction and ligand selection would be crucial, and although chiral ligands are most commonly used for enantioselectivity, they can also efficiently control other types of selectivity . Studies from our laboratory have been directed at using heterocyclic chiral biaryl ligands in enantioselective transformations and we postulated that our Stack ligands might also control other types of selectivity. We recently reported conjugate addition to Meldrum's acid derivatives in water, and we decided that this would be a suitable reaction platform from which to build a subsequent catalytic transformation to form the six‐membered lactone 7 .…”

Tuning StackPhim Ligands: Applications in Enantioselective Borylation and Alkynylation

“…Recent work from our laboratory has been focused on developing five-membered nitrogen heterocycle based stack ligands. 11 12 13 14 15 Although many reactions work well with our parent ligand, now dubbed StackPhos, the need for tuning has arisen. Since these are five-membered heterocycles, we identified the imidazole as a tunable element and our initial report on modified ligands involved the enantioselective alkynylation of Meldrum’s acid acceptor 1 (Scheme 1a ).…”

Copper-catalyzed C2-selective alkynylation of chromones via 1,4-conjugate addition

“…Recently, Aponick and Mattson developed the addition of copper acetylides to benzopyrylium tri ates in the presence of ligands (Scheme 1B) [25][26][27][28]. So far, many elegant examples demonstrate the applicability of this strategy.…”