Rhodium-Catalyzed Highly Regio- and Enantioselective Reductive Cyclization of Alkyne-Tethered Cyclohexadienones

Abstract

Rhodium-catalyzed asymmetric hydrogenation of alkyne-tethered cyclohexadienones enables highly regio- and enantioselective reductive cyclization to afford cis-hydrobenzofurans and cis-hydroindoles in high yields. Desymmetrization of 1,3-diyne-tethered cyclohexadienones was also explored, wherein the intramolecular coordination of a Rh complex with the cyclohexadienone ring induces exclusive regioselectivity. Mechanistic studies including hydrogen–deuterium crossover experiments suggested that hydrogen activation is the rate-determining step for tandem reductive cyclization. Moreover, this highly practical and atom-economical transformation has tolerance to many functional groups with a broad range of substrate scope, allowing further transformations to expand the structural complexity of the bicyclic scaffolds.

Hydroalkynylative cyclization of 1,6-enynes with terminal alkynes

“…A cyclohexadienone tethered terminal alkyne ( 1a ) was selected as one partner in this reaction, because this prochiral electron-deficient diene is an excellent Michael acceptor with which to build chiral cis -hydrobenzofuranones by organo- or transition-metal-catalyzed desymmetrization reactions 10,11. The aromatic alkyne ( 2a ), bearing an alkyne proton which is more acidic than that in aliphatic alkynes,12 was chosen as the second partner to react with the enyne ( 1a ) in the presence of a rhodium catalyst.…”

Fe‐catalyzed hydrohalogenative cyclization of cyclohexadienone‐containing enynes

“…A number of cyclization methods with different coupling reagents such as acetic acid, arene C–H, azides bis(pinacolato)diboron, boronic acids, bromodifluoroalkanes, silylacetylenes, and silylboronate were developed for the synthesis of cyclohexenone‐annulated products in a chiral or achiral fashion. In addition, an enantioselective desymmetrization of alkynyl‐cyclohexadienone followed by intermolecular [4 + 2] cycloaddition with activated alkenes to give tricyclic products and reductive cyclization with various hydrogen donors were also reported. In this context, new methodology development for the desymmetrization of alkynyl‐cyclohexadienone would be beneficial for molecular construction.…”

Visible Light Mediated Sulfenylation‐Annulation Cascade of Alkyne Tethered Cyclohexadienones

“…Thiols, thiophenols and photocatalysts were purchased from either Sigma Aldrich or TCI and were used without further purification. Alkyne‐tethered cyclohexadieneones were synthesized as per the previous literatures . The reactions were carried out in the LED setups made in our laboratory from commercially available 5 W LED strips.…”