Asymmetric Benzylic Functionalizations of 3-Vinyl Benzofurans via Cascade Formal Trienamine–Vinylogous Iminium Ion Activation

Abstract

An efficient approach to construct chiral 1,1-disubstituted ethane derivatives is presented. This strategy relies on the formation of the key dearomatizative vinylogous iminium ion species through protonation of the formal trienamine intermediates between 2-(3-vinylbenzofuran-2-yl)ethan-1-ones and a chiral primary amine. An array of nucleophiles, including 4-hydroxycoumarins, indoles, etc., have been effectively assembled at the benzylic site, delivering the expected 1,1-disubstituted ethane products in moderate to excellent enantioselectivity.

Polyenals and Polyenones in Aminocatalysis: A Decade Building Complex Frameworks from Simple Blocks

“…The trienamine intermediate was transformed to the vinylogous iminium ion by ε‐protonation, which allows nucleophilic attack with 4‐hydroxycoumarins 163 to furnish the corresponding 1,1‐disubstituted ethane benzofurans 164 . The reaction proceeded with moderate to excellent yields and fair to excellent enantoselectivities (Scheme ) …”

Asymmetric Benzylic Allylic Alkylation Reaction of 3‐Furfural Derivatives by Dearomatizative Dienamine Activation

“…Melchiorre and co‐workers reported that β‐3‐indolyl‐ or 3‐furyl acroleins underwent Diels–Alder reactions with activated alkenes by the formation of o ‐QDM‐embedded trienamine species (Scheme b) . We also uncovered the generation of intriguing o ‐QDMs III tethering to iminium ions from 2‐(3‐vinylbenzofuran‐2‐yl)ethan‐1‐ones, which were enantioelectively attacked at benzylic sites by diverse nucleophiles (Scheme c) . Nevertheless, the asymmetric reactions involving catalyst‐tethered dearomatizative o ‐QDMs are still relatively limited, and the expansion on substitution patterns and constructing structural diversity is also in high demand.…”

Asymmetric Formal Vinylogous Iminium Ion Activation for Vinyl-Substituted Heteroaryl and Aryl Aldehydes

“…Asymmetric aminocatalysis, by using a chiral primary or secondary amine to generate active HOMO-raised enamine or LUMO-lowered iminium ion intermediates with enolizable or unsaturated carbonyls, respectively, has been extensively explored in the field of organocatalysis . Although aliphatic-type carbonyl substrates are generally utilized in aminocatalysis, some specific aromatic or heteroaryl rings can be HOMO-raised by generating conjugated formal trienamine intermediates and participate in [4 + 2] cycloaddition or Friedel–Crafts reactions stereoselectively . Moreover, a few recent examples further demonstrate that five-membered heteroaryl (especially furyl) aldehydes can form catalyst-tethered dearomative dienamine and even polyenamine species, which significantly broaden the application potential of aminocatalysis (Scheme a) …”