P(NMe₂)₃-Mediated Reductive Intramolecular Annulation of Benzoylformates Tethered with a Trisubstituted Alkene Unit and Synthesis of 2,2-Disubstituted 2H-Chromenes

Abstract

In this report, a P­(NMe2)3-mediated reductive intramolecular annulation reaction has been developed with benzoyl formates bearing a trisubstituted alkene unit. It provides a facile synthesis of highly functionalized 2,2-disubstituted 2H-chromenes with a broad substrate scope and high efficiency. Experimental results suggest this annulation reaction proceeds via a cascade of alkene isomerization/vinyl o-quinone methide formation/6π-electrocyclization. As a key intermediate, the vinyl-substituted o-quinone methide is presumably generated by a Kukhtin–Ramirez adduct initiated O → C vinyl migration.

Lewis Base-Catalyzed Intramolecular Vinylogous Aldol Reaction and Chemoselective Syntheses of 3-Hydroxy-2,3-Disubstituted Dihydrobenzofurans and Indolines

“…According to our experimental results and reported literature, , a plausible mechanism for formation of products 3 and 5 is depicted in Scheme . Initially, substrate 1 or 2 undergoes deprotonation with the aid of Lewis base DBU to generate resonance-stabilized carbanion intermediate I .…”

“…Recently, Suresh and co-workers have disclosed two similar base-promoted intramolecular vinylogous Michael addition reactions as the key step to construct 2,3-disubstituted benzofurans and 2-alkenyl indoles (Scheme b). , A few examples of Lewis base-catalyzed intramolecular vinylogous aldol reactions have also been documented for construction of functionalized benzofurans and indoles. , As part of our continuous interest in exploring the reactivity of 1,2-dicarbonyls with Lewis bases, in 2016, we developed a phosphine-catalyzed intermolecular [4 + 1] annulation reaction of o -hydroxyphenyl or o -aminophenyl ketoesters with allylic carbonates to construct functionalized 3-hydroxy-2,3-disubstituted dihydrobenzofurans and indolines in high yields with good diastereoselectivity (Scheme c) . Recently, we designed and synthesized two kinds of new functionalized 1,2-dicarbonyl substrates o -(allyloxy)­phenyl ketoesters 1 and o -(allylamino)­phenyl ketoesters 2 and successfully developed two novel intramolecular annulation reactions to construct a variety of O - or N -heterocycles via the chemistry of Kukhtin–Ramirez adducts . Encouraged by our prior work, we recently continued to explore the reactivity of 1,2-dicarbonyl substrates 1 and 2 and found that substrates 1 and 2 could undergo an intramolecular vinylogous aldol reaction with the aid of Lewis bases to afford 3-hydroxy-2,3-disubstituted dihydrobenzofurans or indolines (Scheme d).…”

An Intramolecular Umpolung Cascade Kukhtin–Ramirez Reaction/Michael Addition-Initiated Cyclization: Stereoselective Synthesis of Tetrasubstituted Cyclopropane Fused 1-Indanones

“…However, the regioselectivity of an unsymmetrical α-dicarbonyl is hugely directed by the steric and electronic factors as well as substrate geometry. Although the chemistry of K–R adducts was characterized about half a century ago by chemists Kukhtin and Ramirez, utilization of this intermediate as a C1 carbene surrogate or free carbene remained almost untouched until the past decade. − In this context, Radosevich, Ashfeld, and He research groups have contributed adequately to a stage where organic chemists can think forward as a scope to explore this field to a greater height . To date, the K–R intermediates illustrated many transformations intermolecularly, such as carbene equivalent formal C–H insertion, alkylation, 1,2-annulation, 1,4-annulation, and others, where these can act as electrophiles or nucleophiles depending on the counterpart present in the reaction medium. , Moreover, the P­(III)/P­(V) redox cycling reaction of α-keto esters and carboxylic acids by Radosevich and co-workers has added an additional thrill to this reactivity in the era of catalysis .…”

“…Although the chemistry of K–R adducts was characterized about half a century ago by chemists Kukhtin and Ramirez, utilization of this intermediate as a C1 carbene surrogate or free carbene remained almost untouched until the past decade. − In this context, Radosevich, Ashfeld, and He research groups have contributed adequately to a stage where organic chemists can think forward as a scope to explore this field to a greater height . To date, the K–R intermediates illustrated many transformations intermolecularly, such as carbene equivalent formal C–H insertion, alkylation, 1,2-annulation, 1,4-annulation, and others, where these can act as electrophiles or nucleophiles depending on the counterpart present in the reaction medium. , Moreover, the P­(III)/P­(V) redox cycling reaction of α-keto esters and carboxylic acids by Radosevich and co-workers has added an additional thrill to this reactivity in the era of catalysis . However, the intramolecular variant was scarce until the very recent publications from the He group, where solvent and substituent-dependent product diversity on P­(NMe 2 ) 3 mediated intramolecular annulation of o -benzoyl formate tethered trisubstituted electron-deficient alkenes has been documented. , These are the only prior reports on intramolecular K–R adduct-triggered cascade Michael addition cyclopropanation or 2,2-disubstituted chromenes synthesis.…”