α′-Hydroxyenones as Mechanistic Probes and Scope-Expanding Surrogates for α,β-Unsaturated Aldehydes in N-Heterocyclic Carbene-Catalyzed Reactions

Abstract

N-heterocyclic carbene catalyzed reactions of α,β-unsaturated aldehydes and a variety of electrophiles allow the facile preparation of a diverse array of annulation products including trisubstituted cyclopentenes, γ-lactams, and bicyclic β-lactams. The substrate scope of these reactions, however, is limited by the difficulties of preparing the startingα,β-unsaturated aldehydes. We now report that α′-hydroxyenones, which can be prepared in a single convenient step from aromatic and heteroaromatic aldehydes, can serve as efficient surrogates for enals in the annulation reactions. This protocol allows the facile preparation and use of substrates bearing nitrogen heterocycles. These reagents have also allowed us to demonstrate that, in contrast to other classes of aldehydes, the formation of the Breslow intermediate from enals and N-heterocyclic carbenes is irreversible under the reaction conditions.

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes

“…178 A limitation is that the increased steric demand of these substrates inhibits their use with bulky chiral catalysts. In 2013, Chi and co-workers demonstrated that saturated esters are potential homoenolate precursors.…”

“…178,206 A wide variety of aromatic and heteroaromatic substituents are tolerated as reaction partners for annulation with vinylogous amides. The product 3,4-dihydropyridinones are isolated in good-to-excellent yields (59–99%).…”

Intra- and intermolecular thermal transformations of 2-acyl- and 2-alkoxycarbonyl-N-phthalimidoaziridines

“…Benzalacetone (2a) and dibenzalacetone (2d) were prepared according to Golodnikov and Mandel'shtam [16]. Treatment of -benzoylacrylic [(2E)-4-oxo-4-phenylbut-2-enoic] acid [17] with thionyl chloride and subsequent addition of excess methanol gave the corresponding methyl ester 2e [18]. The ethyl ester of (Z)-2-benzylidene-3-oxobutanoic acid 2f was prepared according to Anaç et al [19].…”

Benzene construction via organocatalytic formal [3+3] cycloaddition reaction

“…Intramolecular ester formation with the release of NHC catalyst yields a bicyclic adduct VII containing a four-membered b-lactone. Spontaneous decarboxylation [36][37][38][39] and oxidation [40][41][42] of VII effectively affords benzene product bearing four substituents in predictable substitution patterns. Decarboxylation of b-lactone fused with a six-membered ring similar to intermediate VII is a highly effective process, as exemplified in Lupton's [4 þ 2] reaction via carbene catalysis 39 .…”