Organocatalytic Route to Dihydrocoumarins and Dihydroquinolinones in All Stereochemical Configurations

Abstract

A straightforward stereodivergent route to dihydrocoumarins and dihydroquinolinones based on cinchona alkaloid catalyzed addition reactions of monothiomalonates (MTMs) to functionalized nitroolefins followed by deprotection and chemoselective cyclization has been developed. The synthesis proceeds under mild conditions and yields heterocycles with adjacent quaternary and tertiary stereogenic centers in very high yields and stereoselectivities. Moreover, full control over the relative and absolute configuration is achieved by the use of (pseudo)enantiomeric catalysts and the difference in reactivity of thioester versus oxoester moieties.

Organocatalytic Friedel–Crafts Alkylation/Lactonization Reaction of Naphthols with 3‐Trifluoroethylidene Oxindoles: The Asymmetric Synthesis of Dihydrocoumarins

“…As ar esult, many methods for the synthesis of dihydrocoumarin derivatives,e specially in an asymmetric manner,h ave been developed, among which organocatalysis [8] has recently been used as an efficient and mild approach. [14] Despite these advances,t he development of new strategies allowing the direct and efficient construction of optically pure dihydrocoumarins bearing versatile functionalities remains ac hallenging task. [12] Cinchona-alkaloid-derived bifunctional catalysts promoted the cyclization reaction of 1,3-dicarbonyls to o-QMs [13] and nitroalkenes.…”

“…Guided by the donor/acceptor concept, [4+ +2] cycloaddition reactions of phenol derivatives bearing electrophilic carbon atoms on the ortho-position are most commonly used strategies to generate the dihydrocoumarin core.T hese strategies include reactions such as the N-heterocyclic carbine catalyzed enantioselective cycloaddition of o-quinone methides (o-QMs), and its equivalents with silylketene acetals, [9] ketenes, [10] acyl imidazoles, [11] and the cascade reaction of enals with nitroalkenes (Scheme 1). [14] Despite these advances,t he development of new strategies allowing the direct and efficient construction of optically pure dihydrocoumarins bearing versatile functionalities remains ac hallenging task. [14] Despite these advances,t he development of new strategies allowing the direct and efficient construction of optically pure dihydrocoumarins bearing versatile functionalities remains ac hallenging task.…”

“…[12] Cinchona-alkaloid-derived bifunctional catalysts promoted the cyclization reaction of 1,3-dicarbonyls to o-QMs [13] and nitroalkenes. [14] Despite these advances,t he development of new strategies allowing the direct and efficient construction of optically pure dihydrocoumarins bearing versatile functionalities remains ac hallenging task. This challenge is exemplified by the synthesis of enantioenriched a-arylated dihydrocoumarins,w hich are abundant in nature and possess many important pharmaceutical properties.…”

Aerobic C–C Bond Cleavage of Indoles by Visible‐Light Photoredox Catalysis with Ru(bpy)32+

“…[2‐(Methylamino)phenyl]methanol (3c): Light green oil (34.5 mg, 84 % yield). 1 H NMR (400 MHz, [D 6 ]DMSO): δ = 7.08–7.04 (m, 2.0 H), 6.52 (t, J = 7.4 Hz, 1.0 H), 6.47 (d, J = 8.0 Hz, 1.0 H), 5.09 (d, J = 4.8 Hz, 1.0 H), 5.03 (t, J = 5.4 Hz, 1.0 H), 4.35 (d, J = 5.6 Hz, 2.0 H), 2.68 (d, J = 5.2 Hz, 3.0 H) ppm.…”

Synthesis of Monothiomalonates – Versatile Thioester Enolate Equivalents for C–C Bond Formations

“…The reactivity of the MTMs depends on the thio‐ and oxoester moieties, which also influence the stereoselectivity of the addition reactions. [ ][ ][ ] Thus, a viable synthetic route to MTMs must tolerate different substituents at C( α ) and allow for variations of the oxo‐ and thioester moieties.…”