Asymmetric organocatalytic synthesis of β-Hydroxyynones with a quaternary carbon center under aqueous conditions

Abstract

A reação aldólica direta de metil inonas não-modificadas sob condições aquosas catalisada pela amina terciária quiral de tiouréia é descrita. Este procedimento evitou a reação retroaldólica dos produtos β-hidroxinonas, e admite as isatinas (1H-indol-2,3-diona) e os menos ativos ésteres α-ceto acíclicos como aceptores, oferecendo um arranjo estruturalmente diverso de β-hidroxinonas tendo um centro de carbono quaternário, com rendimentos de moderado a bom e enancioseletividade. The chiral tertiary amine thiourea catalyzed direct aldol reaction of unmodified methyl ynones under aqueous conditions is described. This procedure avoided the retro-aldol reaction of the β-hydroxyynone products, and tolerated both the isatin (1H-indole-2,3-dione) and the less active acyclic α-keto esters as acceptors, affording a structurally diverse array of β-hydroxyynones bearing a quaternary carbon center with moderate to good yields and enantioselectivities.

Conjugated Ynones in Organic Synthesis

“…The enantioselective aldol reaction between ynones ( 71 ) and isatins ( 600 ) in the presence of a chiral thiourea ( 777 ) and CaCl 2 in water at −10 °C gave the corresponding chiral tertiary alcohols 778 (Scheme ). The reaction was extended to acyclic α-keto esters ( 779 ) with similar results . Other substituents at the N atom of isatin (Me, CH 2 CHCH 2 , n Pr, and Ph) afforded the same yields and enantioselectivities, but the absolute configuration of the new stereocenter was not assigned.…”

“…The reaction was extended to acyclic α-keto esters (779) with similar results. 544 Other substituents at the N atom of isatin (Me, CH 2 CHCH 2 , nPr, and Ph) afforded the same yields and enantioselectivities, but the absolute configuration of the new stereocenter was not assigned. Trost and Quintard 545 have studied the aldol reaction of ynone 16 with octanal in the presence of Et 2 Zn and the chiral ligand ProPhenol (780) which furnished dehydrated ketone 781 in good yield (Scheme 343).…”

Regioselectivity‐Reversed Asymmetric Aldol Reaction of 1,3‐Dicarbonyl Compounds

“…Despite these advances, the search for new aldol‐type processes with the goal of increasing the substrate diversity, product utility, as well as exploring new catalysis models continues. Very recently, Zhao11 and Singh12 reported alkaloid–thiourea‐ and urea‐catalyzed enantioselective enolate‐mediated aldol reactions of ketones with excellent results; independently, our group presented a tertiaryamine–thiourea‐catalyzed asymmetric aldol reaction between ynones and active ketones under aqueous conditions based on a similar activation model 13. Owing to the fact that secondary amines, such as pyrrolidine, are good catalysts to promote Knoevenagel condensations, we envisioned to regioselectively activate the C‐1 carbon of 1,3‐dicarbonyl compounds by a tertiary amine catalyst via C‐1 intermediate C , which is more nucleophilic than C‐3 intermediate B (Scheme ).…”