A Recyclable Organocatalyst for Asymmetric Michael Addition of Acetone to Nitroolefins

Abstract

Based on different chiral diamine skeletons, a series of bifunctional primary amine-thiophosphoramides were synthesized and screened as the catalysts for the asymmetric Michael addition of acetone to both aromatic and aliphatic nitroolefins. Under the catalysis of a thiophosphoramide derived from 1,2-diphenylethane-1,2-diamine, the corresponding adducts were obtained in high yields (up to >99%) with excellent enantioselectivities (97-99% ee) under mild reaction conditions. Moreover, the catalyst could be recovered via simple phase separation and reused at least five times without any loss of both catalytic activity and stereocontrol.

Diastereoselective and Enantioselective Michael Addition Reactions of Ketones and Aldehydes to Nitro Olefins Catalyzed by C2‐Symmetric Axially‐Unfixed Biaryl‐Based Organocatalysts Derived from Enantiopure α‐Proline

“…(3 S ,4 R )‐3‐Methyl‐5‐nitro‐4‐phenylpentan‐2‐one: See Table 6, Entry 5;4x 6.4 mg, 29 % yield. [ α ] D 18 = –34.1 ( c = 0.05, CHCl 3 ), 88 % ee .…”

1,2‐Diamine‐Derived (thio)Phosphoramide Organocatalysts in Asymmetric Michael Additions

“…Initially we have attempted to prepare phosphoramides and thiophosphoramides from optically pure ( R , R )‐1,2‐cyclohexanediamine ( 1 ), ( S , S )‐1,2‐diphenylethane‐1,2‐diamine ( 2 ) and ent ‐ 2 , by a one‐step procedure using O , O′ ‐diethyl(thio)phosphoric chlorides (Scheme ) . In reactions of 2 (or ent ‐ 2 ) the corresponding products ( 5 , 6 and ent ‐ 6 ) were obtained in good yields (72–76% after purification by flash‐chromatography, Scheme ).…”

“…Accordingly, a three‐step procedure was adopted in order to obtain these derivatives in higher yields. This protocol included the protection of one amino group as phthalimide, followed by acylation with the corresponding phosphoric chloride, and deprotection using N 2 H 4 hydrate . Although this procedure included two flash chromatographic purifications, ent ‐ 3 and 4 were isolated in over 50% overall yields.…”

Catalytic Asymmetric Synthesis of Spiropyrazolones and their Application in Medicinal Chemistry

“…In 2016, followed by their previous study on the asymmetric synthesis of 4‐substituted 5‐nitropentan‐2‐ones 66 from acetone 65 and simple β‐nitrostyrenes 55 by a primary amine‐thiophosphinamide ( Cat. 20 )‐catalyzed Michael addition, the Zhou group uncovered a cascade Michael/aldol reaction between 4‐substituted 5‐nitropentan‐2‐ones 66 and unsaturated pyrazolones 8 to construct spirocyclohexanepyrazolone derivatives 67 with five contiguous stereogenic centers, including two quaternary and three tertiary centers (Scheme ) . Bases have significant influence on the efficacy and diastereoselectivity of the annulation.…”