Enantio- and Diastereoselective Michael Reaction of 1,3-Dicarbonyl Compounds to Nitroolefins Catalyzed by a Bifunctional Thiourea

• Published in: Journal of the American Chemical Society Vol. 127; no. 1; pp. 119 - 125
• Main Authors: Okino, Tomotaka, Hoashi, Yasutaka, Furukawa, Tomihiro, Xu, Xuenong, Takemoto, Yoshiji
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.01.2005; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Exact sciences and technology; Kinetics and mechanisms; Organic chemistry; Physical Sciences; Reactivity and mechanisms; Science & Technology; ACYCLIC NITROALKENES; KETONES; ORGANOBORONIC ACIDS; MOLECULAR RECOGNITION; ASYMMETRIC STRECKER REACTION; BAYLIS-HILLMAN REACTION; BASE CATALYSTS; ALDEHYDES; METAL-FREE; CONJUGATE ADDITION; Michael addition; Nitro compound; Catalytic reaction; Enantioselectivity; Catalyst selectivity; Experimental study; Diastereoselectivity; Structure activity relation; Homogeneous catalysis; Diester; Bicyclic compound; Reaction mechanism; Aromatic compound; Kinetic parameter; Rate constant; Catalyst activity
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja044370p

We synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. Among them, thiourea 1e bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins. Furthermore, we have developed a new synthetic route for (R)-(−)-baclofen and a chiral quaternary carbon center with high enantioselectivity by Michael reaction. In these reactions, we assumed that a thiourea moiety and an amino group of the catalyst activates a nitroolefin and a 1,3-dicarbonyl compound, respectively, to afford the Michael adduct with high enantio- and diastereoselectivity.