Direct Proline-Catalyzed Asymmetric α-Aminoxylation of Aldehydes and Ketones

Abstract

The direct proline-catalyzed asymmetric alpha-aminoxylation of aldehydes and ketones has been developed using nitrosobenzene as an oxygen source, affording alpha-anilinoxy-aldehydes and -ketones with excellent enantioselectivity. Reaction conditions have been optimized, and low temperature (-20 degrees C) was found to be a key for the successful alpha-aminoxylation of aldehydes, while slow addition of nitrosobenzene is essential for that of ketones. The scope of the reaction is presented.

Chiral recognition of cyclic α‐hydroxyketones by CD‐sensitive zinc tetraphenylporphyrin tweezer

“…However, this reduction frequently produces cis and trans diol mixtures, thus necessitating further stereochemical assignments. 22,29 In the following we describe studies aimed at developing a combined chemical/chiroptical protocol for configurational assignments of cyclic a-hydroxyketones by application of the exciton-coupled CD method based on chiral recognition by dimeric zinc porphyrin host 1. As typical ketones, we chose five cyclic a-hydroxyketones, (S)-ahydroxychromanone 2, (R)-hydroxytetralone 3, (R)-ahydroxybenzosuberone 4, (R)-a-hydroxycyclohexanone 5, and (R)-a-hydroxycycloheptanone 6, which were synthesized by Sharpless asymmetric dihydroxylation of the corresponding ketones (Chart 2).…”

Nitrosobenzene

“…Both 3-and 4-substituted cyclohexanones gave the corresponding products with low diastereoselectivity but high enantioselectivity. 9 (F) A stereoselective synthesis of trans-2-substituted 3-amino-2,3,6-trihydropyridines can be achieved by cycloaddition of nitrosobenzene with 2-substituted 1,2-dihydropyridines followed by chemoselective reduction of cycloadducts. In situ hydrogenation of these cycloadducts over palladium in a solution of hydrogen chloride in methanol led to tetrahydropyrroloimidazoles.…”

Chemistry of Epoxyquinols A, B, and C and Epoxytwinol A

“…[60b] On the other hand, our group developed the proline-mediated asymmetric catalytic α-aminoxylation of carbonyl compounds, [61] which is a powerful method for the synthesis of α-hydroxy carbonyl derivatives. By employing this reaction as a key step and via several diastereoselective transformations, we accomplished the asymmetric total synthesis of panepophenanthrin [Equation (10)].…”