A Simple, Scalable Synthetic Route to (+)- and (−)-Pseudoephenamine

Abstract

A three-step synthesis of pseudoephenamine suitable for preparing multigram amounts of both enantiomers of the auxiliary from the inexpensive starting material benzil is described. The sequence involves synthesis of the crystalline mono-methylimine derivative of benzil, reduction of that substance with lithium aluminum hydride, and resolution of pseudoephenamine with mandelic acid.

Stereodefined acyclic trisubstituted metal enolates towards the asymmetric formation of quaternary carbon stereocentres

“…To address this legal issue, Myers and coworkers developed and synthesized in their further studies, an alternative pseudoephenamine auxiliary. 38,39 This superseding analogue of pseudoephedrine auxiliary was successfully applied toward the alkylative construction of quaternary stereogenic centres providing comparable, and, in some cases, better results in terms of diastereoselectivity (Scheme 8). 39 A recent application of Myers' alkylative quaternization methodology was demonstrated in the concise total synthesis of several aspidosperma alkaloids reported by Medley and Movassaghi, 40 where pseudoephenamine auxiliary was successfully used to control trisubstituted enolate formation, and, eventually, the alkylative asymmetric construction of the C-5 quaternary carbon stereocentre of this class of natural compounds.…”

Pseudoephedrine‐Directed Asymmetric α‐Arylation of α‐Amino Acid Derivatives

“…The other enantiomer of the pseudoephedrine auxiliary gave the epimeric starting material 10 b , which rearranged to ( S )‐ 9 a with no evident match/mismatch effects (Table 2, entry 9) 9. 36 Alternative auxiliaries performed less well: ephedrine ( 10 c ) gave poorer selectivity (Table 2, entry 10); pseudephenamine39, 40 ( 10 d ) gave lower yields (entry 11) possibly because of competing benzylic deprotonation27 α to the N atom, and Evans’ oxazolidinone derivative 10 e was unstable to the reaction conditions (entry 12).…”

Preparation and Application of α-Imino Ketones through One-Pot Tandem Reactions Based on Heyns Rearrangement

“…In addition, α-imino ketones can also be converted into β-amino alcohols through a one-pot procedure . The traditional method of synthesizing α-imino ketone relied on the condensation reaction under different conditions with diketone and amine as raw materials (Scheme a) . Subsequently, Suzuki and co-workers developed an interesting way for obtaining α-imino ketones with imidoyl chlorides and aromatic aldehydes as substrate via N -heterocycle carbene-catalyzed aroylation (Scheme b) .…”