Effective construction of quaternary stereocenters by highly enantioselective α-amination of branched aldehydes

Abstract

A highly efficient enantioselective α-amination of branched aldehydes with azadicarboxylates promoted by chiral proline-derived amide thiourea bifunctional catalysts was developed for the first time, affording the adducts bearing quaternary stereogenic centers with excellent yields (up to 99%) and enantioselectivities (up to 97% ee).

Hydrogen‐Bonding in Aminocatalysis: From Proline and Beyond

“…Michael addition of carbonyl compounds to nitroolefins constitutes the most studied possibility 21a,b,f. α‐Amination of carbonyl compounds with diazodicarboxylates is another alternative 21c,d. In this context, it is worth noting that catalyst 41 ag proved efficient in the amination of α‐branched aldehydes leading to the products containing quaternary stereogenic center 21c.…”

Construction of Quaternary Stereocenters: Asymmetric α‐Amination of Branched Aldehydes Catalyzed by Monoimide Substituted Cyclohexane‐1,2‐Diamines

“…On the other hand, our group is interested in developing new methods to construct substituted amino aldehydes and successfully applied chiral thioureas, amino acids in the amination of aldehydes with excellent results. 16, 18, 15j Based on these achievements and our continuing interests in asymmetric synthesis promoted by chiral amine catalysis, herein we report the asymmetric α‐amination of branched aldehydes with azodicarboxylates catalyzed by simple chiral imide monosubstituted 1,2‐diamine derivatives in excellent enantioselectivities.…”

“…[12][13][14][15] However, there were still no efficient and satisfactory asymmetric methods until our group reported a highly effective a-amination of branched aldehydes promoted by chiral proline-derived amide thiourea bifunctional catalysts in excellent yields (up to 99%) and enantioselectivities (up to 97% ee). 16 After that, an ion pair catalyst of 9-amino(9-deoxy)epi-quinine and (-)-CSA was applied in this transformation. 17 And in 2011, our group disclosed that the simple primary amino acid of 3-(1-naphthyl) alanine may catalyze the amination of branched aldehydes with high enantioselectivities.…”

Application of Proline‐Functionalised 1,2‐Diphenylethane‐1,2‐diamine (DPEN) in Asymmetric Transfer Hydrogenation of Ketones

“…Compound 21 has been applied to an aldol reaction of ketones with 1,2-diketones, [31] whilst very similar compounds (SO2Ph in place of Ts) have been prepared via ring opening of a sulfonated aziridine ring and applied to the organocatalysis of aldol reactions. [32] Several derivatives of C2-symmetric DPEN and of trans 1,2-diaminocyclohexane, bearing the combination of prolinamide and carbamate/thiocarbamate, [33][34][35][36][37] or dialkyl substituents, [38] have been reported in organocatalytic asymmetric transformations. We first attempted acetophenone reduction using 20 and 21 with a 5:2 mixture of FA/TEA as the solvent and hydrogen donor (Table 1).…”