Copper(I)-catalyzed asymmetric alkylation of α-imino-esters

Abstract

Asymmetric alkylation of enolates is one of the most direct and important reactions to prepare α-chiral carbonyl compounds. Except for the classical methods that rely on the use of chiral auxiliaries, asymmetric catalysis emerged as a powerful tool, especially asymmetric phase-transfer catalysis. However, in the field of transition metal catalysis, only limited success with asymmetric alkylation of enolates was achieved. Hereby, we disclose a copper(I)-catalyzed asymmetric alkylation of α-imino-esters with various alkyl halides, including allyl bromides, propargyl bromide, benzyl bromides, α-bromo carbonyl compounds, and alkyl iodides. Both linear and cyclic α-imino-esters serve as competent pronucleophiles in the alkylation, which affords α-amino acid derivatives bearing either a trisubstituted or a tetrasubstituted stereogenic carbon center in high to excellent enantioselectivity. Control experiments indicate that the α-imino-ester is activated by a chiral copper(I)-phosphine complex through coordination, thus enabling facile deprotonation to provide a stabilized copper(I)-enolate in the presence of a mild base. Finally, the mildly basic nature allows the asymmetric alkylation of chiral dipeptides with excellent both chemo- and enantioselectivities.

Efficient iron-catalyzed direct acylation of amines with carboxylic acids and esters under oxygenated conditions

“…In this respect, unlike other amidation reactions that require some of the aforementioned activating agents in stoichimetric amounts ( e.g. carbodiimides, 7 benzotriazoles, 8 carbon tetrachloride 9 α,α-dichlorodiphenylmethane 10 or tert -butyl isocyanide and S -phenyl benzenethiosulfonate 11 ), direct acylation of amines with esters or carboxylic acids has been scarcely explored using iron catalysts. 12,13 Indeed, most of the reports on this atom-economical process (Scheme 1) show a scope limited to primary amines and/or aliphatic acid derivatives, 12 b ,13 and no general method for the iron-catalyzed direct acylation of amines using both carboxylic acids and esters as acylating agents has been reported to date.…”

Enhancing the Efficacy of Chiral Ligands and Catalysts: Siloxane-Substituted Oxazoline Ferrocenes as Next-Generation Candidates

“…Originating from independent research in 1995 by Richards [ 1 ], Sammakia [ 2 ], and Uemura’s [ 3 ] groups, chiral ligands based on the oxazoline ferrocene backbone have played a pivotal role in diverse transition metal-catalyzed asymmetric reactions over the past three decades, ranging from academic laboratory researches to industrial productions [ 4 , 5 , 6 ], with more than 600 publications and patents attesting to their significance. Even today, chiral oxazoline phosphine ferrocene ligands ( FOXAP s) remain the preferred choice for many emerging reactions aimed at achieving highly stereoselective products [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Palladium-catalyzed regio- and stereoselective allylic alkylation of 5-vinyloxazolidine-2,4-diones with azlactones: synthesis of chiral (Z)-trisubstituted allylic amino acid derivatives

“…1 A variety of strategies have been invented to synthesize numerous useful unnatural allylic amino acids and derivatives. 2 On the basis of their catalytic systems, these strategies can be categorized as PTC-catalyzed allylic alkylation, 3 metal-catalyzed allylic alkylation, 4 dual metal-cocatalyzed allylic alkylation, 5 organocatalyst-catalyzed allylic alkylation, 6 and organocatalyst and metal-cocatalyzed allylic alkylation. 7 However, these reactions are limited to the preparation of chiral disubstituted allylic amino acid scaffolds with the E -configuration.…”