Highly Enantioselective Aza-Henry Reaction of Ketoimines Catalyzed by Chiral N,N′-Dioxide−Copper(I) Complexes

Abstract

The first example of catalytic enantioselective aza-Henry reaction of ketoimines has been realized using a simple chiral N,N'-dioxide-Cu(I) complex as catalyst. It performs well over a range of substrates to give the corresponding products in moderate to good yields (up to 83%) with high enantioselectivities (up to 96% ee).

Direct Synthesis of Enolizable N‐Sulfonyl Ketimines Under Microwave Irradiation

“…[1] As a consequence, N-sulfonyl imines, in particular N-tosyl imines, are ubiquitous in organic transformations. To name but a few, they have been used as substrates for cycloadditions, [2][3][4][5][6] aziridines [7] and oxazolines [8] preparations, as well as nucleophilic additions [9][10][11][12] and reductions. [13,14] Due to their widespread use, several methodologies for preparing N-sulfonyl imines have been described.…”

The crystal structures of chiral (R/S) (C8H11N)2·CuCl2

“…More and more chiral N-Cu complexes have been widely synthesized and used as the catalysts in asymmetric catalytic fields [1][2][3][4][5], for example, dicopper and dicobalt complexes [1], stable copper(I)-carbonyl carbenes [2], chiral N,N 0 -dioxide-copper(I) complexes [3], and copper (II) chiral bis(oxazoline) complexes [4] have all shown high activity in organic reactions. Inspired by their research work, our research group have first synthesized two opposite chiral complexes (C 8 H 11 N) 2 ÁCuCl 2 by one-pot, simple step [6].…”

Aza‐Henry Reaction of Isatin Ketimines with Methyl 4‐Nitrobutyrate en Route to Spiro[piperidine‐3,3′‐oxindoles]

“…Recently,t he aza-Henryr eactionw ith ketimines has experienced considerable progress, [21] and several groups [22] including ours [23] have developed efficient procedures for the enantioselective aza-Henryr eaction with isatin ketimines leading to 3-aminooxindoles bearing aquaternary stereogenic centre.T hese studies with isatins have been limited to unfunctionalised nitroalkanes.W ee nvisioned that the addition of alkyl nitrobutyrates to isatin ketimines [24,25] would provide chiral 3-aminooxindoles with an ester-functionalised chain at the 3p osition of the oxindole which would make possible the access to highly enantioenriched spiro[piperidine-3,3'-oxindoles] after lactamisation (Scheme 1). [26] In our previous work [23] we performed the enantioselectivea ddition of nitromethane to N-Boc-isatin ketiminesu sing ac opper(II)-Ph 2 BOX (L1)c atalyst with excellent enantiomeric excesses.E lection of the copper salt was crucial for the success of this reaction as the use of copper(II) triflate caused the hydrolysis of the N-Boc-imine,b eingd etrimental to the yield.…”