A highly enantioselective Mannich reaction of silyl ketene imines with isatin-derived ketimines has been realized by using a chiral N,N'-dioxide/Zn(II) catalyst. A variety of β-amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

A catalytic asymmetric intra-and intermolecular haloetherification of electron-deficient alkenes (halogen = Cl, Br, I) has been realized by the use of chiral metal complexes of N,N′-dioxides. In the presence of a chiral Fe(III) complex, a series of tetrahydropyran derivatives were obtained in good yields (up to 99% yield) with a high level of enantioselectivities (up to 97% ee). Promoted by a chiral Ce(III) complex, chiral oxepane derivatives could be given in good results. Moreover, the intermolecular haloetherification of chalcones catalyzed by Sc(III) complex using MeOH as nucleophile is demonstrated. This methodology also can be successfully applied to the synthesis of (−)-Centrolobine. Meanwhile, a reasonable reaction mechanism was proposed.

Scheme 2. Transformations of the product 6 a into other derivatives. Reaction conditions: a) 1) AlCl 3 , LiAlH 4 , Et 2 O; 2) Et 3 N, Boc 2 O; b) Pd-(OAc) 2 , PPh 3 , CH 3 CH = NOH, EtOH/H 2 O (4:1), reflux; c) 1) K 2 CO 3 , MeI, acetone, 93%; 2) CAN, CH 3 CN/H 2 O, then Et 3 N, Boc 2 O. Ar = 2-OH-4-MeC 6 H 3 . Boc = tert-butyloxycarbonyl. Scheme 3. Proposed catalytic model. Angewandte Chemie 3475

An efficient catalytic asymmetric ring-opening reaction of donor–acceptor cyclopropanes with primary arylamines was developed. The reaction was achieved through the utilization of a chiral heterobimetallic catalyst, delivering a variety of chiral γ-amino acid derivatives in up to 93% yield and 99% ee. Stereochemical experiments suggest a dominant role for kinetic resolution in this asymmetric process, which is supported by a computational study of the reaction coordinate. A class of chiral bimetallic Lewis acid catalysts formed through a ligand exchange/transmetalation process was introduced in this work. The symmetric structure of the bimetallic catalyst, i.e., Yb­(OTf)3-Yb­[P]3, was confirmed with X-ray crystallography.

Chiral b-amino nitriles are versatile synthetic intermediates that are readily transformed into optically active compounds such as b-amino acids, and 1,3-diamines. [1] The asymmetric addition of alkyl nitriles to imines provides a straightforward route to such compounds. [2] Although many methods for the asymmetric Mannich reaction have been described, [3] the use of less nucleophilic alkyl nitriles as the nitrile species is a continuing challenge; [4][5][6] one reason for this issue is the poor acidity of the a protons of alkyl nitriles. [5,6] One strategy to solve this problem is the use of an N-metalloketene imine, generated from cyanocarboxylic acid or benzyl nitrile, as an active intermediate; two catalytic asymmetric systems have been reported for such Mannich reactions. [4b,d] As an alkyl nitrile equivalent, silyl ketene imines [7] (SKIs) are competent nucleophiles that can react to form C-substituted nitriles (Scheme 1). Moreover, owing to their unique structure and ready racemization, SKIs are attractive substrates for the construction of vicinal tertiary and quaternary stereogenic carbon centers, [8] which are difficult to synthesize. [9] Since Fu and co-workers reported the first asymmetric acylation of SKIs, [10a] they have become attractive nucleophiles for asymmetric catalytic reactions. [10] The asymmetric aldol-type reaction of SKIs has been reported. [10b,c,e] However, there is only a limited number of examples of the asymmetric addition of SKIs to aldimines and the addition of SKIs to similar substrates has proven somewhat more difficult to achieve and is generally characterized by a narrow substrate scope; the only asymmetric system, which uses stoichiometric quantities of a chiral silicon Lewis acid as the promoter, was reported by Leighton and co-workers. [11] Therefore, the development of a general and efficient asymmetric Mannich reaction of SKIs is particularly desirable. We have recently developed chiral N,N'-dioxide/metal catalysts, which we used for a variety of asymmetric transformations, [12] one of which is the three-component, [13] one-pot addition of N-aryl imines. [14] Herein, we describe a practical and highly efficient Mannich reaction of SKIs to address the challenges mentioned above. A three-component, one-pot method involving the use of a chiral N,N'-dioxide scandium(III) catalyst under mild reaction conditions was developed for the synthesis of bamino nitriles. The desired products, which contain a quaternary stereogenic center, were generated in excellent yield and stereoselectivity (up to 95 % yield, > 95:5 d.r., 97 % ee). The procedure is convenient as no exclusion of air and moisture is required.In the initial study, the reaction between aldimine 1 a [15] and SKI 2 a was performed in EtOAc at À20 8C with 10 mol % of a Lewis acid catalyst, which was prepared in situ from Sc(OTf) 3 and chiral N,N'-dioxide ligand L1. The desired bamino nitrile 3 a was obtained in moderate yield and enantioselectivity and extremely low diastereoselectivity (56:44 d.r.; Table 1, entry ...