Showing papers by "Xiaohua Liu published in 2008"

Asymmetric direct aldol reaction of functionalized ketones catalyzed by amine organocatalysts based on bispidine.

Abstract: Organocatalysts containing primary−secondary amine based on bispidine and amino acid have been designed to catalyze the asymmetric direct aldol reaction of functionalized ketones including α-keto phosphonates, α-keto esters, as well as α,α-dialkoxy ketones as aldol reaction acceptors. The corresponding products with chiral tertiary alcohols were obtained in moderate to high yields (up to 97%) and high enantioselectivities (up to 98% ee). A theoretical study of transition structures demonstrated that protonated piperidine was important for the reactivity and enantioselectivity of this reaction.

An enantioselective biginelli reaction catalyzed by a simple chiral secondary amine and achiral brønsted acid by a dual-activation route.

Abstract: An enantioselective Biginelli reaction that proceeds by a dual-activation route has been developed by using a combined catalyst of a readily available trans-4-hydroxyproline-derived secondary amine and a Bronsted acid. Aromatic, heteroaromatic, and fused-ring aldehydes were found to be suitable substrates for this multicomponent reaction. The corresponding dihydropyrimidines were obtained in moderate-to-good yields with up to 98 % ee under mild conditions. Based on the experimental results and the observed absolute configurations of the products, a plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.

Highly enantioselective strecker reaction of ketoimines catalyzed by an organocatalyst from (S)-BINOL and L-prolinamide.

Abstract: The catalytic asymmetric Strecker reaction has attracted much attention and a number of successful protocols have been disclosed for its great importance in the synthesis of chiral a-amino acids and their derivatives. However, in contrast to the relatively well-developed cyanation of aldimines, limited reports were related to the cyanation of ketoimines to afford pharmaceutically important disubstituted a-amino nitriles. Especially, it is not easy to promote cyanation of ketoimines with organocatalyst. Since the first successful example reported by Jacobsen’s group using chiral urea as catalyst, two types of N,N’-dioxides have been developed by our group for the Strecker reaction of ketoimines and moderate to good results were obtained. Herein, we reported a novel kind of N,N’-dioxide with an axial chirality for the enantioselective cyanation of N-Ts-protected ketoimine, providing excellent results (Figure 1). Before, the linkers of the previously used N,N’-dioxides for the Strecker reaction of ketoimines were achiral moieties. We speculated that the stereocontrol would be enhanced by employing a suitable chiral linker. On the basis of this idea, we designed and synthesized the N,N’-dioxide catalyst derived from BINOL and prolinamide. The general route was given in Scheme 1. Firstly, (S)-BINOL was formylated via three steps to afford A1 which was subsequently subjected to the condensation reaction with l-prolinamide. Then the product B1 was oxidized to achieve the desired novel N,N’-dioxide 1a. Notably, the absolute configuration of the newly formed chiral center in catalyst 1a was identified as R based on the observation of strong NOE signal between H1 and H2 (see Supporting Information). However, the attempt to synthesize the similar structure from (R)-BINOL and lprolinamide was failed, which might be attributed to the instability of the corresponding N,N’-dioxide. Interestingly, when two hydroxyl groups of B1 were replaced by two methoxy group, N,N’-dioxide 1c could not be prepared as diastereomerically pure form in the oxidation step. Instead, the mixture of the two epimers with a ratio of 1:1.8 was obtained (see Supporting Information). Other catalysts displayed in Figure 1 were prepared in a similar process (Scheme 1) for the preparation of 1a. To examine the initial hypothesis, we evaluated these catalysts in the asymmetric Strecker reaction of N-tosyl ketoimines with TMSCN. It was found that a promising result (80 % ee) was obtained by employing 5 mol% N,N’-dioxide 1a as catalyst, while inferior asymmetric induction was ob[a] Z. Hou, J. Wang, Dr. X. Liu, Prof. Dr. X. Feng Key Laboratory of Green Chemistry & Technology (Sichuan University), Ministry of Education College of Chemistry, Sichuan University Chengdu 610064 (PR China) and State Key Laboratory of Oral Diseases, Sichuan University Chengdu 610041 (PR China) Fax: (+86) 28-8541-8249 E-mail : xmfeng@scu.edu.cn Supporting information for this article is available on the WWW under http://www.chemistry.org or from the author. Figure 1. Catalysts used in this research.

Direct Allylation of Aldimines Catalyzed by C2‐Symmetric N,N′‐Dioxide–ScIII Complexes: Highly Enantioselective Synthesis of Homoallylic Amines

Abstract: Optically active homoallylic amines are useful intermediates for the preparation of bioactive natural products and relevant compounds. The asymmetric allylation of imines provides direct access to them and considerable efforts have been devoted to devising enantioselective versions of this transformation. Among these methods, catalytic asymmetric allylation of imines, as a more efficient method, has made significant progress. Despite these creative efforts, the development of new methods, the design and synthesis of new catalysts remain considerable challenge. Simplified and environmentally friendly multicomponent strategy has been successfully adopted in the synthesis of racemic homoallylic amines. Herein, we reported an efficient catalytic asymmetric direct allylation of aldimines promoted by readily accessible and tuneable C2-symmetric N,N’-dioxide-Sc III complexes under mild conditions. As a versatile catalyst, chiral N,N’-dioxide compounds and their complexes with different metals have showed superiority in the enantioselective reactions of carbonyl compounds and imines. In our study of chiral N,N’-dioxidemetal complexes in catalytic asymmetric reactions, they have exhibited good ability for the activation of allylstannane reagent and 2-aminophenol-derived aldimines. We sought to take advantage of the activation abilities of this kind of catalysts for the asymmetric allylation of 2-aminophenol-derived aldimines, which has been extensively documented well in the allylation by Kobayashi, Leighton and Tsogoeva e] et al. With the three-component reaction of benzaldehyde, 2-aminophenol and allyltributyltin as benchmark, catalytic ability of different metals complexed with l-proline-derived N,N’-dioxide L1 was tested. The significant effect of the central metal on both reactivity and enantioselectivity was observed, as shown in Table 1. When Zr ACHTUNGTRENNUNG(OiPr)4 [6] and Pd ACHTUNGTRENNUNG(OAc)2 [5b–d] were adopted, the reaction did not take place (Table 1, entries 1, 2). Racemic products were obtained with good yields in the presence of CuACHTUNGTRENNUNG(OTf)2 [5h] and In ACHTUNGTRENNUNG(OTf)3 (Table 1, entries 3, 4). Inspiringly, L1-Sc ACHTUNGTRENNUNG(OTf)3 complex catalyzed the reaction smoothly, giving the desired allylic amine in 77 % yield with 82 % ee (Table 1, entry 5).

Asymmetric three-component Strecker reactions catalyzed by trans-4-hydroxy-L-proline-derived N,N'-dioxides.

Abstract: Novel trans-4-hydroxy-L-proline-derived N,N'-dioxides have been developed and used as efficient organocatalysts for the one-pot three-component Strecker reaction with an aldehyde, (1,1-diphenyl)methylamine, and TMSCN. Both aromatic and aliphatic aldehydes were found to be suitable substrates. The corresponding alpha-amino nitriles were obtained in high yields with up to 95 % ee (ee=enantiomeric excess) under mild conditions. Optically pure products could be obtained after a single recrystallization. The catalyst can be easily prepared from trans-4-hydroxy-L-proline and a diamine in three steps. Based on the experimental results and the observed absolute configurations of the products, a possible transition state has been proposed to explain the origin of the asymmetric induction.

Asymmetric Direct Aldol Reaction of Functionalized Ketones Catalyzed by Amine Organocatalysts Based on Bispidine.

Abstract: Organocatalysts containing primary−secondary amine based on bispidine and amino acid have been designed to catalyze the asymmetric direct aldol reaction of functionalized ketones including α-keto phosphonates, α-keto esters, as well as α,α-dialkoxy ketones as aldol reaction acceptors. The corresponding products with chiral tertiary alcohols were obtained in moderate to high yields (up to 97%) and high enantioselectivities (up to 98% ee). A theoretical study of transition structures demonstrated that protonated piperidine was important for the reactivity and enantioselectivity of this reaction.

Highly Enantioselective Henry (Nitroaldol) Reaction of Aldehydes and α‐Ketoesters Catalyzed by N,N′‐Dioxide‐Copper(I) Complexes.

Abstract: A new chiral N,N'-dioxide-Cu(I) catalyst has been developed for the asymmetric Henry (nitroaldol) reaction. The approach benefited from the easy modification of the chiral space. As the highly effective N-oxide ligand, 1d has been adopted for the Henry reaction with both aromatic and heteroaromatic aldehydes. The corresponding nitro-alcohol products were obtained in good yields with high enantiomeric excesses up to 98%. Moreover, alpha-ketoesters were also catalyzed by this catalyst to give attractive optically active alpha-hydroxy beta-nitro esters containing chiral quaternary carbon centers (up to 99% ee). On the basis of a combination of several techniques including the 1H NMR, ESI-HRMS, and MM2 calculations, the proposed mechanism was presented to explain the origin of reactivity and asymmetric inductivity.

Asymmetric Three‐Component Strecker Reactions Catalyzed by trans‐4‐Hydroxy‐L‐proline‐Derived N,N′‐Dioxides.

Abstract: Novel trans-4-hydroxy-L-proline-derived N,N'-dioxides have been developed and used as efficient organocatalysts for the one-pot three-component Strecker reaction with an aldehyde, (1,1-diphenyl)methylamine, and TMSCN. Both aromatic and aliphatic aldehydes were found to be suitable substrates. The corresponding alpha-amino nitriles were obtained in high yields with up to 95 % ee (ee=enantiomeric excess) under mild conditions. Optically pure products could be obtained after a single recrystallization. The catalyst can be easily prepared from trans-4-hydroxy-L-proline and a diamine in three steps. Based on the experimental results and the observed absolute configurations of the products, a possible transition state has been proposed to explain the origin of the asymmetric induction.