Letter pubs.acs.org/OrgLett
Asymmetric Synthesis of Glutamic Acid Derivatives by SilverCatalyzed Conjugate Addition−Elimination Reactions Yang Yuan,† Bo Yu,† Xing-Feng Bai,† Zheng Xu,† Zhan-Jiang Zheng,*,† Yu-Ming Cui,† Jian Cao,† and Li-Wen Xu*,†,‡ †
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 311121, P. R. China ‡ Suzhou Research Institute and State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, P. R. China S Supporting Information *
ABSTRACT: The enantioselective construction of a family of chiral glycine-derived aldimino esters is described. The asymmetric tandem conjugate addition−elimination procedure is characterized by its exceptional mild reaction conditions and features with an exquisite enantioselectivity profile using commercially available silver/DTBM-SegPhos catalyst, allowing for the facile preparation of a variety of substituted and chiral glutamic acid derivatives (up to 99% ee) bearing Schiff base in a straightforward manner.
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scenario, the challenges for the synthesis of glutamic acid derivatives bearing aldimino Schiff base are that (1) the enantioselectve construction of glutamic acid derivatives bearing aldimino Schiff base has rarely been investigated in asymmetric catalysis, (2) the choice of a suitable metal catalyst to efficiently control enantioselectivity is required to possess enough stability of the aldimino Schiff base to isolate the chiral products, and (3) the selection of the appropriate ligand to allow a compromise between enantioselectivity and reactivity in the metal-catalyzed tandem conjugate addition−elimination is not an easy task. Herein, we report a highly efficient and enantioselective synthesis of chiral 4-benzylidene glutamic acid derivatives, an important type of α-allylated amino esters, by silver-catalyzed tandem conjugate addition−elimination reaction of glycinederived aldimino esters with MBH-type acetates. In this work, a wide range of stable and functionalized Schiff base products, bearing aldimino, ester, and alkene groups, were obtained with high regioselectivities, good to excellent yields, and enantioselectivities. It provided a new method for the synthesis of functionalized and chiral glutamic acid derivatives bearing a Schiff base that could be used in the construction of synthetically useful and complicated molecules. The research was initially inspired by the unique behavior of our Xing-Phos ligand in a silver-catalyzed asymmetric Michael addition initiated [3 + 2] cycloaddition reaction,11 and then we found that the silver catalyst (AgOAc) was a promising catalyst in this reaction in terms of yield and enantioselectivity (see Scheme 1, 86% yield and 89% ee) in the presence of Xing-Phos.
ue to the wide application of amino acid derivatives in the synthesis of synthetically useful or biologically active molecules, the development of efficient synthetic methods or new catalytic strategies to access an amino acid−base structural motif in an optically active form has long been an important topic in organic chemistry and catalysis.1 In this context, substantial progress has been made in the enantioselective transition-metal-catalyzed transformation of glycine derivatives.2 Although glycine aldimino Schiff bases have been widely used as glycine anion equivalents in the cycloaddition,3 Michael reactions,4 Mannich reactions,5 and alkylations6 to afford various type of amino acid derivatives, there are limited methods for building a monosubstituted glutamic acid derivatives by transition-metal-catalyzed allylic substitutions of glycine derivatives.2 The catalytic construction of optically pure α-allylated glycine derivatives proved quite difficult because of possible racemization under the 1,3-dipolar addition reaction conditions. To our knowledge, only a few examples have been documented for the synthesis of 4-substituted glutamate analogues by the tandem conjugate addition−elimination reaction.7−10 For example, Ramchandran et al.8 established an enantioselective synthesis of glutamic acid derivatives via the tandem conjugate addition−elimination of glycine benzophenone Schiff bases with activated allylic acetates (MBH adducts) under chiral phase-transfer catalysts conditions.8 However, there are some limitations regarding the enantioselectivity in some cases and the scope of substrates. In addition, despite the copper-catalyzed tandem conjugate addition−elimination reaction being utilized in the synthesis of α-allylated amino esters, there is no report on the asymmetric Ag-catalyzed tandem conjugate addition−elimination of readily available and simple glycine aldimino derivatives with MBH-type acetates. In this © 2017 American Chemical Society
Received: August 1, 2017 Published: August 28, 2017 4896
DOI: 10.1021/acs.orglett.7b02378 Org. Lett. 2017, 19, 4896−4899
Letter
Organic Letters
pleased to observe that the same high level of enantioselectivity was reserved in different solvents, which suggested the high stability for enantioselective induction of Ag/DTBM-SegPhos in this reaction. It should be noted that the combination of copper catalyst with (R)-DTBM-SegPhos was not suitable for this reaction because of only moderate yield and enantioselectivity (see Table S4, 52% yield and 64% ee). With the optimized reaction conditions in hand, we then explored the substrate generality of the glycine aldimino esters and MBH adducts. As shown in Tables 1 and 2, the silver-
Scheme 1. Preliminary Results of the Catalytic Performance of Representative Phosphine Ligands in the Asymmetric Tandem Conjugate Addition−elimination Reaction of Glycine-Derived Aldimino Ester 1a with MBH-Type Acetate 2a
Table 1. Silver-Catalyzed Tandem Conjugate Addition− Elimination Reaction of Glycine Aldimino Esters 1 with MBH Adducts 2a
However, different from that of previous reports on the coppercatalyzed tandem conjugate addition−elimination reaction of different imino esters with MBH adducts,9,10 copper catalysis had no ability to promote this tandem conjugate addition− elimination reaction of 1a with 2a (
