Catalytic enantioselective synthesis of beta-lactams: intramolecular Kinugasa reactions and interception of an intermediate in the reaction cascade.
Catalytic enantioselective synthesis of beta-lactams: intramolecular Kinugasa reactions and interception of an intermediate in the reaction cascade.
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DOI：
10.1002/anie.200352103
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发表时间：
2003-09
影响因子：
--
通讯作者：
R. Shintani;G. C. Fu
中科院分区：
文献类型：
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作者：
R. Shintani;G. C. Fu
Ryo Shintani and Gregory C. Fu* β-Lactams have been intensely investigated as a result of both their biological activity and their utility as synthetic intermediates.[1, 2] For example, in the pharmaceutical arena, penicillins and cephalosporins are widely prescribed antibiotics,[1] ezetimibe (zetia) serves as a potent hypocholesterolemic agent,[3] and a β-lactam is employed in the commercial synthesis of the anticancer drug paclitaxel (taxol) to install a β-amino acid derived side chain.[4] Because of the wide-ranging significance of β-lactams, the development of efficient methods for their enantioselective synthesis is an important objective. A number of noteworthy strategies have been described, almost all of which rely upon the generation of chiral, nonracemic precursors, followed by formation of the four-membered ring.[1, 2] In contrast, very few catalytic enantioselective routes to β-lactams from achiral precursors have been reported.[5] Based on the pioneering work of Kinugasa et al.,[6] Miura et al.,[7] and others,[8] we recently described a copper/bisazaferrocene-catalyzed method for the asymmetric coupling of alkynes with nitrones (the Kinugasa reaction;[Eq.(1)] and Figure 1).[9] This mild approach to the generation of β-lactams is very attractive owing to its convergence, its high functional-group tolerance, and the ready availability and stability of alkynes and nitrones. In our initial study, planar-chiral bisazaferrocene 1 proved to be the most effective ligand among those that we examined. This early investigation explored the generation of monocyclic β-lactams exclusively. Bicyclic and polycyclic βlactams also constitute important targets, both as endpoints (eg, penicillins [1] and trinems/tribactams [10]) and as synthetic intermediates.[11] Although, in principle, an intramolecular Kinugasa reaction would provide efficient access to these classes of compounds, to the best of our knowledge no
