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DOI: 10.1055/s-2007-968263
Metathesis-Mediated Route to 6,6-Bicyclic Malonamides
Contributor(s):Victor Snieckus, Heiko ScharlUniversity of Oregon, Eugene, USA
Convenient Synthesis of 6,6-Bicyclic Malonamides: A New Class of Conformationally Preorganized Ligands for f-Block Ion Binding
J. Org. Chem. 2006, 71: 9622-9627
Publication History
Publication Date:
20 February 2007 (online)
Key words
bicyclic malonamides - Grubbs I catalyst - reductive amination - ozonolysis
Significance
A synthetic approach involving classical Grignard and modern metathesis chemistry affording 6,6-bicyclic malonamides (BMA) is presented. Starting with a double allyl Grignard addition to ethyl formate followed by base-mediated malonate alkylation affords the requisite metathesis precursor which, under Grubbs I catalytic conditions, leads to the expected cyclopentene. Pedagogically well-accepted strategy for the construction of acyclic functionalized derivatives by ozonolysis of cyclic olefins is then followed and leads to a diamine precursor which, upon reductive amination and hydrogenolysis, affords the BMA derivatives. The synthesis of 10 BMAs is described.
Comment
The synthesized 6,6-bicyclic malonamides belong to a class of ligands that provide a preorganized binding site for f-block ions, in particular trivalent lanthanides. To date, only a few examples of BMAs have been available by a method based on the cyclization of acyclic diamines, generated by hydrogenolysis of dicyanides, with malonates (C. Altomare, A. Carotti, G. Casini, S. Cellamare, M. Ferappi, E. Gavuzzo, F. Mazza, G. Pantaleoni, R. Giorgi J. Med. Chem. 1988, 31, 2153-2158). The described route appears to present an excellent alternative synthesis which provides a diversity of BMAs owing to the late introduction of the amine component.