The incorporation of nitrogen atom(s) into pharmaceutical lead compounds can often drastically alter their molecular properties to bring forth the intended physiological effects1. Hence, it is perhaps not surprising that a staggering 60% of all FDA-approved medicines contains at least one nitrogen atom in a cyclic form, collectively referred to as N-heterocycles2. Cross-coupling reactions and Buchwald-Hartwig amination have revolutionized methods for the synthesis of N-heteroaromatics - 'flat' N-heterocycles -via C-C and C-N bond formations. Saturated (or partially saturated) N-heterocycles containing non-planar sp~3-hybridized atoms have recently been suggested to be better pharmaceutical lead scaffolds compared with unsaturated compounds3. However, strategies for the syntheses of molecules with increased saturation have so far largely relied on intramolecular cyclization, which can be difficult to apply when trying to access structural diversity (Fig. 1a).
Prabagar Baskaran、Wei Li
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Department of Chemistry and Biochemistry, The University of Toledo, Toledo, OH, USA
NSTL
