Functionalized azamacrocycles and large-ring alpha-amino esters by one-potsyntheses from methyl 2-siloxy-2-vinylcyclopropanecarboxylates

Siloxycyclopropane I served as starting material for intermediate alkylatio n products 2, 7, 11, 14, and 17, which were elongated to provide a variety of precursor compounds bearing terminal N-benzyl groups. These substrates w ere subjected to a cesium fluoride-promoted ring-opening/ring-closure seque nce to afford azamacrocycles 19, 21, 22, 23, 25, 26, 27, and 28 in moderate to good yields. The cyclic products have different ring sizes and numbers of nitrogen atoms, and may incorporate meta-substituted benzene or pyridine units. A second approach employed glycine derivative 29 as the key buildin g block for construction of precursors 31 and 34, which on fluoride treatme nt furnished macrocyclic a-amino esters 32 and 35, respectively, in moderat e yields. A few reactions, such as transformations into macrocyclic pyridaz inone derivatives 37 and 38, illustrate the potential of the synthesized az amacrocycles for preparation of complex compounds. Our concept for construc tion of macrocyclic compounds using siloxycyclopropane I as zwitterionic sy nthon A has thus successfully been extended to the synthesis of a variety o f highly functionalized azamacrocycles.