Functionalized Azamacrocycles and Large-Ring α-Amino Esters by One-Pot Syntheses from Methyl 2-Siloxy-2-vinylcyclopropanecarboxylates

Abstract

Siloxycyclopropane 1 served as starting material for intermediate alkylation products 2, 7, 11, 14, and 17, which were elongated to provide a variety of precursor compounds bearing terminal N-benzyl groups. These substrates were subjected to a cesium fluoride-promoted ring-opening/ring-closure sequence 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 building block for construction of precursors 31 and 34, which on fluoride treatment furnished macrocyclic α-amino esters 32 and 35, respectively, in moderate yields. A few reactions, such as transformations into macrocyclic pyridazinone derivatives 37 and 38, illustrate the potential of the synthesized azamacrocycles for preparation of complex compounds. Our concept for construction of macrocyclic compounds using siloxycyclopropane 1 as zwitterionic synthon A has thus successfully been extended to the synthesis of a variety of highly functionalized azamacrocycles.