Synthesis of Highly Functionalized Macrocycles by the Peripheral Functionalization of Macrocyclic Diimines

The easily available macrocyclic diimines 4−7 can be stereoselectively transformed to macrocyclic bis-β-amino acids 13−17, macrocyclic bisazetidines 18−20, and macrocyclic bisamides 21 and 22 by means
of the corresponding bis-β-lactam scaffolds 8−12. These key intermediates are available through standard
Staudinger reaction and obtained as the cis-cis diastereomers, exclusively. An interesting relation between
the proximity of the reactive CN bonds and the selectivity in the formation of the bis-β-lactams 8−12
is observed. Thus, diimine 4 leads to low selectivities, producing a 1:1 mixture of cis-syn-cis and cis-anti-cis diastereomers, while diimines 5−7 having the diimine sites more separated lead almost exclusively
to the cis-anti-cis diastereomers. The stereochemistry of all the products was unambiguously assigned
by X-ray diffraction analysis of compounds cis-syn-cis 8 and cis-anti-cis 12-Co2CO6 complex.