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-beta-amino acids 13-17, macrocyclic bisazetidines 18-20, and macrocyclic bisamides 21 and 22 by means of the corresponding bis-beta-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-beta-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.
Sierra
Miguel A
MA
Departamento de Química Organica and Laboratorio de Difracción de Rayos X, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain. sierraor@quim.ucm.es
Pellico
Daniel
D
Gómez-Gallego
Mar
M
Mancheño
María José
MJ
Torres
Rosario
R