Carbon-Heteroatom Bond Formation for Medium Ring Heterocycles
Pp. 171-247 (77)
Bhaskar Chatterjee, Prateek Bhamboo, Dhananjoy Mondal and Smritilekha Bera
In major classes of natural products and pharmaceutical compounds,
functional groups containing carbon-heteroatom bonds are present and often
responsible for significant biological activities. Among them, medium-ring
heterocycles are found in a wide range of drug candidates. While the synthesis of fiveand
six-membered ring systems is quite common, however, the formation of seven-,
eight- and nine-membered heterocycles is not as abundant as entropy factors and
transannular interactions often hinder the cyclization method. The ubiquitous presence
and use of heteroatoms in both synthetic and naturally occurring pharmaceutical
compounds support the review of carbon-heteroatom (particularly, C–N, C–O, C–S,
C–S, C–Se, C–Te) bond-forming reactions reported in the literature. In general, the
nucleophilic cyclization, organocatalyzed reactions, green synthesis, heterocycloaddition,
ring-closing metathesis, radical cyclization, metal-mediated transition
cycloaddition, macrolactonization are discussed as the most commonly used strategies
for medium-ring construction. The ring expansion strategies, such as pericyclic and
sigmatropic rearrangements, play an important role in the formation of C-X bonds. The
challenges faced involving structural complexity and biological activities prompted us
to review the literature for the synthesis of the heterocycles of the medium-ring size.
This chapter is dedicated to recent developments for the construction of C–X bonds in
seven-, eight- and nine-membered heterocycles.
Green synthesis, Heterocycles, Medium ring, Metal catalysed
cyclization, Nucleophilic cyclization.
School of Chemical Sciences, Central University of Gujarat, Gandhinagar-382030, India.