Biomedical Engineering Reference
In-Depth Information
SCHEME 3.17 Synthesis of substituted pyrrolidines through silver(I)-catalyzed azomethine
cycloaddition.
Pyrrolidines are common scaffolds present both in natural products and in small-
molecule pharmaceuticals. For this reason, continuous efforts have been directed
toward the development of new synthetic protocols, which could generate pyrrolidines
efficiently and with complete control over the stereochemistry. In this context, Chen
et al. described the synthesis of pyrrolidine-based scaffolds 56 through 1,3-dipolar
cycloaddition of unactivated olefins with azometine ylides. The reaction proceeded
enantioselectively, and up to four stereocenters were generated (Scheme 3.17) [31].
Based on the Ag(I)-catalyzed enentioselective cycloaddition developed by Longmire
et al. [32], the authors found Ag(I) acetate/QUINAP to be the best catalyst system
when a series of different
-imino esters, derived from a large variety of aromatic
aldehydes, were utilized with various dipolarophiles. Good enantioselectivity was
also observed when glycinate was replaced by various amino esters. This was the
first example of a quaternary center at the 2-position of pyrrolidine generated by a
catalytic asymmetric [3
α
2] cycloaddition reaction.
A few years later, Garner et al. reported an Ag(I)-catalyzed asymmetric coupling
synthesis of highly functionalized pyrrolidine structures 57 (Scheme 3.18) [33]. The
+
SCHEME 3.18 Silver(I)-catalyzed cycloaddition reaction of in situ-generated azomethine
ylides with electron-deficient alkenes.
Search WWH ::




Custom Search