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Updated: Mar 16, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Isothiourea-catalysed enantioselective pyrrolizine synthesis: synthetic and computational studies
Daniel G Stark1, Patrick Williamson, Emma R Gayner
1EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK. ads10@st-andrews.ac.uk.
Abstract:
The catalytic enantioselective synthesis of a range of cis-pyrrolizine carboxylate derivatives with outstanding stereocontrol (14 examples, >95 : 5 dr, >98 : 2 er) through an isothiourea-catalyzed intramolecular Michael addition-lactonisation and ring-opening approach from the corresponding enone acid is reported. An optimised and straightforward three-step synthetic route to the enone acid starting materials from readily available pyrrole-2-carboxaldehydes is delineated, with benzotetramisole (5 mol%) proving the optimal catalyst for the enantioselective process. Ring-opening of the pyrrolizine dihydropyranone products with either MeOH or a range of amines leads to the desired products in excellent yield and enantioselectivity. Computation has been used to probe the factors leading to high stereocontrol, with the formation of the observed cis-steroisomer predicted to be kinetically and thermodynamically favoured.
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