Enantioselective organocatalytic Michael additions to acrylic acid derivatives: generation of all-carbon quaternary stereocentres.

Acrylic esters, thioesters and N-acryloyl pyrrole have been identified as effective electrophiles in the enantioselective Michael addition reaction with beta-keto ester pro-nucleophiles catalysed by a cinchona alkaloid derived bifunctional organocatalyst; enantiomeric excesses of up to 98% and yields of up to 96% can be obtained for a range of Michael acceptors and pro-nucleophiles.

Enantioselective partial reduction of 2,5-disubstituted pyrroles via a chiral protonation approach.

[reaction: see text] The partial reduction of 2,5-pyrrole diester 1 followed by enantioselective protonation in situ to furnish synthetically useful building blocks is described. An enantiomeric excess of up to 74% was achieved using (-)-ephedrine and related analogues as chiral proton sources. The pyrroline product obtained could be recrystallized to give enantiomerically pure material.

Construction of perhydro indol-2-ones by a methoxide catalyzed deacetylation-Michael-aldol cascade.

An efficient, stereoselective Michael-aldol cascade for the one-pot construction of the perhydro indol-2-one bicyclic ring system using an acetate protected doubly-activated pyrrole-2-one pro-nucleophile and alpha,beta-unsaturated carbonyl compounds has been developed. Initiated by a methoxide deacetylation in methanol at room temperature, the cascade is easy to perform, stereoselective, efficient and broad in scope to this synthetically relevant structure.

Flexible strategy for the synthesis of pyrrolizidine alkaloids.

A general strategy for the production of pyrrolizidine alkaloids is described, starting from intermediate (+)-9. The key features are diastereoselective dihydroxylation, inversion at the ring junction by hydroboration of an enamine, and ring closure to form the bicyclo ring system. This route is attractive because of its brevity and versatility; four natural products were prepared with differing stereochemistry and substitution patterns. Finally, this work allowed assignment of the absolute stereochemistry of 2,3,7-triepiaustraline and hyacinthacine A 7.

An enzymatic approach to the desymmetrization of disubstituted pyrrolines.

The enzymatic desymmetrization of 2,2- and 2,5-disubstituted pyrroline compounds is reported in a procedure which gives access to both enantiomers in excellent enantiomeric excess and good yield. The enzyme reaction precursors are formed easily from two readily available substituted pyrroles using both ammonia (Na/NH3) and ammonia-free (Li/DBB) Birch reduction conditions.