Asymmetric total synthesis of alkaloids 223A and 6-epi-223A.

Concise and asymmetric total synthesis of the title compounds are described. The key ring system was constructed using an intramolecular Schmidt reaction on a norbornenone derivative, which was subsequently subjected to ring-opening metathesis followed by reduction. An unusual isomerization of the C-6 ethyl group afforded the desired stereochemistry of the natural product. The synthesis is readily adaptable to analogue production.

Nonbonded, attractive cation-pi interactions in azide-mediated asymmetric ring expansion reactions.

The influence of attractive, nonbonded interactions on the reactions of 1,2- and 1,3-hydroxyalkyl azides with ketones has been investigated through experimental and computational means. A series of 1,3-hydroxyalkyl azides bearing electronically tuned aromatic groups at the 2 position were prepared and reacted along with several derivatives designed to conformationally restrict the rotational orientation of the aromatic substituent. These studies showed that a cation-pi interaction between an aryl moiety and an N2(+) leaving group plays a role in determining the stereoselectivity of these reactions. A series of ab initio calculations supported this hypothesis. A computational and experimental analysis suggested a primarily steric model for the analogous reactions of substituted 2-azido-1-ethanol analogues.

Synthesis of enantiomerically enriched (R)-5-tert-butylazepan-2-one using a hydroxyalkyl azide mediated ring-expansion reaction.

A procedure for the conversion of a symmetrical ketone to an enantiomerically pure lactam is described. The technique described here involves a ring-expansion reaction of a 4-substituted cyclohexanone accomplished with a chiral 1,3-azidopropanol derivative. The procedure entails first a one-step preparation of (R)-1-phenyl-3-azidopropanol from a commercially available halide precursor, which is then reacted with the ketone using BF(3) x OEt(2) as a Lewis acid promoter. The resulting lactam is subsequently converted into a chiral lactam of high enantiopurity via the two-stage removal of the chiral nitrogen substituent. The present protocol carries out the diastereoselective ring-expansion reaction with higher selectivity than competing processes and is generally useful for the preparation of 5-substituted caprolactams.

Concise construction of novel bridged bicyclic lactams by sequenced Ugi/RCM/Heck reactions.

Herein we report a concise protocol for the diastereoselective synthesis of novel bridged bicyclic lactams from commercially available components by the sequence of Ugi, ring-closing metathesis (RCM), and Heck reactions. X-ray diffraction studies revealed that the bicyclic products contain varying degrees of pyramidalization of the bridgehead nitrogen atom.