Curtius rearrangement stereochemistry

From the perspective of synthetic utility (see Section 1.1.4.4), a crucial mechanistic feature of the Curtius rearrangement is that migration of sp carbons occurs stereospecifically, with retention of configuration. Wallis showed that the product from rearrangement of enantiomerically enriched a-benzyl propionyl azide 13 remained optically active. Kenyon and coworkers proved that preservation of optical activity corresponded to retention of configuration by studying rearrangement of 15. The product 16 was obtained with > 99% retention of stereochemistry. ... 

Condensation of the vinylogous carbamate (40) with acetaldehyde and isocyanic acid afforded the pyrimidine derivative (41) which was converted to the urea derivative (42) by Curtius rearrangement in 65% overall yield. Treatment of (42) with acetic acid at 50° afforded exclusively the desired product (39), whereas treatment with trifluoroacetic acid gave a mixture of (39) and stereoisomer (43). The stereochemistry was established by comparing the coupling constants involving H-5 and H-6 with those of saxitoxin (1). Different cyclization mechanisms were suggested for the acetic acid and trifluoroacetic acid catalyzed cyclization to account for the different stereochemistry of the products. 

Preservation of stereochemistry upon rearrangement is the key in these applications of the Curtius process in asymmetric synthesis. Additional examples featuring this stereospecificity, particularly directed toward natural product synthesis, are foimd in the Variations and Improvements Section. 

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