β-Amino Esters from the Reductive Ring Opening of Aziridine-2-carboxylates

A general study is undertaken to examine the scope of the reductive ring opening of aziridine-2-carboxylates with samarium diiodide. The competition between CC and CN bond cleavage is examined as a function of the nature of the N-substituent of the aziridine, the nature of the substituent in the 3-position of the aziridine, and whether the substituent in the 3-position is in a cis or trans relationship with the carboxylate in the 2-position. The desired CN bond cleavage leads to beta-amino esters that are the predominant products for most aziridines with an N-activating group. However, CC cleavage products are observed with an aryl group in the 3-position; this can be particularly pronounced with cis-aziridines where a nearly equal mixture of the two is observed. Exclusive formation of the CN cleavage product is observed for all aziridines with the strongly N-activating p-toluene sulfonate group. Similarly high selectivity is observed for the 2-trimethylsilylethyl sulfonate group (SES), which is easier to remove. The utility of these methods is illustrated in the synthesis of protected forms of (R)-beta(3)-DOPA and l-DOPA from the same aziridine, the former by SmI2-mediated reductive opening at C-2 and the latter by palladium-mediated reductive opening at C-3.