β-amino esters from the reductive ring opening of aziridine-2-carboxylates

J Org Chem. 2014 Nov 7;79(21):10068-80. doi: 10.1021/jo501694h. Epub 2014 Oct 20.

Abstract

A general study is undertaken to examine the scope of the reductive ring opening of aziridine-2-carboxylates with samarium diiodide. The competition between C-C and C-N 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 C-N bond cleavage leads to β-amino esters that are the predominant products for most aziridines with an N-activating group. However, C-C 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 C-N 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)-β(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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aziridines / chemistry*
  • Benzenesulfonates / chemistry
  • Esters
  • Palladium / chemistry
  • Stereoisomerism
  • Trimethylsilyl Compounds / chemistry

Substances

  • 2-trimethylsilylethyl sulfonate
  • Aziridines
  • Benzenesulfonates
  • Esters
  • Trimethylsilyl Compounds
  • aziridine-2-carboxylic acid
  • Palladium
  • 4-toluenesulfonic acid