A synthesis of a common intermediate to the lactone-pyrrolidinone ring systems in oxazolomycin A and neooxazolomycin

A 5-exo-dig radical cyclisation of the bromoamide 34 derived from the enantiopure α-ethynyl substituted amino alcohol 31 led to a 2:1 mixture of β-C3 and α-C3 methyl epimers of the pyrrolidinone 35a-36a in a combined yield of 73%. Treatment of the homoallylic alcohol 35b, derived from 35a, with OsO4-TMEDA, gave a single diastereoisomer of the pyrrolidinone triol 37, resulting from selective dihydroxylation from the β-face, i.e. syn to the CH2OH group of 35b. The pyrrolidinone triol 37 is a potential common precursor, cf. 9, to the spiro β-lactone pyrrolidinone 8 and the γ-lactone pyrrolidinone 10 ring systems in oxazolomycin A (1) and neooxazolomycin 2, respectively. Sequential protection of the 1,2-diol functionality in 37 as the acetonide 39, and the primary alcohol group in 39 as the SEM ether 41a, followed by methylation of the nitrogen centre in 41a, using NaH-MeI, then gave the selectively protected pyrrolidinone 42.