Chelation controlled 1,3-dipolar cycloaddition of 5,6-Dihydro-5-phenyl-1,4-oxazin-2-one N-oxide with allyl alcohols: A short-step synthesis of clavalanine intermediate

Abstract

( R)-5,6-Dihydro-5-phenyl-1,4-oxazin-2-one N-oxide {( R)- 2} reacts with allyl alcohols 3a-c in the presence of magnesium bromide from the less hindered face via exo-mode to afford corresponding cycloadducts 4a-c with excellent stereoselection. Treatment of ( R)- 2 with three equivalents of racemic secondary allyl alcohols 3d-g under the same conditions causes partial kinetic resolution to give 4d-g as main products among eight possible stereoisomers. Cycloadduct ent- 4a from ( S)- 2 and 3a was converted directly to g-lactone 6, which is known as the key synthetic intermediate of antibiotic clavalanine.