Studies of Acyl Nitrene Insertions. A Stereocontrolled Route toward Lankacidin Antibiotics.

ABSTRACT

Photochemically generated acyl nitrenes undergo facile addition to 4,5-dihydrofurans 20 and 24b to yield the novel 2-ethoxyoxazolines 21 and 25. The regiocontrolled C=C insertion has provided for introduction of the sterically hindered C-3 amido appendage of the lankacidins 1-4 with high stereoselectivity. High chemoselectivity for the C=C insertion pathway was demonstrated upon production of the acyl nitrene intermediate from azide 33b. Intramolecular competition for allylic C(3)-H insertion versus C=C addition yielded exclusive formation of seven-membered N-acyl aziridines 34a,b. The latent aldehydic functionality of oxazolines such as 21 and 25 is exposed upon a brief hydrolysis, permitting further chemical elaboration. Wittig condensation of the lactol from 25 has led to the synthesis of the lactone fragment 5, containing all of the necessary stereochemistry and functionality for incorporation into the lankacidin antibiotics. The acyl nitrene insertion into 4,5-dihydrofurans affords a route toward unusual beta-amido acids and amino sugar derivatives as shown via stereocontrolled formation of the amidofuranose derivatives 31 and 32. The three-step process of acyl nitrene addition, hydrolysis of the resulting 2,5-dialkoxy oxazoline intermediates, and Wittig carbon chain elongation provides the stereocontrolled formation of novel beta-amido esters.