K. S. K. Murthy

Formation of functionalized cyclic ethers by intramolecular nitrile oxide cycloadditions

Abstract The reaction of O-trimethylsilyl α-bromo aldoximes with unsaturated alcohols produces oximino ethers which can be readily oxidized with sodium hypochlorite. The transient nitrile oxide intermediate formed undergoes spontaneous cyclization affording fused isoxazolines. MM2 calculations help rationalize the observed stereoselectivity.

α-Bromination of aldoximes. A route to fused azetidines.

Abstract Unlike aldehydes and aldoximes, O-silylated aldoximes 2 are smoothly α-brominated with NBS to produce 3 , useful intermediates in the conversion to vinylnitroso species or in α-substitution reactions. For instance, 3 + 9 → 10 provided precursors for nitrile oxide-olefin cycloadditions.

Stereoselective synthesis of ptilocaulin and its 7-epimer

Abstract A versatile stereoselective synthesis of ptilocaulin 1 and its 7-epimer 22 , involving formation of the B-ring by intramolecular nitrile oxide cyclization, is described.

Fused β-lactams via intramolecular dipolar cycloaddition

Abstract Two routes were examined that permit conversion of 4-vinyl-2-azetidinones 7 via intramolecular nitrile oxide-olefin or azide-olefin cycloaddition into tricyclic β-lactams. Stereoselectivity in these cycloadditions as well as further chemoselective transformation of the products were shown to be dependent on the size of the newly formed ring.

Enantioselective synthesis of 3-substituted-4-aryl piperidines useful for the preparation of paroxetine ☆

Abstract The asymmetric conjugate addition reaction between 4-fluorophenylmagnesium bromide and various chiral α,β-unsaturated esters and enoylsultam substrates was explored to prepare a key intermediate useful in the preparation of paroxetine. The most selective auxiliary was found to be Oppolzers (1S)-(−)-camphorsultam. Interestingly, the diastereoselection was opposite to that reported for acyclic enoylsultams.

Stereoselectivity during intramolecular nitrile oxide olefin cycloadditions. Synthesis of fused azetidines.

Abstract Vinyl azetidines 7 can be converted to nitro olefins 8 , 9 or to unsaturated aldoximes 21 – 23 , which are useful precursors for intramolecular nitrile oxide - olefin cycloadditions (INOC). Such INOC reactions proceed with a fair degree of stereoselectivity producing novel heterocycles.