Synthesis of oxaspirannic building blocks by regioselective nitroso-Diels-Alder reactions.

Spirocyclic structures: Nitroso-Diels-Alder reactions of 1,3-disubstituted cyclohexadienes were found to be regiodivergent, depending on the nitroso derivative used. Cycloaddition with Wightman's chloronitroso derivative was totally regio- and stereoselective. This methodology was applied to the synthesis of heterospiranic frameworks after N-O bond cleavage and cyclization (see scheme; Boc=tert-butoxycarbonyl, Tf=trifluoromethanesulfonyl).

Stereodivergent synthesis of piperidine alkaloids by ring-rearrangement metathesis/reductive lactam alkylation of nitroso Diels-Alder cycloadducts.

A general methodology for the stereoselective synthesis of 2-(2-hydroxyalkyl)piperidine alkaloids by ring-rearrangement metathesis of nitroso Diels-Alder cycloadducts is reported. The approach is illustrated by the formal synthesis of porantheridine and the total synthesis of andrachcinidine through a diastereodivergent allylation of an N-alkoxy bicyclic lactam. The asymmetric synthesis of the latter alkaloid provides new insights into the configurational stability of cycloadducts between chloronitroso reagents and cyclopentadiene.

Synthetic approaches to racemic porantheridine and 8-epihalosaline via a nitroso Diels-Alder cycloaddition/ring-rearrangement metathesis sequence.

The application of a sequence involving a nitroso Diels-Alder cycloaddition and a ring-rearrangement metathesis to the total synthesis of (+/-)-8-epihalosaline and the formal synthesis of (+/-)-porantheridine is described. The formation of the 2,6-trans-disubstituted piperidine backbone of porantheridine has been accomplished by addition of a Grignard reagent onto an N-benzylpiperidone followed by a highly diastereoselective reduction of the imminium intermediate in one pot.