Acylnitrenium ions

A series of benzisothiazolone derivatives 238 has been prepared from methylthiosalicylate 235 O60L4811>. The key cyclization step features the formation of a TV-acylnitrenium ion 237, generated by the hypervalent iodine reagent, phenyliodine(III)bis(trifluoroacetate) (PIFA). This ion cyclizes to benzisothiazol-3-one 238 upon intramolecular trapping of the thiol moiety. 

Oxidation of hydroxamic esters in an alcoholic solvent may prove to be useful in certain cases. Phenyliodine(III)bis(trill uoroacetate) (PIFA) oxidation of the proline derivative (185) in trifluoroethanol afforded a 26% yield of the A-methoxy-Af-trifluoroethoxy derivative (187), presumably via an intermediate Af-methoxy-A-acylnitrenium ion (186) (equation 23). ... 

Intramolecular interception of an Af-alkoxy-AT-acylnitrenium ion by an aromatic ring results in a spirocyclic species [203], There follows a C-migration (instead of N-migration) to restore aromaticity. This migration is assisted by the stabilization of the incipient carbocation by the resident donor nitrogen atom N-migration would not profit from this favorable electronic interaction. 

Alanine was the starting point for the synthesis of new fused 1,4-diazepine-2-ones (e.g. 67), using A-acylnitrenium ion formation and intramolecular trapping by the thiophene moiety in the key cyclisation step <03T7103>. 

Kawase, M., et al.. Electrophilic Aromatic Substitution with N-Methoxy-N-acylnitrenium Ions Generated from N-Chloro-N-methoxyamides Syntheses of Nitrogen Heterocyclic Compounds Bearing a N-Methoxy-amide Group, J. Org. Chem., 54 3394-3403 (1989). 

Acylnitrenium ions, 120 Acyloxy radicals, 112 Adamantanones, 279, 280 2-Adamantyl cation, 280 Adenine, 138 Agostic interaction, 191 Alane (AIH3), 278... 

The synthesis of racemic desmethylamino FR901483 was reported by Snider in 1998 [9] (3.1.1). Three years later, using the A-alkoxy-A-acylnitrenium ion methodology for the azaspirocyclization step (3.2.1), Wardrop published a formal synthesis of desmethylamino FR901483 [10] having reached the advanced intermediate 15 previously reported in Snider s pioneering work (Scheme 8). 

In summary, Wardrop developed a synthetic route to azatricycle 15 (16 steps), which Snider had previously transformed to 19. Accordingly, a formal synthesis of racemic desmethylamino FR901483 was achieved, the key steps being (i) formation of the azaspirodecane ring by an N-methoxy-A-acylnitrenium ion-induced spirocyclization (ii) construction of the bridge framework by a 6-exo-trig radical cyclization, and (iii) installation of the C(6) p-methoxybenzyl side chain by Lewis acid-mediated alkylation of a silyl enol ether. 

In summary, the enantioselective total synthesis of (-)-TAN1251A was accomplished by Wardrop in 17 steps and with 3% overall yield, the key step being the jV-methoxy-yV-acylnitrenium ion-induced spirocyclization. 

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