Eschenmoser fragmentation

The Eschenmoser fragmentation (often referred to Eschenmoser Ohloff or Eschenmoser - Tanabe fragmentation) is a name reaction in organic chemistry. Describes the synthesis of alkynes, and ketones from α, β -unsaturated ketones and derived from α, β - epoxyketones. Here, either acid or base catalysis worked ( here base catalysis with sodium carbonate ) is required and arylsulfonic acid hydrazide. The reaction is named after its discoverer Albert Eschenmoser and went out of his collaboration with Firmenich researchers led by Günther Ohloff in the synthesis of macrocyclic musks muscone and other produce.

Mechanism

The required α, β - epoxy ketones 1 are usually synthesized by Weitz - Scheffer epoxidation of α, β - unsaturated ketones. In the first steps condenses arylsulfonic acid hydrazide (see first reaction arrow), for example, p - toluenesulfonyl, with the epoxy ketone 1 to give the sulfonyl hydrazone 4 The subsequent fragmentation step can be initiated acid - base catalysis or protonated with either the epoxide oxygen, or the sulfonamide nitrogen is deprotonated. In both cases, this results in the compound 6 In this mechanism, work is base catalysis with sodium carbonate. Typically, however, is acid catalyzed with glacial acetic acid in dichloromethane at -18 ° C worked. By elimination of the arylsulfinic acid and nitrogen fragments of the ketone intermediate 6 7 8 and the alkyne driving force of the reaction is the formation of molecular nitrogen.

There is also a radical variant of this α, β - enone → alkynone fragmentation with 1,2- dibromo -5 ,5- dimethyl hydantoin ( DDH ) in sec -butanol, which does not require epoxidation and directly from α, β -unsaturated hydrazone emanates. Here, a Allylbromierung with DDH on sulfonamide nitrogen, the capto - dative stabilized radical site takes place, and the bromide ion acts as a leaving group in the subsequent nucleophilic attack of an alkoxide ion. This Fehr- Ohloff - Büchi variant of the Eschenmoser fragmentation Ohloff handle it the epoxidation step, which often results in the case of sterically demanding substrates in poor yields of the classic Eschenmoser fragmentation. By using bicyclic epoxy ketones bearing the epoxy on both bridgeheads are obtained cyclic 1,6 - Inone, which is the synthesis of macrocycles of importance.