New synthetic strategies based on the photochemical Wolff rearrangement of diazo ketones
A new annulation strategy for the rapid assembly of highly substituted aromatic compounds has been developed. This methodology produces polycyclic and heteroaromatic substrates by the irradiation of a dichloroethane solution of an aryl or vinyl [alpha]-diazo ketone and an acetylene. The products are formed regioselectively by an initial photochemical Wolff rearrangement of the [alpha]-diazo ketone followed by three subsequent pericyclic reactions. A variety of substituted phenols, naphthols, indoles, carbazoles, benzofurans, and benzothiophenes can be constructed. Hyellazole, a naturally occurring carbazole alkaloid, was prepared using the photochemical aromatic annulation as a key step. An improved method for the preparation of [alpha]-diazo ketones has been developed. The new procedure involves the reaction of the ketone substrate with 1.1 equiv of lithium hexamethyldisilazide in THF at -78[degrees]C to form the corresponding lithium enolate, which is then acylated by exposure to 1.2 equiv of trifluoroethyl trifluoroacetate at -78[degrees]C for 5 min. The resulting [alpha]-trifluoroacetyl ketone is treated at room temperature with methanesulfonyl azide in acetonitrile containing 1 equiv of water and 1.5 equiv of triethylamine. A wide variety of [alpha]-diazo ketones have been prepared using this procedure, including [alpha],[beta]-unsaturated [alpha][prime]-diazo ketones that cannot be prepared in good yield employing alternative methods. The generation and subsequent reactivity of alkynylketones was explored. These transient species can be formed by the photochemical Wolff rearrangement of [alpha]-alkynyl-[alpha][prime]-diazo ketones, and can be trapped by alcohols and amides as the corresponding homologated esters and amides. Alkynylketenes can also participate in a cascade of pericyclic reactions related to our original aromatic annulation strategy to provide highly substituted aromatic products, although in lower yield.
- Research Organization:
- Massachusetts Inst. of Tech., Cambridge, MA (United States)
- OSTI ID:
- 7069330
- Resource Relation:
- Other Information: Thesis (Ph.D.)
- Country of Publication:
- United States
- Language:
- English
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