Ketones furano

Challenging applications in the field of macrocyclic furans have been investigated. The major synthetic advantage is the cyclization to the furan after the macro-cyclization. This will avoid a problematic ring closure to macrocycles (to 1,3-furano-phanes) with a furan substrate ( furan latest strategy ). Test substrates demonstrated the viability of this concept [50], as shown below for the synthesis of the [8]furano-phane 91 from the macrocyclic ketone 90 (Scheme 15.22) [39]. 

Annelation of steroidal dienamines with substituted phenacyl bromides (7 examples) or with benzenediazonium salts (11 examples) has been shown to lead to the corresponding furano- and indolo-steroids.89 Thus the A3,5-dienamine derived from A4-androstene-3,17-dione reacted with p-bromophenacyl bromide to yield the A5-androstano[3,4-h]furan (199) in 26% yield, and reaction of the same A3,5-dienamine with benzenediazonium fluoroborate at -45 °C led to formation of the hydrazone (200) which underwent Fischer-indole cyclization on treatment with phosphorus oxychloride to produce the A4-androstano[6,7-6]indole (201). The A3,5-dienamine derived from 17/3-acetoxyandrost-4-en-3-one has been converted into the benz[4,5,6]-steroid (202 R1 = Me, R2 = H) by reaction with methyl vinyl ketone and into the analogous benzsteroid (202 R1 = H, R2 = Me) on treatment with crotonal-dehyde.90 A route to the condensed pyrroline ring system (203) has been devised... 

Alkenylsilane acylation has been employed for the synthesis of two furano monoterpenes, dehydroel-sholzione (1) and isoegomaketone (2 Scheme 5). Acylation of isobutene with 3-methyl-2-furoyl chloride gave dehydroelsholzione in poor yield with a variety of Lewis acid catalysts (SnCU, AlCb, TiCU), but using the equivalent silane substrate, the ketone was obtained in 55% overall yield. Probably as a result of work-up conditions, the initial reaction gave a mixture of three products, the conjugated and deconjugated ketones, together with the chloro ketone addition product. Isomerization and dehydrochlorination were effected with a tertiary amine base to maximize the yield of the desired product. 

The application of this cycloaddition strategy to the synthesis of norsecurinine was then undertaken. Thus the oxazole-pyrrolidine derivative 188 was prepared in four steps from o-proline (Fig. 3.57). Coupling 188 with enynone 189, prepared in four steps from maleic anhydride, afforded a near-quantitative yield of the acetylenic ketone 190 as a 2 1 mixture of C-7 epimers. After refluxing for 30 min in mesitylene, 190 underwent cycloaddition to produce a 2 1 mixture of the tricyclic furano-ketone 191 and the C-7 epimer in 50% overall yield from 189. The undesired epimer could be recycled by epimerizing with sodium carbonate to give a 1 1 mixture of epimers. The tricyclic furano-ketone 191 was then converted to (-)-norsecurinine in six steps. (+)-Norsecurinine was synthesized using an identical route starting with L-proline. 

The herbicidins continue to prove a synthetic challenge, and this year Gallagher s group have reported the synthesis of 142 and 143 possessing the furano-pyrano-pyran skeleton of the herbicidins. Key synthetic stq>s are fluoride-mediated alkoxide cyclization onto a ketone functionality after desulfurization (Scheme 36). ... 

The same carbocationic intermediates are postulated in the reactivity of fuUerene epoxide with ketones and aldehydes to afford 1,3-dioxolane derivatives 12 in the presence of various Lewis acids (10P7671219,08JOC2518). In the same reaction conditions, anilines and phenols react with fiillerene oxide to afford indolino[2, 3 l,2][60]fuUerenes 13 and benzo[lt]furano[2, 3 l,2] [60]fullerenes 14, respectively (08CL1018,09ECST33). 

Hymecromone 6084 Isobutyl propyl ketone 7311 Isopropyl 2-furanoate 6497... 

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