Furans nitrile oxide intramolecular cycloadditions

The intramolecular cycloaddition reactions of the nitrile oxides 357 (n = 1, 2, 3, 9), obtained in situ from the 2,5-difunctional furan hydroximoyl chlorides or nitro compounds (415) has specific features because of the 2,5-arrangement of two open chains bearing acetylenic and fulminic moieties. Only with 357 (n = 3) is the expected furanoisoxazolophane 358 formed, in acceptable yield. Compound 357 ( =9) gives a complex product mixture whereas 357 ( = 1, 2) gives rise to the exclusive reaction of the dipole with a double bond of the furan system. 

The intramolecular cycloaddition of nitrile oxides to substituted furans was reported to occur with low stereoselectivity (274). Inserting a stereogenic unit within the chain connecting the dipole and dipolarophile did not increase the stereoselectivity (274). 

The sesquiterpene skeleton has also been assembled by the intramolecular nitrile oxide cycloaddition sequence. Oxime 238 (obtained from epoxy silyl ether 237), on treatment with sodium hypochlorite gave isoxazoline 239, which was sequentially hydrolyzed and then subjected to the reductive hydrolysis conditions-cyclization sequence to give the furan derivative 240 (330) (Scheme 6.93). In three additional steps, compound 240 was converted to 241. This structure contains the C11-C21 segment of the furanoterpene ent-242, that could be obtained after several more steps (330). 

Intermolecular [3+2] 1,3-dipolar cycloaddition of a D-glyceraldehyde-derived nitrile oxide to the 4,5-double bond of 2-methylfuran gave a 60 40 diastereomeric ratio of the two furoisozaxoline isomers. This chemistry was employed in the synthesis of L-furanomycin <2005EJ03450>. As depicted in Scheme 43, an intramolecular cycloaddition of a furan with a carbonyl ylide dipole proceeded under rhodium-catalyzed microwave-promoted conditions to provide the cycloadduct in a modest yield <20040L3241>. 

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