Furan synthesis, spiro

Spirofuran-2(5H),2 (3 H)furo[2,3-i]furan synthesis, 4, 659 Spirofuranones synthesis, 3, 734 Spiro[3.3]heptane... 

Spirofuran-2(5H),2 (3 H)furo[2,3-6]furan synthesis, 4, 659 Spirofuranones synthesis, 3, 734 Spiro[3.3]heptane physical properties, 1, 590 Spiroindazoles irradiation, 5, 252 Spiroisoarsindolinium salts, 1, 544 Spiroisoxazolines synthesis, 6, 108 Spirolactones synthesis, 3, 846-847 Spiro-/3-lactones synthesis, 7, 395 Spiro nomenclature, 1, 26 Spirooxadiazoles synthesis, 4, 822 Spirooxaziridines photorearrangement, 7, 541 (8-scission, 7, 211 Spirooxetanes synthesis, 7, 393 Spirooxiranes cleavage... 

An alternative furan synthesis is based upon allylic C-H insertion upon reaction with a ketone-derived enol ether. Reduction and hydrolysis affords the furan (eq 6). With aldehyde-derived enol ethers, copper(I) induced reaction with dimethyl diazomalonate yields an alkoxycyclopropane diester, whose reduction, hydrolysis, and oxidation affords a spiro- -methylene-y-lactone (eq7). 

Benzo[c]furans (isobenzofurans) are reactive molecules usually employed as reactive dienes in the synthesis of more complex molecules. In the synthesis of spiro compounds related to fredericamycin A, Kumar generated the trimethylsiloxytrimethylsilylbenzo[c]furan 125 from phthalide via two consecutive deprotonations and silylations of the resulting anions. Diels-Alder reaction of the isobenzofuran as shown below with a spiroenedione leads to the formation of an endo-exo mixtures that can be smoothly converted to the dihydroxydione <00IJC(B)738>. 

Numerous examples of natural products with the benzo[6]furan nucleus have been identified. It occurs under many guises dibenzofurans, /3-coumaranones, a-pyranobenzo[6]furans, y-pyranobenzo[6]furans, and the spiro-2,3-dihydrobenzofurans such as griseofulvin. Many of the natural benzo[6]furans have physiological, pharmacological and toxic properties and as a result an active interest exists in their chemical synthesis. 

The deMayo-type photochemistry of 1,3-dioxin-4-ones has been beautifully applied by Winkler et al. to the synthesis of complex natural products. Substrate 133 gave under sensitized irradiation (with acetone as cosolvent) product 134 as single diastereoisomer (Scheme 6.47). The diastereoselectivity results from cyclic stereocontrol exerted by the two stereogenic centers in the spiro-bis-lactone part of the starting material. After installation of the furan, saponification and bond scission in a retro-aldol fashion generated a keto carboxylic add, which produced the natural product ( )-saudin (135) by simultaneous formation of two acetal groups [128]. 

Janecki, T., A convenient synthesis of substituted 2-cyano-l,3-butadienes, Synthesis. 167, 1991. Ting, P.C., and Solomon, D.M., Synthesis of spiro[4, 5, 10,11-tetrahydro-5//-dibenzo[a,d]cyclohep-ten-5-yl-2 (37/)-furans] as potential cytokine inhibitors, J. Heterocycl. Chem., 32, 1027, 1995. Armesto, D., flail ego, M.G., Horspool, W.M., and Agarrabeitia, A.R., A new photochemical synthesis of cyclopropanecarboxylic acids present in pyrethroids by the aza-di-Jt-methane reanangement. Tetrahedron, 51, 9223, 1995. 

Acid catalysed cyclisation of the substituted furans 20 led to formation of the spiro-systems 21 and 22, the latter being formed preferably <97TL7641>. Other syntheses involving the intermediacy of an oxonium ion include the preparation of thieno[2]azepines <97JHC1494>, l,2,3,4-tetrahydro-5//-l-benzazepine-6,9-quinones <97H(45)1703> and a new synthesis of ( )-cis- and ( )-/ra 8-clavicipitic acid <97T51 >. 

The Diels-Alder reaction is undoubtedly a very useful route to spirocyclic compounds, and has now been extended to allenic ketones, so giving ready access to polyfunctional spiro-systems as shown in the preparation of (132). Furan-terminated cationic cycliza-tions have been applied to the synthesis of spiro-compounds such as... 

Scheme 3.43 Synthesis of spiro[furan-2,4 -tetrahydroquinoline] developed by Barluenga.

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