Diols fragmentation reactions

Formation and /S-fission of bicyclic tertiary alkoxyl radicals from the corresponding alcohols are well known [38] [40]. The treatment of 5a-cholestane-3/3,5-diol-3-acetate, VII/70, and the 5/3-alcohol, VII/71, respectively (Scheme VII/15), with one molar equivalent of lead tetraacetate in the presence of anhydrous calcium carbonate gives radical fragmentation reactions. The products are the two (E)- and (Z)-3/3-acetoxy-5,10-seco-l(10)-cholesten-5-ones (VII/72 + VII/73) [40]. The ratio of VII/73 VII/72 is 63 10 [41] [42] [43]. 

Fluoride-induced fragmentation reactions were used in two stages of a synthesis of hexahydrocannabi-nol methyl ether (144 Scheme 52). One of the phenolic hydroxy functions in the resorcinol derivative (140) was selectively liberated from the SEM ether to give the diol (141), which was converted to the bis (trimethylsilyl) ether (142). Subsequent treatment with CsF resulted in a 1,4-elimination to the o-quinone methide (143) intermediate, which underwent an intramolecular [4 -i- 2] cycloaddition to give the product in good yield. 

One of the key steps during the first total synthesis of (-)-aspinolide B by A. de Meijere and co-workers was the NHK reaction to form the ten membered lactone ring. The precursor for this key macrocyclization step was prepared by forming an ester from a three-carbon monoprotected diol fragment and a seven-carbon vinyl iodide fragment. Deprotection of the primary alcohol and its subsequent oxidation afforded the desired vinyl iodide aldehyde precursor. Exposure of this precursor to 15 equivalents of CrCl2 doped with 0.5% of NiCb at high dilution in DMF afforded the desired diastereomer in a 1.5 1 ratio. 

The fragmentation reaction is not restricted to monosulfonates of 1,3-diols, and various leaving groups together with various electron-releasing groups can be used. The borate species formed by hydroboration (on the less-hindered face) of the... 

Shimizu et al. prepared the cyclic ( )-vinyl ether (270) in moderate yield by an addition-fragmentation reaction of the diol (271) by treatment with sodium hydride in THF overnight. The conjugate addition of the alkoxide to the vinyl selenone generates (272), then (273), leading to bond rupture and the expulsion of phenylselenone to form (270) (Scheme 31) <84JOC1230>. 

Fragmentations are reactions in which the molecule breaks open by the cleavage of a C—C single bond, and we start this section with some examples. Both diastereoisomers of this cyclic diol fragment in acid to give an aldehyde. 

Secolongifolene diol is one of the metabolites of the fungus Helminthosporium sativum (725). Recently, a simple synthesis of its optical antipode (193) has been achieved by exploiting the electrophilic addition-fragmentation reaction (726) of homoallylic alcohols. The homoallylic alcohol (191), which can be obtained from longicyclene (44) by cyclo-... 

There are three potential options for the mechanism of Grob fragmentation reactions, one concerted and two stepwise. The stepwise reactions, which result from initial loss of either the nucleofuge or electrofuge, are less useful in synthesis since they often promote side reactions. However, one highly efficient stepwise transformation was reported by Kato. Treatment of diol 6 with pyridinium chloride results in formation of benzyl carbocation 8. Cleavage of this alcohol yields monocycle 9 and, ultimately, the ketone product 10. ... 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

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