Alcohols cyclic, oxidative cleavage

The next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

The obvious Vfittig disconnection gives stabilised ylid (5fi) and keto-aldehyde (57). We have used many such long-chain dicarbonyl compounds in this Chapter and they are mostly produced from available alkenes by oxidative cleavage (e.g. ozonolysis). In this case, cyclic alkene (58) is the right starting material, and this can be made from alcohol (59) by elimination,... 

Intramolecular hydrosilylation.1 Hydrosilylation of internal double bonds requires drastic conditions and results in concomitant isomerization to the terminal position. However, an intramolecular hydrosilylation is possible with allylic or homoallylic alcohols under mild conditions by reaction with 1 at 25° to give a hydrosilyl ether (a), which then forms a cyclic ether (2) in the presence of H2PtCl6-6H20 at 60°. Oxidative cleavage of the C—Si bond results in a 1,3-diol (3). 

A method for oxidative cleavage of cyclic ketones involves a four-stage process. First, the ketone is converted to an a-phenylthio derivative (see Section 4.7). The ketone is then converted to an alcohol, either by reduction or addition of an organolithium reagent. This compound is then treated with lead tetraacetate to give an oxidation... 

IOB alone can oxidize some alcohols, but catalysed oxidations are much more efficient. Thus, in the presence of RuCl2(PPh3)2 primary aliphatic alcohols were oxidized cleanly to aldehydes, at room temperature the use of m-iodosylbenzoic acid instead of IOB considerably increased the yields for example, hexanal was formed from hexanol quantitatively (by GC) [19], Another catalytic system involved the use of simple lanthanide salts such as ytterbium triacetate [20]. Cyclic y-stannyl alcohols, readily available from cyclic vinyl ketones and Bu3SnLi, underwent oxidation accompanied by carbon-carbon bond cleavage (Grab fragmentation), when treated with IOB.BF3 and DCC. The products were unsaturated aldehydes or ketones. 

There exists also a synthesis of cyclopentadecanone (VII/81) and ( )-mus-cone, based on a three-carbon annulation of cyclic ketones followed by the regioselective radical cleavage of the zero bridge of the so formed bicyclic system [44], The synthesis of cyclopentadecanone is summarized in Scheme VII/16. The cyclization of VII/78 to the bicyclic alcohol VII/79 proceeds best (94 % yield) with samarium diiodide in the presence of hexamethylphosphoric acid triamide and tetrahydrofuran [45], The oxidative cleavage of VII/79 to the ring expanded product VII/80, was performed by treatment with mercury(II)-oxide and iodine in benzene, followed by irradiation with a 100 Watt high pressure mercury arc. Tributyltinhydride made the de-iodination possible. 

The tandem 0s04-catalyzed oxidative cleavage of olefin 269 with Oxone as the co-oxidant and sequential direct oxidation of intermediate aldehyde in alcoholic media led to cyclic keto lactone 270 in 45% yield (Equation 34) <20030L3089>. Similar oxidative cyclization with KMnCT-GuSITr resulted in 32% yield of 270 <1994T11709>. 

Cleavage of allylic alcohols. The system selectively cleaves the double bond and the adjacent bond bearing the hydroxyl group of acyclic and aromatic allylic alcohols. Cyclic allylic alcohols are oxidized in low yield to dicarboxylic acids. 

Triphenylbismuth carbonate (2) displays remarkable chemoselecdvity, aUowing alcohol oxidation in the presence of benzenethiol, pyrrolidine, indole, aniline, dimethyl aniline and 3-pyrolidinocholesta-3,S-diene. The diol moiety in (3) is cleaved selectively without oxidizing the dithioacetal function (equation 3). The rate of the stoichiometric oxidative cleavage of ciJ-cyclohexane-l,2-diol to adipic aldehyde with Ph3BiC03 is faster than that of the trans isomer, suggesting the formation of a cyclic organobismuth intermediate (4 Scheme 1). ... 

Reaction of allylic alcohol 396 with paraformaldehyde using a catalytic amount of p-toluenesulfonic acid gave cyclic carbamate 397, which upon reduction with lithium aluminum hydride afforded aminodiol 398. Oxidative cleavage of the double bond of 398, achieved by dry silica gel ozonization (80JA5968) of the trifluoro acetate salt of aminodiol 398, gave ( )-5-epi-desosamine (399) (Scheme 49). 

Koreeda and Hamann have reported the use of silyl tethers in stereocontrolled syntheses of branched-chain 1,4-diols and 1,5-diols [61]. Exposure of (bromomethyl)silyl ethers prepared from the corresponding homoallylic alcohols with Bu SnH in the presence of AIBN allowed smooth conversion to the corresponding cyclic siloxanes, from which diol products were obtained using standard, oxidative cleavage protocols. While monosubstituted olefin 149 selectively underwent 1-endo cyclization, di- and trisubsti-tuted olefins 150 and 151 preferentially reacted through the 6-exo mode with complete stereocontrol, affording the diol products 152 and 153, respectively (Scheme 10-50). 

Cleavage of cyclic orthoesters. The regioselective oxidative cleavage of protected pyranosides to give mainly the primary alcohols makes orthoesters derived from phthalide a useful device for protection or differentiation. 

In general, tertiary alcohols are unaffected by chromic acid, but tertiary 1,2-diols are cleaved readily to give ketones, provided they are capable of forming cyclic chromate esters. For oxidative cleavage of diols, see Section 5.4. 

Additional examples of synthetic application of periodic acid as an oxidant include the oxidative iodination of aromatic compounds [1336-1341], iodohydrin formation by treatment of alkenes with periodic acid and sodium bisulfate [1342], oxidative cleavage of protecting groups (e.g., cyclic acetals, oxathioacetals and dithioacetals) [1315, 1343], conversion of ketone and aldehyde oximes into the corresponding carbonyl compounds [1344], oxidative cleavage of tetrahydrofuran-substituted alcohols to -y-lactones in the presence of catalytic PCC [1345] and direct synthesis of nitriles from alcohols or aldehydes using HsIOe/KI in aqueous ammonia [1346],... 

The stereochemistry of the macro cyclic moiety in pinnatoxins B (2) and C (3) was determined as follows. Reduction of the imino group in 2 and 3 with NaBH4 followed by oxidative cleavage with NaI04 provided aldehyde 6 (Scheme 1). Aldehyde 6 was also obtained by the reduction of iminium and a carboxylic acid moiety in pinnatoxin A methyl ester (5) followed by oxidation of the resulting alcohol. Since the spectroscopic data of 6 derived from 2 and 3 and that from 5 were identical, the relative stereochemistry of the macrocyclic core in 2 and 3 was confirmed to be the same as that in piima-toxin A (1). 

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