Acyloin reaction 100 SUBJECT

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with N-bromosuccinimide from cyclo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - The present procedure, based on the last method, is relatively simple and uses inexpensive starting materials. Step A exemplifies the 2 + 2 cycloaddition of dichloroketene to an olefin, " and the specific oycloadduot obtained has proved to be a useful intermediate in other syntheses. " Step B has been the subject of several mechanistic studies, " and its yield has been greatly improved by the isolation technique described above. This synthesis has also been extended to the preparation of various tropolone derivatives. - " ... 

Chiral cyanohydrins serve as the alcohol moieties of several commercial pyre-throid insecticides (see below) [1527]. Hydrolysis or alcoholysis of the nitrile group affords chiral a-hydroxyacids or -esters and Grignard reactions provide acyloins [1528], which in turn can be reduced to give vicinal diols [1529], Alternatively, the cyanohydrins can be subjected to reductive amination to afford chiral ethanol-amines [1530]. a-Aminonitriles as well as aziridines are obtained via the corresponding a-sulfonyloxy nitriles [1531]. 

The final twistane synthesis we will consider originates from the one-bond disconnection indicated by Path D in Unnatural Products-1. Just as with Path A, the synthesis uses a Diels-Alder reaction to establish the bicyclo[2.2.2]octane substructure of key intermediate 9. The cycloaddition of cyclohexadiene 43 and methyl propiolate afforded a mixture of regioiso-meric cycloadducts 44 and 45. Catalytic hydrogenation of the mixture occured from the sterically most accessible face of the olefin to afford meso-compound 46 and its diastereomer 9. Diester 9 was subjected to an acyloin condensation, and catalytic hydrogenation of the resulting a-hydroxyketone gave diol 47. A Corey-Winter reaction was used to convert 47 to 49 via thionocarbonate 48. Catalytic hydrogenation completed the synthesis. 

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