Epoxidation from chloroketones

The western part was obtained from chloroketone 431, which by various reductases could be transformed into chloroalcohol 433. Subsequent base treatment led to epoxide 435 in 92% yield. 

Diazomethane is generated by the reaction of aqueous NaOH with N-methyl-N-nitroso-p-toluenesulfonamide (Diazald ) in DMSO. The diazomethane is generated quantitatively and is removed by a stream of N2 into a packed column containing a stream of mixed anhydride formed from an N-protected (BOC or CBZ) amino acid and ethyl chloroformate. The diazoketone is converted to the chloroketone using HCI, as shown in Scheme 11.10. The chiral epoxide can then be formed via diastereoselective reduction with NaBH4 and treatment with base. 

By 1950 five distinct mechanisms had been suggested to account for the formation of the major products of the Favorskii rearrangement. Four involved epoxide, ketene, enol, and carbene intermediates. A fifth mechanism related to the benzylic acid rearrangement was also proposed. Then, in 1951 Loftfield isolated two esters with identical isotope distributions at their a and P carbons from treatment of a radiolabeled, cyclic a-chloroketone with an alkoxide. These two products suggested a symmetrical intermediate, leading Loftfield to postulate the existence of a cyclopropanone along the reaction pathway. ... 

Two syntheses of the trail pheromone, neocembrene (435), of Nasu-titermes spp. termites have been reported. Kodama et al. 185) (Scheme 78) prepared the allylic phenyl thioether (430) from trans,trans-gQX iny linalool (429). Terminal epoxidation of (430) followed by intromolecular cyclization, desulfurization, and dehydration led to (435). Kitahara et al. 186) cyclized fra 5-geranylgeranic acid chloride (436) with SnCU to afford chloroketone (437) (Scheme 79). Dehydrohalogenation of (437) and subsequent reduction of ketone (438) via acetate (441) gave neocembrene (435). 

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