Diketene synthesis procedure

There has been considerable activity in the synthesis of orsellinic acids in the past decade. On account of their ready decarboxylation all these procedures also give access to 5-alkylresorcinols. These routes are summarised in the scheme shown. Homologous alkyl acetoacetates (R = R = alkyl) with thallium ethoxide or sodium hydride followed by reaction with diketene (route a) afford the corresponding homologous alkyl orsellinates (ref.23). In a related method (route b) methyl orsellinate (R = Me) results from the interaction of the monoanion with the dianion of methyl acetoacetate (ref.24). 

The Carroll rearrangement is often used as one of many key steps in the preparation of natural products due to its reliability as a stereodifferentiating reaction. Snider and Beal recently showed this in their formal synthesis of isocomene (41) (Scheme 8.17) [19]. Ketone 36 was reduced to alcohol 37 and treated with diketene to form the yS-keto ester 38. The [3,3]-sigmatropic Carroll rearrangement was performed using Wilson s procedure (2eq. of LDA, -78 to 65 °C) [6] to give the desired ketone 39 in 72% yield. This step was key in setting up the desired hindered carbon-carbon bond needed in the final product. An intramolecular cycloaddition and a few additional steps provided ketone 40, which is a late intermediate in Wenkert s isocomene (41) synthesis [20]. 

A more economical synthesis of isophytol using diketene was devised and developed to a manufacturing procedure by Kimel et of. (1958) of Hoff-mann-La Roche Inc. in Nutley, New Jersey. In Kimers procedure, methyl-butenol and its isoprenologs are condensed with diketene to give its acetoacetate, from which on pyrolysis methylheptenone and its isoprenologs are formed in high yields under evolution of CO, (cf. Kimel and Cope, 1943). 

A general route to 6-substituted valerolactones (112) is by condensation between aldehydes and the dianion derived from butynoic acid followed by hydrogenation using Lindlar s catalyst.During the synthesis of some steroid derivatives, use has been made of an intramolecular Wadsworth-Emmonds procedure to construct an unsaturated valerolactone group (114) from phos-phonate (113) (c/. 3, 87). A new preparation of ( )-pestalotin (115) has as its pivotal step a Lewis acid-catalysed condensation between 2-benzyloxyhexanol and diketen. /3-Ethylenic valerolactones (116) can be obtained from the corresponding /3-allenic acids by treatment with methanolic boron trifluoride (c/. 3, 89). 

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