Abstract
The Lewis acid mediated Diels-Alder reactions of three 2-phosphono-2-alkenoates including triethyl 2-phosphonoacrylate (1), triethyl 2-phosphonobut-2-enoate (2), and ethyl 2-(diethoxyphosphono)-3-methylbut-2-enoate (3) have been investigated. Of several Lewis acids tested, tin(IV) chloride was shown to be the most effective at enhancing the regio- and stereoselectivity of the reactions of 1 with the electron-rich dienes to result in the formation of the single regio- and/or stereoisomers in good yields. Bearing the beta methyl group(s), 2 displayed much less reactivity than 1 while 3 was completely unreactive under the study's conditions. Throughout the investigation, we found that the cycloadditions of 2, especially of the Z-isomer, could be efficiently induced by using zinc chloride at elevated temperatures. Furthermore, a lithium naphthalenide (LN)-induced reductive alkylation process was applied to the resulting Diels-Alder adducts 4 to allow the phosphono group at the quaternary carbon centers to be replaced by various alkyl groups to afford the alkyl-substituted esters 12, therefore practically turning 1 and 2 into the useful synthetic equivalents of the corresponding 2-alkyl 2-alkenoates that usually display poor Diels-Alder reactivity. Application of this combined operation has facilitated the total synthesis of the sesquiterpene natural product alpha-alasken-8-one (8) in racemic form.
Published Version
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