Investigation of Lewis Acid Mediated Diels-Alder Reactions of α-Phosphono α,β-alkenoates. Total Synthesis of (±)-α-Alasken-8-one.

• Main Authors: Chuan-Chen Liao, 廖川成
• Other Authors: Jia-Liang Zhu
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/65429292024996768177

碩士 === 國立東華大學 === 化學系 === 97 === The Lewis acid-mediated Diels-Alder reactions of three α-phosphono α,β-alkenoates including triethyl 2-phosphonoacrylate (1)，ethyl 2-(diethoxyphosphono)-but-2-enoate (2) and ethyl 2-(diethoxyphosphono)-3-methyl-but-2-enoate (3) have been investigated. Among which, 1 was found to be the most reactive toward the electron-rich dienes, and tin (IV) chloride used in a dichloromethane solution was proven to be the most effective at enhancing the regio- and stereoselectivity of its reactions, in giving in the exclusive formation of the single isomeric adducts in good yields. On the other hand, compound 2 displayed the much less reactivity than 1, presumably due the steric hindrance exerted by the β methyl group. However, its cycloadditions, in particular of the Z-isomer, still could be efficiently induced by zinc chloride at the elevated temperatures. The structures of the resulting adducts were all unambiguously confirmed by spectroscopic methods or the X-ray analysis of their derivatives. Subsequently, a lithium naphthalenide (LN)-induced reductive alkylation process was attempted on the resulting adducts to allow the phosphono group to be intentionally replaced by various alkyl groups, therefore practically turning 1 and 2 into the useful synthetic equivalents of the corresponding 2-alkyl 2-alkenoates that always display poor Diels-Alder reactivity. Application of this strategy has facilitated the first total synthesis of (±)-α-alasken-8-one (8), a sesquiterpene natural product isolated from liverwort Calypogeia fissa. In the sequence, we first converted the alkylated product 11b into 8-methylspiro[4.5]deca-3,7-dien-2-one (17) in 4 steps. From which, the synthesis of 8 could be achieved in a straightforward fashion.