CHIRAL MICHAEL ADDITION - METHYL VINYL KETONE ADDITION CATALYZED BY CINCHONA ALKALOID DERIVATIVES
CHIRAL MICHAEL ADDITION - METHYL VINYL KETONE ADDITION CATALYZED BY CINCHONA ALKALOID DERIVATIVES
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DOI：
10.1021/jo00374a039
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发表时间：
1986-11-28
影响因子：
3.6
通讯作者：
WEINSTOCK, LM
中科院分区：
文献类型：
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作者：
CONN, RSE;LOVELL, AV;WEINSTOCK, LM
甲基乙烯基酮（MVK）与茚满酮2-羧酸酯的手性迈克尔加成在文献中已有很好的先例。然而，这些方法中的许多不适用于2-烷基茚酮，例如1，其含有比β-酮基酯酸性小的质子。2在这里，我们报道了j.®-a由金鸡纳生物碱的季盐催化的MVK对茚满酮1的加成，产率为95%，对映体过量（ee）高达80%。这种手性迈克尔加成，3然后羟醛缩合以完成罗宾逊加成，是我们制备候选药物3的关键步骤。4金鸡纳生物碱的碱性不足以催化迈克尔加成到2-丙基茚酮1。Wynberg报道，相应的季盐作为催化剂不如游离碱有效。5然而，在这些实验室中，用季金鸡纳生物碱催化剂6进行相转移烷基化得到了优异的结果，导致采用
Chiral Michael additions of methyl vinyl ketone (MVK) to indanone 2-carboxylic esters are well precedented in the literature. 1 However, many of these methods are not applicable to 2-alkylindanones such as 1, containing a proton less acidic than the/3-keto ester. 2 Here we report j.®-a an addition of MVK to indanone 1 catalyzed by the qua-ternary salts of Cinchona alkaloids in 95% yield and up to 80% enantiomeric excess(ee). This chiral Michael addition, 3 followed by aldol condensation to complete the Robinson annelation, was the key step in our preparation of drug candidate 3.4Cinchona alkaloids are not basic enough to catalyze Michael additions to the 2-propylindanone 1. Wynberg reportslb that the corresponding quaternary salts are not as effective as catalysts as the free bases. 5 However, excellent results have been obtained in these laboratories in phase-transfer alkylations with quaternary Cinchona alkaloid catalysts6 leading to a synthesis of 3 employing