Ward Dale E, Sales Marcelo, Sasmal Pradip K
Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon SK S7N 5C9, Canada.
J Org Chem. 2004 Jul 9;69(14):4808-15. doi: 10.1021/jo049626o.
A variety of aldol adducts are shown to undergo efficient syn-anti isomerization in the presence of imidazole by an enolization mechanism. Isomerizations are high yielding and occur with little or none of the usual byproducts arising from competing elimination or retroaldol reactions. Most substrates reach equilibrium within 0.3-3 days at ambient temperature in chloroform, benzene, or dichloromethane containing 0.3-1 M imidazole. The process is particularly facile for aldols derived from tetrahydro-4H-thiopyran-4-one with rate constants for equilibration varying over ca. 1 order of magnitude for the adducts studied; structurally related aldols derived from cyclohexanone isomerized ca. 3-4 times slower. Isomerization of the acyclic aldol 5-hydroxy-4-methyl-5-phenyl-3-pentanone required heating to 60 degrees C but was achieved with minimal (<5%) retroaldol or elimination. A methoxymethyl ether derivative isomerized 30-40 times slower than the parent aldol. Isomerization of alpha,alpha'-disubstituted aldols and alpha,alpha'-bisaldols indicated low regioselectivity in the enolization. The synthetic utility of the process was demonstrated with the effective preparation of aldol stereoisomers unobtainable by direct methods.
结果表明，多种羟醛加成物在咪唑存在下通过烯醇化机理可高效地进行顺反异构化。异构化反应产率高，且几乎不产生或完全不产生由竞争性消除或逆羟醛反应生成的常见副产物。在含有0.3 - 1 M咪唑的氯仿、苯或二氯甲烷中，大多数底物在室温下0.3 - 3天内达到平衡。对于由四氢-4H-硫代吡喃-4-酮衍生的羟醛，该过程特别容易进行，所研究的加成物的平衡速率常数变化约为1个数量级；由环己酮衍生的结构相关的羟醛异构化速度约慢3 - 4倍。无环羟醛5-羟基-4-甲基-5-苯基-3-戊酮的异构化需要加热至60℃，但逆羟醛或消除反应最少（<5%）。甲氧基甲基醚衍生物的异构化速度比母体羟醛慢30 - 40倍。α,α'-二取代羟醛和α,α'-双羟醛的异构化表明烯醇化反应的区域选择性较低。通过有效制备直接方法无法获得的羟醛立体异构体，证明了该过程的合成实用性。
