SYNTHESIS OF 1,4-DIKETONES BY OXIDATIVE COUPLING OF KETONE ENOLATES WITH CUCL2
SYNTHESIS OF 1,4-DIKETONES BY OXIDATIVE COUPLING OF KETONE ENOLATES WITH CUCL2
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DOI：
10.1021/ja00447a035
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发表时间：
1977-01-01
影响因子：
15
通讯作者：
SAEGUSA, T
中科院分区：
文献类型：
--
作者：
ITO, Y;KONOIKE, T;SAEGUSA, T
研究了烯醇酸锂的全范围氧化偶联反应，为1,4 -二酮的制备提供了一种通用且高效的方法。以酮和二异丙酰胺锂为原料，在THF -78℃下制备酮烯醇酯，在DMF中与CuCh进行氧化偶联反应。DMF共溶剂的使用对铜促进烯醇化锂的氧化偶联至关重要。甲基酮（RCOCH3）氧化二聚成1,4 -二酮（RCOCH2CH2COR），产率优异至中等；但是，增加偶联位点的烷基取代导致1,4 -二酮的产率显著降低。两种不同的甲基酮（CH3COR和CH3COR‘）的交叉偶联，其中一种酮烯醇酯比另一种酮烯醇酯多三倍，导致形成特定的不对称1,4 -二酮（RCOCHaCHaCOR’），收率和选择性令人满意。采用丙酮与(Z)-5-辛烯-2- 1和丙酮与5-己烯-2- 1氧化交联的新方法合成了m-茉莉酮（22）和烯丙基再王座（23）。还研究了二烯醇二酮的分子内偶联。1,1 ‘-二乙酰二茂铁的二烯酸酮氧化环化得到’，'-二氧四亚甲基二茂铁（24），产率为55%，而1,2 -二聚乙烯二烯酸酮脱氢得到- 1,2 -二聚乙烯（27），产率为75%。最后，研究了一些甲基酮与乙酸酯（£）- 2,2 -二甲基-4-己烯-3-酮（29）和（£）-巴东酸乙酯（32）的氧化偶联反应。在THF和HMPA的混合溶剂中，用二异丙酰胺锂处理甲基酮和醋酸酯的乙烯基树脂，在78℃下原位生成烯醇化锂。值得注意的是，烯醇化物的氧化偶联产生了甲基酮和醋酸酯，偶联二聚体和-偶联二聚体，-偶联二聚体只产生了微量。这一发现与甲基酮和醋酸酯的烯醇化物只在a碳上发生亲核反应（烷基化和原生水解）的事实形成鲜明对比。由于1,4 -二酮是合成环戊烯酮和呋喃环体系的一些天然产物和相关化合物的多功能中间体，因此开发了多种制备1,4 -二酮的合成方法。1,4 -二酮的一个具有代表性和吸引力的途径是共轭加成酰基阴离子等价物，如氮稳定碳离子，3锂二-
A full scope of oxidative coupling of lithium enolates providing a general and efficient preparation of 1, 4-diketones was examined. The oxidative coupling of lithium enolates was performed by treating ketone enolates, which were prepared from ketoneand lithium diisopropylamide in THF at-78 C, with CuCh in DMF. The use of DMF cosolvent was very crucial in the copper promoted oxidative coupling of lithium enolates. Methyl ketones (RCOCH3) were oxidatively dimerizedto 1, 4-diketones (RCOCH2CH2COR) in excellentto moderate yields; but, increasing alkyl substitution at the coupling site resulted in a remarkable reduction in the yield of 1, 4-diketone. Cross coupling of two different methyl ketones (CH3COR and CH3COR'), in which a threefold excess of one ketone enolate over another is used, led to the formation of a specific unsymme-trical 1, 4-diketone (RCOCHaCHaCOR') in a satisfactory yield and selectivity. m-Jasmone (22) and allyl rethrone (23) were synthesized by a new route via the oxidative cross coupling of acetone with (Z)-5-octen-2-one and of acetone with 5-hexen-2-one, respectively. Intramolecular coupling of diketone dienolates was also examined. Diketone dienolate of l, l'-diacetylferro-cene was oxidatively cyclized to give «,'-dioxotetramethyleneferrocene (24) in 55% yield, while diketone dienolate of 1, 2-dipivaroylethane underwent dehydrogenation to give (£)-1, 2-dipivaroylethylene (27) in 75% yield. Finally, the oxidative coupling of some vinylogs of methyl ketones and acetates such as (£)-2, 2-dimethyl-4-hexen-3-one (29) and (£)-ethyl crotonate (32) was investigated. Lithium enolates of vinylogs of methyl ketones and acetates were generated in situ at—78 C by treating vinylogs of methyl ketones and acetates with lithium diisopropylamide in a mixed solvent of THF and HMPA. It is noteworthy that the oxidative coupling of enolates of vinylogs of methyl ketones and acetates produced,-coupling dimers and,-coupling dimers prominently, a,«-Coupling dimer was produced only in a trace amount. Thisfinding is in remarkable contrast with the factthat the enolates of vinylogs of methyl ketones and acetates undergo the nucleophilic reaction (alkylation and protolysis) at the a carbon exclusively.A variety of synthetic methods for the preparation of 1, 4-diketones have been developed, since 1, 4-diketones are versatile intermediates for syntheses of some natural products and re-lated compounds consisting of cyclopentenone1 and furan2 ring systems. One of the representative and attractive routes to 1, 4-diketones involves the conjugate addition of acyl anion equivalents, such as nitro-stabilized carbanion, 3 lithium di-