Novel Domino Cross-aldol/Tishchenko Reaction Promoted by NaH

我们发现，当醛(2eq)加到酮和NaH(1.1eq)的混合物中时，在0℃的四氢呋喃中，发生多米诺Aldol-Tishchenko反应，得到带有C(2)-取代基的1，3-二醇作为单一的非对映异构体。值得注意的是，当酮和NaH在THF中的混合物在该温度下搅拌时，没有观察到氢气的析出，而醛的滴加引发了氢气的析出，有趣的是，氢气的析出与醛的加入是同步的。Aldol-Tishchenko产品被证明具有无与伦比的抗Aldol和抗Tishchenko的立体化学结果。此外，当醛(2eq)被两种不同的醛A(1eq)和B(1eq)取代时，对空间的要求较低，或者如果A和B的要求性质相似，则在Aldol工艺中加入活性较高的醛，剩余的醛用作Tishchenko工艺中的氢化物供体。氯三甲基硅烷也不影响反应b…更多的是你的方法。所有这些发现可能表明，酮、两种醛和NaH的四个组分通过保持组装的微妙平衡而通过它们之间的弱相互作用组装在一起：没有不同的烯醇中间体不能被干预。受这种化学的强烈启发，我们关注了其他传统碱，如叔丁醇钾，并发现了单酮生成热力学控制的烯醇的隐藏方面，这在导致环己烷-1，3-二酮的Michael-Claisen反应中起着重要作用。我们还发现，在DMSO中，用氢氧化铵碱处理时，炔类化合物会生成相应的乙炔阴离子。这一化学激发了人们对炔烃作为双向扩链工具的兴趣，并开发了几种以1-烯丙基丙烯酰基硬脂三甲基硅醚为原料，在Lewis酸的作用下，利用丙烯基烯丙基杂化阳离子进行的合成有机反应。较少

We have found that when an aldehyde (2 eq) was added to a mixture of a ketone and NaH (1.1 eq) in THF at 0℃, domino aldol-Tishchenko reaction took place to afford a 1,3-diol with C(2)-substituent as a single diastereoisomer. It should be noted that no evolution of hydrogen gas was observed when the mixture of the ketone and NaH in THF was stirred at that temperature, and the dropwise addition of the aldehyde triggered the evolution of hydrogen gas which interestingly synchronized to the addition of aldehyde. The aldol-Tishchenko product was proven to have unexceptionally anti-aldol and anti-Tishchenko stereochemical outcome. Furthermore, when the aldehyde (2 eq) was replaced with two different aldehydes A (1 eq) and B (1 eq), Sterically less demanding or, if demanding nature of A and B was similar, more reactive one was incorporated into the aldol process, remaining aldehyde being used as a hydride donor in the Tishchenko process. Also chlorotrimethylsilane didn't affect the reaction b … More y any means. All these findings might indicate that the four component involving the ketone, two of aldehydes, and NaH assemble together through weak interaction among them by keeping delicate balance of the assembly : no distinct enolate intermediate could not intervened.Being strongly inspired by such chemistry, we paid attention to other traditional bases such as potassium tert-butoxide and found hidden aspects of thermodynamically-controlled enolate generated from simple ketone which plays an important role in domino Michael-Claisen reaction leading to cyclohexane-1,3-dione. We have also found that alkynes can lead to the corresponding acetylide anions on treatment with ammonium hydroxide base in DMSO. This chemistry gave strong incentive to be concerned with alkynes as two directional chain extension tool, and developed several synthetic organic reactions using propargyl-allyl hybrid cation which can be prepared from 1-allylpropargyl ssitrimethylsilyl ether by the action of Lewis acid. Less