Department of Chemistry, School of Science, The University of Tokyo.
Proc Jpn Acad Ser B Phys Biol Sci. 2023 Oct 11;99(8):328-333. doi: 10.2183/pjab.99.022. Epub 2023 Sep 6.
Catalytic asymmetric direct-type aldol reactions of ketones with aldehydes are a perennial puzzle for organic chemists. Notwithstanding the emergence of a myriad of chiral catalysts to address the inherent reversibility of the aldol products, a general method to access acyclic α-chiral ketones from prochiral aryl ketones has remained an unmet synthetic challenge. The approach outlined herein is fundamentally different to that used in conventional catalysis, which typically commences with an α-proton abstraction by a Brønsted base. The use of a chiral 2,2'-bipyridine scandium complex enabled the hydroxymethylation of propiophenone to be run under base-free conditions, which avails effectual suppression of hydrolytic deactivation of the Lewis acid catalyst. Intriguingly, the use of water as a reaction medium had an overriding effect on the progress of the reaction. The sagacious selection of sodium dodecyl sulfate and lithium dodecyl sulfate as surfactants allowed a variety of propiophenone derivatives to react in a highly enantioselective manner.
酮与醛的催化不对称直接型羟醛反应是有机化学家长期以来的难题。尽管出现了许多手性催化剂来解决羟醛产物的固有可逆性，但从潜手性芳基酮中获得非环 α-手性酮的一般方法仍然是一个未满足的合成挑战。本文所概述的方法与传统催化中使用的方法有根本的不同，传统催化通常从布朗斯台德碱的α-质子抽提开始。使用手性 2,2'-联吡啶钪络合物，可以在无碱条件下进行丙酰苯的羟甲基化，有效地抑制了路易斯酸催化剂的水解失活。有趣的是，水作为反应介质的使用对反应的进展有至关重要的影响。明智地选择十二烷基硫酸钠和十二烷基磺酸钠作为表面活性剂，可以使各种丙酰苯衍生物以高度对映选择性的方式反应。
