Yu Kai, Lu Ping, Jackson Jeffrey J, Nguyen Thuy-Ai D, Alvarado Joseph, Stivala Craig E, Ma Yun, Mack Kyle A, Hayton Trevor W, Collum David B, Zakarian Armen
Department of Chemistry and Biochemistry, University of California , Santa Barbara, California 93106, United States.
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University , Ithaca, New York 14853, United States.
J Am Chem Soc. 2017 Jan 11;139(1):527-533. doi: 10.1021/jacs.6b11673. Epub 2016 Dec 20.
Lithium enolates derived from carboxylic acids are ubiquitous intermediates in organic synthesis. Asymmetric transformations with these intermediates, a central goal of organic synthesis, are typically carried out with covalently attached chiral auxiliaries. An alternative approach is to utilize chiral reagents that form discrete, well-defined aggregates with lithium enolates, providing a chiral environment conducive of asymmetric bond formation. These reagents effectively act as noncovalent, or traceless, chiral auxiliaries. Lithium amides are an obvious choice for such reagents as they are known to form mixed aggregates with lithium enolates. We demonstrate here that mixed aggregates can effect highly enantioselective transformations of lithium enolates in several classes of reactions, most notably in transformations forming tetrasubstituted and quaternary carbon centers. Easy recovery of the chiral reagent by aqueous extraction is another practical advantage of this one-step protocol. Crystallographic, spectroscopic, and computational studies of the central reactive aggregate, which provide insight into the origins of selectivity, are also reported.
源自羧酸的烯醇锂盐是有机合成中普遍存在的中间体。使用这些中间体进行不对称转化是有机合成的核心目标，通常通过共价连接的手性助剂来实现。另一种方法是利用与烯醇锂盐形成离散、明确聚集体的手性试剂，从而提供有利于不对称键形成的手性环境。这些试剂有效地充当非共价或无痕手性助剂。锂酰胺是此类试剂的一个明显选择，因为已知它们会与烯醇锂盐形成混合聚集体。我们在此证明，混合聚集体可在几类反应中实现烯醇锂盐的高度对映选择性转化，最显著的是在形成四取代和季碳中心的转化中。通过水相萃取轻松回收手性试剂是此一步法方案的另一个实际优势。还报道了对中心反应性聚集体的晶体学、光谱学和计算研究，这些研究有助于深入了解选择性的来源。
