Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany.
Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo 001-0021, Japan.
J Am Chem Soc. 2021 Sep 15;143(36):14475-14481. doi: 10.1021/jacs.1c07447. Epub 2021 Aug 26.
Protected aldols (i.e., true aldols derived from aldehydes) with either - or - stereochemistry are versatile intermediates in many oligopropionate syntheses. Traditional stereoselective approaches to such aldols typically require several nonstrategic operations. Here we report two highly enantioselective and diastereoselective catalytic Mukaiyama aldol reactions of the TBS- or TES- enolsilanes of propionaldehyde with aromatic aldehydes. Our reactions directly deliver valuable silyl protected propionaldehyde aldols in a catalyst controlled manner, either as or isomer. We have identified a privileged IDPi catalyst motif that is tailored for controlling these aldolizations with exceptional selectivities. We demonstrate how a single atom modification in the inner core of the IDPi catalyst, replacing a CF-group with a CFH-group, leads to a dramatic switch in enantiofacial differentiation of the aldehyde. The origin of this remarkable effect was attributed to tightening of the catalytic cavity via unconventional C-H hydrogen bonding of the CFH group.
受保护的羟醛缩合产物（即，由醛衍生而来的真正羟醛缩合产物）具有或立体化学结构，是许多寡丙酸盐合成中的多功能中间体。传统的对这类羟醛缩合产物的立体选择性方法通常需要进行几个非策略性操作。在这里，我们报告了两种高度对映选择性和非对映选择性的催化 Mukaiyama 羟醛反应，使用丙醛的 TBS-或 TES-烯基硅烷与芳族醛反应。我们的反应以催化剂控制的方式直接提供有价值的硅烷基保护的丙醛羟醛缩合产物，无论是作为或异构体。我们已经确定了一个特权的 IDPi 催化剂基序，该基序经过精心设计，可用于以优异的选择性控制这些羟醛缩合反应。我们展示了如何通过在 IDPi 催化剂的内核心中进行单个原子修饰，用 CFH 基团代替 CF 基团，导致醛的对映面区分发生显著变化。这种显著效果的起源归因于 CFH 基团通过非常规的 C-H 氢键使催化腔收紧。
