Catalytic C−C Activation/Functionalization of Ketones and Amides

摘要：我们正在系统地开发催化碳-碳(C-−-C) 用于开发新的、通用的和综合有用的方法的键活化。我们的目标是 拟议的资助期，将重点放在酮和C-−-C的活化和功能化 胺化物，因为它们很容易获得，并且在原料化学品中广泛存在。穿过 利用过渡金属催化剂的力量，有时还辅以有机活化剂， 一套涉及酮和酰胺的C−C活化的新的、选择性的和有效的方法将 被开发出来。具体地说，我们将：(I)探索允许快速访问的新C−C激活模式 对于复杂的富含SP3的环系统，(Ii)实现了一种新的和广泛适用的交叉耦合 通过无张力的酮的脱酰化反应，以及(Iii)允许选择性地激活α-C−C键 无张力的酰胺。提出的研究有望提供一种原子经济的方法。 用于从现成的底物制备新型复杂的富含SP3的分子支架，其 应该有助于在“平地”之外获得更大的化学空间。预计它还将简化 通过键断开的新策略进行合成，并支持骨架编辑 氧化还原中性条件下的复杂分子，大写C-−-C 酮和酰胺的活化/官能化。

Abstract: We are engaged in the systematic efforts to exploit catalytic carbon–carbon (C−C) bond activation for developing new, general and synthetically useful methods. Our objective, in the proposed funding period, is to focus on C−C activation and functionalization of ketones and amides, as they are easily accessible and widely found in feedstock chemicals. Through harnessing the power of transition-metal catalysts, sometimes assisted by an organic activator, a suite of new, selective, and efficient methods involving C−C activation of ketones and amides will be developed. Specifically, we will: (i) explore new C−C activation modes that allow rapid access to complex sp3-rich ring systems, (ii) enable a novel and broadly applicable cross-coupling reaction via deacylation of unstrained ketones, and (iii) allow selective activation of α-C−C bonds of unstrained amides. The research proposed is expected to offer an atom-economical approach for preparing novel complex sp3-rich molecular scaffolds from readily available substrates, which should help to access greater chemical space beyond the “flatland”. It is also expected to simplify synthesis through new strategies for bond disconnections and to enable skeletal editing of complex molecules under redox-neutral conditions, capitalizing on C−C activation/functionalization of ketones and amides.