Non-Organometallic Partners as Radical Precursors for the Diversification of Dual Catalytic Cross-Coupling Processes

 描述(申请人提供)：提出的研究目标是通过探索用于交叉偶联的非传统试剂并利用这种试剂的独特属性来促进有机分子的构建。这将通过采用最近开发的涉及双重催化循环的交叉偶联的范式转换方法来实现。两个循环，即光氧化还原催化循环和交叉耦合循环协同工作，将促进单电子转金属反应，允许在温和的条件下进行交叉耦合，并通过立体聚合转化与适当的配体实现高水平的对映体选择性。 特别是，将寻求从廉价的、稳定的、商品化的非金属有机前体中实现这一点的方法。使用这种材料的过程将是健壮的、具有成本效益的和可扩展的，从而导致从学术环境到过程开发设施的轻松过渡。采用在有机三氟硼酸盐交叉偶联研究中被证明有效的双重催化体系，该方案将扩展到非有机金属主体来源材料，即联氨和亚硫酸盐。对这些商品材料的研究将侧重于在光氧化还原条件下影响自由基形成的实用方法，并评估其进入贱金属催化循环的可行性。将探索有机催化剂和廉价的无机材料作为潜在的光催化剂，以增强已开发工艺的可持续概况。基于光流的技术和战略将作为提高可伸缩性和有效性的手段进行审查。将审查不同的亲电偶联伙伴，并将开发立体聚合过程以获得富含对映体的烷基亚结构。这一协议将通过非传统、廉价的偶联伙伴的交叉偶联来实现前所未有的C-C键结构，这将是一种变革性的方法。

 DESCRIPTION (provided by applicant): The goal of the research proposed is to facilitate the construction of organic molecules by exploring unconventional reagents for cross-coupling and exploiting the unique attributes of such reagents. This will be accomplished by employing a recently developed, paradigm-shifting approach to cross-coupling involving a dual catalytic cycle. The two cycles, a photoredox catalytic cycle and a cross-coupling cycle, working in concert, will facilitate a single electron transmetalation protocol, allowing cross-coupling under mild conditions and, with the appropriate ligand, high levels of enantioselectivity via stereoconvergent transformations. In particular, methods to do so from inexpensive, bench-stable, commodity nonmetallic organic precursors will be sought. A process using such materials would be robust, cost-effective, and scalable, leading to a facile transition from the academic setting to a process development facility. Employing the dual catalytic systems that have proven effective in studies on the cross-coupling of organotrifluoroborates, the protocol will be extended to non-organometallic bulk source materials, namely hydrazines and sulfinate salts. Studies on these commodity materials will focus on practical methods of effecting radical formation under photoredox conditions and assessing their viability in being funneled into the base metal catalytic cycle. Organocatalysts and inexpensive inorganic materials will be explored as potential photocatalysts to enhance the sustainable profile of developed processes. Photoflow-based technologies and strategies will be examined as a means of enhancing scalability and effectivity. Diverse electrophilic coupling partners will be examined, and stereoconvergent processes will be developed to access enantioenriched alkyl substructures. This protocol will be transformative in enabling unprecedented C-C bond construction via cross-coupling from nonconventional, inexpensive coupling partners.