Department of Chemistry & Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, United States.
J Am Chem Soc. 2020 Sep 2;142(35):14831-14837. doi: 10.1021/jacs.0c07043. Epub 2020 Aug 24.
We report an iodoarene-catalyzed enantioselective synthesis of β,β-difluoroalkyl bromide building blocks. The transformation involves an oxidative rearrangement of α-bromostyrenes, utilizing HF-pyridine as the fluoride source and -CPBA as the stoichiometric oxidant. A catalyst decomposition pathway was identified, which, in tandem with catalyst structure-activity relationship studies, facilitated the development of an improved catalyst providing higher enantioselectivity with lower catalyst loadings. The versatility of the difluoroalkyl bromide products was demonstrated via highly enantiospecific substitution reactions with suitably reactive nucleophiles. The origins of enantioselectivity were investigated using computed interaction energies of simplified catalyst and substrate structures, providing evidence for both CH-π and π-π transition state interactions as critical features.
我们报告了一种碘芳烃催化的 β,β-二氟烷基溴化物砌块的对映选择性合成。该转化涉及α-溴代苯乙烯的氧化重排，利用 HF-吡啶作为氟源和-CPBA 作为化学计量氧化剂。确定了催化剂分解途径，结合催化剂结构-活性关系研究，促进了改进催化剂的开发，该催化剂在较低的催化剂负载下提供更高的对映选择性。通过与合适的反应性亲核试剂进行高度对映选择性取代反应，证明了二氟烷基溴化物产物的多功能性。使用简化的催化剂和底物结构的计算相互作用能研究了对映选择性的起源，为 CH-π 和 π-π 过渡态相互作用作为关键特征提供了证据。
