Landge Vinod G, Mishra Ankita, Thotamune Waruna, Bonds Audrey L, Alahakoon Indunil, Karunarathne Ajith, Young Michael C
Department of Chemistry & Biochemistry, School of Green Chemistry & Engineering, The University of Toledo, Toledo, OH 43606, USA.
Department of Chemistry, Saint Louis University, 3501 Laclede Avenue, St. Louis, MO 63103, USA.
Chem Catal. 2023 Nov 16;3(11). doi: 10.1016/j.checat.2023.100809. Epub 2023 Nov 8.
An outstanding challenge in the Pd-catalyzed functionalization of allylamines is the control of stereochemistry. Terminal alkenes preferentially undergo Heck-type reactions, while internal alkenes may undergo a mixture of Heck and C-H activation reactions that give mixtures of stereochemical products. In the case of unprotected allylamines, the challenge in achieving C-H activation is that facile formation of Pd nanoparticles leads to preferential formation of rather than -substituted products. In this study we have demonstrated the feasibility of using mono-protected amino acid (MPAA) ligands as metal protecting groups to prevent aggregation and reduction, allowing the selective synthesis of free -arylated allylamines. This method complements Heck-selective methods, allowing complete stereochemical control over the synthesis of cinnamylamines, an important class of amine that can serve as therapeutics directly or as advanced intermediates. To highlight the utility of the methodology, we have demonstrated rapid access to mu opioid receptor ligands.
钯催化烯丙胺官能化过程中的一个突出挑战是立体化学的控制。末端烯烃优先发生Heck型反应，而内烯烃可能会发生Heck反应和C-H活化反应的混合，从而产生立体化学产物的混合物。对于未保护的烯丙胺，实现C-H活化的挑战在于钯纳米颗粒的容易形成导致优先形成β-而非α-取代产物。在本研究中，我们证明了使用单保护氨基酸（MPAA）配体作为金属保护基团以防止聚集和还原的可行性，从而能够选择性地合成游离的芳基化烯丙胺。该方法补充了Heck选择性方法，能够对肉桂胺的合成实现完全的立体化学控制，肉桂胺是一类重要的胺，可直接用作治疗药物或作为高级中间体。为了突出该方法的实用性，我们展示了快速获得μ阿片受体配体的方法。
