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 in situ formation of Pd nanoparticles leads to preferential formation of trans rather than cis substituted products. In this study, we have demonstrated the feasibility of using mono-protected amino acid ligands as metal-protecting groups to prevent aggregation and reduction, allowing the selective synthesis of free cis-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 (γ) opioid receptor ligands.

Pd 催化烯丙基胺官能化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，而内部烯烃可以经历 Heck 和 C-H 活化反应的混合物，得到立体化学产物的混合物。在未受保护的烯丙基胺的情况下，实现 C-H 活化的挑战在于 Pd 纳米颗粒的易位置形成导致优先形成反式而不是顺式取代产物。在这项研究中，我们证明了使用单保护氨基酸配体作为金属保护基团以防止聚集和还原的可行性，从而允许选择性合成游离的顺式芳基烯丙基胺。该方法补充了 Heck 选择性方法，允许对肉桂胺的合成进行完全立体化学控制，肉桂胺是一类重要的胺，可以直接用作治疗剂或作为高级中间体。为了突出该方法的实用性，我们已经证明了 mu （γ） 阿片受体配体的快速可及性。