Wagner-Carlberg Noah, Rovis Tomislav
Department of Chemistry, Columbia University, New York, New York 10027, United States.
ACS Catal. 2023 Dec 15;13(24):16337-16343. doi: 10.1021/acscatal.3c05075. Epub 2023 Dec 6.
Hydroamination of terminal alkenes represents a powerful and well-established way to introduce nitrogenous functionality to feedstock chemicals. Remote hydroamination reactions are far less known, and represent a way to functionalize unactivated C(sp) centers distal to the site of the alkene. These transformations commonly take place via metal hydride-mediated chain walking, and as such, regioselectivity can be challenging. The remote introduction of amides is of particular interest due to their prevalence in pharmaceuticals. Herein we report a Rh(III)-catalyzed hydroamidation procedure to functionalize the terminal position of internal alkenes, using dioxazolones as amidation reagents and -PrOH as a hydride source. The reaction proceeds with high yield and regioselectivity, and tolerates a variety of functionality. Regioconvergent synthesis of a single linear amide from a mixture of isomeric alkenes is demonstrated. Key to the development of this reaction was determining that inorganic bases poison the catalyst, and identifying a suitable trialkylamine replacement.
末端烯烃的氢胺化反应是一种向原料化学品中引入含氮官能团的强大且成熟的方法。远程氢胺化反应则鲜为人知，它是一种使烯烃位点远端未活化的C(sp)中心官能化的方法。这些转化通常通过金属氢化物介导的链行走发生，因此区域选择性可能具有挑战性。由于酰胺在药物中普遍存在，因此酰胺的远程引入特别受关注。在此，我们报道了一种铑(III)催化的氢酰胺化方法，该方法使用二恶唑酮作为酰胺化试剂，以异丙醇作为氢化物源，使内烯烃的末端位置官能化。该反应以高产率和区域选择性进行，并能耐受多种官能团。证明了从异构烯烃混合物中区域收敛合成单一的线性酰胺。该反应开发的关键在于确定无机碱会使催化剂中毒，并确定合适的三烷基胺替代物。
