A one-pot, multi-component reaction cascade for the rapid synthesis of diversely functionalized heteroaryl methyl substrates

作者：Jeffries Daniel E; Lindsley Craig W

来源：Tetrahedron Letters, 2017, 58(1): 112-116.

DOI：10.1016/j.tetlet.2016.11.120

• Suzuki-Miyaura coupling
• Sonogashira coupling
• Multi-component
• Heterocyclic chemistry

A novel one-pot, "green" protocol to rapidly access pharmaceutically relevant heteroaryl methyl substrates is described. This process allows for a tandem S(N)2/Suzuki-Miyaura reaction or Sonogashira reaction across a breadth of chemical diversity with yields ranging between 31 and 87% for the tandem Suzuki-Miyaura process and 50-66% for the tandem Sonogashira process. This procedure tolerates S, N, and O heteroatom linkers and is amenable for both rapid and robust lead development screening. In addition, T-type and N-type calcium channel blocker (15) was synthesized in 43% yield using this methodology which stands as an improvement in both yield and reaction time of the previously reported synthesis. The one-pot protocol also allows for the inclusion of greater chemical diversity within the scaffold of 15.

• 出版日期2017-1-4