Discovery Chemistry , Merck & Co., Inc. , West Point , Pennsylvania 19486 , United States.
Department of Process Research and Development , Merck & Co., Inc. , Rahway , New Jersey 07065 , United States.
Org Lett. 2020 Feb 21;22(4):1648-1654. doi: 10.1021/acs.orglett.0c00242. Epub 2020 Jan 28.
Bicyclo[1.1.1]pentane motifs have gained increasing popularity in medicinal chemistry as bioisosteres because of their ability to impact key physicochemical properties. However, reports of direct C(sp)-C(sp) cross-coupling of these fragments to afford biaryl isosteres have been scarce. Herein we describe the development of continuous flow-enabled synthesis of bench-stable bicyclo[1.1.1]pentane trifluoroborate salts. Furthermore, we demonstrate the use of metallaphotoredox conditions to enable cross-coupling of these building blocks with complex aryl halide substrates.
双环[1.1.1]戊烷结构因其能够影响关键物理化学性质而在药物化学中作为生物等排体日益受到关注。然而，有关这些片段直接 C(sp)-C(sp)交叉偶联以提供芳基等排体的报道却很少。在此，我们描述了连续流技术在合成稳定的双环[1.1.1]戊烷三氟硼酸盐中的应用。此外，我们还证明了利用金属光氧化还原条件可以实现这些砌块与复杂芳基卤化物底物的交叉偶联。
