Synthesis of Polysubstituted Isoquinolines and Related Fused Pyridines from Alkenyl Boronic Esters via a Copper-Catalyzed Azidation/Aza-Wittig Condensation Sequence

Vankudoth Jayaram (1) , Tailor Sridhar (1) , Gangavaram V. M. Sharma (1) , Fabienne Berrée (2) , Bertrand Carboni (2)

1 IICT - CSIR Indian Institute of Chemical Technology
2 ISCR - Institut des Sciences Chimiques de Rennes

An efficient and straightforward synthesis of isoquinolines is reported from internal alkenyl boronic esters, easily prepared from the corresponding 1,2-bis(boronates), via a sequential copper-catalyzed azidation/aza-Wittig condensation. This synthetic method has been used to synthesize quinisocaine, a topical anesthetic used for the treatment of pain and pruritus, and further extended to thieno[2,3-c]pyridines by using 2-thiophenecarboxaldehyde as coupling partner in the first step.

Domains: Chemical Sciences; Organic chemistry

Vankudoth Jayaram, Tailor Sridhar, Gangavaram V. M. Sharma, Fabienne Berrée, Bertrand Carboni. Synthesis of Polysubstituted Isoquinolines and Related Fused Pyridines from Alkenyl Boronic Esters via a Copper-Catalyzed Azidation/Aza-Wittig Condensation Sequence. Journal of Organic Chemistry, 2018, 83 (2), pp.843-853. ⟨10.1021/acs.joc.7b02831⟩. ⟨hal-01709528⟩