Efficient Alkylation of Tetrahydroisoquinolines and Isochroman

Efficient Alkylation of Tetrahydroisoquinolines and Isochroman

Author: ChemistryViews.org

Zhihua Peng and colleagues, China University of Petroleum (East China), Qingdao, have developed an efficient C(sp3)–H bond alkylation of tetrahydroisoquinolines (THIQs) or isochroman with alkylzinc reagents (product pictured; X = NR’ or O; R = alkyl). THIQs and isochroman derivatives show a variety of biological activities, which makes these compounds interesting for pharmaceutical chemistry.

The team used phenyliodine bis(trifluoroacetate) (PIFA) as an oxidant to convert THIQs (X = NR’) to iminium cations in dichloroethane (DCE) at 80 °C. These were then reacted with alkylzinc reagents coordinated with MgCl2 and LiCl at 25 °C to give the desired products. The less reactive isochroman (X = O) can be converted under the same conditions.

The reaction proceeds without a heavy-metal catalyst under mild conditions. It tolerates sensitive functional groups such as cyano groups or boronic acid pinacol esters and can be performed on a gram scale.


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