Mild-condition synthesis of allenes from alkynes and aldehydes mediated by tetrahydroisoquinoline (THIQ).

A practical 1,2,3,4-tetrahydroisoquinoline (THIQ)-mediated synthesis of 1,3-disubstituted allenes from terminal alkynes and aldehydes under mild conditions in the presence of CuBr first and then ZnI2 was reported. This telescoped allene synthesis reaction includes three consecutive steps and two reactions: first, a room-temperature CuBr-catalyzed synthesis of propargylamines, exo-yne-THIQs, from terminal alkynes, aldehydes, and THIQ, then filtration of the CuBr catalyst, and finally the ZnI2-mediated allene synthesis from the generated exo-yne-THIQs under mild conditions (either at room temperature or heating at 50 or 75 °C). A wide range of aliphatic or aromatic aldehydes and terminal alkynes are tolerated, affording the allene products in up to 92% yield. Especially, temperature-sensitive aldehydes can be used in the reaction system. Preliminary exploration of the asymmetric allene synthesis has also been conducted, and a moderate enantioselectivity has been achieved. Finally, the relative reactivities of several secondary amines were compared with THIQ, showing that THIQ is the best of these amines in the synthesis of allenes under mild reaction conditions.

CuI-catalyzed C1-alkynylation of tetrahydroisoquinolines (THIQs) by A3 reaction with tunable iminium ions.

A CuI-catalyzed A(3) (amines, aldehydes and alkynes) reaction of tetrahydroisoquinolines (THIQs), aldehydes, and alkynes to give C1-alkynylated THIQ products (endo-yne-THIQs) was developed. This redox neutral C1-alkynylation of THIQs, which was conducted under mild conditions, has a broad scope for the used aldehydes and alkynes. It was proposed that the A(3) reaction first generates in situ exo-iminium ions, which then isomerize to endo-iminium ions and react with copper acetylides to give the endo alkynylated THIQs (endo-yne-THIQs).