Hypervalent Iodine-mediated Intramolecular Functionalization Of Benzylic Methylene In N-aryltetrahydroisoquinoline Derivatives

Tetrahydroisoquinolines and quinazolinones are important mother nucleus structure,many of their derivatives possess important biological properties.tetrahydroisoquinoline alkaloids manifest many biological activities such as anti-tumor,disease-resistant original microbes,antifungal,anti-inflammatory,which draws more and more attention by researchers.At the same time,Quinazoline ketone compounds show a variety of biological activities and clinical applications such as the activity of antibacterial,antitumor,anti-allergic,anti-inflammatory and analgesic and activity of enzyme inhibitors.Up till now,literature survey shows a handful of strategies already developed for the construction of the tetrahydroisoquinolines,but some of the methods suffer the drawbacks such as the involvement of transition metals?Pd and Pt?or illumination.Taking those issues into considerations,we believe that developing more economic and convenient methods is still in demand.Herein,we disclosed a cross-dehydrogenative coupling?CDC?reactions of tetrahydroisoquinoline derivatives mediated by hypervalent iodine reagent.It mainly includes three types: 1)PIDA-mediated intramolecular C-N bond-forming reactions.2)PIDA-mediated intramolecular C-O bond-forming reactions.3)PIFA-mediated intramolecular C-C bond-forming reactions.We chose tetrahydroisoquinoline-N-benzamides 133 as substrates,PIDA as oxidant,NaN₃ as additive,and cyclic compounds 134 have been synthesized in MeOH under 60 oC.Under the same conditions,two cyclic products 143 were constructed by the tetrahydroisoquinoline-N-benzoicacids.In the presence of PIFA/NaN₃,two cyclic compounds 145 have been offered by tetrahydroisoquinoline-N-acetophenone.All the compounds have been characterized by ¹H NMR,13 C NMR,and HRMS.Advantages of this method include the readily availability of the starting materials,great functional-group tolerance and the mild reaction conditions.