Base-Promoted Tandem Synthesis of 3,4-Dihydroisoquinolones

Abstract

Using benzaldehydes, NaN(SiMe3)2, and N-acylpyrroles, an operationally simple tandem method to produce a wide array of 3,4-dihydroisoquinolones is presented (37 examples, yields up to 98%). A unique feature of this method stems from the sequential aminobenzylation of aldehydes and transamidation of the corresponding N-(trimethylsilyl)imines in one pot. In this process, three new bonds are generated (one C–C and two C–N bonds).

Masters of Mediation: MN(SiMe3)2 in Functionalization of C(sp3)−H Latent Nucleophiles

“…With this powerful tool in hand, Liang, Walsh and co‐workers further contributed in this MN(SiMe 3 ) 2 mediated transformation by synthesizing 3,4‐dihydroisoquinolones 65 by synergistic amide bond cleavage and further net [4+2] annulation occurring by sequential aminobenzylation, transamidation and cyclisation of benzylic C−H bond in one‐pot tandem method (Scheme 30). [84] In such as way, they could build three new bonds (one C−C and two C−N bonds). Since the reaction undergoing an aminobenzylation process in situ , NaN(SiMe 3 ) 2 exhibited better performance than its counterparts KN(SiMe 3 ) 2 and LiN(SiMe 3 ) 2 which is a common trend in aminobenzylation reactions [24,26,28] .…”

Base-Promoted Synthesis of Isoquinolines through a Tandem Reaction of 2-Methyl-arylaldehydes and Nitriles

“…Some recent examples of our approach include the one-pot aminobenzylation of aldehydes with toluene derivatives (Scheme a) and a convergent synthesis of indoles from benzonitriles and fluorotoluenes (Scheme b) . We also introduced a series of tandem processes for the synthesis of more functionalized indoles, 3,4-dihydroisoquinolones, 2-azaaryl tetrahydroquinolines, and 2,5-disubstituted pyrroles involving the functionalization of benzylic or propargylic C–H bonds under basic conditions (Scheme c). Other impressive examples of the functionalization of toluene derivatives were developed by Kobayashi and co-workers, who introduced an asymmetric addition of toluene-derived benzyl groups to imines .…”