Asymmetric synthesis of tetrazole and dihydroisoquinoline derivatives by isocyanide-based multicomponent reactions

Abstract

Although isocyanide-based multicomponent reactions were proven to be simple, elegant and facile strategies for the synthesis of highly valuable nitrogen-containing heterocycles, their asymmetric versions accessing to optically active nitrogen heterocyclic compounds are rather limited. Here, we illustrate that, relying on the enantioselective addition of simple isocyanides to C=C bonds, several isocyanide-based multicomponent reactions are realized in the presence of a chiral Mg II - N , N ʹ-dioxide catalyst. In the reaction among isocyanide, TMSN 3 , and alkylidene malonate, three- or four-component reactions could be precisely controlled by modulating reaction conditions, supplying two types of enantioenriched tetrazole-derivatives in moderate to high yields. Possible catalytic cycles via a key zwitterionic intermediate, and the vital roles of H 2 O or excess ligand are provided based on control experiments. Moreover, taking advantage of this zwitterionic intermediate as a 1,3-dipole, an enantioselective dearomative [3+2] annulation reaction of nonactivated isoquinolines is achieved, furnishing chiral 1,2-dihydroisoquinolines in good to excellent results.

Novel magnetic propylsulfonic acid-anchored isocyanurate-based periodic mesoporous organosilica (Iron oxide@PMO-ICS-PrSO3H) as a highly efficient and reusable nanoreactor for the sustainable synthesis of imidazopyrimidine derivatives

“…On the other hand, development of simple synthetic procedures for the synthesis of complex and diversityoriented organic molecules from readily available substrates is an important challenge in organic and medicinal chemistry. This can be achieved through multicomponent reactions (MCRs) strategy as a powerful process for the synthesis of molecules useful for pharmaceuticals, biological studies, secret communication and electronic including heterocyclic scaffolds [57][58][59][60][61][62] as well as fabrication of new task-specific materials such as drug delivery systems, nanocomposites, polymers, supramolecular systems and molecular machines [63][64][65][66][67][68] . In MCRs, three or more reactants simultaneously combine together in one reaction vessel to form a final product with high bond forming index such as imidazopyrimidine derivatives [69][70][71][72][73][74][75][76][77] .…”

Sequential and direct multicomponent reaction (MCR)-based dearomatization strategies

“…76 The key strategy involves a domino 1,4-dipolar addition and Diels-Alder reaction of the in situ generated Huisgen 1,4-dipole with two molecules of phenacylideneoxindoles 91 to construct the dispiro compound 92. In the absence of a strong electron-donating group on the pyridine ring, the further Diels-Alder reaction of the spirooxindole with the second molecule of 3-phenacylideneoxindole did not take place (93). Later, the same group extended the work with a wider substrate scope and optimized conditions for a three-component reaction between a pyridine, dimethyl acetylenedicarboxylate, and a 3-phenacylideneoxindole to afford spiro[indoline-3,1-quinolizine] 94 in moderate to good yields (53-93%) and with high diastereoselectivity.…”

“…Relying on the enantioselective addition of simple isocyanides 44 to C=C bonds, a three component reaction was designed for the synthesis of chiral 1,2-dihydroisoquinolines employing a chiral Mg II -N,Nʹ-dioxide catalyst (Scheme 31). 93 Thus, taking advantage of this zwitterionic intermediate as a 1,3-dipole, an enantioselective dearomative [3+2] annulation reaction of nonactivated isoquinolines is achieved, furnishing chiral 1,2-dihydroisoquinolines 151 in moderate to good yields with acceptable enantioselectivity.…”

Synthesis of Dihydroisoquinoline and Dihydropyridine Derivatives via Asymmetric Dearomative Three-Component Reaction

“…1 For instance, hydroisoquinoline skeletons are prevalent in bioactive alkaloids and drug molecules, such as crystamidine (A), jamtine (B), haiderine (C) and emetine (D) (Scheme 1a). [5][6][7][8][9][10][11] Note also that hydropyridines are useful synthetic intermediates for the synthesis of complex nitrogenous natural products and pharmaceutical targets. [12][13][14][15] As exemplified by a practical asymmetric synthesis of the influenza drug (-)oseltamivir (Tamiflu, E).…”