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.
A highly enantioselective dearomative cascade reaction between 2-isocyanoethylindoles and 3-alkenyl-oxindoles was realized using a chiral N,N'-dioxide-Mg(II) complex catalyst. This reaction provides a straightforward access to polycyclic 3-spirooxindoles bearing cyclopenta[b]indole units with four contiguous stereocenters in excellent yields and moderate to good stereoselectivities via a Michael/Friedel-Crafts/Mannich cascade.
A highly efficient asymmetric inverse-electron-demand oxa-Diels-Alder reaction of o-quinone methides with fulvenes has been realized using a chiral N,N'-dioxide/Sc(iii) complex as the catalyst. The corresponding optically active chromane derivatives were obtained in high yields with excellent dr and ee values (up to 99% yield, >19 : 1 dr and 94% ee).
Catalytic asymmetric
synthesis of hydrothiazole derivatives was
developed via a well-organized formal [2 + 1 + 2] cycloaddition reaction
triggered by asymmetric addition of isocyanide to alkylidene malonate.
Various chiral hydrothiazole derivatives were readily provided in
good yield with high enantioselectivity (up to 98% yield, 98.5:1.5
er) utilizing a chiral Mg(OTf)2/N,N′-dioxide complex as the catalyst under mild conditions.
Based on the experimental studies and the structure of the catalyst,
a possible catalytic cycle was proposed to elucidate the reaction
process and activation mode.
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