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

Abstract

We reported the first asymmetric three-component nucleophilic addition/dearomative [4+2] cycloaddition/isomerization cascade of the transient dipoles generated from N-heteroarenes and allenoates with methyleneindolinones in the presence of chiral N,N′-dioxide/metal complexes, which enabled a rapid access to versatile chiral polycyclic N-heterocycles with good to excellent enantioselectivities under mild reaction conditions in spite of the strong background reaction, including 1,2-dihydroisoquinoline, 1,2-dihydropyridine derivatives and others. Meanwhile, a series of control experiments were conducted to elucidate the reaction mechanism and the roles of additives.

Enantioselective Synthesis of Azetidines through [3 + 1]-Cycloaddition of Donor–Acceptor Aziridines with Isocyanides

“…Nevertheless, the nature of isocyanides makes it inevitable for the competitive reactions between [3 + 1]-cycloaddition and [3 + 1 + 1]-cycloaddition, as well as acyclic byproducts of other nucleophiles . Encouraged by the excellent performance of chiral N , N′ -dioxides/metal complexes in Lewis acid catalyzed asymmetric reactions, herein, we demonstrate the first enantioselective [3 + 1]-cycloaddition of racemic donor–acceptor 2,2′-diester aziridines with isocyanides using a chiral N , N′ -dioxides/Mg II complex as catalyst (Scheme c). Various enantioenriched azetidines bearing an exo -cyclic CN bond were obtained with moderate to excellent yields (up to 99%) and ee values (up to 94%).…”

Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis

“…In the initial investigation, the addition product C1 from A1 and B1 catalyzed by Sc­(OTf) 3 (10 mol %) was obtained with a 19% yield at room temperature under 10 W LEDs (400 nm) irradiation in MeCN (Table , entry 1). The addition of chiral N , N ′-dioxide ligand − L 3 -RaPr 2 (10 mol %) significantly increased the yield of C1 to 82% with a 73:27 enantiomeric ratio (er) (Table , entry 2). Other Lewis acids were also tested, such as Mg­(OTf) 2 and Y­(OTf) 3 , giving poor yields and enantioselectivities (Table , entries 3–4; see the Supporting Information for details).…”

Asymmetric Catalytic Aerobic Oxidative Radical Addition/Hydroxylation/1,4-Aryl Migration Reaction of Olefins

“…The initial radical addition step is considered to be the enantio-determining step, and 1,4-aryl migration is the diastereo-determining step. According to our previous study, − the coordination of N , N ′-dioxide L 3 -PiPr 3 with Mg­(ClO 4 ) 2 affords the chiral Lewis acid catalyst L* -Mg II , which would bind the ketoamide A1 to form an octahedral intermediate Int-1 . After hydrogen atom transfer, the formed Int-2 undergoes radical addition with alkene B1 at the less hindered CC bond.…”

“…We began our studies by examining the behavior of different oxidants in the reaction between indanonecarboxamide A1 and alkene B1 (Table ). Previously, the treatment of the two reactants with Ag 2 O in the presence of 10 mol % of Ni­(ClO 4 ) 2 and Feng N , N ′-dioxide − gave the spiro-iminolactone D1 as the major product, which was likely to be generated via a radical–polar crossover cascade (Table , entries 1 and 2) . Interestingly, when the CuI/air condition was introduced, a new and interesting product C1 with up to 19:1 d.r.…”