Nickel(II)‐Catalyzed Diastereo‐ and Enantioselective [3+2] Cycloaddition of α‐Ketoesters with 2‐Nitrovinylindoles and 2‐Nitrovinylpyrroles

Abstract

asymmetric catalysis, nickel, cycloaddition, α-ketoester, pyrrolo[1,2-a]indole, synthetic methods * Summary of main observation and conclusionThe catalytic asymmetric *3+2+ cycloaddition of α-ketoesters with 2-nitrovinylindoles and 2-nitrovinylpyrroles has been established. This strategy allowed the construction of structurally diverse pyrrolo[1,2-a]indoles bearing three contiguous stereocenters in generally high yields and good to excellent stereoselectivities (up to 98% yield, > 98 : 2 dr, 99% ee). The efficient synthesis of tetracyclic psychotropic compound analogue via the derivatization of cycloadduct showed the great synthetic potential of this strategy.

Dynamics in Catalytic Asymmetric Diastereoconvergent (3 + 2) Cycloadditions with Isomerizable Nitrones and α-Keto Ester Enolates

“…Our study interest is in exploring an artificial synthetic workflow where both the catalyst and substrates are dynamically responsive in the TS. In our previous studies − on the inverse-electron-demand (3 + 2) cycloaddition − of nitrones 1 by HOMO-raising activation − of an α-keto ester to generate formal 1,3-dipolarophiles, we reported a prototypical diastereoconvergent reaction of an E / Z isomerizable nitrone (R 1 = Me, EWG = CO 2 t Bu) ,− with an α-keto ester using a Ni­(OAc) 2 /( R,R )-diamine 3 complex. − This reaction selectively provides anti,anti - tert -butyl 5-hydroxyisoxazolidine-5-carboxylate 4 (henceforth 5-hydroxyisoxazolidine; it structurally resembles Bode’s intermediate in the synthesis of β-amino acids) in 90% yield, albeit with 64% ee (Scheme i). The observed stereochemical outcomes can be explained if the E -form nitrone binds to the amine ligand − in our proposed Mode A, in which the ketone carbonyl in the α-keto ester coordinates to Ni­(II) at the pseudoequatorial position.…”

Nickel(II)‐Catalyzed Diastereo‐ and Enantioselective Michael/ Hemiacetalization Cascade Reaction of α‐Ketoesters with 2‐(2‐Nitrovinyl)phenols

“…In 2012, Huang and co‐workers established a copper(II)‐catalyzed enantioselective Michael/Michael/Henry tandem reaction between one equivalent of α‐ketoesters and two equivalents of nitroalkenes for the synthesis of cyclohexanes with seven substituents. Recently, our group demonstrated the nickel(II)/diamine‐catalyzed enantioselective Michael/ N ‐hemiacetalization of α‐ketoesters with 2‐nitrovinylindoles for the construction of enantioenriched pyrrolo[1,2‐a]indoles (Scheme a). In 2013, Wang, Zhou and co‐workers reported an organocatalytic enantioselective Michael/hemiacetalization/retro‐aldol cascade reaction of 2‐(2‐nitrovinyl)phenols with γ‐oxo‐α‐ketoesters, while sterically more congested 2‐(2‐nitrovinyl)phenol was required to prevent the acyl transfer reaction, and generate structurally important chromane compound (Scheme b) .…”

“…Initially, we test the feasibility of this Michael/ hemiacetalization cascade reaction by using 2‐(2‐nitrovinyl)phenol 1 a and α‐ketoester 2 a as the model substrates. Based on our previous report, Ni(OAc) 2 ‐diamine L1 complex was applied in this reaction along with 10 mol% of Et 3 N in 2‐propanol at −20 °C (Table , entry 1), and the intermediate hemiacetal 3 a was directly acetylated in a one‐pot procedure for the subsequent characterization. Pleasingly, the desired highly substituted chiral chromane 4 a was obtained in 73% yield with excellent diastereoselectivity (>20:1 dr) and enantioselectivity (96% ee).…”

“…Based on our previous report, [6] Ni(OAc) 2diamine L1 complex was applied in this reaction along with 10 mol% of Et 3 N in 2-propanol at À 20°C (Table 1, entry 1), and the intermediate hemiacetal 3 a was directly acetylated in a one-pot procedure for the subsequent characterization. Based on our previous report, [6] Ni(OAc) 2diamine L1 complex was applied in this reaction along with 10 mol% of Et 3 N in 2-propanol at À 20°C (Table 1, entry 1), and the intermediate hemiacetal 3 a was directly acetylated in a one-pot procedure for the subsequent characterization.…”

“…spectrum were recorded on a Bruker DPX 400 MHz spectrometer in CDCl 3 or DMSO-d6 . Chemical shifts were reported in ppm with the internal TMS signal at 0.0 ppm as a standard.…”