Fe(III)-Based Tandem Catalysis for Amidomethylative Multiple Substitution Reactions of α-Substituted Styrene Derivatives

Abstract

Developing tandem multiple C–H substitution reactions of simple alkenes provides rapid access to structurally complex unsaturated building blocks. Amidomethylative reactions that reserve CC double bonds have been composed sequentially for tandem catalytic substitutions around the CC bonds of alkenes. As a proof-of-concept demonstration, tandem catalytic amidomethylative processes, which effectively form multiple C–C bonds, have been developed to directly and selectively transform α-substituted styrenes into unsaturated N-heterocycles. Using Fe­(OTf)3 as the sole catalyst, the operationally simple protocols employ bench-stable bisamidomethane as the sole reagent to produce hexahydropyrimidines and 1,2,3,6-tetrahydropyridine derivatives. Moreover, the practical catalytic processes constituted facile two-step pathways, from simple α-substituted styrenes, to access unsaturated 1,3-diamine and bispidine derivatives.

Iron-Based Tandem Catalysis: From Petroleum toward Pharmaceutical Laboratories for Organic Undergraduate Students─Product Identification by TLC and 1H NMR

“…Herein, we describe an air-stable tandem catalysis laboratory activity designed for organic II chemistry from the Cui research group. 24 Inside the homogeneous catalytic reactions of this laboratory activity are known mechanisms: iminium generation, imino-ene reaction, and aza-Prins reaction, which overlap with previously covered reactions. The experiment produces core structures in pharmaceutical molecules that combine α-methylstyrene with bis(tosylamido)methane using the Lewis acid iron triflate as the homogeneous catalyst.…”

“…Catalytic reactions can involve homogeneous or heterogeneous catalysts. Herein, we describe an air-stable tandem catalysis laboratory activity designed for organic II chemistry from the Cui research group . Inside the homogeneous catalytic reactions of this laboratory activity are known mechanisms: iminium generation, imino-ene reaction, and aza-Prins reaction, which overlap with previously covered reactions.…”

Catalytic Amidomethylative [2+2+2] Cycloaddition of Formaldimine and Styrenes toward N-Heterocycles

“…Our recent work has adopted bis(tosylamido)methane (BTM), a bench-stable releaser for the labile tosylformaldimine, as an effective amidomethylating reagent for ruthenium(II)-catalyzed C-H amidomethylation reactions 23 and iron(III)-catalyzed tandem cyclization reactions with alkenes (Scheme 3). 24 While the freshly prepared tosylformaldimine was shown to be ineffective, BTM was rationalized to have a properly controlled rate of the release of the formaldimine, which may match the rates of the C-H amidomethylation process to enable the reaction. On the other hand, recently we have developed a practical synthesis of 1,2-ditosyl-1,2-diazetidine (DTD, Scheme 3, I).…”

Mechanism of the Fe(iii)-catalyzed synthesis of hexahydropyrimidine with α-phenylstyrene: a DFT study

“…Recently, inspired by the above [2 + 2 + 2] tandem cycloaddition reaction [30][31][32][33][34] catalytic pathway, Cui et al reported a tandem amidomethylative reaction catalyzed by Fe(III). 35 When multiple amidomethylation steps occurred through the elimination of the recovered C]C bonds, HHPs were directly synthesized from a-substituted styrene derivatives. As shown in Scheme 1, the yield of HHP (P) from the reaction of bis(tosylamido)methane (A) and a-phenylstyrene (B) is 69% (DCE ¼ 1,2dichloroethane, 70 C, 2 h).…”