Brønsted Acid or Lewis Acid Catalyzed [3+3] Cycloaddition of Azomethine Imines with N-Benzyl Azomethine Ylide: A Facile Access to Bicyclic N-Heterocycles

Abstract

Contents General Information S1 Preparation of N-Benzyl Substituted Compound 1 S1 General Procedure for the Synthesis of Azomethine Imines 3 S2 General Procedure for the [3 + 3] Annulation Reaction of N-Benzyl Azomethine Ylide 1 and Azomethine Imines 3 S2 Procedure for four-component one-pot Reaction of the [3 + 3] Annulation Reaction of N-benzyl-1-(trimethylsilyl)methanamine 5 and Azomethine Imines 3a. S2 Characterization Data for [3 + 3] Annulation Products 4 S3-S11 1 H and 13 C NMR Spectra of [3 + 3] Annulation Products 4 S12-S30 S1 General Information: All reactions were carried out under argon atmosphere in oven dried glassware with magnetic stirring. Unless otherwise stated, all reagents were purchased from commercial suppliers and used without further purification. Organic solutions were concentrated under reduced pressure on a rotary evaporator or oil pump. Reactions were monitored by thin-layer chromatography (TLC) on silica gel precoated glass plates (0.25 mm thickness, Qingdao Haiyang). Chromatograms were visualized by fluorescence quenching with UV light at 254 nm. Flash column chromatography was performed using Qingdao Haiyang flash silica gel (200-300 mesh). Infrared spectra were recorded using a Perkin-Elmer Spectrum One FT-IR instrument. 1 H and 13 C NMR spectra were recorded in CDCl 3 on Bruker ARX-400 as indicated. Chemical shifts (δ ppm) are relative to tetramethylsilane (TMS) with the resonance of the undeuterated solvent or TMS as internal standard. 1 H NMR data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constants (Hz) and integration. Data for 13 C NMR spectra are presented in terms of chemical shift. Accurate mass measurements were performed using an Agilent instrument with the TOF-MS technique. Preparation of N-Benzyl Substituted Compound 1. To a solution of chloromethyltrimethylsilane (13.4g, 0.11mol) in CH 3 CN (100mL) was added benzylamine (23.45g, 0.22mol) and the reaction mixture was heated at reflux for 16h. The reaction mixture was cooled to room temperature ,and the precipitate of benzylamine hydrochloride was removed by filtration. The filtrate was concentrated under vacuum and the residue was diluted with water (50mL).The reaction mixture was extrated with PE (50mL*2).The organic extracts were combined and washed with water (50mL*2) and brine (50mL) and dried over Na 2 SO 4. The filtrate was concentrated under vacumm to give 18.8g crude product. 88.9% Yield. The above-mentioned crude product (18.8g，0.098mol) was added to a mixture of 37% formaldehyde (9.49g 0.118mol)and methanol (3.78g, 0.118mol) at 0°C over a period of 60 min. The reaction mixture was further stirred at 0°C for 1.5h and at 10-15°C for 3h. To the reaction mixture was then added anhydrous K 2 CO 3 (16.3g, 0.118mol) ,and this mixture stirred overnight. The oily layer was separated, added K 2 CO 3 (1.63g, 0.012mol) and stirred for 15min and again decanted. The remaining residual material from the K 2 CO 3 was recovered by washin...

Mechanistic Study of Copper-Catalyzed C-H Hydroxylation/C-S Coupling by ESI-HR MS and DFT Calculations

“…It has been reported that the S atom easily coordinates with the Cu ( Scheme 5 ) [ 28 , 29 , 30 ]. The coordination of DMSO with intermediate A resulted in the formation of intermediate B ([ B − I] + , m/z = 332.0387, please see Supplementary Materials Figure S4 ) [ 31 , 32 ].…”

[3+3] Cycloaddition of Azomethine Imine: Synthesis of Bi‐ or Tricyclic N‐Heterocycle

“…Synthesis of 1,2,4-hexahydrotriazine derivative (36) was developed by Chao-Ze Zhu et alvia [Rh(NBD) 2 ]BF 4 catalyzed [3 + 3] cycloaddition reaction of (R)-vinyl aziridines (34) with Nimino isoquinolium ylide (35) (Scheme 12). [23] The product was formed through consecutive (б + п) rhodium species subse- [3 + 3]-cycloaddition reaction of α-acidic isocyanide with azomethine imine in presence of Cu catalyst.…”

“…An effective synthesis of fused six member triazine derivatives (62) was proposed by Shuoning-Li et al using the Brønsted acid or Lewis acid as catalyst via [3 + 3] cycloaddition of azomethine imine (2) with azomethine ylide (61) (Scheme 22). [34] The reaction was monitored with varying catalysts [TFA,TfOH,AcOH,HCl,HSbF 6 ,LiF,TBAF,TMSOTf,Zn (OAc) 2 , AgOAc, Zn(OTf) 2 , AgOTf, ZnCl 2 and TiCl 4 ], solvents (DCM, CHCl 3 , DCE, MeCN, DMF and THF) and reaction temperature (0, 10, 25 and 40°C). The highest yield was achieved when TFA was used as catalyst in DCM solvent at 10°C.…”

Copper-Catalyzed Azomethine Imine–Alkyne Cycloadditions (CuAIAC)

“…dropyrazolo[1,2-a][1,2,4]triazine derivatives 98 in good yields, however, no conversion was observed with the cyclohexyl-substituted dipole 47 (Scheme 30). 73 Finally, an interesting and unexpected formal [3+3] cycloaddition also took place upon treatment of dipoles 47 with N-vinylpyrroles 99 in the presence of silver trifluoroacetate in chlorobenzene at 120 °C. In the absence of a Lewis acid catalyst normal [3+2] cycloaddition took place (Scheme 30).…”