Catalytic Enantioselective 1,3-Dipolar Cycloaddition of C,N-Cyclic Azomethine Imines with α,β-Unsaturated Aldehydes

Abstract

General Information. Infrared (IR) spectra were recorded on a Shimadzu IRPrestige-21 spectrometer. 1 H NMR spectra were measured on a JEOL JNM-FX400 (400 MHz) spectrometer. Data were reported as follows: chemical shifts in ppm from tetramethylsilane as an internal standard in CDCl 3 , integration, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad), and coupling constants (Hz). 13 C NMR spectra were measured on a JEOL JNM-FX400 (100 MHz) spectrometer with complete proton decoupling. Chemical shifts were reported in ppm from the residual solvent as an internal standard. High performance liquid chromatography (HPLC) was performed on Shimadzu 10A instruments at 254 nm using 4.6 mm x 25 cm Daicel Chiral Coulmns. High-resolution mass spectra (HRMS) were performed on Brucker microTOF. Optical rotations were measured on a JASCO DIP-1000 digital polarimeter. For thin layer chromatography (TLC) analysis throughout this work, Merck precoated TLC plates (silica gel 60 GF 254 , 0.25 mm) were used. The products were purified by flash column chromatography silica gel 60 (Merck, 230-400 mesh) or preparative thin layer chromatography silica gel (Merck, PLC 60 F 254 . 0.5 mm).In experiments requiring dry solvent, CH 2 Cl 2 , toluene and THF were purchased from Kanto Chemical Co. Inc. as "Dehydrated" and further purified by passing through neutral alumina under nitrogen atmosphere. Enals were distilled prior to use. Other commercially available reagents were used as received.The relative and absolute configuration of 2 and the relative configuration of 6 were unambiguously assigned by X-ray crystallographic analysis of 2h, 6c', 6f' and 6i'. The stereochemistries of other cycloadducts were tentatively assigned by analogy. Br CHO 2-(2-Bromoethyl)-3-methylbenzaldehydePrepared with 1-methoxy-5-methylisochroman (1.05 g, 5.86 mmol), Bu 4 NBr (1.89 g, 5.86 mmol) and TMSBr (1.55 mL, 11.7 mmol). The crude material was purified by column chromatography on silica gel (eluting with hexane/CH 2 Cl 2 = 3:1) to give the title compound as a colorless oil (9.39 g, 4.13 mmol, 71% yield).

Recent Advances of Catalytic Asymmetric 1,3-Dipolar Cycloadditions

“…Use of C,N-cyclic azomethine imines 111 in asymmetric catalysis was developed by Maruoka's group for the first time (Scheme 53). 84 In the initial report, they disclosed the utility of C,N-cyclic azomethine imines in enantioselective normal electron demand 1,3-DC with enals catalyzed by chiral Ti(IV)/(S)-BINOL complex (see Scheme 21). The reaction with β-substituted or α,β-disubstituted enals gave chiral isoquinolines 112 with high exo-and enantioselectivities.…”

Chemodivergent 1,3-Dipolar Cycloadditions of C,N-Cyclic Azomethine Imines with γ-Sulfonamido-α,β-Unsaturated Ketones to Synthesize Tricyclic Dinitrogen-Fused Heterocycles

“…4 Hz,1H),3.40 (ddd,J = 12.7,6.8,5.7 Hz,1H),3.31 (ddd,J = 11.5,5.7,2.6 Hz,2H), 3.09−3.00 (m, 1H), 3.00−2.89 (m, 1H), 2.74 (d, J = 15.6 Hz, 1H), 2.37 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ 197.6, 170.5, 166.4 (d, J 1 = 256.9 Hz), 143. 5,136.8,134.3,133.7 (d,J 4 = 2.8 Hz),132.8,132.3,132.1 (d,J 3 = 9.6 Hz),130.8,129.8,128.7,128.7,127.7,126.9,126.8,126.1,116.0 (d, J 2 = 21.9 Hz), 67. 7, 66.1, 55.6, 50.0, 46.8, 29.4, 21.5; 19 F NMR (376 MHz, CDCl 3 ): δ −103.07; IR (neat): 2362,2335,1661,1599,1558,1506,1447,1410,1332,1291,1241,1221,1208,1157, 1067 cm −1 ; HRMS (ESI-TOF) m/z: [M] + calcd for C 33 H 30 FN 3 O 4 S, 583.1941;found, 583.1926.…”

“…Following the general procedure I; flash chromatography (EtOAc/CH 2 Cl 2 /hexane = 2:1:7, 44 mg, yield 73%, 6:1 dr), white solid; mp 114−116 °C; 1 H NMR (400 MHz, CDCl 3 ): δ 7.86 (dd, J = 8. 5,1.6 Hz,2H),2H),7.60 (dd,J = 10.8,4.1 Hz,2H),4H),1H),7.19 (d,J = 7.4 Hz,2H),7.10 (d,J = 3.5 Hz,2H),6.85 (dd,J = 7.0,3.0 Hz,1H),6.52 (d,J = 7.8 Hz,1H),6.05 (t,J = 5.7 Hz,1H),4.80 (dd,J = 12.0,5.9 Hz,1H),2H),3H),3.04 (dd,J = 10.3,4.9 Hz,1H),1H),2.74 (d,J = 16.3 Hz,1H), 2.37 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ 198. 2, 170.5, 143.4, 140.7, 136.8, 135.6, 134.3, 132.8, 132.3, 130.8, 130.7, 129.7, 129.7, 129.1, 128.7, 128.7, 127.7, 126.9, 126.8, 126.1, 67.8, 66.2, 55.7, 50.0, 46.7, 29.3, 21.5;IR (neat): 2994IR (neat): , 2970IR (neat): , 2900IR (neat): , 1696IR (neat): , 1653IR (neat): , 1616IR (neat): , 1559IR (neat): , 1521IR (neat): , 1506IR (neat): , 14...…”

“…N-( (1,2,3,5,6,isoquinolin-2-yl)methyl)-4-methylbenzenesulfonamide (4aa). Following the general procedure I; flash chromatography (EtOAc/ CH 2 Cl 2 /hexane = 2:1:8, 50 mg, yield 89%, 7:1 dr), white solid; mp 112−114 °C; 1 H NMR (400 MHz, CDCl 3 ): δ 7.89 (dd, J = 8.4, 1.1 Hz, 2H), 7.83−7.76 (m, 2H), 7.65−7.56 (m, 3H), 7.48−7.39 (m, 3H), 7.39−7.32 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.12−7.05 (m, 2H), 6.87−6.79 (m, 1H), 6.57 (d, J = 7.7 Hz, 1H), 6.16 (t, J = 5.8 Hz, 1H), 4.76 (d, J = 10.0 Hz, 1H), 4.70 (ddd, J = 8.3, 6.4, 4.9 Hz, 1H), 4.60 (dd, J = 9.9, 8.5 Hz, 1H), 3.43 (ddd, J = 13.0, 6.6, 4.9 Hz, 1H), 3.35−3.22 (m, 2H), 3.01−2.87 (m, 2H), 2.74 (d, J = 4.8 Hz, 1H), 2.37 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ): δ 199.0, 170.…”

“…The Journal of Organic Chemistry 4, 170.7, 145.3, 143.3, 136.8, 134.8, 134.3, 132.7, 132.6, 130.8, 129.7, 129.6, 129.3, 128.8, 128.6, 127.7, 127.5, 127.0, 126.8, 126.1, 67.2, 66.0, 55.5, 50.0, 47.7, 29.4, 21.8, 21.5 δ 196.9, 170.7, 164.5, 143.4, 136.8, 134.3, 132.7, 132.6, 131.6, 130.8, 130.3, 129.7, 128.8, 128.5, 127.7, 127.5, 127.0, 126.9, 126.1, 114.1, 67.1, 66.0, 55.6, 55.2, 50.0, 47.6, 29.4, 21.5;IR (neat): 2363IR (neat): , 2356IR (neat): , 2339IR (neat): , 1652IR (neat): , 1595IR (neat): , 1558IR (neat): , 1456IR (neat): , 1409IR (neat): , 1394IR (neat): , 1330IR (neat): , 1255IR (neat): , 1225IR (neat): , 1158IR (neat): , 1075IR (neat): , 1066 N-( 2,3,5,6,10bhexahydropyrazolo[5,isoquinolin-2-yl)methyl) -4-methylbenzenesulfonamide (4da). Following the general procedure I; flash chromatography (EtOAc/CH 2 Cl 2 /hexane = 2:1:10, 51 mg, yield 80%, 7:1 dr), white solid; mp 132−134 °C; 1 H NMR (400 MHz, CDCl 3 ): δ 7.98 (d,J = 8.3 Hz,2H),7.82 (d,J = 7.3 Hz,2H),7.67 (d,J = 8.3 Hz,2H),7.64 (d,J = 7.8 Hz,4H),7.48 (t,J = 7.5 Hz,2H),2H),7.37 (dd,J = 13.9,6.1 Hz,2H),7.18 (d,J = 8.2 Hz,2H),…”