Ring-Opening Cyclization of Spirocyclopropanes Using Sulfoxonium Ylides

Abstract

Ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes using dimethylsulfoxonium methylide proceeded regioselectively to produce 2,3,4,6,7,8-hexahydro-5H-1-benzopyran-5-ones in good to high yields. The reactions of cycloheptane-and cyclopentane-1,3-dione-2-spirocyclopropanes could construct [7.6]-and [5.6]-fused ring systems. This reaction was also carried out using sulfoxonium ethylide, butylide, and benzylide, resulting in the formation of the corresponding 2,3-trans-disubstituted products in good to high yields, and it was shown that the dimethyl group can act as a dummy substituent. It was found that the 2-and 3-phenyhexahydrobenzopyran-5-ones can be readily converted into 5-hydroxyflavan and 5-hydroxyisoflavan, respectively.

Synthesis of 1-Azaazulenes Using Ring-Opening Cyclization of Spirocyclopropane with Amine

“…The combined organic layers were washed with water (5 mL) and brine (5 mL), and dried over anhydrous MgSO4. Filtration was concentrated in vacuo, and the residue was purified by column chromatography (silica gel, 40% EtOAc in hexane) to provide 12 (20 mg, 87%) as a white solid: mp 221.0-222.0 °C; IR (KBr, cm −1 ) 3212, 2925, 2812, 1599, 1462, 1429, 1224, 929, 829, 755, 688; 1 H NMR (400 MHz, CDCl3) δ 8.91 (br s, 1H), 7.47 (d, J = 7.3 Hz, 2H), 7.35 (t, J = 7.8 Hz, 2H), 7.22 (t, J = 7.3 Hz, 1H), 6.91 (d, J = 3.2 Hz, 1H), 3.02 (t, J = 6.4 Hz, 2H), 2.74 (t, J = 6.4 Hz, 2H), 2.00 (quint, J = 6.4 Hz, 2H), 1.92 (quint, J = 6.4 Hz, 2H); 13…”

“…The combined organic layers were washed with saturated aqueous NaHCO3 (2 × 20 mL), water (20 mL) and brine (20 mL), and dried over anhydrous MgSO4. Filtration was concentrated in vacuo, and the residue was purified by column chromatography (silica gel, 70% EtOAc in hexane) to provide 3a (84 mg, 81%) as a red solid: mp 106.5-107.5 °C; IR (KBr, cm −1 ) 3062, 2925, 1603, 1509, 1461, 1441, 1361, 1325, 1228, 1200, 1069, 1046, 909, 807, 760, 687; 1 H NMR (500 MHz, CDCl3) δ 8.60 (d, J = 9.7 Hz, 1H), 8.33 (dd, J = 8.0, 1.7 Hz, 2H), 7.90 (s, 1H), 7.73 (d, J = 10.9 Hz, 1H), 7.64 (t, J = 9.7 Hz, 1H), 7.56 (t, J = 10.3 Hz, 1H), 7.51 (td, J = 6.9, 1.7 Hz, 2H), 7.46 (tt, J = 6.9, 1.7 Hz, 1H); 13 H2NNH2•H2O (38 mg, 0.75 mmol) was added to a solution of 3a (28 mg, 0.12 mmol) in MeOH (2.3 mL).…”

“…The combined organic layers were washed with water (5 mL) and brine (5 mL), and dried over anhydrous MgSO4. Filtration was concentrated in vacuo, and the residue was purified by column chromatography (silica gel, 60% EtOAc in hexane) to provide 3b (6.9 mg, 29% from 3a) as a red powder: mp Hz, 1H), 8.33 (dd, J = 8.0, 1.1 Hz, 2H), 7.79 (t, J = 9.7 Hz, 1H), 7.76 (s, 1H), 7.74 (t, J = 9.7 Hz, 1H), 7.61 (t, J = 9.7 Hz, 1H), 7.52 (td, J = 7.4, 1.1 Hz, 2H), 7.46 (tt, J = 7.4, 1.1 Hz, 1H); 13…”

“…12a In the synthesis of unprotected indole, the benzyl group (R 2 = Bn, Scheme 1, B) worked well as both an effective amino substituent for the ring-opening cyclization of 5 and a stable and easily deprotectable substituent on the nitrogen atom. 12b As such, the reaction of 2-phenylspiro [2.6]nonane-4,9-dione (9a) 13 with benzylamine (6a) was initially examined under our reported conditions (Scheme 2). 12a When the mixture of spirocyclopropane 9a and 1.5 equivalents (eq) of 6a in tetrahydrofuran (THF) was stirred at room temperature for several hours, the reaction did not occur.…”

“…H NMR spectra were recorded on JEOL JNM-ECX400P (400 MHz) and JEOL JNM-ECA500II (500 MHz) spectrometers.Chemical shifts are reported relative to internal standard (tetramethylsilane at H 0.00, CDCl3 at H 7.26, or CD3OD at H 3.31). Data are presented as follows: chemical shift ( , ppm), multiplicity (s = singlet, d = doublet, t = triplet, quint = quintet, m = multiplet, br = broad), coupling constant and integration 13. C NMR spectra were recorded on JEOL JNM-ECX400P (100 MHz) spectrometer.…”