Hypervalent Iodine Reagent Mediated Oxidative Heterocyclization of

Jul 21, 2017 - Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, Minnesota 55812, United States. § Marshall School, D...
1 downloads 0 Views 1MB Size
Download PDF
Article pubs.acs.org/joc

Cite This: J. Org. Chem. 2017, 82, 11742-11751

Hypervalent Iodine Reagent Mediated Oxidative Heterocyclization of Aldoximes with Heterocyclic Alkenes Akira Yoshimura,*,†,∥ Khiem C. Nguyen,‡ Gregory T. Rohde,§ Pavel S. Postnikov,∥ Mekhman S. Yusubov,∥ and Viktor V. Zhdankin*,‡ †

Department of Chemistry, Southern Methodist University, Dallas, Texas 75275, United States Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, Minnesota 55812, United States § Marshall School, Duluth, Minnesota 55811, United States ∥ The Tomsk Polytechnic University, 634050 Tomsk, Russia ‡

S Supporting Information *

ABSTRACT: An efficient cycloaddition of heterocyclic alkenes with nitrile oxides generated in situ from the corresponding aldoximes using organohypervalent iodine(III) reagent, [hydroxy(tosyloxy)iodo]benzene (Koser’s reagent), has been developed. The oxidative cyclization of various aldoximes with 1-propene-1,3-sultone affords the respective isoxazoline-ring-fused heterobicyclic products in moderate to good yields. Furthermore, the reaction of aldoxime with a cyclic phospholene-oxide under similar conditions produces the corresponding heterobicyclic phospholene oxides in moderate yields. The structures of bicyclic phospholene oxide and two sultones were established by single-crystal X-ray crystallography.

■

INTRODUCTION Oxidative heterocycloaddition reactions involving unsaturated substrates provide an efficient approach to the formation of heterocyclic products including various bioactive compounds and natural products.1 Hypervalent iodine compounds have found broad synthetic application as environmentally friendly oxidants useful for various oxidative transformations.2 In particular, the use of iodine(III) species allows facile formation of numerous heterocyclic systems via oxidative formation of C−C, C−N, C−O, C−S, N−N, N−O, or N−S bonds.3 Oxidative cyclization of oximes using hypervalent iodine reagents can provide an efficient synthetic approach to a variety of five-membered heterocyclic systems.4 Especially useful are the hypervalent iodine-promoted cyclizations of aldoximes with unsaturated substrates leading to isoxazoles, isoxazolines, oxadiazoles, and dioxazoles.5 The synthesis of isoxazolines or isoxazoles from aldoximes and alkenes or alkynes has been explored by several research groups using various organohypervalent iodine(III) reagents,6 such as [hydroxy(tosyloxy)iodo]benzene,6a (dichloroiodo)benzene, 6b iodosylbenzene, 6c [bis(trifluoroacetoxy)iodo]benzene,6d−f and (diacetoxyiodo)benzene.6g−i The catalytic version of iodine(III)-mediated oxidative cyclization of © 2017 American Chemical Society

aldoximes with alkenes or alkynes has also been reported by our group7 and Yan’s group.8 Despite recent progress in the hypervalent iodine-mediated oxidative heterocyclization reactions, the synthetic approach to heterobicyclic compounds starting from aldoximes and heterocyclic alkenes remains underdeveloped. Our research group has recently reported the synthesis of isoxazoline-fused heterocycles (pyrrolo-isoxazoline) by the oxidative cyclization of aldoximes with maleimides using catalytic hydroxy(aryl)iodonium species generated in situ from 2-iodobenzoic acid and m-CPBA in the presence of trifluoromethanesulfonic acid.7b However, to the best of our knowledge, hypervalent iodinemediated oxidative cyclization of aldoximes with sulfur- and phosphorus-derived heterocyclic alkenes, such as commercially available 1-propene-1,3-sultone and 3-methyl-1-phenyl-2-phospholene-1-oxide, has not been reported. Herein, we report an efficient hypervalent iodine-mediated oxidative cyclization of aldoximes with 1-propene-1,3-sultone producing isoxazoline-fused bicyclic heterocycles belonging to a Special Issue: Hypervalent Iodine Reagents Received: June 13, 2017 Published: July 21, 2017 11742

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry

time resulted in the lower yields of product 4a (entries 16−20). The unreacted sultone 2 can be isolated from the reaction mixture by column chromatography. Using the optimized conditions with Koser’s reagent 3b, we have investigated the reaction of various substituted aldoximes 1 with sultone 2 leading to the respective isoxazoline-fused heterobicyclic products 4 (Table 2). The structures of products 4p and 4q were established by X-ray crystallography (see Figures S1 and S2 in the Supporting Information). In general, substituted benzaldoximes 1 with either electron-donating or electron-withdrawing groups under optimized reaction conditions afforded target products 4a−o in moderate to good yields with excellent regioselectivity. The reactions of sterically hindered aldoximes, such as 2,6-dimethyl- 1d or 2,6-dicholorobenzaldoxime 1k, gave the corresponding products 4d, 4k only in low yields. Moderate yields of products 4 were observed in the reactions of 4-(methylthio)benzaldehyde oxime 1p, 2hydroxybenzaldehyde oxime 1q, cinnamaldehyde oxime 1r, and hydrocinnamaldehyde oxime 1s, all of which have a relatively low stability toward oxidation. In particular, the yield of product 4p was especially low (30%), probably due to competitive oxidation on sulfur;10 however, we were not able to detect the corresponding sulfoxides in the reaction mixture. The reaction of sultone 2 with heterocyclic aldoximes 1t, 1u or naphthyl aldoximes 1v, 1w proceeded smoothly producing products 4t− w in moderate yields. It is noteworthy that the reactions of a benzene dialdoxime, terephthaldehyde dioxime 1x, using 2.5 equiv Koser’s reagent 3b and 10 equiv of sultone 2, afforded the corresponding product 4x in a moderate yield. Compared to the previously reported cyclization reaction of α-chlorobenzaldoximes with sultone 2, our procedure gives comparable or higher yields of the corresponding heterobicyclic products.9 This oxidative cyclization is also applicable on a larger scale using millimolar quantities of reagents. In particular, the reaction of 1a (1.25 mmol) under optimized conditions afforded product 4a in 81% yield. At the next step, we attempted to prepare the isoxazolinefused bicyclic heterocycles by the reaction of aldoximes with cyclic phospholene oxide using hypervalent iodine(III) reagent under similar conditions. The products of this reaction are potentially important as fungicidal compounds.11 We have tested the heterocyclization of benzaldoxime 1a with 3-methyl1-phenyl-2-phospholene-1-oxide 5 using hypervalent iodine(III) reagents 3 in different solvents at room temperature (Table 3). The reaction of 1a and 5 under the same conditions as the reaction with sultone 2 gave the desired product 6a in 45% yield (entry 1). Screening different solvents has demonstrated that AcOEt is the best solvent for this reaction (entries 1−5). Among several iodine(III) reagents 3 tested, Koser’s reagent 3b was found to be the best oxidant for this reaction (entries 5−9). Increasing amounts of Koser’s reagent 3b or heating the reaction mixture did not improve product yields (entries 10−12). The structure of product 6a was established by a single-crystal X-ray crystallography (see Figure S3 in the Supporting Information). In particular, the solid-state structure of 6a confirmed the trans configuration of the phosphine oxygen atom and methyl group in products 6. According to our results, oxidative cycloaddition reaction of benzaldoximes 1 with phospholene oxide 5 proceeds regioselectively, analogous to the reaction of substrates 1 with sultone 2.9 Using the optimized conditions, we have investigated the conversion of several substituted aldoximes 1 with 3-methyl-1-

potentially important structural class of biologically active compounds.9 We have also investigated oxidative heterocyclization of aldoximes with a cyclic phospholene oxide under similar conditions affording the corresponding isoxazoline-fused phospholene oxides in moderate yields.

■

RESULTS AND DISCUSSION First, we have tested the oxidative cyclization of benzaldoxime 1a (1 equiv) with 1-propene-1,3-sultone 2 (5 equiv) in several solvents using IBA-OTf 3a (1.2 equiv) which is an efficient reagent for preparing pyrrolo-isoxazolines from aldoxime and maleimide.7b We have found that Et2O is the best solvent for the formation of the desired product 4a using reagent 3a (Table 1, entries 1−4). Screening the other hypervalent iodine(III) reagents 3b−3e has demonstrated that Koser’s reagent 3b is the most efficient oxidant in this cyclization (entries 2, 5−8). For the reactions of Koser’s reagent 3b, THF was found to be the best solvent (entries 5, 9−15), and the best yields were achieved using 5 equiv of sultone 2. A reduced amount of 1-propene-1,3-sultone 2 or shortening of reaction Table 1. Optimization of Oxidative Cyclization of Benzaldoxime 1a with Sultone 2 Using Oodine(III) Reagents 3.a

entry

solvent

ArI(III) 3

time (h)

4a (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16d 17e 18 19 20

CH2Cl2 Et2O AcOEt MeOH Et2O Et2O Et2O Et2O THF AcOEt MeCN CHCl3 CH2Cl2 MeOH heptane THF THF THF THF THF

3a 3a 3a 3a 3b 3c 3d 3e 3b 3b 3b 3b 3b 3b 3b 3b 3b 3b 3b 3b

24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 24 3 6 10

0 23 (17) 16 14 52 29 22 39 87 (87) 56 32c 26 8 10 6 51 76 53 67 78

a Reaction conditions: benzaldoxime 1a (1 equiv), sultone 2 (2−5 equiv), and iodine(III) reagent 3 (1.2 equiv) in a solvent was stirred for 24 h at room temperature. bYields of product 4a determined from 1 H NMR spectra of reaction mixtures are shown (numbers in parentheses show yields of 4a after column chromatography). c Formation of oxadiazole as a side-product due to oxidative cycloaddition of MeCN with benzaldoxime was detected. d2 equiv of sultone 2 was used. e3 equiv of sultone 2 was used.

11743

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry Table 2. Oxidative Cyclization of Aldoximes 1 with Sultone 2 Using Koser’s Reagent 3ba,b

a

Reaction conditions: aldoxime 1 (0.25 mmol; 1 equiv) and sultone 2 (1.25 mmol; 5.0 equiv) with Koser’s reagent 3b (0.30 mmol; 1.2 equiv) in THF were stirred for 24 h at room temperature. bYields of products after column chromatography. cLarger scale experiment: benzaldoxime 1a (1.25 mmol; 1 equiv), sultone 2 (6.25 mmol; 5.0 equiv), and Koser’s reagent 3b (1.50 mmol; 1.2 equiv) in THF were stirred for 24 h at room temperature. d Sultone 2 (10 equiv) and Koser’s reagent (2.5 equiv) were used.

compound 6a could be also obtained in 37% yield from a millimolar scale reaction. Based on the previously reported mechanistic studies of aldoxime cyclization reactions using hypervalent iodine(III) reagents, we propose that aldoximes 1 are initially oxidized by Koser’s reagent 3b to generate the highly reactive intermediates, nitrile oxides 7 (Scheme 1).6a,d,i Subsequently, the intermolecular 1,3-dipolar cycloaddition reactions between nitrile oxides 7 and heterocyclic alkenes 2 or 5 occur to give the corresponding heterobicyclic products 4 or 6. Previously, we have demonstrated that nitrile oxides 7 can be generated from aldoximes under catalytic conditions using

phenyl-2-phospholene-1-oxide 5 using Koser’s reagent 3b to the respective isoxazoline-fused bicyclic phosphine products 6 (Table 4). In general, benzaldoximes 1 with either electrondonating or electron-withdrawing substituents under optimized conditions afforded the respective cyclic phosphine compounds 6a−e in moderate yields. However, the reaction of a sterically hindered aldoxime, 2,6-dimethyl substituted benzaldoxime 1d, produced the corresponding compound 6f only in a low yield. In the reaction of cinnamaldehyde oxime 1r or hydrocinnamaldehyde oxime 1s, the respective products 6g and 6h were also obtained in low to moderate yields. Finally, the 11744

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry

iodoarenes as catalysts and oxone as a terminal oxidant.7a We have tried the analogous conditions for the preparation of heterobicyclic products 4 and 6; however, the yields of these products under catalytic conditions were unacceptably low (under 20% yield). In summary, we have developed an efficient oxidative cycloaddition procedure for the preparation of isoxazolinefused heterobicyclic compounds from aldoximes and heterocyclic alkenes using Koser’s reagent. Under optimized conditions, this reaction afforded the corresponding heterobicyclic products generally in moderate to good yields. This oxidative cyclization most likely proceeds via initially generated nitrile oxides followed by intermolecular 1,3-dipolar cyclization to give the final products.

Table 3. Optimization of Oxidative Cyclization of Benzaldoximes 1a with 3-Methyl-1-phenyl-2-phospholene-1oxide 5 Using Iodine(III) Reagents 3.a

entry

solvent

ArI(III) 3

6a (%)b

1 2 3 4 5 6 7 8 9 10d 11e 12f

THF Et2O CH2Cl2 MeCN AcOEt AcOEt AcOEt AcOEt AcOEt AcOEt AcOEt AcOEt

3b 3b 3b 3b 3b 3a 3c 3d 3e 3b 3b 3b

45 49 30 18c 49 (45) 16 22 25 17 32 28 40

■

EXPERIMENTAL SECTION

General Experimental Remarks. All reactions were performed under dry argon atmosphere with flame-dried glassware. Ethyl acetate (AcOEt) and tetrahydrofuran (THF) were distilled immediately prior to use. All commercial reagents were ACS reagent grade and used without further purification. Melting points were determined in an open capillary tube with a Mel-temp II melting point apparatus. Infrared spectra were recorded as a KBr pellet on a PerkinElmer 1600 series FT-IR spectrophotometer. NMR spectra were recorded on a Varian Inova 500 and Varian 300 MHz NMR spectrometer at 500 MHz (1H NMR), 75 MHz (13C NMR), and 121 MHz (31P NMR). Chemical shifts are reported in parts per million (ppm). 1H and 13C chemical shifts are referenced relative to the tetramethylsilane. The known hypervalent iodine compounds, IBA-OTf 3a7d and IBA-OTs 3e,12 were prepared according to the reported procedures. General Procedure for Oxidative Cyclization of Aldoximes and Sultone Using Koser’s Reagent. Method A: Aldoxime 1 (0.125 mmol) and sultone 2 (75 mg, 0.625 mmol) were added to a solution of Koser’s reagent 3b (59 mg, 0.150 mmol) in THF (2 mL). The reaction was stirred at room temperature for 24 h. After completion of the reaction, 5% aqueous Na2S2O3 (5 mL) and saturated NaHCO3 (5 mL) were added, and the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by column chromatography (hexane−ethyl acetate = 3:1 to 2:1) afforded analytically pure products 4. Method B: Aldoxime 1 (0.250 mmol) and sultone 2 (150 mg, 1.25 mmol) were added to a solution of Koser’s reagent 3b (118 mg, 0.300 mmol) in THF (4 mL). The reaction was stirred at room temperature for 24 h. After completion of the reaction, 5% aqueous Na2S2O3 (10 mL) and saturated NaHCO3 (10 mL) were added, and the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by column chromatography (hexane−ethyl acetate = 3:1 to 2:1) afforded analytically pure products 4. 3-Phenyl-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4a).9

a Reaction conditions: benzaldoxime 1a (1 equiv), 3-methyl-1-phenyl2-phospholene-1-oxide 5 (5 equiv), and iodine(III) reagent 3 (1.2 equiv) in a solvent was stirred for 24 h at room temperature. bYields of product 6a determined from 1H NMR spectra of reaction mixtures are shown (numbers in parentheses show yields of 6a after column chromatography). cFormation of oxadiazole as a side-product due to oxidative cycloaddition of MeCN with benzaldoxime was detected. d 1.5 equiv of 3b was used. e2 equiv of 3b was used. fAt 45 °C.

Table 4. Oxidative Cyclization of Aldoximes 1 with 3Methyl-1-phenyl-2-phospholene-1-oxide 5 Using Koser’s Reagent 3ba,b

a Reaction conditions: aldoxime 1 (0.250 mmol; 1 equiv), 3-methyl-1phenyl-2-phospholene-1-oxide 5 (1.25 mmol; 5.0 equiv), and Koser’s reagent 3b (0.30 mmol; 1.2 equiv) were stirred in AcOEt at room temperature for 24 h. bYields of products after column chromatography. cLarger scale experiment: benzaldoxime 1a (1.250 mmol; 1 equiv), 3-methyl-1-phenyl-2-phospholene-1-oxide 5 (6.25 mmol; 5.0 equiv), and Koser’s reagent 3b (1.50 mmol; 1.2 equiv) were stirred in AcOEt at room temperature for 24 h. dMixture of diastereomers.

Reaction of benzaldoxime 1a (15 mg, 0.125 mmol) according to the method A procedure afforded 26 mg (87%) of product 4a, isolated as a white solid: mp 148.1−149.7 °C (lit.,9 mp 145−147 °C); IR (CH2Cl2) cm−1 3073, 2975, 2925, 1562, 1496, 1371, 1158; 1H NMR (500 MHz, CDCl3): δ 7.74 (dd, J = 7.0 Hz, 1.5 Hz, 2H), 7.53−7.43 (m, 3H), 5.76 (dd, J = 9.5 Hz, 3.8 Hz, 1H), 5.18 (d, J = 9.5 Hz, 1H), 4.79 (d, J = 11.4 Hz, 1H), 4.63 (dd, J = 11.4 Hz, 3.8 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 150.9, 131.3, 129.1, 127.3, 126.4, 85.0, 71.0, 66.7; HRMS (ESI-TOF-negative ionization): calcd for C10H8NO4S ([M−H]−): 238.0174, found: 238.0159. This reaction was repeated on a millimolar scale following the general procedure: the reaction of benzaldoximes 11745

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry Scheme 1. Proposed Reaction Mechanism of Aldoximes 1 with Heterocyclic Alkene 2, 5 Using Koser’s Reagent 3b

3-(3-Methoxyphenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4d]isoxazole 4,4-dioxide (4e).

1a (151 mg, 1.25 mmol) with sultone 2 (750 mg, 6.25 mmol) and Koser’s reagent 3b (590 mg, 1.50 mmol) in THF (20 mL) afforded 242 mg (81%) of product 4a. 3-(p-Tolyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4b).9

Reaction of 4-methylbenzaldehyde oxime 1b (17 mg, 0.125 mmol) according to the method A procedure afforded 27 mg (84%) of product 4b, isolated as a white solid: mp 198.5−199.3 °C (lit.,9 mp 185.0−186.0 °C); IR (KBr) cm−1 2986, 2961, 2926, 2859, 1592, 1494, 1369, 1157, 770; 1H NMR (500 MHz, CDCl3): δ 7.63 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 5.73 (dd, J = 9.1 Hz, 3.4 Hz, 1H), 5.16 (d, J = 9.1 Hz, 1H), 4.77 (d, J = 11.3 Hz, 1H), 4.62 (dd, J = 11.3 Hz, 3.4 Hz, 1H), 2.40 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 150.8, 141.9, 129.9, 127.3, 123.6, 84.8, 71.0, 66.9, 21.5. 3-(2,4-Dimethylphenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4c).

Reaction of 3-methoxybenzaldehyde oxime 1e (19 mg, 0.125 mmol) according to the method A procedure afforded 22 mg (65%) of product 4e, isolated as a white solid: mp 128.1−129.5 °C; IR (KBr) cm−1 3073, 3045, 2979, 2844, 1604, 1490, 1366, 1152; 1H NMR (500 MHz, CDCl3): δ 7.41−7.35 (m, 1H), 7.33 (s, 1H), 7.24 (dd, J = 7.0 Hz, 1.6 Hz, 1H), 7.03 (dd, J = 8.3 Hz, 1.6 Hz, 1H), 5.76 (dd, J = 9.3 Hz, 3.5 Hz, 1H), 5.16 (t, J = 9.3 Hz, 1H), 4.78 (d, J = 11.0 Hz, 1H), 4.63 (dd, J = 11.0 Hz, 3.5 Hz, 1H), 3.85 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 159.9, 150.9, 130.1, 127.6, 120.0, 117.8, 111.8, 85.0, 70.9, 66.8, 55.4; HRMS (ESI-TOF-negative ionization): calcd for C11H12NO6S ([M+H2O−H]+): 286.0385, found: 286.0367. 3-(4-Methoxyphenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4d]isoxazole 4,4-dioxide (4f).13

Reaction of 2,4-dimethylbenzaldehyde oxime 1c (37 mg, 0.250 mmol) according to the method B procedure afforded 54 mg (81%) of product 4c, isolated as a white solid: mp 213.5−215.0 °C; IR (KBr) cm−1 2982, 2926, 2857, 1611, 1456, 1365, 1159, 771; 1H NMR (500 MHz, Acetone-d6): δ 7.49 (d, J = 7.8 Hz, 1H), 7.19 (s, 1H), 7.16 (d, J = 7.8 Hz, 1H), 5.97 (dd, J = 9.5 Hz, 3.3 Hz, 1H), 5.81 (d, J = 9.5 Hz, 1H), 4.88 (d, J = 11.9 Hz, 1H), 4.74 (dd, J = 11.9 Hz, 3.3 Hz, 1H), 2.50 (s, 3H), 2.34 (s, 3H); 13C{1H} NMR (75 MHz, Acetone-d6): δ 151.7, 140.2, 138.1, 132.4, 129.5, 126.6, 123.7, 84.8, 71.4, 68.4, 21.8, 20.2; HRMS (ESI-TOF-negative ionization): calcd for C12H12NO4S ([M−H]−): 266.0487, found: 266.0515. 3-(2,6-Dimethylphenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4d).

Reaction of 4-methoxybenzaldehyde oxime 1f (19 mg, 0.125 mmol) according to the method A procedure afforded 25 mg (74%) of product 4f, isolated as a white solid: mp 184.0−185.4 °C (lit.,9 mp 186.0−187.0 °C); IR (KBr) cm−1 3042, 2980, 2925, 2852, 1609, 1515, 1361, 1258, 1154, 1023; 1H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 9.0 Hz, 2H), 6.97 (d, J = 9.0 Hz, 2H), 5.73 (dd, J = 9.3 Hz, 3.5 Hz, 1H), 5.14 (d, J = 9.3 Hz, 1H), 4.78 (d, J = 10.8 Hz, 1H), 4.63 (dd, J = 10.8 Hz, 3.5 Hz, 1H), 3.86 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 161.9, 150.4, 129.0, 118.8, 114.6, 84.6, 71.0, 67.0, 55.4; HRMS (ESITOF-negative ionization): calcd for C11H12NO6S ([M+H]+): 286.0385, found: 286.0393. 3-(2-Chlorophenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4g).9

Reaction of 2,6-dimethylbenzaldehyde oxime 1d (37 mg, 0.25 mmol) according to the method B procedure afforded 25 mg (37%) of product 4d, isolated as a white solid: mp 144.0−145.2 °C; IR (KBr) cm−1 2986, 2961, 2926, 1592, 1464, 1369, 1157, 770; 1H NMR (500 MHz, CDCl3): δ 7.25 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 7.8 Hz, 2H), 5.77 (dd, J = 9.3 Hz, 3.8 Hz, 1H), 5.14 (d, J = 9.3 Hz, 1H), 4.79 (d, J = 11.5 Hz, 1H), 4.58 (dd, J = 11.5 Hz, 3.8 Hz, 1H), 2.37 (s, 6H); 13 C{1H} NMR (75 MHz, CDCl3): δ 149.7, 137.7, 130.1, 128.4, 124.8, 83.3, 72.0, 68.4, 20.5; HRMS (ESI-TOF-negative ionization): calcd for C12H12NO4S ([M−H]−): 266.0487, found: 266.0504.

Reaction of 2-chlorobenzaldehyde oxime 1g (19 mg, 0.125 mmol) according to the method A procedure afforded 25 mg (74%) of product 4g, isolated as a yellow solid: mp 134.0−135.5 °C (lit.,9 mp 140.0−142.0 °C); IR (KBr) cm−1 3064, 3008, 2965, 2924, 2859, 1587, 1484, 1361, 1157; 1H NMR (500 MHz, CDCl3): δ 7.76 (d, J = 7.5 Hz, 1H), 7.49−7.40 (m, 2H), 7.37 (t, J = 7.5 Hz, 1H), 5.81 (dd, J = 9.0 Hz, 3.5 Hz, 1H), 5.72 (d, J = 9.0 Hz, 1H), 4.77 (d, J = 11.3 Hz, 1H), 4.58 (dd, J = 11.3 Hz, 3.5 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 150.0, 132.4, 132.1, 132.0, 130.5, 127.4, 125.4, 85.0, 71.2, 67.2. 11746

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry 3-(3-Chlorophenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4h).9

3-(4-Bromophenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4l).

Reaction of 3-chlorobenzaldehyde oxime 1h (19 mg, 0.125 mmol) according to the method A procedure afforded 21 mg (62%) of product 4h, isolated as a white solid: mp 167.5−168.7 °C (lit.,9 mp 168.0−169.0 °C); IR (KBr) cm−1 3076, 2997, 2968, 2925, 2857, 1559, 1485, 1372, 1161; 1H NMR (500 MHz, CDCl3): δ 7.78 (s, 1H), 7.58 (dd, J = 7.5 Hz, 1.0 Hz, 1H), 7.46 (dd, J = 7.5 Hz, 1.0 Hz, 1H), 7.41 (t, J = 7.5 Hz, 1H), 5.79 (dd, J = 9.4 Hz, 3.4 Hz, 1H), 5.14 (d, J = 9.4 Hz, 1H), 4.80 (d, J = 11.5 Hz, 1H), 4.64 (dd, J = 11.5 Hz, 3.4 Hz, 1H); 13 C{1H} NMR (75 MHz, CDCl3): δ 149.9, 135.3, 131.4, 130.4, 128.2, 127.2, 125.5, 85.3, 71.1, 66.4. 3-(4-Chlorophenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4i).9

Reaction of 4-bromobenzaldehyde oxime 1l (25 mg, 0.125 mmol) according to the method A procedure afforded 22 mg (55%) of product 4l, isolated as a white solid: mp 204.6−206.8 °C; IR (KBr) cm−1 3098, 2996, 2925, 2854, 1590, 1490, 1371, 1158; 1H NMR (500 MHz, CDCl3): δ 7.61 (s, 4H), 5.79 (dd, J = 9.4 Hz, 3.3 Hz, 1H), 5.14 (d, J = 9.4 Hz, 1H), 4.80 (d, J = 11.4 Hz, 1H), 4.64 (dd, J = 11.4 Hz, 3.3 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 150.1, 132.4, 128.7, 125.9, 125.4, 85.2, 71.1, 64.4; HRMS (ESI-TOF-negative ionization): calcd for C10H7NO4S79Br ([M−H]+): 315.9279, found: 315.9279. 4-(4,4-Dioxido-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazol-3-yl)benzonitrile (4m).

Reaction of 4-chlorobenzaldehyde oxime 1i (19 mg, 0.125 mmol) according to the method A procedure afforded 23 mg (68%) of product 4i, isolated as a white solid: mp 209.0−210.1 °C (lit.,9 mp 211.0−212.0 °C); IR (KBr) cm−1 2999, 2925, 2855, 1598, 1497, 1372, 1157; 1H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 5.79 (dd, J = 9.0 Hz, 3.4 Hz, 1H), 5.14 (d, J = 9.0 Hz, 1H), 4.80 (d, J = 11.4 Hz, 1H), 4.64 (dd, J = 11.4 Hz, 3.4 Hz, 1H); 13 C{1H} NMR (75 MHz, CDCl3): δ 150.0, 137.5, 129.5, 128.5, 125.0, 85.2, 71.1, 66.5. 3-(2,4-Dichlorophenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4d]isoxazole 4,4-dioxide (4j).9

Reaction of 4-cyanobenzaldehyde oxime 1m (37 mg, 0.250 mmol) according to the general method B afforded 45 mg (68%) of product 4m, isolated as a white solid: mp 201.5−203.4 °C; IR (KBr) cm−1 3034, 2925, 2857, 2233, 1609, 1583, 1495, 1365, 1154; 1H NMR (500 MHz, Acetone-d6): δ 8.03 (m, 2H), 7.94 (m, 2H), 6.17 (dd, J = 8.6 Hz, 2.0 Hz, 1H), 5.90 (d, J = 8.6 Hz, 1H), 4.96 (d, J = 11.5 Hz, 1H), 4.80 (dd, J = 11.5 Hz, 2.0 Hz, 1H); 13C{1H} NMR (75 MHz, Acetoned6): δ 151.6, 133.6, 132.7, 128.9, 118.8, 114.9, 88.1, 72.6, 66.7; HRMS (ESI-TOF-negative ionization): calcd for C11H7N2O4S ([M−H]−): 263.0127, found: 263.0115. 3-(4-Nitrophenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4n).

Reaction of 2,4-dichlorobenzaldehyde oxime 1j (24 mg, 0.125 mmol) according to the method A procedure afforded 28 mg (73%) of product 4j, isolated as a white solid: mp 124.6−125.9 °C (lit.,9 mp 137.0−138.0 °C); IR (KBr) cm−1 3104, 3072, 2976, 2927, 2857, 1585, 1484, 1374, 1156; 1H NMR (500 MHz, CDCl3): δ 7.72 (d, J = 8.5 Hz, 1H), 7.49 (d, J = 2.0 Hz, 1H), 7.35 (dd, J = 8.5 Hz, 2.0 Hz, 1H), 5.81 (dd, J = 9.5 Hz, 3.5 Hz, 1H), 5.68 (d, J = 9.5 Hz, 1H), 4.76 (d, J = 11.3 Hz, 1H), 4.58 (dd, J = 11.3 Hz, 3.5 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 149.2, 137.7, 133.0, 132.7, 130.4, 127.9, 124.0, 85.3, 71.2, 67.0. 3-(2,6-Dichlorophenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4d]isoxazole 4,4-dioxide (4k).

Reaction of 4-nitrobenzaldehyde oxime 1n (42 mg, 0.250 mmol) according to the method B procedure afforded 50 mg (70%) of product 4n, isolated as a white solid: mp 227.6−228.7 °C; IR (KBr) cm−1 3117, 3089, 3023, 2924, 2855, 1570, 1511, 1370, 1354, 1152; 1H NMR (500 MHz, Acetone-d6): δ 8.39 (m, 2H), 8.12 (m, 2H), 6.20 (dd, J = 8.9 Hz, 3.1 Hz, 1H), 5.95 (d, J = 8.9 Hz, 1H), 4.98 (d, J = 11.3 Hz, 1H), 4.81 (dd, J = 11.3 Hz, 3.1 Hz, 1H); 13C{1H} NMR (75 MHz, Acetone-d6): δ 150.5, 149.0, 133.5, 128.4, 124.0, 87.4, 71.8, 65.9; HRMS (ESI-TOF-negative ionization): calcd for C10H7N2O6S ([M− H]−): 283.0025, found: 283.0037. Methyl 4-(4,4-Dioxido-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4d]isoxazol-3-yl)benzoate (4o).

Reaction of 4-methoxycarbonyl-benzaldehyde oxime 1o (22 mg, 0.125 mmol) according to the method A procedure afforded 23 mg (62%) of product 4o, isolated as a white solid: mp 219.5−220.2 °C; IR (KBr) cm−1 3001, 2974, 2957, 2925, 2855, 1727, 1711, 1610, 1369, 1284, 1161; 1H NMR (500 MHz, CDCl3): δ 8.13 (d, J = 7.8 Hz, 2H), 7.82 (d, J = 7.8 Hz, 2H), 5.82 (dd, J = 9.3 Hz, 6.8 Hz, 1H), 5.20 (d, J = 9.3 Hz, 1H), 4.81 (d, J = 11.4 Hz, 1H), 4.65 (dd, J = 11.4 Hz, 6.8 Hz, 1H), 3.95 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 166.1, 150.3, 132.4, 130.5, 130.3, 127.3, 65.4, 71.1, 66.3, 52.4; HRMS (ESI-TOF-negative ionization): calcd for C12H10NO6S ([M−H]−): 296.0229, found: 296.0225.

Reaction of 2,6-dichlorobenzaldehyde oxime 1k (48 mg, 0.250 mmol) according to the method B procedure afforded 52 mg (68%) of product 4k, isolated as a white solid: mp 160.0−161.5 °C; IR (KBr) cm−1 3080, 3028, 3009, 2926, 2860, 1578, 1459, 1369, 1158; 1H NMR (500 MHz, CDCl3): δ 7.44 (d, J = 8.5 Hz, 2H), 7.36 (t, J = 8.5 Hz, 1H), 5.85 (dd, J = 9.9 Hz, 3.9 Hz, 1H), 5.54 (d, J = 9.9 Hz, 1H), 4.82 (d, J = 11.0 Hz, 1H), 4.60 (dd, J = 11.0 Hz, 3.9 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 146.3, 135.8, 132.0, 128.8, 124.6, 84.1, 72.4, 66.9; HRMS (ESI-TOF-negative ionization): calcd for C10H835Cl2NO5S ([M+H2O−H]−): 323.9500, found: 323.9478. 11747

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry 3-(4-(Methylthio)phenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4p).

3-Phenethyl-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4s).

Reaction of 4-methylthiobenzaldehyde oxime 1p (42 mg, 0.250 mmol) according to the method B procedure afforded 21 mg (30%) of product 4p, isolated as a white solid: mp 145.0−146.8 °C; IR (KBr) cm−1 2986, 2928, 2855, 1594, 1498, 1368, 1156; 1H NMR (500 MHz, Acetone-d6): δ 7.73 (m, 2H), 7.38 (m, 2H), 6.03 (dd, J = 9.0 Hz, 3.4 Hz, 1H), 5.76 (d, J = 9.0 Hz, 1H), 4.89 (d, J = 11.3 Hz, 1H), 4.76 (dd, J = 11.3 Hz, 3.4 Hz, 1H), 2.56 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 150.4, 143.5, 127.5, 125.9, 122.6, 84.9, 71.0, 66.7, 15.0; HRMS (ESI-TOF-negative ionization): calcd for C11H10NO4S2 ([M− H]−): 284.0051, found: 284.0039. Single crystals of product 4p suitable for X-ray crystallographic analysis were obtained by slow evaporation of MeCN solution. For details on crystal structure of compound 4p see the CIF file in Supporting Information. Selected crystallographic data for 4p: Monoclinic, P21, a = 6.5955(3) Å, b = 10.6686(5) Å, c = 17.0119(12) Å, β = 90.016(6)o, V = 1197.04(12) Å3, Z = 4, R (I > 2.0/σ(I)) = 0.0851, Rw (all) = 0.1501, CCDC 1552757. 3-(2-Hydroxyphenyl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4d]isoxazole 4,4-dioxide (4q).

Reaction of 3-phenylpropanal oxime 1s (19 mg, 0.125 mmol) according to the method A procedure afforded 24 mg (73%) of product 4s, isolated as a white solid: mp 92.8−94.0 °C; IR (KBr) cm−1 3063, 3032, 3001, 2925, 2854, 1605, 1498, 1367, 1171; 1H NMR (500 MHz, CDCl3): δ 7.22 (t, J = 7.5 Hz, 2H), 7.27−7.20 (m, 3H), 5.47 (dd, J = 10.3 Hz, 3.5 Hz, 1H), 4.64 (d, J = 10.3 Hz, 1H), 4.46 (dd, J = 10.6 Hz, 3.5 Hz, 2H), 3.13−2.94 (m, 3H), 2.87−2.78 (m, 1H); 13 C{1H} NMR (75 MHz, CDCl3): δ 151.5, 139.7, 128.8, 128.3, 126.7, 82.9, 71.9, 68.1, 32.3, 27.5; HRMS (ESI-TOF-positive ionization): calcd for C12H14NO4S ([M+H]+): 268.0644, found: 268.0628. 3-(Pyridin-2-yl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4t).

Reaction of picolinaldehyde oxime 1t (31 mg, 0.250 mmol) according to the method B procedure afforded 24 mg (40%) of product 4t, isolated as a white solid: mp 70 °C (decomp); IR (KBr) cm−1 3115, 3095, 2980, 2925, 1610, 1456, 1365, 1163; 1H NMR (500 MHz, CDCl3): δ 8.68 (d, J = 5.0 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.80− 7.75 (m, 1H), 7.37 (dd, J = 7.0 Hz, 5.0 Hz, 1H), 5.76 (dd, J = 9.3 Hz, 3.9 Hz, 1H), 5.61 (d, J = 9.0 Hz, 1H), 4.76 (d, J = 11.3 Hz, 1H), 4.62 (dd, J = 11.3 Hz, 3.9 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 153.0, 149.7, 146.3, 136.7, 125.2, 122.0, 84.9, 70.4, 66.5; HRMS (ESITOF-negative ionization): calcd for C9H9N2O5S ([M+H2O−H]−): 257.0232, found: 257.0262. 3-(1,3-Dihydroisobenzofuran-5-yl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4u).9

Reaction of 2-hydroxybenzoaldehyde oxime 1q (17 mg, 0.125 mmol) according to the method A procedure afforded 15 mg (47%) of product 4q, isolated as a white solid: mp 174.8−176.0 °C; IR (KBr) cm−1 3223, 3066, 2979, 2923, 2852, 1592, 1493, 1378, 1362, 1152; 1H NMR (500 MHz, CDCl3): δ 8.99 (s, 1H), 7.44−7.38 (m, 1H), 7.33 (dd, J = 8.8 Hz, 1.3 Hz, 1H), 7.08 (d, J = 9.0 Hz, 1H), 7.05−6.98 (m, 1H), 5.74 (dd, J = 8.6 Hz, 3.3 Hz, 1H), 5.27 (d, J = 8.6 Hz, 1H), 4.83 (d, J = 11.4 Hz, 1H), 4.67 (dd, J = 11.4 Hz, 3.3 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 157.4, 152.3, 133.1, 129.0, 120.2, 117.7, 111.4, 83.8, 70.6, 67.1; HRMS (ESI-TOF-negative ionization): calcd for C10H8N2O5S ([M−H]+): 254.0123, found: 254.0137. Single crystals of product 4q suitable for X-ray crystallographic analysis were obtained by slow evaporation of MeCN solution. For details on crystal structure of compound 4q see the CIF file in Supporting Information. Selected crystallographic data for 4q: Monoclinic, P21/n, a = 13.4331(4) Å, b = 5.3700(2) Å, c = 28.625(2) Å, β = 97.810(7)o, V = 2045.73(18) Å3, Z = 8, R (I > 2.0/ σ(I)) = 0.0801, Rw (all) = 0.1351, CCDC 1552758. (E)-3-Styryl-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4r).

Reaction of benzo[d][1,3]dioxole-5-carbaldehyde oxime 1u (41 mg, 0.250 mmol) according to the method B procedure afforded 38 mg (54%) of product 4u, isolated as a white solid: mp 202.0−203.6 °C (lit.,9 mp 211.0−212.0 °C) IR (KBr) cm−1 3082, 3046, 2972, 2927, 1611, 1565, 1369, 1161, 1150; 1H NMR (500 MHz, Acetone-d6): δ 7.31 (s, 1H), 7.27 (dd, J = 8.5 Hz, 1.3 Hz, 1H), 6.98 (d, J = 8.5 Hz, 1H), 6.12 (s, 2H), 6.01 (dd, J = 9.1 Hz, 3.3 Hz, 1H), 5.72 (d, J = 9.1 Hz, 1H), 4.88 (d, J = 10.9 Hz, 1H), 4.74 (dd, J = 10.9 Hz, 3.3 Hz, 1H); 13 C{1H} NMR (75 MHz, Acetone-d6): δ 151.1, 150.1, 148.4, 122.6, 121.4, 108.3, 106.3, 102.0, 86.1, 71.4, 66.6; HRMS (ESI-TOF-negative ionization): calcd for C11H8NO6S ([M−H]−): 282.0072, found: 282.0060. 3-(Naphthalen-2-yl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4v).

Reaction of cinnamaldehyde oxime 1r (18 mg, 0.125 mmol) according to the method A procedure afforded 13 mg (39%) of product 4r, isolated as a white solid: mp 202.1−203.0 °C; IR (KBr) cm−1 3048, 3024, 2977, 2958, 2924, 2853, 1633, 1493, 1370, 1154; 1H NMR (500 MHz, CDCl3): δ 7.52 (d, J = 8.0 Hz, 2H), 7.43−7.33 (m, 3H), 7.06 (d, J = 16.5 Hz, 1H), 6.98 (d, J = 16.5 Hz, 1H), 5.71 (dd, J = 9.3 Hz, 3.6 Hz, 1H), 5.03 (d, J = 9.3 Hz, 1H), 4.76 (d, J = 11.0 Hz, 1H), 4.62 (dd, J = 11.0 Hz, 3.6 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 151.5, 139.5, 134.9, 129.8, 128.9, 127.4, 114.5, 84.8, 71.0, 65.9; HRMS (ESITOF-negative ionization): calcd for C12H10NO4S ([M−H]−): 264.0331, found: 264.0335.

Reaction of 2-naphthaldehyde oxime 1v (43 mg, 0.250 mmol) according to the method B procedure afforded 48 mg (67%) of product 4v, isolated as a white solid: mp 216.5−217.3 °C; IR (KBr) cm−1 3052, 2991, 2924, 2854, 1594, 1511, 1372, 1153; 1H NMR (500 MHz, Acetone-d6): δ 8.29 (s, 1H), 8.06−7.92 (m, 4H), 7.66−7.55 (m, 2H), 6.12 (dd, J = 8.8 Hz, 3.5 Hz, 1H), 5.93 (d, J = 8.8 Hz, 1H), 4.94 (d, J = 11.3 Hz, 1H), 4.80 (dd, J = 11.3 Hz, 3.5 Hz, 1H); 13C{1H} NMR (75 MHz, Acetone-d6): δ 151.7, 134.3, 133.0, 128.8, 128.6, 128.1, 127.8, 127.7, 127.0, 125.1, 123.4, 86.4, 71.5, 66.4; HRMS (ESI11748

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry TOF-negative ionization): calcd for C14H10NO4S ([M−H]−): 288.0331, found: 288.0317. 3-(Naphthalen-1-yl)-3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide (4w).

(d, 1JCp = 58.4 Hz), 32.9 (d, 3JCp = 8.0 Hz), 28.2 (d, 1JCp = 64.1 Hz), 25.2 (d, 2JCp = 12.6 Hz); 31P NMR (121 MHz, CDCl3): δ 58.5; HRMS (ESI-TOF-positive ionization): calcd for C18H19NO2P ([M+H]+): 312.1153, found: 312.1169. This reaction was repeated on a millimolar scale following the general procedure: the reaction of benzaldoximes 1a (151 mg, 1.25 mmol) with 3-methyl-1-phenyl-2-phospholene-1oxide 5 (1.201 g, 6.25 mmol) and Koser’s reagent 3b (590 mg, 1.50 mmol) in AcOEt (20 mL) afforded 144 mg (37%) of product 6a. Single crystals of product 6a suitable for X-ray crystallographic analysis were obtained by slow evaporation of MeCN solution. For details on crystal structure of compound 6a see the CIF file in Supporting Information. Selected crystallographic data for 6a: Orthorhombic, P212121, a = 5.56120(10) Å, b = 14.2627(3) Å, c = 19.1433(13) Å, V = 1518.40(11) Å3, Z = 4, R (I > 2.0/σ(I)) = 0.0374, Rw (all) = 0.0402, CCDC 1552759. 6a-Methyl-4-phenyl-3-(p-tolyl)-3a,5,6,6atetrahydrophospholo[2,3-d]isoxazole 4-oxide (6b).

Reaction of 1-naphthaldehyde oxime 1w (43 mg, 0.250 mmol) according to the method B procedure afforded 38 mg (53%) of product 4w, isolated as a white solid: mp 172.5−174.6 °C; IR (KBr) cm−1 3054, 2964, 2926, 1602, 1474, 1371, 1194; 1H NMR (500 MHz, CDCl3): δ 8.85 (d, J = 8.5 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.74−7.50 (m, 4H), 5.76 (dd, J = 9.5 Hz, 3.5 Hz, 1H), 5.41 (d, J = 9.5 Hz, 1H), 4.83 (d, J = 11.1 Hz, 1H), 4.65 (dd, J = 11.1 Hz, 3.5 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3): δ 151.2, 134.1, 132.2, 130.6, 128.8, 128.1, 126.8, 126.5, 124.7, 123.3, 83.6, 70.9, 68.8; HRMS (ESI-TOF-negative ionization): calcd for C14H10NO4S ([M− H]−): 288.0331, found: 288.0312. 3,3′-(1,4-Phenylene)bis(3a,6a-dihydro-6H-[1,2]oxathiolo[3,4-d]isoxazole 4,4-dioxide) (4x).

Reaction of 4-methylbenzaldehyde oxime 1b (34 mg, 0.250 mmol) and acetonitrile according to the general procedure afforded 30 mg (37%) of product 6a, isolated as a white solid: mp 141.1−143.5 °C; IR (KBr) cm−1 3060, 3029, 2965, 2943, 2921, 2861, 1616, 1588, 1487, 1437, 1346, 1205, 1177; 1H NMR (500 MHz, CDCl3): δ 7.83−7.73 (m, 2H), 7.68−7.51 (m, 5H), 7.17 (d, J = 8.0 Hz, 2H), 3.70 (d, J = 6.0 Hz, 1H), 2.72−2.57 (m, 1H), 2.55−2.36 (m, 2H), 2.34 (s, 3H), 2.08− 1.98 (m, 1H), 1.56 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 155.1 (d, 2JCp = 6.9 Hz), 140.4, 132.9 (d, 1JCp = 88.1 Hz), 132.7 (d, 4JCp = 3.5 Hz), 129.6 (d, 3JCp = 10.3 Hz), 129.3 (d, 2JCp = 11.5 Hz), 127.2, 126.6, 95.5 (d, 2JCp = 12.6 Hz), 56.1 (d, 1JCp = 58.4 Hz), 32.9 (d, 3JCp = 9.2 Hz), 28.2 (d, 1JCp = 63.0 Hz), 25.2 (d, 2JCp = 12.6 Hz), 21.4; 31P NMR (121 MHz, CDCl3): δ 58.8; HRMS (ESI-TOF-positive ionization): calcd for C19H20NO2P ([M+H]+): 326.1310, found: 326.1308. 3-(4-Methoxyphenyl)-6a-methyl-4-phenyl-3a,5,6,6atetrahydrophospholo[2,3-d]isoxazole 4-oxide (6c).

Terephthalaldehyde dioxime 1x (21 mg, 0.125 mmol) and sultone 2 (150 mg, 1.25 mmol) were added to a solution of Koser’s reagent 3b (123 mg, 0.313 mmol) in THF (4 mL). The reaction was stirred at room temperature for 24 h, and then according to the general procedure afforded 19 mg (38%) of product 4x, isolated as a white solid: mp 145.0−146.8 °C; IR (KBr) cm−1 2925, 2856, 1714, 1595, 1451, 1371, 1156; 1H NMR (500 MHz, Acetone-d6): δ 7.95 (s, 4H), 6.12 (dd, J = 9.1 Hz, 3.3 Hz, 2H), 5.85 (d, J = 9.1 Hz, 2H), 4.94 (d, J = 11.5 Hz, 2H), 4.79 (dd, J = 11.5 Hz, 3.3 Hz, 2H); 13C{1H} NMR (75 MHz, Acetone-d6): δ 151.0, 129.5, 127.7, 86.7, 71.6, 66.1; HRMS (ESI-TOF-positive ionization): calcd for C14H12N2NaO8S2 ([M +Na]+): 422.9933, found: 422.9913. General Procedure for Oxidative Cyclization of Aldoximes and 3-Methyl-1-phenyl-2-phospholene-1-oxide Using Koser’s Reagent. Aldoxime 1 (0.250 mmol) and 3-methyl-1-phenyl-2phospholene-1-oxide 5 (240 mg, 1.25 mmol) were added to a solution of Koser’s reagent 3b (118 mg, 0.300 mmol) in AcOEt (4 mL). The reaction was stirred at room temperature for 24 h. After completion of the reaction, 5% aqueous Na2S2O3 (5 mL) and saturated NaHCO3 (5 mL) were added, and the mixture was extracted with dichloromethane. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by column chromatography (hexane-ethyl acetate = 3:1 to 2:1) afforded analytically pure products 6. 6a-Methyl-3,4-diphenyl-3a,5,6,6a-tetrahydrophospholo[2,3d]isoxazole 4-oxide (6a).

Reaction of 4-methoxbenzaldehyde oxime 1f (38 mg, 0.250 mmol) and acetonitrile according to the general procedure afforded 29 mg (34%) of product 6c, isolated as a yellow solid: mp 170.1−172.9 °C; IR (KBr) cm−1 3058, 2967, 2929, 2862, 1609, 1516, 1346, 1256, 1208, 1179; 1H NMR (500 MHz, CDCl3): δ 7.81−7.73 (m, 2H), 7.68−7.55 (m, 4H), 6.88 (d, J = 9.0 Hz, 2H), 3.80 (s, 3H), 3.68 (d, J = 6.0 Hz, 1H), 2.72−2.56 (m, 1H), 2.54−2.34 (m, 2H), 2.08−1.96 (m, 1H), 1.56 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 161.1, 154.6 (d, 2JCp = 6.8 Hz), 132.9 (d, 1JCp = 88.1 Hz), 132.6 (d, 4JCp = 2.3 Hz), 129.6 (d, 3JCp = 9.2 Hz), 129.3 (d, 2JCp = 11.4 Hz), 128.8, 122.0, 114.2, 95.3 (d, 2JCp = 12.6 Hz), 55.7 (d, 1JCp = 58.4 Hz), 55.3, 32.8 (d, 3JCp = 8.0 Hz), 28.2 (d, 1JCp = 64.1 Hz), 25.3 (d, 2JCp = 11.5 Hz); 31P NMR (121 MHz, CDCl3): δ 58.7; HRMS (ESI-TOF-positive ionization): calcd for C19H20NO3P ([M+H]+): 342.1259, found: 342.1249. 3-(4-Chlorophenyl)-6a-methyl-4-phenyl-3a,5,6,6atetrahydrophospholo[2,3-d]isoxazole 4-oxide (6d).

Reaction of benzaldoxime 1a (30 mg, 0.250 mmol) and acetonitrile according to the general procedure afforded 35 mg (45%) of product 6a, isolated as a white solid: mp 148.5−150.1 °C; IR (KBr) cm−1 3060, 2971, 2940, 2931, 2860, 1559, 1495, 1439, 1348, 1348, 1208, 1184; 1H NMR (500 MHz, CDCl3): δ 7.81−7.75 (m, 2H), 7.70−7.57 (m, 5H), 7.39−7.33 (m, 3H), 3.71 (d, J = 6.0 Hz, 1H), 2.73−2.58 (m, 2H), 2.56−2.35 (m, 2H), 2.08−1.98 (m, 1H), 1.57 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 155.2 (d, 2JCp = 6.9 Hz), 132.8 (d, 1JCp = 89.3 Hz), 132.7 (d, 4JCp = 3.5 Hz), 130.2, 129.6 (d, 3JCp = 3.5 Hz), 129.4, 129.3 (d, 2JCp = 11.5 Hz), 128.7, 127.3, 95.8 (d, 2JCp = 12.5 Hz), 56.0 11749

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry

of product 6g with diastereomers mixture, isolated as a yellow solid: mp 78.7−80.2 °C; IR (CH2Cl2) cm−1 3054, 2967, 2923, 2863, 1718, 1630, 1491, 1448, 1437, 1356, 1203, 1178, 1148; 1H NMR (500 MHz, CDCl3): δ 7.83−7.74 (m, 2H), 7.70−7.57 (m, 3H), 7.38 (d, J = 8.0 Hz, 2H), 7.34−7.24 (m, 3H), 7.13 (d, J = 16.8 Hz, 1H), 6.64 (d, J = 16.8 Hz, 1H), 3.57 (d, J = 5.5 Hz, 1H), 2.72−2.58 (m, 1H), 2.51−2.36 (m, 2H), 2.10−2.00 (m, 1H), 1.55 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 155.8 (d, 2JCp = 6.8 Hz), 153.6 (d, 2JCp = 5.7 Hz), 137.9, 136.7, 136.5, 135.7, 132.7 (d, 1JCp = 90.5 Hz), 132.7 (d, 4JCp = 2.3 Hz), 132.3 (d, 1JCp = 88.5 Hz), 132.1 (d, 4JCp = 2.3 Hz), 129.6 (d, 3JCp = 9.2 Hz), 129.4 (d, 2JCp = 11.4 Hz), 129.3 (d, 3JCp = 9.2 Hz), 128.9, 128.9, 128.8, 128.6, 127.9, 127.8, 127.2, 120.1, 117.8, 95.7 (d, 2JCp = 12.6 Hz), 55.3 (d, 1JCp = 59.5 Hz), 55.2 (d, 1JCp = 59.5 Hz), 32.7 (d, 3JCp = 8.0 Hz), 32.3 (d, 3JCp = 9.2 Hz), 28.0 (d, 1JCp = 64.1 Hz), 27.6 (d, 1JCp = 64.1 Hz), 25.4 (d, 2JCp = 11.5 Hz), 24.9 (d, 2JCp = 12.6 Hz); 31P NMR (121 MHz, CDCl3): δ 58.8, 57.9; HRMS (ESI-TOF-positive ionization): calcd for C20H20NO2P ([M+H]+): 338.1310, found: 338.1304. 6a-Methyl-3-phenethyl-4-phenyl-3a,5,6,6atetrahydrophospholo[2,3-d]isoxazole 4-oxide (6h).

Reaction of 4-chlorobenzaldehyde oxime 1i (39 mg, 0.250 mmol) and acetonitrile according to the general procedure afforded 30 mg (35%) of product 6d, isolated as a white solid: mp 170.5−172.1 °C; IR (KBr) cm−1 3058, 2970, 2928, 2862, 1597, 1588, 1495, 1437, 1341, 1208, 1182, 1091; 1H NMR (500 MHz, CDCl3): δ 7.80−7.72 (m, 2H), 7.68−7.55 (m, 4H), 7.34 (d, J = 9.0 Hz, 2H), 3.68 (d, J = 6.5 Hz, 1H), 2.73−2.58 (m, 1H), 2.54−2.33 (m, 2H), 2.08−1.97 (m, 1H), 1.57 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 154.2 (d, 2JCp = 5.8 Hz), 136.1, 132.8 (d, 4JCp = 2.3 Hz), 132.1 (d, 1JCp = 89.3 Hz), 129.5 (d, 3 JCp = 9.2 Hz), 129.4 (d, 2JCp = 12.6 Hz), 128.9, 128.5, 127.9, 96.0 (d, 2 JCp = 12.6 Hz), 55.8 (d, 1JCp = 58.4 Hz), 33.0 (d, 3JCp = 8.0 Hz), 28.1 (d, 1JCp = 62.9 Hz), 25.3 (d, 2JCp = 12.5 Hz); 31P NMR (121 MHz, CDCl3): δ 58.5; HRMS (ESI-TOF-positive ionization): calcd for C18H17NCl35O2P ([M+H]+): 346.0764, found: 346.0751. 6a-Methyl-4-phenyl-3-(p-tolyl)-3a,5,6,6atetrahydrophospholo[2,3-d]isoxazole 4-oxide (6e).

Reaction of 4-nitrobenzaldehyde oxime 1n (42 mg, 0.250 mmol) according to the general procedure afforded 32 mg (36%) of product 6e, isolated as a yellow solid: mp 192.5−195.0 °C; IR (KBr) cm−1 3066, 3049, 2977, 2929, 1604, 1559, 1515, 1439, 1343, 1208, 1184; 1H NMR (500 MHz, CDCl3): δ 8.21 (d, J = 8.5 Hz, 2H), 7.84 (d, J = 8.5 Hz, 2H), 7.81−7.74 (m, 2H), 7.72−7.58 (m, 3H), 3.73 (d, J = 6.0 Hz, 1H), 2.78−2.63 (m, 1H), 2.52−2.39 (m, 2H), 2.13−2.04 (m, 1H), 1.62 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): δ 153.5 (d, 2JCp = 5.7 Hz), 148.4, 135.5, 133.1, 132.1, (d, 1JCp = 90.5 Hz), 129.5 (d, 2JCp = 11.4 Hz), 129.5 (d, 3JCp = 9.2 Hz), 128.1, 123.9, 96.5 (d, 1JCp = 12.6 Hz), 55.5 (d, 1JCp = 57.3 Hz), 32.7 (d, 3JCp = 9.2 Hz), 28.0 (d, 1JCp = 64.1 Hz), 25.3 (d, 3JCp = 11.5 Hz); 31P NMR (121 MHz, CDCl3): δ 59.2; HRMS (ESI-TOF-positive ionization): calcd for C18H17N2O4P ([M+H]+): 357.1004, found: 357.0988. 3-(2,6-Dimethylphenyl)-6a-methyl-4-phenyl-3a,5,6,6atetrahydrophospholo[2,3-d]isoxazole 4-oxide (6f).

Reaction of 3-phenylpropanal oxime 1s (37 mg, 0.250 mmol) according to the general procedure afforded 16 mg (19%) of product 6h, isolated as a yellow oil: IR (CH2Cl2) cm−1 3063, 3032, 3001, 2925, 2854, 1605, 1498, 1454, 1367, 1171; 1H NMR (500 MHz, CDCl3): δ 7.63−7.50 (m, 5H), 7.24−7.20 (m, 4H), 7.17−7.11 (m, 1H), 3.15− 2.90 (m, 4H), 2.87−2.78 (m, 1H), 2.53−2.21 (m, 3H), 1.81−1.72 (m, 1H), 1.35 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): 156.4 (d, 2JCp = 6.8 Hz), 140.6, 132.5 (d, 1JCp = 89.3 Hz), 132.5 (d, 4JCp = 2.3 Hz), 129.4 (d, 3JCp = 9.2 Hz), 129.2 (d, 2JCp = 11.4 Hz), 128.5, 128.5, 128.5, 126.3, 93.4 (d, 2JCp = 13.7 Hz), 56.8 (d, 1JCp = 59.6 Hz), 32.8, 32.6, 29.2, 27.2 (d, 1JCp = 64.1 Hz), 25.1 (d, 2JCp = 12.5 Hz); 31P NMR (121 MHz, CDCl3): δ 59.2; HRMS (ESI-TOF-positive ionization): calcd for C20H22NO2P ([M+H]+): 340.1466, found: 340.1470.

■

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01462. X-ray crystallographic data for compounds 4p, 4q, and 6a (CIF) Copies of NMR spectra for all compounds (PDF)

Reaction of 2,6-dimethylbenzaldehyde oxime 1d (37 mg, 0.250 mmol) and acetonitrile according to the general procedure afforded 7 mg (8%) of product 6f, isolated as a white solid: mp 143.8−146.5 °C; IR (KBr) cm−1 3060, 3028, 2965, 2920, 2861, 1615, 1437, 1346, 1205; 1H NMR (500 MHz, CDCl3): δ 7.64−7.54 (m, 3H), 7.52−7.48 (m, 2H), 7.16 (t, J = 7.5 Hz, 1H), 7.05 (d, J = 7.5 Hz, 2H), 3.82 (d, J = 8.5 Hz, 1H), 2.66−2.60 (m, 1H), 2.47 (s, 6H), 2.36−2.28 (m, 2H), 1.96−1.84 (m, 1H), 1.67 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3): 154.8 (d, 2 JCp = 5.7 Hz), 137.5, 135.7, 132.7 (d, 1JCp = 82.4 Hz), 132.4 (d, 4JCp = 2.3 Hz), 129.8, 129.4 (d, 3JCp = 9.2 Hz), 129.1 (d, 2JCp = 10.4 Hz), 128.3, 127.6, 94.5 (d, 2JCp = 13.7 Hz), 57.6 (d, 1JCp = 60.7 Hz), 32.3 (d, 3JCp = 9.2 Hz), 27.6 (d, 1JCp = 64.1 Hz), 25.4 (d, 2JCp = 12.6 Hz); 31 P NMR (121 MHz, CDCl3): δ 58.8; HRMS (ESI-TOF-positive ionization): calcd for C20H22NO2P ([M+H]+): 340.1466, found: 340.1467. (E)-6a-Methyl-4-phenyl-3-styryl-3a,5,6,6atetrahydrophospholo[2,3-d]isoxazole 4-oxide (6g).

■

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] *E-mail: [email protected] ORCID

Gregory T. Rohde: 0000-0001-7787-8012 Viktor V. Zhdankin: 0000-0002-0315-8861 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This work was supported by research grants from the National Science Foundation (CHE-1262479) and the Russian Science Foundation (RSF-16-13-10081).

■

REFERENCES

(1) (a) Handbook of Heterocyclic Chemistry, Third edition; Katrizky, A., Ramsden, C. A., Joule, J. A., Zhdankin, V. V., Eds.; Elsevier, 2010.

Reaction of cinnamaldehyde oxime 1r (37 mg, 0.250 mmol) and acetonitrile according to the general procedure afforded 26 mg (31%) 11750

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751

Article

The Journal of Organic Chemistry (b) Katritzky, A. R.; Rachwal, S. Chem. Rev. 2010, 110, 1564−1610. (c) Alvarez-Corral, M.; Munoz-Dorado, M.; Rodriguez-Garcia, I. Chem. Rev. 2008, 108, 3174−3198. (d) Minatti, A.; Muniz, K. Chem. Soc. Rev. 2007, 36, 1142−1152. (e) D’Souza, D. M.; Mueller, T. J. J. Chem. Soc. Rev. 2007, 36, 1095−1108. (f) Chemler, S. R.; Fuller, P. H. Chem. Soc. Rev. 2007, 36, 1153−1160. (g) Tietze, L. F.; Rackelmann, N. Pure Appl. Chem. 2004, 76, 1967−1983. (2) (a) Top. Curr. Chem.; Wirth, T., Ed.; 2016; Vol. 373. (b) Yoshimura, A.; Yusubov, M. S.; Zhdankin, V. V. Org. Biomol. Chem. 2016, 14, 4771−4781 and references cited therein.. (3) (a) Samanta, R.; Matcha, K.; Antonchick, A. P. Eur. J. Org. Chem. 2013, 2013, 5769−5804. (b) Zheng, Z. S.; Zhang-Negrerie, D.; Du, Y. F.; Zhao, K. Sci. China: Chem. 2014, 57, 189−214. (4) Yoshimura, A.; Zhdankin, V. V. ARKIVOC 2017, 84−98. (5) (a) Kotali, A.; Kotali, E.; Lafazanis, I. S.; Harris, P. A. Adv. Org. Synth. 2013, 4, 267−316. (b) Kotali, A.; Kotali, E.; Lafazanis, I. S.; Harris, P. A. Curr. Org. Synth. 2010, 7, 62−77. (c) Ciufolini, M. A. Can. J. Chem. 2014, 92, 186−193. (d) Turner, C. D.; Ciufolini, M. A. ARKIVOC 2011, 410−428. (6) (a) Raihan, M. J.; Kavala, V.; Kuo, C.-W.; Raju, B. R.; Yao, C.-F. Green Chem. 2010, 12, 1090−1096. (b) Radhakrishna, A. S.; Sivaprakash, K.; Singh, B. B. Synth. Commun. 1991, 21, 1625−1629. (c) Tanaka, S.; Ito, M.; Kishikawa, K.; Kohmoto, S.; Yamamoto, M. Nippon Kagaku Kaishi 2002, 471−473. (d) Kumar, R.; Kumar, M.; Prakash, O. Heteroat. Chem. 2016, 27, 228−234. (e) Harding, S. L.; Marcuccio, S. M.; Savage, G. P. Beilstein J. Org. Chem. 2012, 8, 606− 612. (f) Jawalekar, A. M.; Reubsaet, E.; Rutjes, F. P. J. T.; van Delft, F. L. Chem. Commun. 2011, 47, 3198−3200. (g) Yang, H.-T.; Ruan, X.-J.; Miao, C.-B.; Sun, X.-Q. Tetrahedron Lett. 2010, 51, 6056−6059. (h) Mendelsohn, B. A.; Lee, S.; Kim, S.; Teyssier, F.; Aulakh, V. S.; Ciufolini, M. A. Org. Lett. 2009, 11, 1539−1542. (i) Sanders, B. C.; Friscourt, F.; Ledin, P. A.; Mbua, N. E.; Arumugam, S.; Guo, J.; Boltje, T. J.; Popik, V. V.; Boons, G.-J. J. Am. Chem. Soc. 2011, 133, 949−957. (7) (a) Yoshimura, A.; Middleton, K. R.; Todora, A. D.; Kastern, B. J.; Koski, S. R.; Maskaev, A. V.; Zhdankin, V. V. Org. Lett. 2013, 15, 4010−4013. (b) Yoshimura, A.; Nguyen, K. C.; Rohde, G. T.; Saito, A.; Yusubov, M. S.; Zhdankin, V. V. Adv. Synth. Catal. 2016, 358, 2340−2344. (c) Yoshimura, A.; Nguyen, K. C.; Klasen, S. C.; Postnikov, P. S.; Yusubov, M. S.; Saito, A.; Nemykin, V. N.; Zhdankin, V. V. Asian J. Org. Chem. 2016, 5, 1128−1133. (d) Yoshimura, A.; Nguyen, K. C.; Klasen, S. C.; Saito, A.; Nemykin, V. N.; Zhdankin, V. V. Chem. Commun. 2015, 51, 7835−7838. (8) (a) Han, L.; Zhang, B.; Xiang, C.; Yan, J. Synthesis 2014, 46, 503− 509. (b) Xiang, C.; Li, T.; Yan, J. Synth. Commun. 2014, 44, 682−688. (9) Tian, L.; Xu, G.-Y.; Ye, Y.; Liu, L.-Z. J. Heterocycl. Chem. 2003, 40, 1071−1074. (10) For the oxidation of organic sulfides to sulfoxides by Koser’s reagent, see: (a) Xia, M.; Chen, Z.-C. Synth. Commun. 1997, 27, 1315−1320. (b) Liu, P.; Liu, S.-j.; Zhang, J.-Z.; Tian, G.-r. Synth. Commun. 2005, 35, 3173−3177. (c) Yu, B.; Guo, C.-X.; Zhong, C.-L.; Diao, Z.-F.; He, L.-N. Tetrahedron Lett. 2014, 55, 1818−1821. (11) Machetti, F.; Anichini, B.; Cicchi, S.; Brandi, A.; Wieczorek, W.; Pietrusiewicz, K. M.; Gehret, J.-C. J. Heterocycl. Chem. 1996, 33, 1091− 1098. (12) Yoshimura, A.; Klasen, S. C.; Shea, M. T.; Nguyen, K. C.; Rohde, G. T.; Saito, A.; Postnikov, P. S.; Yusubov, M. S.; Nemykin, V. N.; Zhdankin, V. V. Chem. - Eur. J. 2017, 23, 691−695. (13) Zhang, H.; Chan, W. H.; Lee, A. W. M.; Wong, W. Y. Tetrahedron Lett. 2003, 44, 395−397.

11751

DOI: 10.1021/acs.joc.7b01462 J. Org. Chem. 2017, 82, 11742−11751