[3 + 2] Cycloaddition of Azaoxyallyl Cations with Cyclic Ketones

Sep 19, 2017 - Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, 55 Da...
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[3 + 2] Cycloaddition of Azaoxyallyl Cations with Cyclic Ketones: Access to Spiro-4-oxazolidinones Pan-Lin Shao,* Zi-Rui Li, Zhi-Peng Wang, Ming-Hui Zhou, Qi Wu, Ping Hu, and Yun He* Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, 55 Daxuecheng South Road, Shapingba, Chongqing 401331, PR China S Supporting Information *

ABSTRACT: The first formal [3 + 2] cycloaddition reaction of in situ generated azaoxyallyl cation with cyclic ketones has been developed using mild reaction conditions. A variety of spiro-4-oxazolidinones was obtained in excellent yields (up to 99%). The high efficiency of this process, coupled with the operational simplicity, makes it an attractive method for the synthesis of spiro-4-oxazolidinones.

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diseases.5 Sterically hindered polymethylpiperidines F and its analogues are light stabilizers (HALS) and particularly effective in stabilizing polymers, against the deleterious effects of oxidative, thermal and actinic radiation.6 These examples highlight the wide applications of spirooxazolidinones. Herein, we report an efficient [3 + 2] cycloaddition of azaoxyallyl cation with cyclic ketones to synthesize spiro-4-oxazolidinones. In recent years, the preparation of 4-oxazolidinone derivatives has received much attention due to their significant applications. For example, Ye,7 Feng,8 and Smith9 groups utilized oxaziridines to react with ketenes, azlactones or anhydrides to assemble 4-oxazolinones, respectively. Despite these important and elegant advances, it remains highly demanded to develop more practical and efficient synthetic methodologies for the rapid construction of spiro-4-oxazolidinones, which may present more opportunities to the applications of common 4-oxazolidinones. Azaoxyallyl cation intermediates, which can be generally in situ generated from α-halo hydroxamates in the presence of organic or inorganic bases, were recently used as versatile surrogates of “1,3-dipole” in [3 + 1], [3 + 2], [3 + 3] and [4 + 3] cycloaddition reactions with sulfur ylides,10 aldehydes,11 indoles,12 2-alkenylindoles,13 nitrones,14 and electron-rich dienes,15 respectively. Encouraged by the previous works on the synthetic methodology of azaoxyallyl cations, and based on our own research interest in heterocycle synthesis,16 we envisioned that azaoxyallylic cations may also react with cyclic ketones to generate spiro-4-oxazolidinones in a convenient [3 + 2] cycloaddition manner, as proposed in Scheme 1. To the best of our knowledge, no such a work has been reported to date. We initiated our studies by examining the [3 + 2] cycloaddition of benzofuranone 1a with the azaoxyallyl cation in situ generated from N-(benzyloxy)-2-bromo-2-methylpropa-

wing to their inherent three-dimensional architecture and structural novelty, spirocyclic systems are privileged structure moieties found in many biologically active natural products and pharmaceutically important compounds.1 In particular, spiro-4-oxazolidinones, which bear heteroatomsubstituted quaternary stereocenters, are useful building blocks to construct medicinally relevant compounds and advanced materials, but have not been studied thoroughly. As outlined in Figure 1, “Kamiya disulfide” A was found to rearrange to 2β-

Figure 1. Representative compounds containing spiro-4-oxazolidinone moieties.

(benzothiazolylthiomethyl)-penams B upon thermolysis.2 Spirooxazolidinone C and its analogues exhibit antagonistic activity for orexin receptor, and thus are potentially useful for therapeutic or prophylactic treatment of orexin receptorassociated disorders.3 1,2,4-Triazole derivative D and its analogues exhibit promising antitumor activities.4 Spiro-4oxazolidinone E is useful in treating inflammatory and immune © 2017 American Chemical Society

Received: July 11, 2017 Published: September 19, 2017 10680

DOI: 10.1021/acs.joc.7b01728 J. Org. Chem. 2017, 82, 10680−10686

Note

The Journal of Organic Chemistry Scheme 1. Reaction of Azaoxyallyl Cation Intermediate with Cyclic Ketone

14). While changes of temperature did not significantly impact the cycloaddition (entries 15 and 16). The addition of 4 Å molecular sieves improved the reaction with 3a produced in over 95% yield (entry 17). Having identified the optimized reaction conditions, we next explored the substrate scope. All the tested substrates worked well and a wide range of spiro-4-oxazolidinones 3 were prepared in excellent yields as shown in Scheme 2. We

namide 2a (Table 1). Pleasantly, the cycloaddition proceeded smoothly and the desired spiro-4-oxazolidinone 3a was

Scheme 2. [3 + 2] Cycloaddition of Azaoxyallyl Cation with Benzofuranonea,b

Table 1. Optimization of Reaction Conditions

entry

1a:2a

base

solvent

temp

yield (%)a

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17b

1:2 1:2 1:2 1:2 1:2 1:2 1:2 1:2 1:2 1:2 1:2 1:2 1:1 1:3 1:3 1:3 1:3

K2CO3 Na2CO3 Cs2CO3 KHCO3 Et3N DIPEA DIPA DIPA DIPA DIPA DIPA DIPA DIPA DIPA DIPA DIPA DIPA

HFIP HFIP HFIP HFIP HFIP HFIP HFIP TFE THF DCM toluene CH3CN HFIP HFIP HFIP HFIP HFIP

RT RT RT RT RT RT RT RT RT RT RT RT RT RT 0 °C 40 °C RT

56 73 48 62 88 85 90 16 6 95%) (Scheme 4). It is worth mentioning that the cyclization occurred on the carbonyl group, not on the (Z)-2-benzylidene moiety. The structure of 6a was established by single crystal Xray analysis (see Supporting Information for details), and those of other products 3 and 6 were assigned by analogy.19 Other aurone analogues could well tolerate the existence of electron-poor or electron-rich phenyl rings as R2 group, the position of substituents at the para, meta, or ortho positions did not affect the reaction, and furnished products 6 in excellent yields (6b−6g). The benzofuranone moieties with electrondonating groups led to almost quantitative yields (6k, 6l), whereas introduction of electron-donating group (Br) to the benzofuranone moiety led to the corresponding product 6m with a slight loss of yield. Moreover, on replacement of the R2 group of the aurone analogues with β-naphthyl, 2-furanyl, 2thiophenyl and styryl respectively, the reactions could still undergo smoothly, affording the desired products 6h, 6i, 6j in almost quantitative yields in contrast, the aurone analogues 5m, including benzyl as R2 group, provide product 6m in a diminished yield. Introducing of (E)-3-phenylallylidene to the benzofuranone moieties, the desired cycloadduct 6n was generated in excellent yield. Notably, the formed cycloaddition products 6 are highly functionalized, along with alkene moieties which are easy for further structural modifications. As shown in Scheme 5, oxidation of 6a could efficiently afford functionalized epoxide 7 in excellent yield with good diastereoselectivity. Hydrogenation of

a

See Scheme 2 for details.

Scheme 5. Transformation of 6a

6a readily generated product 8 in nearly quantitative yield with moderate diastereoselectivity. The structures of 7 (major isomer) and 8 (major isomer) were unambiguously established by single crystal X-ray analysis (see Supporting Information for details).19 As expected, the same set of reaction conditions could be utilized for the [3 + 2] cycloaddition of azaoxyallyl cation with isatin 9, giving the desired product 10 in decent yield exclusively (Scheme 6).20 In summary, we have developed the first formal [3 + 2] cycloaddition reaction of in situ generated azaoxyallyl cation with cyclic ketones using mild reaction conditions. A variety of spiro-4-oxazolidinones was obtained in excellent yields (up to 99%). The high efficiency of this process, coupled with the operational simplicity, makes it an attractive method for spiro10682

DOI: 10.1021/acs.joc.7b01728 J. Org. Chem. 2017, 82, 10680−10686

Note

The Journal of Organic Chemistry

NMR (400 MHz, CDCl3) δ 7.28 (q, J = 5.8 Hz, 3H), 7.17 (m, J = 5.3 Hz, 3H), 6.57 (dd, J = 3.5 Hz, 1H), 6.43 (d, J = 1.8 Hz, 1H), 5.01 (d, J = 9.9 Hz, 1H), 4.60 (dd, J = 11.2 Hz, 2H), 4.36 (d, J = 10.7 Hz, 1H), 3.81 (s, 3H), 1.57 (s, 3H), 1.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.7, 163.9, 163.5, 134.1, 129.6, 129.1, 128.5, 125.2, 114.6, 109.3, 98.2, 96.2, 79.1, 77.6, 77.5, 55.7, 26.5, 25.8; HRMS (ESI) calcd for C20H21NNaO5+ [M + Na+]: 378.1317, found 378.1309. 3′-(Benzyloxy)-6-isopropoxy-5′,5′-dimethyl-2H-spiro[benzofuran-3,2′-oxazolidin]-4′-one (3d). White solid, yield 39 mg (>95%), mp 97−99 °C; Rf = 0.54 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.28 (q, J = 5.7 Hz, 3H), 7.16 (q, J = 6.2 Hz, 3H), 6.54 (q, J = 3.5 Hz, 1H), 6.42 (d, J = 1.8 Hz, 1H), 5.02 (d, J = 9.8 Hz, 1H), 4.59 (t, J = 9.7 Hz, 2H), 4.54 (q, J = 6.1 Hz, 1H), 4.35 (d, J = 10.7 Hz, 1H), 1.57 (s, 3H), 1.43 (s, 3H), 1.35 (dd, J = 2.8, 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 170.7, 163.6, 162.2, 134.2, 129.6, 129.1, 128.5, 125.2, 114.3, 110.9, 98.2, 97.9, 79.1, 77.6, 77.5, 70.5, 26.5, 25.8, 22.0, 22.0; HRMS (ESI) calcd for C22H25NNaO5+ [M + Na+]: 406.1630, found 406.1621. 3′,6-Bis(benzyloxy)-5′,5′-dimethyl-2H-spiro[benzofuran-3,2′-oxazolidin]-4′-one (3e). White solid, yield 43 mg (>95%), mp 108−109 °C; Rf = 0.5 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.41 (m, J = 6.8 Hz, 4H), 7.34 (t, J = 6.7 Hz, 1H), 7.28 (q, J = 6.8 Hz, 3H), 7.20 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 6.4 Hz, 2H), 6.65 (q, J = 3.5 Hz, 1H), 6.52 (d, J = 1.8 Hz, 1H), 5.08 (s, 2H), 5.02 (d, J = 9.9 Hz, 1H), 4.61 (t, J = 9.6 Hz, 2H), 4.36 (d, J = 10.7 Hz, 1H), 1.58 (s, 3H), 1.44 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.7, 163.5, 163.0, 136.5, 134.1, 129.6, 129.1, 128.8, 128.5, 128.3, 127.6, 125.3, 115.0, 110.0, 98.1, 97.3, 79.1, 77.6, 77.5, 70.4, 26.5, 25.8; HRMS (ESI) calcd for C26H25NNaO5+ [M + Na+]: 454.1630, found 454.1620. 6-(Allyloxy)-3′-(benzyloxy)-5′,5′-dimethyl-2H-spiro[benzofuran3,2′-oxazolidin]-4′-one (3f). White solid, yield 39 mg(>95%), mp 75−76 °C; Rf = 0.4 (silica gel, petroleum ether: EtOAc = 2:1); 1H NMR (400 MHz, CDCl3) δ 7.27 (t, J = 6.4 Hz, 3H), 7.17 (q, J = 7.0 Hz, 3H), 6.59 (dd, J = 1.2, 8.3 Hz, 1H), 6.44 (s, 1H), 6.05 (m, J = 5.4 Hz, 1H), 5.42 (d, J = 17.2 Hz, 1H), 5.31 (d, J = 10.5 Hz, 1H), 5.01 (d, J = 9.8 Hz, 1H), 4.58 (m, J = 6.8 Hz, 4H), 4.36 (d, J = 10.7 Hz, 1H), 1.57 (s, 3H), 1.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.7, 163.5, 162.9, 134.1, 132.8, 129.6, 129.1, 128.5, 125.2, 118.2, 114.8, 109.9, 98.2, 97.1, 79.1, 77.6, 77.6, 69.3, 26.5, 25.8; HRMS (ESI) calcd for C22H23NNaO5+ [M + Na+]: 404.1474, found 404.1465. 3′-(Benzyloxy)-5′,5′-dimethyl-6-(prop-2-yn-1-yloxy)-2H-spiro[benzofuran-3,2′-oxazolidin]-4′-one (3g). White solid, yield 39 mg(>95%), mp 125−126 °C; Rf = 0.35 (silica gel, petroleum ether: EtOAc = 2:1); 1H NMR (400 MHz, CDCl3) δ 7.28 (m, J = 4.7 Hz, 3H), 7.19 (d, J = 8.4 Hz, 1H), 7.14 (q, J = 2.9 Hz, 2H), 6.62 (q, J = 3.5 Hz, 1H), 6.52 (d, J = 2.1 Hz, 1H), 5.02 (d, J = 9.9 Hz, 1H), 4.70 (d, J = 2.3 Hz, 2H), 4.60 (t, J = 10.4 Hz, 2H), 4.36 (d, J = 10.8 Hz, 1H), 2.55 (t, J = 2.3 Hz, 1H), 1.57 (s, 3H), 1.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.8, 163.4, 161.7, 134.1, 129.6, 129.1, 128.5, 125.3, 115.7, 109.8, 98.1, 97.5, 79.1, 78.1, 77.7, 77.6, 76.1, 56.2, 26.5, 25.8; HRMS (ESI) calcd for C22H21NNaO5+ [M + Na+]: 402.1317, found 402.1309. 3′-(Benzyloxy)-6-((10-((tert-butyldimethylsilyl)oxy)decyl)oxy)5′,5′-dimethyl-2H-spiro[benzofuran-3,2′-oxazolidin]-4′-one (3h). Colorless oil, yield 61 mg (>95%); Rf = 0.6 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.28 (m, J = 3.7 Hz, 3H), 7.17 (m, J = 3.9 Hz, 3H), 6.56 (d, J = 8.4 Hz, 1H), 6.41 (s, 1H), 5.01 (d, J = 9.8 Hz, 1H), 4.59 (t, J = 10.8 Hz, 2H), 4.35 (d, J = 10.7 Hz, 1H), 3.95 (t, J = 6.4 Hz, 2H), 3.60 (t, J = 6.6 Hz, 2H), 1.78 (m, J = 6.6 Hz, 2H), 1.57 (s, 3H), 1.48 (m, J = 7.5 Hz, 4H), 1.43 (s, 3H), 1.30 (m, 10H), 0.90 (s, 9H), 0.05 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 170.7, 163.6, 163.5, 134.2, 129.6, 129.1, 128.5, 125.1, 114.4, 109.8, 98.2, 96.8, 79.1, 77.6, 77.5, 68.6, 63.5, 33.0, 29.7, 29.6, 29.6, 29.5, 29.2, 26.5, 26.1, 25.9, 25.8, 18.5, −5.1; HRMS (ESI) calcd for C35H53NNaO6Si+ [M + Na+]: 634.3540, found 634.3533. 5-Benzoyl-3′-(benzyloxy)-5′,5′-dimethyl-2H-spiro[benzofuran3,2′-oxazolidin]-4′-one (3i). White solid, yield 37 mg (86%), mp 95− 96 °C; Rf = 0.40 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.90 (dd, J = 1.6, 8.6 Hz, 1H), 7.78 (d, J = 1.6

Scheme 6. [3 + 2] Cycloaddition of Azaoxyallyl Cation with Isatin

4-oxazolidinone synthesis. The progress of an asymmetric version of this cycloaddition and the application of this methodology to synthesize more promising analogues for biological evaluations are ongoing in our laboratory.

■

EXPERIMENTAL SECTION

General Information. Unless otherwise noted, all chemicals were purchased from commercial suppliers and used without further purification. Dichloromethane (DCM) was distilled from calcium hydride. Methanol (MeOH) was dried under reflux with magnesium and then distilled. Reactions were monitored by analytical thin-layer chromatography (TLC) on Merck silica gel 60 F254 plates (0.25 mm), visualized by ultraviolet light (254 nm) or by staining with ceric ammonium molybdate or basic potassium permanganate solutions as appropriate. 1H NMR spectra were obtained on an Agilent 400MR or 600MR DD2 spectrometer at ambient temperature. Data were reported as follows: chemical shift on the δ scale using residual proton solvent as internal standard [δ 7.26 (CDCl3); TMS: 0.00 ppm], multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets), integration, and coupling constant (J) in hertz (Hz). 13C NMR spectra were obtained with proton decoupling on an Agilent 400MR DD2 (100 MHz) spectrometer and were reported in ppm with residual solvent for internal standard [δ 77.16 (CDCl3)]. High resolution mass spectra were obtained on a Bruker SolariX 7.0T FT-ICR mass spectrometer. General Procedure for the Synthesis of Spiro-4-oxazolidinones. In a 10 mL Schlenk tube was sequentially added furanones (0.1 mmol, 1.0 equiv), DIPA (0.45 mmol, 4.5 equiv), αhalohydroxamates 2 (0.3 mmol, 3.0 equiv), 4 Å MS (100 mg) and HFIP (0.5 mL). Then, the tube was sealed and stirred at room temperature. Once the starting material was completely consumed, the reaction mixture was diluted with ethyl acetate and concentrated under reduced pressure and the resulting residue was purified by flash column chromatography on silica gel to afford the pure product. 3′-(Benzyloxy)-5′,5′-dimethyl-2H-spiro[benzofuran-3,2′-oxazolidin]-4′-one (3a). White solid, yield 33 mg (>95%), mp 88−89 °C; Rf = 0.55 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.39 (m, J = 4.2 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.27 (q, J = 7.1 Hz, 3H), 7.11 (t, J = 3.9 Hz, 1H), 7.01 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 8.2 Hz, 1H), 5.01 (d, J = 9.8 Hz, 1H), 4.60 (d, J = 10.8 Hz, 1H), 4.54 (d, J = 9.8 Hz, 1H), 4.35 (d, J = 10.8 Hz, 1H), 1.60 (s, 3H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.8, 161.9, 134.1, 132.7, 129.6, 129.1, 128.6, 124.8, 122.9, 121.7, 111.5, 98.3, 79.1, 77.9, 76.7, 26.5, 25.9; HRMS (ESI) calcd for C19H19NNaO4+ [M + Na+]: 348.1212, found 348.1204. 3′-(Benzyloxy)-5′,5′-dimethyl-6H-spiro[furo[2,3f ][1,3]benzodioxole-7,2′-oxazolidine]-4′-one (3b). White solid, Yield 37 mg (>95%), mp 116−117 °C; Rf = 0.39 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J = 6.3 Hz, 3H), 7.19 (q, J = 3.0 Hz, 2H), 6.56 (s, 1H), 6.40 (s, 1H), 5.96 (dd, J = 3.7 Hz, 2H), 5.02 (d, J = 10.1 Hz, 1H), 4.68 (d, J = 10.1 Hz, 1H), 4.61 (d, J = 10.8 Hz, 1H), 4.33 (d, J = 10.8 Hz, 1H), 1.55 (s, 3H), 1.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 171.0, 157.6, 151.7, 142.9, 134.3, 129.6, 129.1, 128.5, 113.5, 103.0, 102.0, 98.9, 93.7, 79.0, 77.6, 26.5, 25.8; HRMS (ESI) calcd for C20H19NNaO6+ [M + Na+]: 392.1110, found 392.1101. 3′-(Benzyloxy)-6-methoxy-5′,5′-dimethyl-2H-spiro[benzofuran3,2′-oxazolidin]-4′-one (3c). White solid, yield 36 mg (>95%), mp 74−75 °C; Rf = 0.43 (silica gel, petroleum ether: EtOAc = 5:1); 1H 10683

DOI: 10.1021/acs.joc.7b01728 J. Org. Chem. 2017, 82, 10680−10686

Note

The Journal of Organic Chemistry Hz, 1H), 7.73 (t, J = 3.8 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.49 (d, J = 7.7 Hz, 2H), 7.23 (t, J = 6.8 Hz, 3H), 7.12 (t, J = 3.8 Hz, 2H), 6.97 (d, J = 8.6 Hz, 1H), 5.04 (d, J = 10.2 Hz, 1H), 4.69 (d, J = 16.6 Hz, 1H), 4.66 (d, J= 15.9 Hz, 1H), 4.43 (d, J = 11.0 Hz, 1H), 1.57 (s, 3H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 194.8, 171.2, 165.2, 138.0, 135.8, 134.0, 132.4, 131.7, 129.8, 129.6, 129.3, 128.6, 128.5, 127.9, 123.8, 111.1, 97.6, 79.1, 78.1, 77.6, 26.5, 25.9; HRMS (ESI) calcd for C26H23NNaO5+ [M + Na+]: 452.1474, found 452.1463. 3′-(Benzyloxy)-6-bromo-5′,5′-dimethyl-2H-spiro[benzofuran3,2′-oxazolidin]-4′-one (3j). White solid, yield 37 mg (92%), mp 90− 92 °C; Rf = 0.5 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.29 (m, J = 6.2 Hz, 3H), 7.13 (d, J = 6.9 Hz, 1H), 7.08 (s, 2H), 5.02 (d, J = 10.2 Hz, 1H), 4.60 (dd, J = 10.0 Hz, 2H), 4.33 (d, J = 10.8 Hz, 1H), 1.57 (s, 3H), 1.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 171.1, 162.5, 134.1, 129.6, 129.2, 128.6, 126.2, 125.7, 125.1, 122.4, 115.0, 97.8, 79.0, 77.9, 26.5, 25.8; HRMS (ESI) calcd for C19H18BrNNaO4+ [M + Na+]: 426.0317, found 426.0307. 3′-(Benzyloxy)-5′,5′-dimethyl-2,3-dihydrospiro[indene-1,2′-oxazolidin]-4′-one (3k). White solid, yield 33 mg (>95%), mp 75−76 °C; Rf = 0.55 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.41 (t, J = 6.1 Hz, 2H), 7.28 (m, J = 5.4 Hz, 5H), 7.07 (t, J = 3.8 Hz, 2H), 4.93 (d, J = 9.6 Hz, 1H), 4.31 (d, J = 9.6 Hz, 1H), 2.99 (t, J = 6.9 Hz, 2H), 2.58 (m, J = 6.6 Hz, 1H), 2.30 (m, J = 5.9 Hz, 1H), 1.59 (s, 3H), 1.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 171.0, 144.7, 140.0, 134.3, 130.6, 129.6, 128.9, 128.4, 127.4, 125.3, 124.2, 101.0, 79.0, 36.7, 29.2, 26.6, 25.8; HRMS (ESI) calcd for C20H21NNaO3+ [M + Na+]: 346.1419, found 346.1412. 3′-(Benzyloxy)-5′,5′-dimethylspiro[chromane-4,2′-oxazolidin]-4′one (3l). White solid, yield 34 mg (>95%), mp 84−86 °C; Rf = 0.5 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.41 (q, J = 3.1 Hz, 1H), 7.28 (m, J = 3.7 Hz, 4H), 7.21 (q, J = 3.1 Hz, 2H), 6.98 (t, J = 7.5 Hz, 1H), 6.89 (d, J = 8.3 Hz, 1H), 5.09 (d, J = 9.8 Hz, 1H), 4.67 (d, J = 9.8 Hz, 1H), 4.33 (m, J = 5.0 Hz, 2H), 2.53 (m, J = 4.8 Hz, 1H), 1.96 (m, J = 3.2 Hz, 1H), 1.58 (s, 3H), 1.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 171.8, 157.0, 134.3, 131.3, 129.7, 129.1, 128.5, 127.8, 121.5, 121.0, 117.6, 87.6, 78.7, 77.3, 63.4, 34.6, 26.8, 26.8; HRMS (ESI) calcd for C20H21NNaO4+ [M + Na+]: 362.1368, found 362.1361. (Z)-2H-4′,4′-Dimethyl-3,4-dihydro-2H-spiro[benzo[b]oxepine5,2′-[1,3]dioxolan]-5′-one-O-benzyloxime (3m). White solid, yield 29 mg (83%), mp 105−106 °C; Rf = 0.56 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 7.5 Hz, 1H), 7.35 (m, J = 7.0 Hz, 4H), 7.23 (d, J = 7.9 Hz, 1H), 7.00 (t, J = 7.9 Hz, 2H), 5.07 (s, 2H), 4.34 (m, J = 4.1 Hz, 1H), 3.80 (t, J = 9.9 Hz, 1H), 2.32 (m, J = 4.7 Hz, 1H), 2.22 (q, J = 3.9 Hz, 2H), 1.91 (m, J = 3.5 Hz, 1H), 1.52 (s, 3H), 1.13 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.7, 157.9, 138.1, 134.0, 130.4, 128.5, 128.4, 127.9, 126.0, 123.6, 122.5, 112.5, 80.1, 76.6, 72.8, 38.0, 28.7, 27.4, 25.8; HRMS (ESI) calcd for C21H23NNaO4+ [M + Na+]: 376.1525, found 376.1516. (8R,9S,13S,14S)-3′-(Benzyloxy)-3-hydroxy-5′,5′,13-trimethyl6,7,8,9,11,12,13,14,15,16-decahydrospiro[cyclopenta[a]phenanthrene-17,2′-oxazolidin]-4′-one (4). White solid, yield 38 mg (82%), mp 124−125 °C; Rf = 0.3 (silica gel, petroleum ether: EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 9.06 (s, 1H), 7.37 (m, J = 3.1 Hz, 5H), 7.15 (d, J = 8.5 Hz, 1H), 6.64 (d, J = 8.4 Hz, 1H), 6.59 (s, 1H), 4.95 (s, 2H), 2.84 (d, J = 5.2 Hz, 2H), 2.50 (q, J = 9.2 Hz, 1H), 2.37 (d, J = 9.6 Hz, 1H), 2.25 (d, J = 9.9 Hz, 1H), 2.06 (m, J = 6.0 Hz, 4H), 1.66 (s, 1H), 1.57 (m, J = 9.9 Hz, 3H), 1.50 (s, 6H), 1.44 (q, J = 10.1 Hz, 2H), 0.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 172.3, 151.8, 137.8, 135.2, 129.5, 128.9, 128.7, 126.3, 121.6, 118.9, 81.5, 78.3, 50.5, 48.1, 44.2, 38.3, 36.0, 31.7, 29.6, 26.6, 25.9, 25.4, 25.3, 21.7, 14.0; HRMS (ESI) calcd for C29H35NNaO4+ [M + Na+]: 484.2464, found 484.2451. (Z)-2-Benzylidene-3′-(benzyloxy)-5′,5′-dimethyl-2H-spiro-[benzofuran-3,2′-oxazolidin]-4′-one (6a). White solid, yield 41 mg (>95%), mp 111−113 °C; Rf = 0.55 (silica gel, petroleum ether: EtOAc = 5:1); 1 H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.6 Hz, 2H), 7.42 (m, J = 7.7 Hz, 3H), 7.28 (m, J = 7.8 Hz, 5H), 7.13 (m, J = 7.4 Hz, 4H), 5.98 (s, 1H), 5.01 (d, J = 10.1 Hz, 1H), 4.86 (d, J = 10.0 Hz, 1H), 1.70 (s, 3H), 1.68 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.3, 157.8,

152.5, 134.0, 133.4, 132.5, 129.4, 129.3, 128.9, 128.5, 128.3, 127.7, 125.0, 123.3, 122.9, 111.4, 108.0, 95.5, 78.7, 77.9, 27.5, 27.3; HRMS (ESI) calcd for C26H23NNaO4+ [M + Na+]: 436.1525, found 436.1516. (Z)-3′-(Benzyloxy)-5′,5′-dimethyl-2-(2-methylbenzylidene)-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6b). White solid, yield 39 mg (92%), mp 109−111 °C; Rf = 0.5 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.8 Hz, 1H), 7.43 (t, J = 7.8 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.28 (m, J = 3.9 Hz, 1H), 7.21 (d, J = 12.9 Hz, 5H), 7.12 (m, J = 4.8 Hz, 4H), 6.20 (s, 1H), 5.04 (d, J = 10.0 Hz, 1H), 4.87 (d, J = 10.0 Hz, 1H), 2.36 (s, 3H), 1.71 (s, 3H), 1.69 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.3, 158.0, 152.8, 136.1, 134.2, 132.6, 132.0, 130.3, 129.7, 129.4, 129.0, 128.4, 127.9, 126.2, 125.1, 123.4, 123.1, 111.6, 105.1, 105.1, 95.5, 78.8, 78.0, 27.6, 27.4, 20.3; HRMS (ESI) calcd for C27H25NNaO4+ [M + Na+]: 450.1681, found 450.1673. (Z)-3′-(Benzyloxy)-2-(3-methoxybenzylidene)-5′,5′-dimethyl-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6c). White solid, yield 44 mg (>95%), mp 143−144 °C; Rf = 0.38 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3δ 7.44 (t, J = 7.8 Hz, 1H), 7.31 (q, J = 4.9 Hz, 4H), 7.20 (t, J = 6.2 Hz, 3H), 7.12 (m, J = 4.5 Hz, 4H), 6.84 (m, J = 2.3 Hz, 1H), 5.94 (s, 1H), 4.99 (d, J = 10.0 Hz, 1H), 4.84 (d, J = 10.1 Hz, 1H), 3.86 (s, 3H), 1.68 (s, 3H), 1.66 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 159.7, 158.0, 152.8, 134.8, 134.1, 132.6, 129.6, 129.5, 129.0, 128.5, 125.1, 123.5, 123.0, 122.1, 114.9, 113.5, 111.6, 108.0, 95.7, 78.8, 78.0, 55.4, 27.6, 27.4; HRMS (ESI) calcd for C27H25NNaO5+ [M + Na+]: 466.1630, found 466.1620. (Z)-3′-(Benzyloxy)-2-(4-methoxybenzylidene)-5′,5′-dimethyl-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6d). White solid, yield 45 mg (>95%), mp 149−151 °C; Rf = 0.38 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.7 Hz, 2H), 7.43 (t, J = 7.7 Hz, 1H), 7.32 (d, J = 7.4 Hz, 1H), 7.21 (q, J = 5.7 Hz, 3H), 7.11 (m, J = 6.9 Hz, 4H), 6.93 (d, J = 8.7 Hz, 2H), 5.92 (s, 1H), 4.99 (d, J = 10.1 Hz, 1H), 4.84 (d, J = 10.0 Hz, 1H), 3.84 (s, 3H), 1.67 (s, 3H), 1.66 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.4, 159.2, 158.0, 150.8, 134.2, 132.5, 130.8, 129.5, 129.0, 128.4, 126.3, 125.0, 123.3, 123.1, 114.1, 111.5, 107.9, 95.7, 78.8, 77.9, 55.4, 27.6, 27.4; HRMS (ESI) calcd for C27H25NNaO5+ [M + Na+]: 466.1630, found 466.1620. (Z)-3′-(Benzyloxy)-2-(2-chlorobenzylidene)-5′,5′-dimethyl-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6e). White solid, yield 40 mg (89%), mp 99−100 °C; Rf = 0.45 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 7.9 Hz, 1H), 7.43 (q, J = 8.8 Hz, 2H), 7.33 (q, J = 3.5 Hz, 2H), 7.21 (q, J = 4.3 Hz, 4H), 7.13 (q, J = 7.4 Hz, 4H), 6.51 (s, 1H), 5.03 (d, J = 10.1 Hz, 1H), 4.92 (d, J = 10.1 Hz, 1H), 1.73 (s, 3H), 1.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.3, 157.8, 154.4, 134.3, 133.4, 132.7, 131.4, 130.9, 129.6, 129.5, 128.9, 128.8, 128.5, 127.0, 125.1, 123.7, 123.1, 111.5, 103.5, 95.6, 78.9, 78.3, 27.5, 27.4; HRMS (ESI) calcd for C26H22ClNNaO4+ [M + Na+]: 470.1135, found 470.1125. (Z)-3′-(Benzyloxy)-2-(3-chlorobenzylidene)-5′,5′-dimethyl-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6f). White solid, yield 42 mg (94%), mp 119−120 °C; Rf = 0.45 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.31 (m, J = 4.9 Hz, 2H), 7.26 (s, 1H), 7.17 (m, J = 5.7 Hz, 7H), 5.87 (s, 1H), 5.01 (d, J = 10.2 Hz, 1H), 4.83 (d, J = 10.2 Hz, 1H), 1.69 (s, 3H), 1.68 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 157.8, 153.7, 135.3, 134.5, 134.1, 132.7, 129.8, 129.5, 129.1, 129.0, 128.5, 127.7, 127.5, 125.1, 123.7, 122.9, 111.6, 106.6, 95.6, 78.7, 78.1, 27.6, 27.4; HRMS (ESI) calcd for C26H22ClNNaO4+ [M + Na+]: 470.1135, found 470.1130. (Z)-3′-(Benzyloxy)-2-(4-bromobenzylidene)-5′,5′-dimethyl-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6g). White solid, yield 46 mg (93%), mp 128−129 °C; Rf = 0.5 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.6 Hz, 2H), 7.50 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 15.6 Hz, 1H), 7.32 (d, J = 7.4 Hz, 1H), 7.20 (q, J = 5.7 Hz, 3H), 7.13 (m, J = 5.6 Hz, 4H), 5.86 (s, 1H), 4.99 (d, J = 10.2 Hz, 1H), 4.82 (d, J = 10.2 Hz, 1H), 1.67 (s, 3H), 1.66 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 157.8, 153.2, 134.1, 132.7, 132.5, 131.8, 130.9, 129.5, 129.0, 128.5, 125.1, 123.6, 122.9, 121.7, 111.6, 106.8, 95.6, 78.5, 78.1, 27.6, 27.4; HRMS 10684

DOI: 10.1021/acs.joc.7b01728 J. Org. Chem. 2017, 82, 10680−10686

Note

The Journal of Organic Chemistry (ESI) calcd for C26H22BrNNaO4+ [M + Na+]: 514.0630, found 514.0621. (Z)-3′-(Benzyloxy)-5′,5′-dimethyl-2-(naphthalen-2-ylmethylidene)-2H-spiro[benzofuran-3,2′-oxazolidin]-4′-one (6h). White solid, yield 46 mg (>95%), mp 165−166 °C; Rf = 0.55 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.93 (q, J = 3.3 Hz, 1H), 7.85 (m, J = 5.5 Hz, 3H), 7.47 (m, J = 3.5 Hz, 3H), 7.35 (d, J = 7.6 Hz, 1H), 7.20 (m, J = 3.4 Hz, 4H), 7.13 (m, J = 4.3 Hz, 3H), 6.12 (s, 1H), 5.02 (d, J = 10.1 Hz, 1H), 4.87 (d, J = 10.1 Hz, 1H), 1.73 (s, 3H), 1.69 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 158.0, 152.9, 134.2, 133.6, 132.8, 132.6, 131.2, 129.5, 129.0, 128.8, 128.5, 128.4, 128.2, 127.8, 127.1, 126.4, 125.1, 123.5, 123.1, 111.6, 108.2, 95.7, 78.8, 78.1, 27.6, 27.5; HRMS (ESI) calcd for C30H25NNaO4+ [M + Na+]: 486.1681, found 486.1680. (Z)-3′-(Benzyloxy)-5′,5′-dimethyl-2-(thiophen-2-ylmethylidene)2H-spiro[benzofuran-3,2′-oxazolidin]-4′-one (6i). White solid, yield 42 mg (>95%), mp 105−107 °C; Rf = 0.45 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.44 (t, J = 7.8 Hz, 1H), 7.37 (d, J = 5.0 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.23 (t, J = 5.8 Hz, 4H), 7.13 (m, J = 7.4 Hz, 4H), 7.06 (t, J = 4.3 Hz, 1H), 6.25 (s, 1H), 4.99 (d, J = 10.2 Hz, 1H), 4.84 (d, J = 10.1 Hz, 1H), 1.67 (s, 3H), 1.66 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 157.7, 150.7, 136.3, 134.2, 132.6, 129.5, 129.0, 128.4, 128.1, 127.2, 125.0, 123.5, 123.3, 111.6, 102.3, 102.3, 95.2, 78.7, 77.9, 27.5, 27.4; HRMS (ESI) calcd for C24H21NNaO4S+ [M + Na+]: 442.1089, found 442.1078. (Z)-2-Benzylidene-3′-(benzyloxy)-6-methoxy-5′,5′-dimethyl-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6j). White solid, yield 44 mg (>95%), mp 153−155 °C; Rf = 0.45 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3 δ 7.70 (d, J = 7.8 Hz, 2H), 7.38 (t, J = 7.6 Hz, 2H), 7.28 (d, J = 7.5 Hz, 1H), 7.19 (m, J = 3.7 Hz, 6H), 6.65 (m, J = 3.7 Hz, 2H), 5.92 (s, 1H), 4.99 (d, J = 10.1 Hz, 1H), 4.85 (d, J = 10.1 Hz, 1H), 3.86 (s, 3H), 1.67 (s, 3H), 1.64 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.4, 163.6, 159.6, 153.4, 134.3, 133.6, 129.5, 129.4, 129.0, 128.6, 128.5, 127.8, 125.6, 114.7, 110.5, 107.8, 96.8, 95.5, 78.8, 77.8, 55.9, 27.7, 27.3; HRMS (ESI) calcd for C27H25NNaO5+ [M + Na+]: 466.1630, found 466.1620. (Z)-6-Benzylidene-3′-(benzyloxy)-5′,5′-dimethyl-6H-spiro[furo[2,3-f ][1,3]benzodioxole-7,2′-oxazolidine]-4′-one (6k). White solid, yield 46 mg (>95%), mp 162−163 °C; Rf = 0.38 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 7.6 Hz, 2H), 7.38 (t, J = 7.5 Hz, 2H), 7.28 (d, J = 7.6 Hz, 1H), 7.22 (t, J = 8.3 Hz, 5H), 6.63 (s, 1H), 6.56 (s, 1H), 6.00 (d, J = 6.5 Hz, 1H), 5.90 (s, 1H), 4.96 (q, J = 11.0 Hz, 2H), 1.66 (s, 3H), 1.62 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.6, 153.5, 151.3, 144.1, 134.4, 133.5, 129.5, 129.4, 129.0, 128.6, 128.4, 127.8, 113.9, 110.2, 107.9, 103.6, 102.2, 96.2, 94.0, 78.7, 77.7, 27.8, 27.3; HRMS (ESI) calcd for C27H23NNaO6+ [M + Na+]: 480.1423, found 480.1412. (Z)-2-Benzylidene-3′-(benzyloxy)-6-bromo-5′,5′-dimethyl-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6l). White solid, yield 46 mg (94%), mp 145−146 °C; Rf = 0.55 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 7.5 Hz, 2H), 7.40 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 8.4 Hz, 2H), 7.22 (m, J = 3.8 Hz, 4H), 7.15 (d, J = 6.4 Hz, 2H), 7.09 (d, J = 8.1 Hz, 1H), 5.97 (s, 1H), 4.98 (d, J = 10.4 Hz, 1H), 4.91 (d, J = 10.4 Hz, 1H), 1.68 (s, 3H), 1.64 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.7, 158.4, 152.2, 134.2, 133.2, 129.5, 129.1, 128.7, 128.5, 128.1, 126.7, 126.0, 125.9, 122.3, 115.1, 108.9, 95.2, 78.7, 78.1, 27.6, 27.4; HRMS (ESI) calcd for C26H22BrNNaO4+ [M + Na+]: 514.0630, found 514.0629. (Z)-3′-(Benzyloxy)-5′,5′-dimethyl-2-(2-phenylethylidene)-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6m). White solid, yield 35 mg (81%), mp 129−130 °C; Rf = 0.5 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.41 (m, J = 4.2 Hz, 1H), 7.28 (m, J = 3.6 Hz, 4H), 7.22 (d, J = 4.2 Hz, 1H), 7.17 (m, J = 3.0 Hz, 1H), 7.08 (m, J = 3.2 Hz, 4H), 5.35 (t, J = 7.8 Hz, 1H), 4.93 (d, J = 9.9 Hz, 1H), 4.76 (d, J = 9.9 Hz, 1H), 3.74 (q, J = 7.9 Hz, 1H), 3.64 (q, J = 7.7 Hz, 1H), 1.63 (s, 3H), 1.57 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.3, 158.0, 153.5, 139.7, 134.3, 132.6, 129.4, 128.9, 128.7, 128.5, 128.5, 126.4, 125.1, 123.8, 123.0, 111.3, 107.9, 94.2, 78.7, 78.0, 31.6, 27.6, 27.2; HRMS (ESI) calcd for C27H25NNaO4+ [M + Na+]: 450.1681, found 450.1674.

(Z)-3′-(Benzyloxy)-5′,5′-dimethyl-2-((E)-3-phenylallylidene)-2Hspiro[benzofuran-3,2′-oxazolidin]-4′-one (6n). White solid, yield 44 mg (>95%), mp 132−133 °C; Rf = 0.55 (silica gel, petroleum ether: EtOAc = 5:1); 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 7.5 Hz, 2H), 7.43 (t, J = 7.8 Hz, 1H), 7.32 (m, J = 6.0 Hz, 4H), 7.23 (t, J = 8.7 Hz, 3H), 7.15 (q, J = 3.0 Hz, 2H), 7.09 (t, J = 7.9 Hz, 2H), 6.63 (d, J = 15.8 Hz, 1H), 5.89 (d, J = 11.0 Hz, 1H), 4.99 (d, J = 10.1 Hz, 1H), 4.83 (d, J = 10.1 Hz, 1H), 1.66 (s, 3H), 1.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.4, 157.7, 152.9, 137.2, 134.2, 133.8, 132.6, 129.5, 129.0, 128.8, 128.5, 128.1, 126.8, 125.1, 123.5, 123.2, 121.3, 111.3, 108.9, 94.7, 78.8, 77.9, 27.6, 27.3; HRMS (ESI) calcd for C28H25NNaO4+ [M + Na+]: 462.1681, found 462.1671. 3′-(Benzyloxy)-5′,5′-dimethylspiro[indoline-2,2′-oxazolidine]3,4′-dione (10). Light green oil, yield 30 mg (89%); Rf = 0.25 (silica gel, petroleum ether: EtOAc = 3:1); 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.6 Hz, 1H), 7.46 (q, J = 5.1 Hz, 1H), 7.36 (m, J = 5.5 Hz, 3H), 7.27 (s, 2H), 6.87 (t, J = 7.5 Hz, 1H), 6.57 (t,J = 4.2 Hz, 1H), 5.14 (d, J = 10.9 Hz, 1H), 4.91 (d, J = 10.9 Hz, 1H), 4.02 (s, 1H), 1.64 (s, 3H), 1.49 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 194.6, 172.1, 158.3, 138.7, 134.9, 130.2, 129.3, 129.3, 128.7, 128.6, 125.5, 120.8, 117.8, 112.2, 96.5, 79.6, 78.6, 27.0, 26.0; HRMS (ESI) calcd for C19H18N2NaO4+ [M + Na+]: 361.1164, found 361.1154. Synthesis of Compound 7. To a solution of 6a (100 mg, 0.24 mmol) in DCM (3 mL) was added m-CPBA (83.6 mg, 0.48 mmol) and the reaction mixture was stirred for 36 h at room temperature. The complete consumption of 6a was confirmed by TLC (Hexane:EtOAc = 5:1). The white precipitate was filtered, the filtrate was washed with aq NaHCO3 (5 mL) and brine (5 mL), and then the organic layer was dried with anhydrous Na2SO4. The solvents were removed under reduced pressure and purified by flash column chromatography (Hexane:EtOAc = 1:4 to 1:2) to afford the product 7 as a white solid. 3-(Benzyloxy)-5,5-dimethyl-3″-phenyldispiro[oxazolidine-2,3′benzofuran-2′,2″-oxiran]-4-one (7). White solid, yield 99 mg (96%, dr = 8.2:1), mp 135−136 °C; Rf = 0.25 (silica gel, petroleum ether: EtOAc = 2:1); 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 6.7 Hz, 6H), 7.28 (t, J = 6.8 Hz, 2H), 7.21 (t, J = 7.4 Hz, 2H), 7.05 (q, J = 7.2 Hz, 3H), 6.88 (d, J = 8.2 Hz, 1H), 5.01 (d, J = 9.9 Hz, 1H), 4.67 (d, J = 9.9 Hz, 1H), 4.20 (s, 1H), 1.64 (s, 3H), 1.56 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 171.4, 159.0, 133.9, 133.0, 132.4, 129.4, 129.1, 128.7, 128.5, 128.3, 127.2, 125.0, 123.0, 122.1, 111.9, 95.3, 93.9, 79.2, 78.6, 27.7, 25.6; HRMS (ESI) calcd for C26H23NNaO5+ [M + Na+]: 452.1474, found 452.1464. Synthesis of Compound 8. To a solution of 6a, 100 mg, 0.24 mmol) in ethanol (3 mL) was added 5% Pd/C (30 mg) and evacuated with house vacuum (water aspirator) and flushed with H2 gas through a balloon. The reaction mixture was stirred under H2 gas balloon at room temperature for 12 h. The complete consumption of 6a was confirmed by TLC (Hexane:EtOAc = 5:1). The mixture was passed through a Celite bed and washed with EtOAc (20 mL). The collected filtrate was concentrated under reduced pressure. Purification by flash column chromatography (Hexanes: EtOAc = 2:1) afforded the product 8 as a white solid. 2-Benzyl-3′-hydroxy-5′,5′-dimethyl-2H-spiro[benzofuran-3,2′-oxazolidin]-4′-one (8). White solid, yield 77 mg (99%, dr = 5.2:1), mp 149−150 °C; Rf = 0.2 (silica gel, petroleum ether: EtOAc = 2:1); 1H NMR (400 MHz, CDCl3) δ 9.72 (s, 1H), 7.35 (m, J = 5.8 Hz, 5H), 7.25 (d, J = 2.6 Hz, 2H), 7.01 (t, J = 7.4 Hz, 1H), 6.91 (d, J = 8.2 Hz, 1H), 4.79 (q,J = 4.7 Hz, 1H), 3.34 (q, J = 8.0 Hz, 1H), 3.15 (q, J = 6.5 Hz, 1H), 1.56 (s, 3H), 1.22 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.8, 137.5, 132.6, 129.4, 128.8, 126.9, 124.9, 122.9, 121.5, 111.5, 100.8, 89.7, 35.0, 27.2, 25.8; HRMS (ESI) calcd for C19H19NNaO4+ [M + Na+]: 348.1212, found 348.1205.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01728. X-ray analysis, and NMR spectra (PDF) 10685

DOI: 10.1021/acs.joc.7b01728 J. Org. Chem. 2017, 82, 10680−10686

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The Journal of Organic Chemistry

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Jeffrey, C. S. Synthesis 2013, 45, 1825−1836. (c) Barnes, K. L.; Koster, A. K.; Jeffrey, C. S. Tetrahedron Lett. 2014, 55, 4690−4696. (d) Acharya, A.; Eickhoff, J. A.; Chen, K.; Catalano, V. J.; Jeffrey, C. S. Org. Chem. Front. 2016, 3, 330−334. (16) (a) Zang, Z.-L.; Karnakanti, S.; Zhao, S.; Hu, P.; Wang, Z.; Shao, P.-L.; He, Y. Org. Lett. 2017, 19, 1354−1357. (b) Shao, P.-L.; Chen, X.-Y.; Sun, L.-H.; Ye, S. Tetrahedron Lett. 2010, 51, 2316−2318. (c) Shao, P.-L.; Liao, J.-Y.; Ho, Y. A.; Zhao, Y. Angew. Chem., Int. Ed. 2014, 53, 5435−5439. (d) Liao, J.-Y.; Shao, P.-L.; Zhao, Y. J. Am. Chem. Soc. 2015, 137, 628−631. (17) (a) Wang, Z.; Bae, E. J.; Han, Y. T. Arch. Pharmacal Res. 2017, 40, 695−703. (b) Boumendjel, A. Curr. Med. Chem. 2003, 10, 2621− 2630. (c) Zwick, V.; Chatzivasileiou, A.-O.; Deschamps, N.; Roussaki, M.; Simões-Pires, C. A.; Nurisso, A.; Denis, I.; Blanquart, C.; Martinet, N. Bioorg. Med. Chem. Lett. 2014, 24, 5497−5501. (d) Okombi, S.; Rival, D.; Bonnet, S.; Mariotte, A.-M.; Eric Perrier, E.; Boumendjel, A. J. Med. Chem. 2006, 49, 329−333. (18) (a) Wang, M.; Rong, Z.-Q.; Zhao, Y. Chem. Commun. 2014, 50, 15309−15312. (b) Zhang, C.-B.; Dou, P.-H.; Zhang, J.; Wei, Q.-Q.; Wang, Y.-B.; Zhu, J.-Y.; Fu, J.-Y.; Ding, T. ChemistrySelect 2016, 1, 4403−4407. (c) Hu, W.-Q.; Cui, Y.-S.; Wu, Z.-J.; Zhang, C.-B.; Dou, P.-H.; Niu, S.-Y.; Fu, J.-Y.; Liu, Y. RSC Adv. 2015, 5, 70910−70914. (19) CCDC 1554427 (6a), 1560536 (7), 1560971 (8), 1572853 (3m) contain the crystallographic data for this paper. The data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Selected data are also included in the Supporting Information. (20) Jiang, S.; Li, K.; Yan, J.; Shi, K.; Zhao, C.; Yang, L.; Zhong, G. J. Org. Chem. 2017, 82, 9779−9785.

Crystal data (CIF)

AUTHOR INFORMATION

Corresponding Authors

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

Yun He: 0000-0002-5322-7300 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful to the National Natural Science Foundation of China (No. 21402150, 21372267, 21572027), Fundamental Research Funds for the Central Universities (10611201CDJXY460001) and Chongqing University for financial support of this research. We thank Dr. Zhen Wang (Chongqing University) for useful discussion. We thank Dr. Yong-Liang Shao (Lanzhou University) and Xiangnan Gong (Chongqing University) for the X-ray crystallographic analysis.

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REFERENCES

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DOI: 10.1021/acs.joc.7b01728 J. Org. Chem. 2017, 82, 10680−10686