HETEROCYCLES

Communication | Special issue | Vol. 80, No. 1, 2010, pp. 187-198
Received, 15th July, 2009, Accepted, 18th August, 2009, Published online, 19th August, 2009.
DOI: 10.3987/COM-09-S(S)54

■ Synthesis of Functionalized Chromanes via a Formal [3+3]Cycloaddition of Allene Sulfonamides to Phenols

Ken Hashimoto, Yoshikazu Horino,* and Shigeyasu Kuroda*

Department of Applied Chemistry, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

The Brønsted acid catalyzed formal [3 + 3] cycloaddition reaction of allene sulfonamides 1 with phenols 2 provides functionalized chromanes. This formal [3 + 3] cycloaddition reaction is proposed to proceed via a stepwise process involving intermolecular hydroarylation followed by intramolecular cyclization.

The transition metal catalyzed intramolecular addition of phenolic oxygen nucleophiles to alkenes1 and the hydroarylation2 of oxygen-tethered arene-ene substrates are two of the most promising strategies for the synthesis of chromanes, which are of great interest due to their potentially broad range of biological activities.3 Furthermore, intermolecular reactions, which are an attractive and much simpler strategy for the synthesis of chromanes from commercially available phenols and allylic alcohols4 or 1,3-dienes,5 have also been extensively studied. A few approaches for the synthesis of chromanes which do not involve metal based catalysts, such as direct aromatic carbon-oxygen bond formation using tertiary phosphines,6 amines7 or Ipy2BF48 as a catalyst, or stoichiometric amount of hypervalent iodine reagent,9 have also been reported. However, Brønsted acid catalyzed approaches are particularly rare.10 We envisioned that regioselective intermolecular hydroarylation at the terminal sp2 carbon atom of an allene possessing an electron withdrawing group (EWG) with phenols could be a straightforward approach to the direct formation of the corresponding chromanes upon intramolecular addition of the phenolic hydroxy group to the internal allenic double bond (eq. 1). However, selective intermolecular nucleophilic addition to the terminal sp2 carbon atom rather than the central carbon atom of allenes is usually difficult11 as the vinyl anion generated is less stable.12

To overcome this problem, we decided to use the easily prepared allene sulfonamides 113 as their terminal sp2 carbon double bond has been found to behave as an enone toward heteronucleophiles.13b Thus, allene sulfonamide 1a reacts with phenol to form a carbon-oxygen bond at the terminal sp2 carbon atom of the allene. During the course of our study aimed at the synthesis of chromanes by a formal [3 + 3] cycloaddition reaction as shown in equation (1), we found that addition of a catalytic amount of a Brønsted acid to a mixture of 1a and p-cresol (2a; 2.0 equiv) completely suppresses carbon-oxygen bond formation at the terminal sp2 carbon atom of the allene bond to give 4, and the only product of the reaction (3a) is that resulting from a formal [3 + 3] cycloaddition reaction via a hydroarylation/cyclization pathway (Table 1).

We examined several Brønsted acids and found that the reaction rate increased with the acidity of the Brønsted acid (TfOH > Tf2NH > p-TsOH > CSA). The use of a strong Brønsted acid such as trifluoromethanesulfonic acid (TfOH) or trifluoromethanesulfonimide (Tf2NH) gave the best catalytic activity (entries 4 and 5). Furthermore, the use of Tf2NH as a catalyst allowed a lower catalyst loading with no effect on the yield of 3a (entry 6). It should be noted that the reaction could be carried out at room temperature (entry 7). To the best of our knowledge, there are no reports of the Brønsted acid catalyzed hydroarylation of allenes at room temperature.14

Under the optimized reaction conditions in hand, the scope of the reaction was investigated with a variety of functionalized phenols (see Table 2). The reaction feature has turned out to occur dependently of the electronic nature of the substituent on the benzene ring. For example, substrates containing electron　donating group afforded the desired products 3b in excellent yield (entry 1), whereas the presence of an electron withdrawing group resulted in a much longer reaction time and the corresponding products were obtained in only modest yield (entries 2-4). The structure of 3a was confirmed unequivocally by X-ray diffraction (Figure 1). Likewise, an electron-withdrawing group on the nitrogen of 1a is essential for the present reaction. Thus, while the use of 1b, which possesses a benzoyl group on nitrogen, also provided the corresponding chromanes 3f in high yield (entry 5), changing this substituent to a benzyl group resulted in none of the desired product being obtained. Trimethylhydroquinone (2f), which is used in the synthesis of tocopherol,10 also gave the corresponding chromane 3g in excellent yield (entry 6). As for asymmetrical substrates, o-cresol (2g) afforded the desired product 3h in low yield along with the hydroarylation product 5a (entry 7). The stereochemistry of 5a was determined to be E by NOE experiments. A similar result was obtained with m-cresol (2h; entry 8), whereas resorcinol (2i) gave 3k in rather better yield (entry 9). 1-Naphthol (2j) also reacted in a similar manner to 2a to give a mixture of 3l and 5b respectively (entry 10). In contrast, the reaction with 2-naphthol (2k) afforded the desired tricyclic product 3m selectively in excellent yield (entry 11).

Interestingly, substrates 1c and 1d, which possess a substituent at the C5 position on the 2-oxazolidinone ring, reacted with 2a to give desired products 3n and 3o, respectively, in good to excellent yield (Scheme 1). Compound 3n was obtained with very high diastereoselectivity, thereby suggesting that a carbocationic intermediate generated via an enamide is involved in the intramolecular addition of the hydroxyl group of 2a in the second step. The structure of 3n was also confirmed by X-ray diffraction analysis (Figure 1).

In conclusion, we have demonstrated that allene sulfonamides 1a-d undergo a formal [3 + 3] cycloaddition with phenols under mild reaction condition in the presence of a catalytic amount of a Brønsted acid to give the corresponding functionalized chromanes in good to excellent yield. This reaction follows a hydroarylation/cyclization pathway and is a rare example of a selective intermolecular hydroarylation at the terminal sp2 carbon atom of an allenic double bond which does not require the presence of a metal based catalyst. Further work concerning the scope of this reaction is currently underway and will be reported in due course.

ACKNOWLEDGEMENTS
We gratefully acknowledge the Center for Instrument Analysis in University of Toyama.

References

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14. The reaction of N-benzyl-N-(1,2-propadienyl) p-toluenesulfonamide, 1-triphenylsilyl-1,2-propadiene or 6-phenyl-1,2-hexadiene with p-cresol did not give the desired product under the optimized reaction condition.
15. All melting points were obtained on a YANAKO melting apparatus and are uncorrected. Infrared spectra were recorded on a Perkin Elmer FT/IR PARAGON 1000 spectrometer. The 1H NMR spectra were determined in CDCl3 using CHCl3 as an internal reference with a JEOL α-GX 400 FT NMR. 13C NMR spectra were recorded on a JEOL α-GX 400 spectrometer operating at 100 MHz with complete proton decoupling and referenced to CDCl3 (77.0 ppm). High resolution mass spectra were taken with a JEOL MStation JMS-700. Unless otherwise noted, all commercial materials were used without purification. TLC analysis of reaction mixture was performed on Merck silica gel 60 F254 TLC plates. Flash chromatography was carried out on Merck 60 silica gel (32-63 µm): Spiro[6-methyl-3,4-dihydrochroman-2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3a): White solid, mp 187.2-187.7 oC, Rf = 0.62 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (82%); IR (KBr) 1085, 1125, 1164, 1193, 1283, 1377, 1498, 1596, 1789 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.26 (s, 3H), 2.27 (ddd, J = 2.0, 5.6, 13.6 Hz, 1H), 2.46 (s, 3H), 2.73 (ddm, J = 5.6, 17.2 Hz, 1H), 2.94 (dm, J = 17.2, 1H), 3.28 (dt, J = 5.6, 13.6 Hz, 1H), 4.12 (d, J = 9.2Hz, 1H), 4.23 (d, J = 9.2 Hz, 1H), 6.62 (d, J = 8.4 Hz, 1H), 6.94 (s, 1H), 6.98 (d, J = 8.4 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 20.5, 21.7, 22.6, 29.2, 73.2, 92.9, 116.9, 119.7, 128.9, 129.2, 129.6, 129.8, 131.4, 135.1, 145.6, 149.5, 152.3; HRMS: (EI) m/z Calcd. for C19H19NO5S: 373, Found (relative intensity): 373 (M+, 100), 155 (71); Anal. Calcd for C19H19NO5S: C, 61.11; H, 5.13; N, 3.75; S, 8.59, Found: C, 61.29; H, 5.17; N, 3.78; S, 8.62. Spiro[6-methoxyl-3,4-dihydrochroman-2,4'-(3'-p-toluensulfonyl)- oxazolidin]-2'-one (3b): White solid, mp 190.0-190.8 oC, Rf = 0.51 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (85%); IR (KBr): 1037, 1165, 1217, 1282, 1336, 1497, 1794 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.29 (ddd, J = 2.0, 5.2, 13.2 Hz, 1H), 2.48 (s, 3H), 2.78 (ddm, J = 5.2, 16.8 Hz, 1H), 2.97 (ddd, J = 2.0, 5.2, 16.8 Hz, 1H), 3.30 (dt, J = 13.2, 5.2 Hz, 1H), 3.77 (s, 3H), 4.14 (d, J = 9.6 Hz, 1H), 4.25 (d, J = 9.6 Hz, 1H), 6.65 (d, J = 2.8 Hz, 1H), 6.67 (d, J = 8.8 Hz, 1H), 6.76 (dd, J = 2.8, 8.8 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 21.7, 22.9, 29.1, 55.7, 73.0, 92.9, 113.5, 114.5, 117.9, 120.6, 129.2, 129.7, 135.0, 145.5, 145.6, 152.3, 154.5; HRMS: (EI) m/z Calcd. for C19H19NO6S: 389.0933, Found: 389.0926. Spiro[6-bromo-3,4-dihydrochroman-2,4'-(3'-p- toluensulfonyl)oxazolidin]-2'-one (3c): White solid, mp 201.1-202.0 oC, Rf = 0.58 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (30%); IR (KBr): 1087, 1124, 1164, 1205, 1279, 1378, 1477, 1792 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.32 (ddd, J = 2.0, 5.6, 13.6 Hz, 1H), 2.48 (s, 3H), 2.78 (ddm, J = 5.6, 17.2 Hz, 1H), 2.97 (ddd, J = 2.0, 5.6, 17.2 Hz, 1H), 3.30 (dt, J = 13.6, 5.6 Hz, 1H), 4.16 (d, J = 9.2 Hz, 1H), 4.24 (d, J = 9.0 Hz, 1H), 6.64 (d, J = 9.2 Hz, 1H), 7.28 (s, 1H), 7.29 (d, J = 9.2 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 8.03 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 21.8, 22.4, 28.8, 73.1, 92.9, 114.3, 118.9, 122.1, 129.3, 129.7, 131.3, 131.9, 134.9, 145.9, 150.8, 152.0; HRMS: (EI) m/z Calcd. for C18H16BrNO5S: 436.9933, Found: 436.9939. Spiro[6-iodo-3,4-dihydrochroman-2,4'- (3'-p-toluensulfonyl)oxazolidin]-2'-one (3d): White solid, mp 198.3-199.1 oC, Rf = 0.55 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (45%); IR (KBr): 1084, 1124, 1164, 1204, 1279, 1376, 1474, 1793 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.29 (ddd, J = 2.0, 5.2, 13.2 Hz, 1H), 2.48 (s, 3H), 2.78 (ddm, J = 5.2, 16.8 Hz, 1H), 2.97 (ddd, J = 2.0, 5.2, 16.8 Hz, 1H), 3.30 (dt, J = 5.6, 13.2 Hz, 1H), 4.14 (d, J = 9.6 Hz, 1H), 4.25 (d, J = 9.6 Hz, 1H), 6.52 (d, J = 9.2 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.45-7.48 (m, 2H), 8.02 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 21.8, 22.2, 28.7, 73.1, 84.4, 92.9, 119.3, 122.7, 129.3, 129.6, 134.8, 137.1, 137.9, 145.8, 151.6, 152.0; HRMS: (EI) m/z Calcd. for C18H16INO5S: 484.9794, Found: 484.9783. Spiro[6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)-2,4'-(3'-p-toluensulfonyl)- oxazolidin]-2'-one (3e): White solid, mp 232.2-235.3 oC, Rf = 0.52 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (43%); IR (KBr): 1084, 1164, 1274, 1359, 1795 cm-1; 1H NMR (CDCl3, 400 MHz): δ 1.34 (s, 12H) 2.33 (ddd, J = 1.6, 5.2, 13.6 Hz, 1H), 2.48 (s, 3H), 2.78 (ddm, J = 5.6, 16.8 Hz, 1H), 3.02 (ddd, J = 1.6, 4.4, 16.8 Hz, 1H), 3.31 (dt, J = 13.6, 5.6 Hz, 1H), 4.16 (d, J = 9.6 Hz, 1H), 4.24 (d, J = 9.6 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.62 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 21.8, 22.3, 24.81, 24.84, 29.2, 73.3, 83.8, 93.1, 116.6,, 119.4, 129.3 129.7, 134.9, 135.0, 136.3, 145.7, 152.2, 154.3; HRMS: (EI) m/z Calcd. for C24H28BNO7S: 485.1680, Found: 485.1685. Spiro[6-methyl-3,4-dihydrochroman-2,4'-(3'-benzoyl)oxazolidin]- 2'-one (3f): White solid, mp 100-100.5 oC, Rf = 0.45 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (79%); IR (KBr): 1088, 1126, 1219, 1306, 1340, 1382, 1450, 1498, 1699, 1794 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.16 (ddd, J = 2.4, 5.2, 13.2 Hz, 1 H), 2.28 (s, 3 H), 2.81 (ddm, J = 5.6, 16.8 Hz, 1 H), 2.96 (ddd, J = 2.4, 6.0, 16.8 Hz, 1 H), 3.13 (dt, J = 6.0, 13.2 Hz, 1H), 4.27 (d, J = 9.2 Hz, 1 H), 4.42 (d, J = 9.2 Hz, 1 H), 6.82 (d, J = 8.4 Hz, 1 H), 6.93 (s, 1H), 6.98 (d, J = 8.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.58 (d, J = 7.6 Hz, 1H), 7.71 (d, J = 7.6 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 20.5, 22.4, 26.9, 73.1, 117.4, 119.6, 128.1, 128.8, 129.1, 129.3, 131.0, 132.9, 133.7, 149.9, 153.7, 169.3; HRMS: (EI) m/z Calcd. for C19H17NO4: 323.1158, Found: 323.1153. Spiro[5,7,8-trimethyl-6-hydroxy-3,4-dihydrochroman- 2,5'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3g): White solid, mp 196.2-197.0 oC, Rf = 0.50 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (69%); IR (KBr): 1087, 1160, 1278, 1371, 1456, 1636, 1788, 2924, 3566 cm-1; 1H NMR (CDCl3, 400 MHz): δ 1.89 (s, 3H), 2.13 (s, 3H), 2.15 (s, 3H), 2.34 (ddd, J = 1.6, 6.0, 13.2 Hz, 1H), 2.46 (s, 3H), 2.58 (ddm, J = 6.0, 16.8 Hz, 1H) ), 2.99 (dd, J = 5.2, 16.8 Hz, 1H), 3.28 (dt, J = 6.0, 13.2 Hz, 1H), 4.10 (d, J = 9.6 Hz, 1H), 4.29 (d, J = 9.6 Hz, 1H), 4.40 (brs, 1H), 7.34 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 11.5, 11.9, 12.2, 21.3, 21.7, 29.2, 72.3, 92.7, 116.5, 118.6, 122.3, 123.2, 129.3, 129.6, 135.2, 143.5, 145.5, 146.4, 152.5; HRMS: (EI) m/z Calcd. for C21H23NO6S: 417.1246, Found 417.1235. Spiro[8-methyl-3,4-dihydrochroman-2,4'-(3'-p- toluensulfonyl)oxazolidin]-2'-one (3h) : White solid, mp 161.0-162.0 oC, Rf = 0.51 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (24%); IR (KBr): 1086, 1125, 1163, 1280, 1376, 1468, 1794 cm-1; 1H NMR (CDCl3, 400 NHz): δ 2.03 (s, 3H), 2.33 (ddd, J = 1.6, 5.6, 13.2 Hz, 1H), 2.46 (s, 3H), 2.79 (ddm, J = 5.6, 17.2 Hz, 1H), 3.03 (ddd, J = 1.6, 5.6, 17.2 Hz, 1H), 3.32 (dt, J = 5.6, 13.2 Hz, 1H), 4.16 (d, J = 9.6 Hz, 1H), 4.25 (d, J = 9.6 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H), 6.97 (d, J = 7.2 Hz, 1H), 7.02 (d, J = 7.2 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 8.09 (d, J = 8.0 Hz, 2H).13C NMR (CDCl3, 100 MHz): δ 15.8, 21.7, 22.8, 29.1, 73.1, 93.1, 119.6, 121.6, 126.77, 126.80, 129.3, 129.5, 129.6, 135.2, 145.6, 149.9, 152.3; HRMS: (EI) m/z Calcd. for C19H19NO5S: 373.0984, Found: 373.0987. Spiro[7-methyl-3,4-dihydrochroman- 2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3i): Isolated as an inseparable mixture of 3j; white solid, Rf = 0.42 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (36%); IR (KBr): 1084, 1121, 1180, 1281, 1377, 1458, 1792 cm-1; 1H NMR (CDCl3, 400 NHz): δ 2.27-2.33 (m, 1 H), 2.31 (s, 3H), 2.49 (s, 3H), (ddm, J = 5.2, 16.4 Hz, 1H), 2.96 (dm, J = 16.4 Hz, 1H), 3.29 (dt, J = 5.6, 13.6 Hz, 1H), 4.15 (d, J = 9.6 Hz, 1H), 4.26 (d, J = 9.6 Hz, 1H), 6.57 (s, 1H), 6.78 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 8.4 Hz, 2H); HRMS: (EI) m/z Calcd. for C19H19NO5S: 373.0984, Found: 373.0988. Spiro[5-methyl-3,4-dihydrochroman-2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3j): Isolated as an inseparable mixture of 3i; white solid, Rf = 0.42 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (15%): 1H NMR (CDCl3, 400 NHz): δ 2.27-2.33 (m, 1 H), 2.31 (ddm, J = 5.2, 16.4 Hz, 1H), 2.96 (dm, J = 16.4 Hz, 1H), 3.29 (dt, J = 5.6, 13.6 Hz, 1H), 4.15 (d, J = 9.6 Hz, 1H), 4.26 (d, J = 9.6 Hz, 1H), 6.57 (s, 1H), 6.78 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 8.07 (d, J = 8.4 Hz, 2H). Spiro[7-hydroxy-3,4-dihydrochroman-2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3k): White solid, mp 215.3-216.1 oC, Rf = 0.34 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (59%); IR (film): 1084, 1163, 1272, 1366, 1456, 1624, 1782, 3465 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.29 (ddd, J = 2.0, 5.2, 13.6 Hz, 1H), 2.47 (s, 3H), 2.70 (ddm, J = 5.2, 16.8 Hz, 1H), 2.92 (ddm, J = 5.2, 16.8 Hz, 1H), 3.28 (dt, J = 6.0, 13.6 Hz, 1H), 4.15 (d, J = 9.6 Hz, 1H), 4.26 (d, J = 9.6 Hz, 1H), 6.25 (d, J = 2.4 Hz, 1H), 6.47 (dd, J = 2.4, 8.4 Hz, 1H), 6.97 (d, J = 2.4 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 21.7, 21.9, 29.3, 73.2, 93.0, 103.8, 109.8, 112.1, 129.3, 129.7, 130.0, 135.0, 145.7, 152.3, 152.5, 155.8; HRMS: (EI) m/z Calcd. for C18H17NO6S: 375.0777, Found: 375.0777. Spiro[3,4-dihydrobenzo[h]chroman-2,4'-(3'-p-toluensulfonyl)oxazolidin]-2'-one (3l) : White solid, mp 214.7-215.3 oC, Rf = 0.50 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (24%); IR (film) 1085, 1160, 1280, 1372, 1457, 1508, 1542, 1791, 2924, 3566 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.44 (ddd, J = 2.0, 6.0, 13.6 Hz, 1H), 2.53 (s, 3H), 2.94 (ddm, J = 5.6, 13.6, 16.8 Hz, 1H), 3.13 (ddd, J = 2.0, 6.0, 16.8 Hz, 1H), 3.45 (dt, J = 6.0, 13.6 Hz, 1H), 4.20 (d, J = 9.6 Hz, 1H), 4.30 (d, J = 9.6 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.27-7.42 (m, 3H), 7.45-7.51 (m, 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H), 8.14 (dm, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 21.8, 22.9, 28.9, 73.0, 93.4, 114.2, 121.2, 121.7, 124.8, 125.6, 126.3, 126.7, 127.6, 129.5, 129.8, 133.4, 135.2, 145.7, 146.3, 152.5; HRMS: (EI) m/z Calcd. for C22H19NO5S: 409.0984, Found 409.0982. Spiro[3,4-dihydrobenzo[f]chroman-2,4'-(3'-p- toluensulfonyl)oxazolidin]-2'-one (3m) : White solid, mp 234.2-235.3 oC, Rf = 0.53 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (82%); IR (KBr): 1084, 1164, 1280, 1378, 1596, 1793 cm-1; 1H NMR (CDCl3, 400 MHz): δ 2.49 (s, 3H), 2.50 (m, 1H), 2.90 (m, 1H), 3.41-3.50 (m, 2H), 4.24 (d, J = 10.0 Hz, 1H), 4.29 (d, J = 10.0 Hz, 1H), 6.94 (d, J = 8.8 Hz, 1H), 7.39-7.45 (m, 2H), 7.56 (dt, J = 1.2, 8.0 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.81-7.83 (m, 2H), 8.11 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 19.5, 21.8, 28.8, 72.8, 92.7, 112.4, 118.3, 122.0, 124.4, 127.1, 128.6, 129.1, 129.3, 129.5, 129.8, 132.2, 135.0, 145.7, 149.1, 152.3; HRMS: (EI) m/z Calcd. for C22H19NO5S: 409.0984, Found: 409.0978. Spiro[6- methyl-3,4-dihydrochroman-2,4'-(5’-phenyl-3'-p-toluensulfonyl)oxazolidin]-2'-one (3n): White solid, mp 188.9-189.6 oC, Rf = 0.65 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (73%); IR (KBr): 1070, 1164, 1379, 1498, 1790 cm-1; 1H NMR (CDCl3, 400 MHz): δ 1.99 (ddd, J = 2.0, 5.6, 14.0 Hz, 1H), 2.30 (s, 3 H), 2.38 (ddm, J = 6.0, 17.2 Hz, 1H), 2.49 (s, 3H), 2.56 (ddd, J = 2.0, 6.0, 17.2 Hz, 1H), 3.18 (dt, J = 6.0, 13.6 Hz, 1H), 5.21 (s, 1H), 6.67 (d, J = 8.4 Hz, 1H ), 6.89 (s, 3H), 7.00 (d, J = 8.4 Hz, 1H), 7.30 (dd, J = 1.6, 8.0 Hz, 2H), 7.35-7.47 (m, 5H), 8.07 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): δ 20.5, 21.8, 21.9, 25.5, 85.3, 96.1, 116.9, 120.2, 127.8, 128.7, 129.0, 129.2, 129.6, 129.9, 130.3, 130.5, 133.0, 135.1, 145.6, 149.4, 152.6; HRMS: (EI) m/z Calcd. for C25H23NO5S: 449.1297, Found: 449.1291. Spiro[6- methyl-3,4-dihydrochroman-2,4'-(5’,5’-dimethyl-3'-p-toluensulfonyl)oxazolidin]-2'-one (3o): White solid, mp 185.2-185.9 oC, Rf = 0.60 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (68%); IR (film): 899, 922, 991, 1085, 1174, 1221, 1276, 1350, 1376, 1453, 1497, 1596, 1784, 2924 cm-1; 1H NMR (400 MHz, CDCl3): δ 1.22 (s, 3 H), 1.52 (s, 3 H), 2.28 (s, 3 H), 2.40 (ddd, J = 2.8, 4.8, 14.0 Hz, 1 H), 2.47 (s, 3 H), 2.70 (ddm, J = 5.2, 16.8 Hz, 1H), 2.94 (ddd, J = 2.4, 5.6, 16.8 Hz, 1H), 3.42 (dt, J = 6.0, 14.0 Hz, 1 H), 6.60 (d, J = 8.4 Hz, 1 H), 6.91 (s, 1H), 6.98 (d, J = 8.4 Hz, 1 H), 7.33 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 20.5, 21.7, 22.8, 22.9, 23.4, 24.8, 87.2, 97.2, 115.6, 119.9, 128.9, 129.0, 129.4, 129.9, 130.9, 135.3, 145.4, 150.9; HRMS: (EI) m/z Calcd. for C21H23NO5S: 401.1297, Found: 401.1295. (E)-3-(p-Toluenesulfonyl)-4-(2-p-tolyloxyethylidene)- oxazolidin-2-one (4): White solid, mp 104.2-105.0 oC, Rf = 0.52 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (55%); IR (film): 1088, 1160, 1278, 1378, 1456, 1509, 1542, 1783, 2923 cm-1; 1H NMR(CDCl3, 400 MHz): δ 2.30 (s, 3H), 2.46 (s, 3H), 4.52 (dt, J = 5.6, 1.2 Hz, 2H), 4.94 (dt, J = 2.4, 1.2 Hz, 2H), 6.30 (tt, J = 2.4, 5.6 Hz, 1H), 6.77 (d, J = 8.0, 2H), 7.09 (d, J = 8.0 Hz, 2H), 7.94 (d, J = 8.0 Hz, 2H); 13C NMR(CDCl3,100 MHz): δ 20.5, 21.7, 63.6, 66.1, 102.3, 114.5, 128.3, 129.9, 130.0, 130.1, 130.9, 134.2, 146.3, 151.5, 155.7; HRMS: (EI) m/z Calcd. for C22H19NO5S: 373.0984, Found: 373.0985. (E)-4-[2-(4-Hydroxy-3- methylphenyl)-ethylidene]-3-(p-toluenesulfonyl)-oxazolidin-2-one (5a): Yellow solid, mp 115.1-116.5 oC, Rf = 0.29 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (40%); 1H NMR(CDCl3, 400 MHz): δ 2.23 (s, 3H), 2.46 (s, 3H), 3.17 (d, J = 8.0 Hz, 2H), 4.78 (s, 1H), 4.82 (m, 2H), 6.16 (tt, J = 2.4, 8.0 Hz, 1H), 6.71 (d, J = 8.0 Hz, 1H), 6.84 (dm, J = 8.0 Hz, 1H), 6.88 (s, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H); 13C NMR(CDCl3,100 MHz): δ 15.8, 21.7, 31.9, 65.7, 106.9, 115.1, 124.1, 126.5, 128.2, 128.6, 129.9, 130.60, 130.64, 134.3, 146.1, 151.9, 152.6; HRMS: (EI) m/z Calcd. for C19H19NO5S: 373.0984, Found: 373.0986. (E)-4-[2-(4-Hydroxy-1-naphthalenyl)-ethylidene]-3-(p-toluenesulfonyl)- oxazolidin-2-one (5b): White solid, mp 112.5-113.5 oC, Rf = 0.60 (50% EtOAc/hexane), purified by column chromatography over silica gel (20% EtOAc/hexane) (27%); IR (film): 1086, 1163, 1267, 1373, 1457, 1508, 1542, 1771, 3567 cm-1; 1H NMR(CDCl3, 400 MHz): δ 2.44 (s, 3H), 3.61 (d, J = 7.2 Hz, 2H), 4.79 (m, 2H), 4.82 (m, 2H), 5.44 (brs, 1H), 6.29 (tt, J = 2.8, 7.2 Hz, 1H), 6.75 (d, J = 7.6 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 7.28 (dm, J = 8.0 Hz, 2H), 7.52-7.57 (m, 2H), 7.82 (m, 1H), 7.87 (d, J = 8.6 Hz, 1H), 8.27 (m, 1H); 13C NMR(CDCl3,100 MHz): δ 21.7, 29.8, 65.7, 106.5, 107.9, 122.6, 123.3, 124.9, 125.2, 125.5, 126.8, 126.9, 128.1, 128.9, 129.9, 132.6, 134.2, 146.1, 150.9, 151.9; HRMS: (EI) m/z Calcd. for C22H19NO5S: 409.0984, Found: 409.0984. X-Ray Crystal Strucutuer Analysis of Compound 3a (CCDC 739400)16: C19H19NO5S, Mr = 373.42 g/mol, colorless plate, crystal size 0.40 x 0.40 x 0.40 mm, monoclinic, space group P21/c (#), a = 9.223(8) Å, b = 12.854(10) Å, c = 15.780(8) Å, α = 90o, β = 105.43(5)o, γ = 90o, V = 1803(2) Å3, T = 296 K, Z = 4, Dcalc = 1.375 g/cm3, λ = 0.71069 Å, F(000) = 784, µ(Μο−Κα) = 2.09 cm-1, 5799 measured reflections, 4114 reflections with I > 0.00σ(Ι), 235 parameters, R = 0.156, wR = 0.091, residual electron density +0.48 / -0.43 e Å -3. X-Ray Crystal Strucutuer Analysis of Compound 3n (CCDC 739401) 16: C25H23NO5S, Mr = 449.52 g/mol, colorless prismatic, crystal size 0.20 x 0.20 x 0.30 mm, orthorhombic, space group Pbca (#61) a = 20.654(6) Å, b = 17.908(6) Å, c = 11.846(5) Å, α = 90o, β = 105.43(5)o, γ = 90o, V = 4381(4) Å 3, T = 296 K, Z = 84, Dcalc = 1.363 g/cm3, λ = 0.71069 Å, F(000) = 1888.00, µ(Μο−Κα) = 1.85 cm-1,7044 measured reflections, 1804 reflections with I > 3.00σ(Ι), 289 parameters, R = 0.047, wR = 0.061, residual electron density +0.16 / -0.20 e Å -3.
16. Crystallographic data for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 739400 and CCDC 739401. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44(0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk].