Ruthenium-Catalyzed Enantioselective Intramolecular Propargylation

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Organometallics 2009, 28, 2920–2926

Ruthenium-Catalyzed Enantioselective Intramolecular Propargylation of Thiophenes with Propargylic Alcohols Keiichiro Kanao, Yoshihiro Miyake, and Yoshiaki Nishibayashi* Institute of Engineering InnoVation, School of Engineering, The UniVersity of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-8656, Japan ReceiVed February 13, 2009

Ruthenium-catalyzed enantioselective cyclization of propargylic alcohols bearing a thiophene moiety affords the corresponding propargylated thiophenes in good to high yields with a high enantioselectivity (up to 97% ee). This catalytic reaction is proposed to proceed via chiral ruthenium-allenylidene complexes as key intermediates. Introduction Recently, we reported the first successful example of ruthenium-catalyzed enantioselective propargylic substitution reactions of propargylic alcohols with nucleophiles to give the corresponding propargylic-substituted products in good yields with a high enantioselectivity (up to 82% ee).1 In this reaction system, attack of nucleophiles on the Cγ of the allenylidene2-4 complex should occur from the site that is not blocked by π-π interaction of the phenyl rings between the chiral ligand and the allenylidene moieties. As an extension of our study, we have * To whom correspondence should be addressed. E-mail: ynishiba@ sogo.t.u-tokyo.ac.jp. (1) Inada, Y.; Nishibayashi, Y.; Uemura, S. Angew. Chem., Int. Ed. 2005, 44, 7715. (2) For reviews, see: (a) Touchard, D.; Dixneuf, P. H. Coord. Chem. ReV. 1998, 178-180, 409. (b) Selegue, J. P. Coord. Chem. ReV. 2004, 248, 1543. (c) Bruce, M. I. Coord. Chem. ReV. 2004, 248, 1603. (d) Cadierno, V.; Gamasa, M. P.; Gimeno, J. Coord. Chem. ReV. 2004, 248, 1627. (e) Bruneau, C.; Dixneuf, P. H. Angew. Chem., Int. Ed. 2006, 45, 2176. (f) Metal Vinylidenes and Allenylidenes in Catalysis: From ReactiVity to Applications in Synthesis; Bruneau, C., Dixneuf, P. H., Eds.; Wiley-VCH: Weinheim, Germany, 2008. (3) For recent selected examples, see: (a) Yen, Y.; Lin, Y.; Huang, S.; Liu, Y.; Sung, H.; Wang, Y. J. Am. Chem. Soc. 2005, 127, 18037. (b) Bustelo, E.; Jimene´z-Tenorio, M.; Puerta, M. C.; Valerga, P. Organometallics 2006, 25, 4019. (c) Bustelo, E.; Jimene´z-Tenorio, M.; Puerta, M. C.; Valerga, P. Organometallics 2007, 26, 4300. (d) Zhong, Y.; Matsuo, Y.; Nakamura, E. Chem. Asian J. 2007, 2, 358. (e) Bolan˜o, T.; Castarlenas, R.; Esteruelas, M. A.; On˜ate, E. J. Am. Chem. Soc. 2007, 129, 8850. (f) Castarlenas, R.; Esteruelas, M. A.; Lalrempuia, R.; Oliva´n, M.; On˜ate, E. Organometallics 2008, 27, 795. (g) Kessler, F.; Szesni, N.; Po˜hako, K.; Weiberd, B.; Fischer, H. Organometallics 2009, 28, 348. (h) Pino-Chamorro, J. A.; Bustelo, E.; Puerta, M. C.; Valerga, P. Organometallics 2009, 28, 1546. (4) (a) Nishibayashi, Y.; Milton, M. D.; Inada, Y.; Yoshikawa, M.; Wakiji, I.; Hidai, M.; Uemura, S. Chem.-Eur. J. 2005, 11, 1433. (b) Ammal, S. C.; Yoshikai, N.; Inada, Y.; Nishibayashi, Y.; Nakamura, E. J. Am. Chem. Soc. 2005, 127, 9428. (c) Onodera, G.; Nishibayashi, Y.; Uemura, S. Organometallics 2006, 25, 35. (d) Inada, Y.; Yoshikawa, M.; Milton, M. D.; Nishibayashi, Y.; Uemura, S. Eur. J. Org. Chem. 2006, 881. (e) Yamauchi, Y.; Onodera, G.; Sakata, K.; Yuki, M.; Miyake, Y.; Uemura, S.; Nishibayashi, Y. J. Am. Chem. Soc. 2007, 129, 5175. (f) Yamauchi, Y.; Yuki, M.; Tanabe, Y.; Miyake, Y.; Inada, Y.; Uemura, S.; Nishibayashi, Y. J. Am. Chem. Soc. 2008, 130, 2908. (g) Daini, M.; Yoshikawa, M.; Inada, Y.; Uemura, S.; Kanao, K.; Miyake, Y.; Nishibayashi, Y. Organometallics 2008, 27, 2046. (h) Yada, Y.; Miyake, Y.; Nishibayashi, Y. Organometallics 2008, 27, 3614. (i) Miyake, Y.; Endo, M.; Yuki, M.; Tanabe, Y.; Nishibayashi, Y. Organometallics 2008, 27, 6039. (j) Yamauchi, Y.; Miyake, Y.; Nishibayashi, Y. Organometallics 2009, 28, 48. (k) Tanabe, Y.; Kanao, K.; Miyake, Y.; Nishibayashi, Y. Organometallics 2009, 28, 1138. (l) Sakata, K.; Miyake, Y.; Nishibayashi, Y. Chem. Asian J. 2009, 4, 81. (m) Nishibayashi, Y.; Uemura, S. Curr. Org. Chem 2006, 10, 135, and references therein.

more recently found the ruthenium-catalyzed enantioselective propargylation of aromatic compounds such as N,N-dimethylanilines, furans, and indoles with propargylic alcohols to give the corresponding propargylated aromatic compounds in good to high yields with a high to excellent enantioselectivity (up to 95% ee).5 The synthetic method provides a novel protocol for the catalytic asymmetric Friedel-Crafts alkylation of aromatic compounds6,7 by using propargylic alcohols as a new type of electrophiles. This result prompted us to investigate the enantioselective propargylation of thiophenes with propargylic alcohols using a chiral ruthenium complex (1a) because the thiophene unit is a well-established fundamental framework in the field of molecular electronics.8,9 In fact, the propargylation of 2-methylthiophene with 1-phenyl-2-propyn-1-ol in the presence of a catalytic amount of 1a took place, but only a moderate enantioselectivity was observed, as shown in Scheme 1. After a detailed investigation, we have found that the intramolecular propargylation of thiophenes with propargylic alcohols proceeded smoothly with a high to excellent enantioselectivity (up to 97% ee). Herein, we describe the result of the rutheniumcatalyzed enantioselective cyclization of propargylic alcohols bearing a thiophene moiety.

Results and Discussion Heating of 1-(o-(2-thienylmethyl)phenyl)-2-propyn-1-ol (3a) in 1,2-dichloroethane in the presence of 5 mol % of a chiral (5) (a) Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Angew. Chem., Int. Ed. 2007, 46, 6488. (b) Matsuzawa, H.; Kanao, K.; Miyake, Y.; Nishibayashi, Y. Org. Lett. 2007, 9, 5561. (c) Kanao, K.; Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Synthesis 2008, 23, 3869. (6) For reviews, see: (a) Jørgensen, K. A. Synthesis 2003, 1117. (b) Bandini, M.; Melloni, A.; Umani-Ronchi, A. Angew., Chem. Int. Ed. 2004, 43, 550. (c) Bandini, M.; Emer, E.; Tommasi, S.; Umani-Ronchi, A. Eur. J. Org. Chem. 2006, 3527. (d) Poulsen, T. B.; Jørgensen, K. A. Chem. ReV. 2008, 108, 2903. (7) (a) Liu, H.; Lu, S.; Xu, J.; Du, D. Chem. Asian J. 2008, 3, 1111. (b) Yuan, Z.; Lei, Z.; Shi, M. Tetrahedron: Asymmetry 2008, 19, 1339. (c) Tang, H.; Lu, A.; Zhou, Z.; Zhao, G.; He, L.; Tang, C. Eur. J. Org. Chem. 2008, 1406. (d) Zhao, J.; Liu, L.; Gu, C.; Wang, D.; Chen, Y. Tetrahedron Lett. 2008, 49, 1476. (e) Liu, W.; He, H.; Dai, L.; You, S. Org. Lett. 2008, 10, 1815. (f) Trost, B. M.; Mu¨ller, C. J. Am. Chem. Soc. 2008, 130, 2438. (g) Kang, Q.; Zheng, X.; You, S. Chem.-Eur. J. 2008, 14, 3539. (h) Itoh, J.; Fuchibe, K.; Akiyama, T. Angew. Chem., Int. Ed. 2008, 47, 4016. (i) Singh, P. K.; Singh, V. K. Org. Lett. 2008, 10, 4121. (j) Blay, G.; Ferna´ndez, I.; Monleo´n, A.; Pedro, J. R.; Vila, C. Org. Lett. 2009, 11, 441. (8) For recent reviews of thiophene-based materials, see: (a) Barbarella, G.; Melucci, M.; Sotgiu, G. AdV. Mater. 2005, 17, 1581. (b) Perepichka, I. F.; Perepichka, D. F.; Meng, H.; Wudl, F. AdV. Mater. 2005, 17, 2281. (c) Ong, B. S.; Wu, Y.; Li, Y.; Liu, P.; Pan, H. Chem.-Eur. J. 2008, 14, 4766.

10.1021/om9001186 CCC: $40.75  2009 American Chemical Society Publication on Web 04/06/2009

Ru-Catalyzed Propargylation of Thiophenes Scheme 1

thiolate-bridged diruthenium complex (1a), which was prepared in situ from [Cp*RuCl]4 (Cp* ) η5-C5Me5) and the corresponding chiral disulfide (2a) in tetrahydrofuran (THF) at room temperature for 12 h, and NH4BF4 at 60 °C for 24 h, afforded 4-ethynyl-4,9-dihydronaphtho[2,3-b]thiophene (4a) in 45% isolated yield with 94% ee (Scheme 2a). The presence of three phenyl groups at the 2-, 3-, and 5-positions in the benzene ring of the chiral ligand is necessary to achieve the high enantioselectivity. In fact, the use of other chiral complexes (1b and 1c) in place of 1a apparently decreased the enantioselectivity. The introduction of p-tert-butylphenyl groups in the benzene ring of the chiral ligand did not improve the enantioselectivity. A higher yield of 4a was obtained when the isolated 1a was used as a catalyst.10 The reaction at slightly lower reaction temperature such as 40 °C gave the best result, where 4a was obtained in 78% isolated yield with 96% ee. In sharp contrast to the reaction of 3a, where the high enantioselectivity was achieved (96% ee), the reaction of an isomer, 1-(o-(3-thienyl)methyl)phenyl-2-propyn-1-ol (3a′), under the same reaction conditions gave 9-ethynyl-4,9-dihydronaphtho[2,3-b]thiophene (4a′) in 79% isolated yield with 86% ee (Scheme 3). No formation of 4-ethynyl-4,9-dihydronaphtho[2,3c]thiophene (4a′′) was observed at all. This result indicates that the propargylation at the R-position of thiophene occurred more selectively. Unfortunately, a substantially lower enantioselectivity was observed in the reaction of 3a′. Although the reason we observed the different enantioselectivity on propargylation at the R- and β-positions of thiophene is not clear, reactions of 1-(o-(2-thienyl)methyl)phenyl-2-propyn-1-ols were carried out. Reactions of propargylic alcohols bearing a substituent on the thiophene ring were investigated at 40 °C using the isolated 1a as a catalyst. The nature of the substituent at the R-position of the thiophene ring did not much affect the enantioselectivity (Scheme 4). But a longer reaction time is necessary when a (9) For recent selected example of thiophene-based materials, see: (a) Sotgiu, G.; Zambianchi, M.; Barbarella, G.; Aruffo, F.; Cipriani, F.; Ventola, A. J. Org. Chem. 2003, 68, 1512. (b) Tebesco, E.; Sala, F. D.; Barbarella, G.; Albesa-Jove, D.; Pisignano, D.; Gigli, G.; Cingolani, R.; Harris, K. D. M. J. Am. Chem. Soc. 2003, 125, 12277. (c) Sonmez, G.; Sonmez, H. B.; Shen, C. K. F.; Wudl, F. AdV. Mater. 2004, 16, 1905. (d) Mazzeo, M.; Vitale, V.; Sala, F. D.; Anni, M.; Barbarella, G.; Favaretto, L.; Sotgiu, G.; Cingolani, R.; Gigli, G. AdV. Mater. 2005, 17, 34. (e) Ramey, M. B.; Hiller, J. A.; Rubner, M. F.; Tan, C.; Schanze, K. S.; Reynolds, J. R. Macromolecules 2005, 38, 234. (f) Wang, F.; Luo, J.; Yang, K.; Chen, J.; Huang, F.; Cao, Y. Macromolecules 2005, 38, 2253. (g) Baumgartner, T.; Bergmans, W.; Ka´rpa´ti, T.; Neumann, T.; Nieger, M.; Nyula´szi, L. Chem.-Eur. J. 2005, 11, 4687. (h) Li, Y.; Wu, Y.; Liu, P.; Birau, M.; Pan, H.; Ong, B. S. AdV. Mater. 2006, 18, 3029. (i) Takimiya, K.; Ebata, H.; Sakamoto, K.; Izawa, T.; Otsubo, T.; Kunugi, Y. J. Am. Chem. Soc. 2006, 128, 12604. (j) Nakao, K.; Nishimura, M.; Tamachi, T.; Kuwatani, Y.; Miyasaka, H.; Nishinaga, T.; Iyoda, M. J. Am. Chem. Soc. 2006, 128, 16740. (k) Pan, H.; Li, Y.; Wu, Y.; Liu, P.; Ong, B. S.; Zhu, S.; Xu, G. J. Am. Chem. Soc. 2007, 129, 4112. (l) Williams-Harry, M.; Bhaskar, A.; Ramakriahna, G.; Goodson, T., III.; Imamura, M.; Mawatari, A.; Nakao, K.; Enozawa, H.; Nishinaga, T.; Iyoda, M. J. Am. Chem. Soc. 2008, 130, 3252. (10) See Experimental Section for details.

Organometallics, Vol. 28, No. 9, 2009 2921 Scheme 2a

Scheme 3a

a The absolute configurations of 4a and 4a′ were assigned by consideration of the stereochemical pathway.

large substituent such as a phenyl group was introduced at the R-position of the thiophene ring. On the other hand, the introduction of a methyl group at the β-position of the thiophene ring inhibited the propargylation completely. Next, reactions of propargylic alcohols bearing a substituent on the benzene ring were investigated under the same reaction

2922 Organometallics, Vol. 28, No. 9, 2009

Kanao et al.

Scheme 4a

Figure 1. ORTEP drawing of (R)-4e. a The absolute configurations of 4b, 4c, and 4d were assigned by consideration of the stereochemical pathway.

Scheme 6a

Scheme 5a

a The absolute configurations of 6 were assigned by consideration of the stereochemical pathway.

Scheme 7

a The absolute configurations of 4 except for 4e were assigned by consideration of the stereochemical pathway. The absolute configuration of 4e was determined by X-ray analysis.

conditions (Scheme 5). The presence of substituents such as methyl, methoxy, chloro, and fluoro on the benzene ring of 2 did not much affect the enantioselectivity. In all cases, the intramolecular propargylation proceeded with a high to excellent enantioselectivity. A longer reaction time such as 48 h increased the yields of dihydronaphtho[2,3-b]thiophenes. After one recrystallization of crude 4e, the enantiomerically pure 4e was isolated and its absolute configuration (R) at the propargylic position was determined by X-ray analysis.10 An ORTEP drawing of (R)-4e is shown in Figure 1. In addition to the enantioselective formation of dihydronaphtho[2,3-b]thiophenes 4, the formation of 4-ethynyl-4H-indeno[1,2-b]thiophenes (6) proceeded with a high enantioselectivity (Scheme 6). In reactions of 1-(o-(2-thienyl)phenyl)-2propyn-1-ols (5), unfortunately, only moderate yields were

obtained even at higher reaction temperature (60 °C) for a longer reaction time (96 h). Separately, we confirmed that the reaction of 5a at 40 °C gave 6a with the same enantioselectivity. The absolute configuration of 4e as shown in Figure 1 indicates that major enantioisomers of 4 have an R-configuration at the propargylic position. This result supports our previously proposed reaction pathway1,4,11 in the propargylation of aromatic compounds, where π-π interaction of the phenyl rings between the chiral ligand and allenylidene moieties was considered to play an important role to achieve the high enantioselectivity as shown in Scheme 7. Here, thiophene should intramolecularly attack the alkynyl complex (B) having a cationic Cγ from the (11) Fukamizu, K.; Miyake, Y.; Nishibayashi, Y. J. Am. Chem. Soc. 2008, 130, 10498.

Ru-Catalyzed Propargylation of Thiophenes

si face, where B is a resonance structure of the allenylidene complex (A) prepared from a propargylic alcohol and the chiral diruthenium complex 1a. In summary, we have found that the ruthenium-catalyzed enantioselective cyclization of propargylic alcohols bearing a thiophene moiety afforded the corresponding propargylated thiophenes in good to high yields with a high enantioselectivity (up to 97% ee). This catalytic reaction can be explained to proceed by proposing chiral ruthenium-allenylidene complexes as key intermediates. The method described in this paper provides a novel method for the asymmetric Friedel-Crafts alkylation of thiophenes by using propargylic alcohols as a new type of electrophile. Optically active dihydronaphthothiophene and indenothiophene skeletons prepared in this paper are expected to be useful ligands of transition metal complexes utilized to polymerize propylene12 and attractive monomers for optically active helical poly(acetylenes) bearing thiophene-based pendants.13,14 Further work is currently in progress to broaden its synthetic applicability to natural products and pharmaceuticals.

Experimental Section General Method. The 1H NMR (270 MHz) and 13C NMR (67.8 MHz) spectra were recorded on a JEOL Excalibur 270 spectrometer using CDCl3. Elemental analyses were performed at the Microanalytical Center of The University of Tokyo. Mass spectra were measured on a JEOL JMS-700 mass spectrometer. HPLC analyses were performed on a Hitachi L-7100 apparatus equipped with a UV detector using 25 cm × 4.6 mm DAICEL Chiralcel OD, OJ-H columns. All reactions were carried out under a dry nitrogen atmosphere. Solvents were dried by the usual methods and distilled before use. [Cp*RuCl]415,16 and chiral disulfides (2) were prepared according to our previous procedure.1 o-(2-Thienylmethyl)benzaldehydes17 and o-(2-thienyl)benzaldehydes18 were prepared according to literature methods. Preparation of 1a. To a suspension of [Cp*RuCl]4 (109.0 mg, 0.1 mmol) in THF (5 mL) was added 2a (152.0 mg, 0.2 mmol), and the mixture was stirred at room temperature for 12 h. After the removal of the solvent under reduced pressure, the residue was recryatallized from CH2Cl2/n-hexane to give dark brown crystals of 1a (116.2 mg, 0.089 mmol, 44%): 1H NMR δ 0.69 (t, J ) 7.1 Hz, 6H), 1.31 (s, 30H), 1.88-2.01 (m, 4H), 5.87 (dd, J ) 3.9 and 12.8 Hz, 2H), 7.05-7.29 (m, 20H), 7.39 (t, J ) 7.5 Hz, 4H), 7.61 (d, J ) 1.5 Hz, 2H), 7.84 (d, J ) 7.4 Hz, 4H), 8.26 (d, J ) 7.4 Hz, 2H), 8.38 (d, J ) 2.0 Hz, 2H). Anal. Calcd for C74H76OCl2Ru2S2 · 2CH2Cl2: C, 61.99; H, 5.48. Found: C, 61.85; H, 5.69. (12) (a) Ewen, J. A.; Elder, M. J.; Jones, R. L.; Rheingold, A. L.; LiableSacds, L. M.; Sommer, R. D. J. Am. Chem. Soc. 2001, 123, 4763. (b) Ryabov, A. N.; Gribkov, D. V.; Izmer, V. V.; Voskoboynikov, A. Z. Organometallics 2002, 21, 2842. (c) Grandini, C.; Camurati, I.; Guidotti, S.; Mascellani, N.; Resconi, L.; Nifant’ev, I. E.; Kashulin, I. A.; Ivchenko, P. V.; Mercandelli, P.; Sironi, A. Organometallics 2004, 23, 344. (13) For recent reviews of polyacetylenes, see: (a) Lam, J. W. Y.; Tang, B. Z. Acc. Chem. Res. 2005, 38, 745. (b) Masuda, T. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 165. (c) Yashima, E.; Maeda, K.; Furusho, Y. Acc. Chem. Res. 2008, 41, 1166. (14) For recent examples of optically active polyacetylenes, see: (a) Suzuki, Y.; Shiotsuki, M.; Sanda, F.; Masuda, T. Macromolecules 2007, 40, 1864. (b) Kobayashi, S.; Morino, K.; Yashima, E. Chem. Commun. 2007, 2351. (c) Ohsawa, S.; Maeda, K.; Yashima, E. Macromolecules 2007, 40, 9244. (d) Suzuki, Y.; Shiotsuki, M.; Sanda, F.; Masuda, T. Chem. Asian J. 2008, 3, 2075. (15) Fagan, P. J.; Ward, M. D.; Calabrese, J. C. J. Am. Chem. Soc. 1989, 111, 1698. (16) Fagan, P. J.; Mahoney, W. S.; Calabrese, J. C.; Williams, I. D. Organometallics 1990, 9, 1843. (17) Hartman, G. D.; Halczenko, W.; Phillips, B. T. J. Org. Chem. 1986, 51, 142. (18) Fu¨rstner, A.; Mamane, V. J. Org. Chem. 2002, 67, 6264.

Organometallics, Vol. 28, No. 9, 2009 2923 Preparation of 3. A typical experimental procedure for the preparation of 3a is described below. To a solution of o-(2thienylmethyl)benzaldehyde (2.01 g, 10.0 mmol) in THF (15 mL) was added dropwise a solution of ethynylmagnesium bromide (30.0 mL of a 0.5 M solution in THF, 15.0 mmol) at 0 °C, and the mixture was stirred at ambient temperature for 1 h. After the reaction mixture was quenched by addition of saturated NH4Cl(aq), the solution was extracted with diethyl ether. The combined organic layers were washed by brine and then dried over anhydrous MgSO4. After the removal of the solvent, the crude oil was purified by column chromatography on silica gel (hexane/ethyl acetate, 3:2) to give 3a (1.57 g, 6.9 mmol, 69% yield) as a yellow oil: 1H NMR δ 2.13 (br, 1H), 2.64 (d, J ) 2.2 Hz, 1H), 4.30 (d, J ) 16.3 Hz, 1H), 4.39 (d, J ) 16.3 Hz, 1H), 5.66 (d, J ) 2.2 Hz, 1H), 6.73-6.76 (m, 1H), 6.89-6.93 (m, 1H), 7.14 (dd, J ) 1.2 and 5.2 Hz, 1H), 7.21-7.35 (m, 3H), 7.71-7.77 (m, 1H); 13C NMR δ 32.7, 61.9, 75.0, 83.2, 124.1, 125.3, 126.9, 127.2, 127.4, 129.0, 130.5, 137.7, 137.9, 143.4; HRMS (EI) calcd for C14H12OS [M] 228.0609, found 228.0605. Spectroscopic data and isolated yields of other 3 are as follows. 3a′: 91%; dark red oil; 1H NMR δ 2.36 (d, J ) 5.6 Hz, 1H), 2.58 (d, J ) 2.1 Hz, 1H), 4.08 (d, J ) 16.2 Hz, 1H), 4.16 (d, J ) 16.2 Hz, 1H), 5.56-5.58 (m, 1H), 6.81 (s, 1H), 6.87 (d, J ) 4.9 Hz, 1H), 7.14-7.28 (m, 4H), 7.70-7.73 (m, 1H); 13C NMR δ 33.0, 61.5, 74.8, 83.3, 121.4, 125.7, 126.9, 127.0, 128.2, 128.7, 130.4, 137.7, 137.9, 140.6; HRMS (EI) calcd for C14H12OS [M] 228.0609, found 228.0605. 3b: 86%; yellow oil; 1H NMR δ 2.37 (s, 3H), 2.43 (d, J ) 5.6 Hz, 1H), 2.59 (d, J ) 2.3 Hz, 1H), 4.16 (d, J ) 16.2 Hz, 1H), 4.25 (d, J ) 16.2 Hz, 1H), 5.61-5.64 (m, 1H), 6.48-6.52 (m, 2H), 7.19-7.28 (m, 3H), 7.68-7.72 (m, 1H); 13C NMR δ 15.2, 32.8, 61.7, 74.9, 83.2, 124.7, 125.0, 127.0, 127.1, 128.8, 130.3, 137.6, 137.9, 138.5, 140.9; HRMS (EI) calcd for C15H14OS [M] 242.0765, found 242.0756. 3c: 96%; brown oil; 1H NMR δ 2.54 (br, 1H), 2.57 (d, J ) 2.3 Hz, 1H), 4.22 (d, J ) 16.4 Hz, 1H), 4.31 (d, J ) 16.4 Hz, 1H), 5.62 (br, 1H), 6.66 (d, J ) 3.6 Hz, 1H), 7.07 (d, J ) 3.6 Hz, 1H), 7.14-7.30 (m, 6H), 7.47-7.50 (m, 2H), 7.68-7.72 (m, 1H); 13C NMR δ 32.8, 61.7, 75.1, 83.1, 122.7, 125.4, 126.3, 127.0, 127.1, 127.3, 128.7, 128.8, 130.4, 134.3, 137.5, 137.6, 142.9; HRMS (EI) calcd for C20H16OS [M] 304.0922, found 304.0929. 3d: 74%; yellow oil; 1H NMR δ 2.15 (s, 3H), 2.43 (d, J ) 5.3 Hz, 1H), 2.59 (d, J ) 2.7 Hz, 1H), 4.19 (d, J ) 16.4 Hz, 1H), 4.28 (d, J ) 16.4 Hz, 1H), 5.61 (d, J ) 2.7 Hz, 1H), 6.51 (s, 1H), 6.67 (s, 1H), 7.18-7.29 (m, 3H), 7.69-7.72 (m, 1H); 13C NMR δ 15.6, 32.7, 61.7, 74.9, 83.2, 119.1, 127.1, 127.2, 127.7, 128.8, 130.4, 137.4, 137.6, 137.8, 143.0; HRMS (EI) calcd for C15H14OS [M] 242.0765, found 242.0757. 3e: 82%; yellow oil; 1H NMR δ 2.11 (d, J ) 4.0 Hz, 1H), 2.53 (d, J ) 2.5 Hz, 1H), 2.56 (s, 3H), 4.34 (d, J ) 16.5 Hz, 1H), 4.42 (d, J ) 16.5 Hz, 1H), 5.89-5.92 (m, 1H), 6.72-6.73 (m, 1H), 6.87-6.90 (m, 1H), 7.07-7.22 (m, 4H); 13C NMR δ 20.4, 33.9, 60.1, 74.3, 83.0, 124.0, 125.2, 126.8, 128.5, 128.8, 130.4, 135.8, 137.6, 138.4, 144.2; HRMS (EI) calcd for C15H14OS [M] 242.0765, found 242.0759. 3f: 89%; yellow oil; 1H NMR δ 2.42 (d, J ) 2.3 Hz, 1H), 3.91 (s, 1H), 3.92 (s, 3H), 4.27 (br, 2H), 5.72-5.76 (m, 1H), 6.73-6.75 (m, 1H), 6.85-6.91 (m, 3H), 7.13 (dd, J ) 1.2 and 5.1 Hz, 1H), 7.24 (t, J ) 8.0 Hz, 1H); 13C NMR δ 33.2, 55.9, 59.0, 72.1, 83.9, 110.5, 123.3, 124.0, 125.3, 126.8, 127.0, 129.2, 138.4, 142.9, 157.7; HRMS (EI) calcd for C15H14O2S [M] 258.0715, found 258.0712. 3g: 95%; yellow oil; 1H NMR δ 2.32 (s, 3H), 2.48 (d, J ) 5.4 Hz, 1H), 2.57 (d, J ) 2.3 Hz, 1H), 4.19 (d, J ) 16.3 Hz, 1H), 4.28 (d, J ) 16.3 Hz, 1H), 5.55-5.58 (m, 1H), 6.69-6.71 (m, 1H), 6.84-6.88 (m, 1H), 7.07-7.09 (m, 3H), 7.51 (s, 1H); 13C NMR δ 21.0, 32.2, 61.6, 74.8, 83.3, 123.9, 125.1, 126.7, 127.7, 129.4, 130.3,

2924 Organometallics, Vol. 28, No. 9, 2009 134.7, 136.8, 137.4, 143.7; HRMS (EI) calcd for C15H14OS [M] 242.0765, found 242.0759. 3h: >99%; brown oil; 1H NMR δ 2.52 (br, 1H), 2.59 (d, J ) 2.1 Hz, 1H), 3.78 (s, 3H), 4.19 (d, J ) 16.6 Hz, 1H), 4.26 (d, J ) 16.6 Hz, 1H), 5.57 (br, 1H), 6.70-6.72 (m, 1H), 6.81 (dd, J ) 2.8 and 8.4 Hz, 1H), 6.86-6.90 (m, 1H), 7.09-7.14 (m, 2H), 7.29 (d, J ) 2.8 Hz, 1 H); 13C NMR δ 31.9, 55.2, 61.6, 74.9, 83.1, 112.6, 114.0, 123.9, 125.0, 126.8, 129.8, 131.5, 138.9, 144.0, 158.6; HRMS (EI) calcd for C15H14O2S [M] 258.0715, found 258.0702. 3i: 70%; yellow oil; 1H NMR δ 2.53 (d, J ) 5.3 Hz, 1H), 2.62 (d, J ) 2.3 Hz, 1H), 4.22 (d, J ) 16.5 Hz, 1H), 4.30 (d, J ) 16.5 Hz, 1H), 5.56-5.57 (m, 1H), 6.72-6.74 (m, 1H), 6.88-6.92 (m, 1H), 7.13-7.26 (m, 3H), 7.63 (d, J ) 8.2 Hz, 1H); 13C NMR δ 32.3, 61.2, 75.3, 82.7, 124.4, 125.7, 126.9, 127.2, 128.6, 130.2, 134.5, 136.1, 139.8, 142.0. HRMS (EI) calcd for C14H11ClOS [M] 262.0219, found 262.0217. 3j: 89%; yellow oil; 1H NMR δ 2.39 (s, 3H), 2.43 (d, J ) 4.5 Hz, 1H), 2.63 (d, J ) 2.3 Hz, 1H), 4.14 (d, J ) 16.3 Hz, 1H), 4.22 (d, J ) 16.3 Hz, 1H), 5.59 (br, 1H), 6.50-6.55 (m, 2H), 7.20-7.26 (m, 2H), 7.63 (d, J ) 8.2 Hz, 1H); 13C NMR δ 15.2, 32.5, 61.2, 75.3, 82.8, 124.8, 125.4, 127.2, 128.6, 130.1, 134.5, 136.1, 138.9, 139.6, 139.9; HRMS (EI) calcd for C15H13ClOS [M] 276.0376, found 276.0366. 3k: 95%; yellow oil; 1H NMR δ 2.59 (d, J ) 2.3 Hz, 1H), 2.82 (d, J ) 3.6 Hz, 1H), 4.20 (d, J ) 16.5 Hz, 1H), 4.29 (d, J ) 16.5 Hz, 1H), 5.54-5.57 (m, 1H), 6.72-6.74 (m, 1H), 6.85-6.95 (m, 3H), 7.11 (dd, J ) 1.2 and 5.1 Hz, 1H), 7.64 (dd, J ) 5.8 and 8.4 Hz, 1H); 13C NMR δ 32.2, 61.1, 75.2, 82.9, 113.7 (d, 2JC-F ) 21.2 Hz), 116.9 (d, 2JC-F ) 22.3 Hz), 124.3, 125.7, 126.9, 129.1 (d, 3 JC-F ) 8.4 Hz), 133.3 (d, 4JC-F ) 2.8 Hz), 140.5 (d, 3JC-F ) 7.8 Hz), 142.0, 162.6 (d, 1JC-F ) 247.5 Hz); HRMS (EI) calcd for C14H11FOS [M] 246.0515, found 246.0518. Preparation of 5. A typical experimental procedure for the preparation of 5a is described below. To a solution of o-(2thienyl)benzaldehyde (451.9 mg, 2.4 mmol) in THF (8 mL) was added dropwise a solution of ethynylmagnesium bromide (7.2 mL of a 0.5 M solution in THF, 3.6 mmol) at 0 °C, and the mixture was stirred at ambient temperature for 1 h. After the reaction mixture was quenched by addition of saturated NH4Cl(aq), the solution was extracted with diethyl ether. The combined organic layers were washed by brine and then dried over anhydrous MgSO4. After the removal of the solvent, the crude oil was purified by column chromatography on silica gel (hexane/ethyl acetate, 3:2) to give 5a (460.3 mg, 2.1 mmol, 88% yield) as a yellow oil: 1H NMR δ 2.58 (d, J ) 2.3 Hz, 1H), 2.65 (d, J ) 4.9 Hz, 1H), 5.60-5.63 (m, 1H), 7.06 (dd, J ) 3.5 and 5.1 Hz, 1H), 7.21 (dd, J ) 1.2 and 3.5 Hz, 1H), 7.31-7.41 (m, 4H), 7.84-7.87 (m, 1H); 13 C NMR δ 61.3, 74.8, 84.0, 126.1, 127.3, 127.5, 127.6, 128.4, 128.5, 130.9, 133.2, 138.2, 140.7; HRMS (EI) calcd for C13H10OS [M] 214.0452; found 214.0463. Spectroscopic data and isolated yields of other 5 are as follows. 5b: 82%; yellow oil; 1H NMR δ 2.15 (s, 3H), 2.24 (d, J ) 5.1 Hz, 1H), 2.56 (d, J ) 2.1 Hz, 1H), 5.32-5.35 (m, 1H), 6.94 (dd, J ) 1.1 and 3.4 Hz, 1H), 7.10-7.13 (m, 1H), 7.23-7.26 (m, 1H), 7.33-7.42 (m, 2H), 7.69 (d, J ) 7.7 Hz, 1H); 13C NMR δ 20.6, 61.8, 74.4, 84.1, 124.3, 126.2, 127.1, 127.9, 128.9, 130.0, 132.6, 138.6, 138.9, 140.5; HRMS (EI) calcd for C14H12OS [M] 228.0609, found 228.0605. 5c: 92%; orange oil; 1H NMR δ 2.34 (d, J ) 5.3 Hz, 1H), 2.56 (d, J ) 2.3 Hz, 1H), 3.75 (s, 3H), 5.35-5.38 (m, 1H), 6.93 (dd, J ) 1.5 and 7.9 Hz, 1H), 7.05 (dd, J ) 1.3 and 3.5 Hz, 1H), 7.08-7.12 (m, 1H), 7.37-7.48 (m, 3H); 13C NMR δ 56.0, 61.5, 74.4, 84.0, 110.9, 119.1, 122.1, 126.5, 126.7, 128.7, 129.9, 135.2, 141.4, 157.7; HRMS (EI) calcd for C14H12O2S [M] 244.0558, found 244.0549. 5d: 93%; yellow oil; 1H NMR δ 2.58 (d, J ) 2.3 Hz, 1H), 2.87 (d, J ) 5.3 Hz, 1H), 3.79 (s, 3H), 5.58-5.61 (m, 1H), 6.85 (dd, J

Kanao et al. ) 2.7 and 8.5 Hz, 1H), 7.01-7.04 (m, 1H), 7.13 (dd, J ) 1.2 and 3.5 Hz, 1H), 7.20-7.32 (m, 2H), 7.40 (d, J ) 2.8 Hz, 1H); 13C NMR δ 55.3, 61.3, 74.8, 83.9, 112.3, 114.3, 125.4, 125.6, 127.1, 127.2, 132.1, 139.6, 140.6, 159.5; HRMS (EI) calcd for C14H12O2S [M] 244.0558, found 244.0549. 5e: 94%; orange oil; 1H NMR δ 2.61 (dd, J ) 0.6 and 2.4 Hz, 1H), 2.91 (dd, J ) 5.3 and 9.4, 1H), 5.68 (td, J ) 2.4 and 9.4 Hz, 1H), 7.07-7.15 (m, 3H), 7.19 (dd, J ) 1.2 and 7.8 Hz, 1H), 7.24-7.35 (m, 1H), 7.38 (dd, J ) 1.3 and 5.1 Hz, 1H); 13C NMR δ 58.9, 74.1, 82.9, 115.9 (d, 2JC-F ) 21.8 Hz), 126.6, 126.7 (d, 2 JC-F ) 11.7 Hz), 127.0 (d, 4JC-F ) 2.8 Hz), 127.4, 128.1, 129.4 (d, 3JC-F ) 10.1 Hz), 135.0 (d, 3JC-F ) 4.5 Hz), 139.6 (d, 4JC-F ) 2.8 Hz), 161.8 (d, 1JC-F ) 248.6 Hz); HRMS (EI) calcd for C13H9FOS [M] 232.0358, found 232.0362. 5f: 90%; yellow oil; 1H NMR δ 2.49-2.50 (m, 4H), 2.60 (d, J ) 2.3 Hz, 1H), 5.67-5.70 (m, 1H), 6.72-6.73 (m, 1H), 6.99 (d, J ) 3.3 Hz, 1H), 7.31-7.40 (m, 3H), 7.83-7.87 (m, 1H); 13C NMR δ 15.1, 61.4, 74.8, 84.1, 125.6, 127.5, 127.6, 128.2, 128.4, 130.8, 133.6, 138.1, 138.3, 140.7; HRMS (EI) calcd for C14H12OS [M] 228.0609, found 228.0605. Ruthenium-Catalyzed Enantioselective Intramolecular Propargylation of 3 and 5. A typical experiment procedure for the reaction of 3a catalyzed by 1a is described below. In a 20 mL Schlenk flask were placed 1a (13.0 mg, 0.010 mmol) and NH4BF4 (2.1 mg, 0.020 mmol) under N2. Anhydrous 1,2-dichloroethane (10 mL) was added, and the mixture was magnetically stirred at room temperature. After the addition of 3a (48.4 mg, 0.212 mmol), the reaction flask was kept at 40 °C for 24 h. The solvent was concentrated under reduced pressure, and then the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate, 99:1) to give 4a as a pale yellow oil (34.9 mg, 0.166 mmol, 78% isolated yield): 1H NMR δ 2.33 (d, J ) 2.8 Hz, 1H), 4.07 (dd, J ) 4.7 and 19.9 Hz, 1H), 4.19 (dd, J ) 3.5 and 19.9 Hz, 1H), 4.99-5.03 (m, 1H), 7.16-7.34 (m, 5H), 7.68 (d, J ) 6.4 Hz, 1H); 13C NMR δ 29.7, 32.8, 70.3, 84.8, 123.0, 126.7, 126.9, 127.1, 128.5, 128.8, 133.0, 133.1, 133.4, 133.8; HRMS (EI) calcd for C14H10S [M] 210.0503, found 210.0500. The optical purity of 4a was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 90/10, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 38.3 min (S) and 41.9 min (R), 96% ee; [R]25D +7.8 (c 0.76, CHCl3). Spectroscopic data and isolated yields of other 4 are as follows. 4a′: 79%; orange oil; 1H NMR δ 2.39 (d, J ) 2.6 Hz, 1H), 3.92 (dd, J ) 4.8 and 19.8 Hz, 1H), 4.05 (dd, J ) 3.3 and 19.8 Hz, 1H), 5.16 (br, 1H), 6.90 (d, J ) 5.1 Hz, 1H), 7.23-7.31 (m, 4H), 7.66 (d, J ) 6.4 Hz, 1H); 13C NMR δ 30.7, 32.4, 70.9, 84.5, 124.0, 126.6, 126.7, 127.2, 128.2, 128.8, 133.5, 133.7, 133.8; HRMS (EI) calcd for C14H10S [M] 210.0503, found 210.0500. The optical purity of 4a′ was determined by HPLC analysis; DAICEL Chiralcel OJH, hexane/iPrOH ) 90/10, flow rate ) 1.0 mL/min, λ ) 254 nm, retention time 19.7 min (R) and 41.0 min (S), 86% ee; [R]25D -6.4 (c 1.69, CHCl3). 4b: 80%; brown oil; 1H NMR δ 2.28 (d, J ) 2.6 Hz, 1H), 2.45 (s, 3H), 3.95 (dd, J ) 4.7 and 20.0 Hz, 1H), 4.07 (dd, J ) 3.5 and 20.0 Hz, 1H), 4.88-4.92 (m, 1H), 6.79 (s, 1H), 7.19-7.29 (m, 3H), 7.61-7.65 (m, 1H); 13C NMR δ 15.3, 29.5, 32.5, 69.9, 85.1, 124.6, 126.7, 127.0, 128.5, 128.8, 130.9, 132.3, 133.0, 133.7, 137.5; HRMS (EI) calcd for C15H12S [M] 224.0660, found 224.0658. The optical purity of 4b was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 90/10, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 31.6 min (S) and 32.7 min (R), 90% ee; [R]25D +16.1 (c 2.00, CHCl3). 4c: 71%; brown solid; mp 104.9-105.6 °C; 1H NMR δ 2.35 (d, J ) 2.6 Hz, 1H), 4.07 (dd, J ) 4.7 and 20.2 Hz, 1H), 4.19 (dd, J ) 3.4 and 20.2 Hz, 1H), 4.99-5.03 (m, 1H), 7.24-7.39 (m, 7H), 7.59-7.62 (m, 2H), 7.68-7.70 (m, 1H); 13C NMR δ 29.7, 32.7, 70.4, 84.7, 122.6, 125.6, 126.9, 127.1, 127.3, 128.5, 128.7, 128.8,

Ru-Catalyzed Propargylation of Thiophenes 132.7, 133.0, 133.6, 133.9, 134.4, 142.0; HRMS (EI) calcd for C20H14S [M] 286.0816, found 286.0824. The optical purity of 4c was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 90/10, flow rate ) 1.0 mL/min, λ ) 254 nm, retention time 28.3 min (S) and 48.8 min (R), 96% ee; [R]25D -56.9 (c 1.24, CHCl3). 4e: 81%; pale yellow solid; mp 80.3-80.8 °C; 1H NMR δ 2.12 (d, J ) 2.6 Hz, 1H), 2.55 (s, 3H), 4.09 (dd, J ) 2.1 and 19.9 Hz, 1H), 4.24 (dd, J ) 2.6 and 19.9 Hz, 1H), 5.04-5.06 (m, 1H), 7.06-7.24 (m, 5H); 13C NMR δ 19.7, 30.0, 30.2, 68.8, 83.9, 123.4, 126.4, 126.6, 127.1, 128.9, 132.5, 133.4, 133.5, 134.3, 136.9; HRMS (EI) calcd for C15H12S [M] 224.0660, found 224.0663. The optical purity of 4e was determined by HPLC analysis; DAICEL Chiralcel OD, hexane/iPrOH ) 98/2, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time; 16.3 min (R) and 18.4 min (S), 88% ee; [R]25D +30.7 (c 0.62, CHCl3). 4f: 70%; dark brown solid; mp 85.2-86.4 °C; 1H NMR δ 2.06 (d, J ) 2.5 Hz, 1H), 3.94 (s, 3H), 4.08 (dd, J ) 2.4 and 20.0 Hz, 1H), 4.23 (dd, J ) 2.7 and 20.0 Hz, 1H), 5.22-5.25 (m, 1H), 6.82 (d, J ) 8.2 Hz, 1H), 6.89 (d, J ) 7.7 Hz, 1H), 7.08 (d, J ) 7.7 Hz, 1H), 7.18-7.27 (m, 2H); 13C NMR δ 27.2, 29.6, 55.8, 67.3, 85.0, 108.8, 120.9, 123.2, 123.3, 126.5, 127.9, 133.6, 133.9, 135.1, 157.3; HRMS (EI) calcd for C15H12OS [M] 240.0609, found 240.0597. The optical purity of 4f was determined by HPLC analysis; DAICEL Chiralcel OD, hexane/iPrOH ) 98/2, flow rate ) 0.5 mL/ min, λ ) 254 nm, retention time 22.3 min (R) and 24.0 min (S), 97% ee; [R]25D +10.6 (c 1.84, CHCl3). 4g: 76%; brown solid; mp 69.5-70.0 °C; 1H NMR δ 2.32 (d, J ) 2.6 Hz, 1H), 2.37 (s, 3H), 4.01 (dd, J ) 4.5 and 19.9 Hz, 1H), 4.14 (dd, J ) 3.2 and 19.9 Hz, 1H), 4.96 (br, 1H), 7.05-7.22 (m, 4H), 7.47 (s, 1H); 13C NMR δ 21.1, 29.3, 32.7, 70.1, 85.0, 122.9, 126.7, 128.0, 128.3, 129.2, 129.9, 133.1, 133.5, 133.7, 136.4; HRMS (EI) calcd for C15H12S [M] 224.0660, found 224.0648. The optical purity of 4g was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 95/5, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 46.2 min (R) and 54.8 min (S), 96% ee; [R]25D +31.9 (c 1.69, CHCl3). 4h: 96%; brown solid; mp 77.8-78.8 °C; 1H NMR δ 2.34 (d, J ) 2.6 Hz, 1H), 3.83 (s, 3H), 4.00 (dd, J ) 4.8 and 19.9 Hz, 1H), 4.12 (dd, J ) 3.5 and 19.9 Hz, 1H), 4.96-5.00 (m, 1H), 6.84 (dd, J ) 2.6 and 8.6 Hz, 1H), 7.14-7.24 (m, 4H); 13C NMR δ 28.9, 33.0, 55.4, 70.4, 84.7, 113.4, 113.5, 122.9, 125.1, 126.6, 129.3, 132.8, 133.9, 134.9, 158.4; HRMS (EI) calcd for C15H12OS [M] 240.0609, found 240.0605. The optical purity of 4h was determined by HPLC analysis; DAICEL Chiralcel OD, hexane/iPrOH ) 98/2, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 18.1 min (R) and 20.8 min (S), 97% ee; [R]25D +68.3 (c 0.83, CHCl3). 4i: 77%; pale yellow solid; mp 90.2-90.5 °C; 1H NMR δ 2.34 (d, J ) 2.6 Hz, 1H), 4.04 (dd, J ) 4.8 and 20.2 Hz, 1H), 4.16 (dd, J ) 3.5 and 20.2 Hz, 1H), 4.94-4.96 (m, 1H), 7.15 (d, J ) 5.1 Hz, 1H), 7.21 (d, J ) 5.1 Hz, 1H), 7.25-7.29 (m, 2H), 7.60-7.63 (m, 1H); 13C NMR δ 29.6, 32.4, 70.7, 84.2, 123.4, 126.6, 127.1, 128.2, 130.2, 132.4, 132.7, 132.8, 132.9, 134.9. Anal. Calcd for C14H9ClS: C, 68.71; H, 3.71. Found: C, 68.48; H, 3.90. The optical purity of 4i was determined by HPLC analysis; DAICEL Chiralcel OD, hexane/iPrOH ) 98/2, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 13.3 min (R) and 14.5 min (S), 97% ee; [R]25D +25.2 (c 1.05, CHCl3). 4j: 81%; pale yellow solid; mp 104.8-105.6 °C; 1H NMR δ 2.31 (d, J ) 2.6 Hz, 1H), 2.46 (s, 3H), 3.93 (dd, J ) 4.9 and 20.3 Hz, 1H), 4.05 (dd, J ) 3.5 and 20.3 Hz, 1H), 4.85 (br, 1H), 6.79 (br, 1H), 7.21-7.25 (m, 2H), 7.56 (d, J ) 8.2 Hz, 1H); 13C NMR δ 15.3, 29.4, 32.1, 70.3, 84.5, 124.5, 126.9, 128.2, 130.2, 132.1, 132.3, 132.7, 134.9, 138.0; HRMS (EI) calcd for C15H11ClS [M] 258.0270, found 258.0265. The optical purity of 4j was determined by HPLC analysis; DAICEL Chiralcel OD, hexane/iPrOH ) 99/1,

Organometallics, Vol. 28, No. 9, 2009 2925 flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 10.8 min (R) and 12.8 min (S), 89% ee; [R]25D +14.9 (c 1.20, CHCl3). 4k: 79%; yellow solid; mp 52.2-53.0 °C; 1H NMR δ 2.34 (d, J ) 2.6 Hz, 1H), 4.05 (dd, J ) 4.6 and 20.3 Hz, 1H), 4.17 (dd, J ) 3.2 and 20.3 Hz, 1H), 4.96 (br, 1H), 6.94-7.04 (m, 2H), 7.14-7.25 (m, 2H), 7.61-7.67 (m, 1H); 13C NMR δ 29.8, 32.2, 70.5, 84.6, 114.1 (d, 2JC-F ) 21.2 Hz), 114.7 (d, 2JC-F ) 21.2 Hz), 123.3, 126.7, 129.5 (d, 4JC-F ) 2.8 Hz), 130.4 (d, 3JC-F ) 8.4 Hz), 132.7, 133.1, 135.1 (d, 3JC-F ) 7.8 Hz), 161.7 (d, 1JC-F ) 245.8 Hz); HRMS (EI) calcd for C14H9FS [M] 228.0409, found 228.0399. The optical purity of 4k was determined by HPLC analysis; DAICEL Chiralcel OD, hexane/iPrOH ) 98/2, flow rate ) 0.5 mL/ min, λ ) 254 nm, retention time 12.0 min (S) and 12.7 min (R), 95% ee; [R]25D +24.3 (c 0.89, CHCl3). 6a: 50%; brown solid; mp 69.0-69.8 °C; 1H NMR δ 2.23 (d, J ) 2.7 Hz, 1H), 4.61 (d, J ) 2.7 Hz, 1H), 7.20 (d, J ) 4.8 Hz, 1H), 7.25 (dt, J ) 1.5 and 7.4 Hz, 1H), 7.32-7.37 (m, 2H), 7.43-7.46 (m, 1H), 7.59-7.62 (m, 1H); 13C NMR δ 36.0, 70.0, 80.7, 119.1, 122.1, 124.9, 125.8, 128.0, 128.1, 137.4, 142.9, 146.4, 146.9; HRMS (EI) calcd for C13H8S [M] 196.0347, found 196.0341. The optical purity of 6a was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 99/1, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 16.1 min (R) and 17.5 min (S), 92% ee; [R]25D +19.3 (c 1.01, CHCl3). 6b: 66%; yellow solid; mp 91.7-92.5 °C; 1H NMR δ 2.22 (d, J ) 2.7 Hz, 1H), 2.52 (s, 3H), 4.60 (d, J ) 2.7 Hz, 1H), 7.15-7.17 (m, 2H), 7.23 (d, J ) 4.9 Hz, 1H), 7.38 (d, J ) 4.9 Hz, 1H), 7.43-7.46 (m, 1H); 13C NMR δ 19.3, 36.0, 69.9, 81.0, 122.0, 122.3, 126.0, 128.5, 129.1, 129.4, 136.7, 142.3, 146.1, 146.2; HRMS (EI) calcd for C14H10S [M] 210.0503, found 210.0500. The optical purity of 6b was determined by HPLC analysis; DAICEL Chiralcel OJH, hexane/iPrOH ) 99/1, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 14.3 min (R) and 17.8 min (S), 87% ee; [R]25D +7.3 (c 1.42, CHCl3). 6c: 64%; brown solid; mp 102.5-103.2 °C; 1H NMR δ 2.23 (d, J ) 2.8 Hz, 1H), 3.96 (s, 3H), 4.63 (d, J ) 2.8 Hz, 1H), 6.87-6.91 (m, 1H), 7.19 (d, J ) 4.9 Hz, 1H), 7.22-7.25 (m, 2H), 7.34 (d, J ) 4.9 Hz, 1H); 13C NMR δ 36.3, 55.7, 70.0, 80.8, 110.0, 117.4, 121.6, 126.6, 127.2, 128.4, 140.2, 145.2, 147.9, 152.1; HRMS (EI) calcd for C14H10OS [M] 226.0452, found 226.0450. The optical purity of 6c was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 99/1, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 35.0 min (R) and 47.8 min (S), 84% ee; [R]25D +2.3 (c 1.48, CHCl3). 6d: 20%; brown solid; mp 77.2-78.5 °C; 1H NMR δ 2.23 (d, J ) 2.6 Hz, 1H), 3.85 (s, 3H), 4.57 (d, J ) 2.6 Hz, 1H), 6.88 (dd, J ) 2.4 and 8.3 Hz, 1H), 7.15 (d, J ) 4.9 Hz, 1H), 7.18-7.19 (m, 1H), 7.24 (d, J ) 4.9 Hz, 1H), 7.33 (d, J ) 8.3 Hz, 1H); 13C NMR δ 36.1, 55.6, 70.0, 80.9, 111.4, 113.5, 119.5, 122.1, 126.5, 130.5, 145.5, 148.3, 158.5; HRMS (EI) calcd for C14H10OS [M] 226.0452, found 226.0443. The optical purity of 6d was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 99/1, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 29.8 min (S) and 34.8 min (R), 94% ee; [R]25D +18.5 (c 0.85, CHCl3). 6e: 58%; yellow solid; mp 115.0-115.5 °C; 1H NMR δ 2.25 (d, J ) 2.6 Hz, 1H), 4.72 (d, J ) 2.6 Hz, 1H), 6.94 (t, J ) 8.8 Hz, 1H), 7.20-7.25 (m, 2H), 7.30-7.39 (m, 2H); 13C NMR δ 33.3, 70.2, 78.9, 113.2 (d, 2JC-F ) 20.1 Hz), 115.2 (d, 4JC-F ) 3.4 Hz), 122.1, 129.1, 130.4 (d, 3JC-F ) 7.3 Hz), 130.9 (d, 2JC-F ) 16.2), 140.2 (d, 3JC-F ) 6.1 Hz), 147.4, 147.5, 159.1 (d, 1JC-F ) 249.7 Hz); HRMS (EI) calcd for C13H7FS [M] 214.0252, found 214.0254. The optical purity of 6e was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 99/1, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 17.8 min (S) and 20.4 min (R), 79% ee; [R]25D +20.6 (c 1.26, CHCl3). 6f: 43%; brown solid; mp 89.2-90.1 °C; 1H NMR δ 2.21 (d, J ) 2.8 Hz, 1H), 2.55 (s, 3H), 4.53 (br, 1H), 6.88 (s, 1H), 7.20 (dt,

2926 Organometallics, Vol. 28, No. 9, 2009 J ) 1.7 and 7.3 Hz, 1H), 7.28-7.36 (m, 2H), 7.57 (d, J ) 7.3 Hz, 1H); 13C NMR δ 16.3, 36.2, 70.0, 80.9, 118.5, 120.3, 124.7, 125.2, 128.0, 137.9, 140.4, 143.6, 145.6, 146.5; HRMS (EI) calcd for C14H10S [M] 210.0503, found 210.0513. The optical purity of 6f was determined by HPLC analysis; DAICEL Chiralcel OJ-H, hexane/iPrOH ) 99/1, flow rate ) 0.5 mL/min, λ ) 254 nm, retention time 15.2 min (R) and 17.4 min (S), 82% ee; [R]25D +9.1 (c 0.93, CHCl3). X-ray Diffraction Study of 4e and Absolute Configurations of 4 and 6. Colorless thick needles (size, 0.50 × 0.20 × 0.15 mm) suitable for X-ray study were obtained by further recrystallization of 4e from ethanol. Diffraction data for 4e were collected at -100 °C on a Rigaku RAXIS RAPID imaging plate area detector with graphite-monochromated Mo KR radiation (λ ) 0.71075 Å). Reflections were collected for the 2θ range of 5° to 55°. Intensity data were corrected for empirical absorptions, for Lorentz and polarization effects, and for secondary extinction (coefficient, 212(8)). The structure solution and refinements were carried out by using the CrystalStructure package,19 which revealed that the crystal of 4e contains two crystallographically independent structures. The positions of non-hydrogen atoms were determined by direct methods (SIR97)20 and subsequent Fourier syntheses (DIRDIF99)21 and were refined on Fo2 using all the unique (19) (a) CrystalStructure 3.80: Single Crystal Structure Analysis Software; Rigaku Corp: Tokyo, Japan, and MSC: The Woodlands, TX, 20002007. (b) Carruthers, J. R.; Rollett, J. S.; Betteridge, P. W.; Kinna, D.; Pearce, L.; Larsen, A.; Gabe, E. CRYSTALS Issue 11; Chemical Crystallography Laboratory: Oxford, UK, 1999. (20) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 1999, 32, 115. (21) Beurskens, P. T.; Beurskens, G.; de Gelder, R.; Garcı´a-Granda, S.; Gould, R. O.; Israe¨l, R.; Smits, J. M. M. The DIRDIF-99 program system; Crystallography Laboratory, University of Nijmegen: Nijmegen, The Netherlands, 1999.

Kanao et al. reflections by full-matrix least-squares with anisotropic thermal parameters. All the hydrogen atoms were placed at the calculated positions [C-H distance of 0.95 Å] with fixed isotropic parameters. Crystallographic data: C15H12S; fw ) 224.32; orthorhombic; space group P212121; a ) 4.6647(3) Å, b ) 17.0822(9) Å, c ) 29.1293(13) Å; V ) 2321.1(2) Å3; Z ) 8; dcalcd ) 1.284 g cm-3; µ ) 2.453 cm-1; R1 (wR2) ) 0.390 (0.1011) for 5273 unique reflections and 333 variables; GOF ) 1.000; Flack parameter ) -0.00(9). The absolute configuration was determined by refinement of the Flank parameter. This was found to be -0.00(9), where the expected values are 0 (within 3 estimated standard deviations). Details of the other crystallographic data are given in a CIF file (see Supporting Information). As shown in Figure 1, the absolute configuration of 4e produced by the use of 1a as a catalyst was determined to be (R)-(+) by X-ray analysis. The absolute configurations of other propargylated compounds 4 and 6 were assigned by consideration of the stereochemical pathway as shown in Scheme 7.

Acknowledgment. This work was supported by Grantin-Aids for Scientific Research for Young Scientists (S) (No. 19675002) and for Scientific Research on Priority Areas (No. 18066003) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Y.N. thanks the Tonen General Sekiyu Foundation for the Promotion of Science and Technology and Ube Industries LTD. K.K. acknowledges the Global COE Program for Chemistry Innovation. Supporting Information Available: Crystallographic data for (R)-4e are available in CIF format. This material is available free of charge via the Internet at http://pubs.acs.org. OM9001186