J. Org. Chem. 2001, 66, 5915-5918
First Example of a Lewis Acid-Promoted [2 + 1] Cycloaddition of a 1-Thio-2-silylethene
5915 Scheme 1
Shoko Yamazaki,* Yuichiro Yanase, Kyosuke Kamimoto, and Kuriko Yamada Department of Chemistry, Nara University of Education, Takabatake-cho, Nara 630-8528, Japan
Kagetoshi Yamamoto Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan
[email protected] Received February 7, 2001
Introduction Cycloaddition reactions of olefins with heteroatom substituents are extremely useful in organic synthesis.1 The heteroatoms function as directing elements that serve to control chemo-, regio-, and stereoselectivities. Recently, we have developed a novel [2 + 1] cycloaddition reaction of (E)-1-(phenylseleno)-2-(trimethylsilyl)ethene (1) and various electophilic olefins in the presence of Lewis acids (eq 1).2 This new approach to cyclopropane
construction is based on a 1,2-silicon migration process, and we have recently revealed the mechanism of the crucial silicon migration and ring closure steps using DFT (density functional theory) calculations.3 In a general sense, the variations of Lewis acid, coordinating atom a, and migrating atom d in Scheme 1 suggest that it should be possible to effect cyclopropanation when a suitable combination, including substrates and conditions, is chosen. So far, the only example for a is selenium and for d is silicon, as shown in eq 1. (1) For example, [2 + 2] cycloadditions: (a) Huisgen, R. Acc. Chem. Res. 1977, 10, 117-124, 199-206. (b) Narasaka, K.; Hayashi, Y.; Shimadzu, H.; Niihata, S. J. Am. Chem. Soc. 1992, 114, 8869. (c) Srisiri, W.; Padius, A. B.; Hall, H. K., Jr. J. Org. Chem. 1994, 59, 5424. (d) Bach, T. Synthesis 1998, 683. [4+2] Cycloadditions: (e) Danishefsky, S. Acc. Chem. Res. 1981, 14, 400. (f) Trost, B. M.; Vladuchick, W. C.; Bridges, A. J. J. Am. Chem. Soc. 1980, 102, 3548. [3 + 2] Cycloadditions: (g) DeShong, P.; Lander, S. W., Jr.; Leginus, J. M.; Dicken, C. M. Advances in Cycloaddition; Curran, D. P., Ed.; JAI Press: Greenwich, 1988; Vol. 1, p 87. (h) Panek, J. S. Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 1, p 579. (2) (a) Yamazaki, S.; Tanaka, M.; Yamaguchi, A.; Yamabe, S. J. Am. Chem. Soc. 1994, 116, 2356. (b) Yamazaki, S.; Tanaka, M.; Inoue, T.; Morimoto, N.; Kumagai, H.; Yamamoto, K. J. Org. Chem. 1995, 60, 6546. (c) Yamazaki, S.; Kumagai, H.; Takada, T.; Yamabe, S.; Yamamoto, K. J. Org. Chem. 1997, 62, 2968. (d) Yamazaki, S.; Takada, T.; Imanishi, T.; Moriguchi, Y.; Yamabe, S. J. Org. Chem. 1998, 63, 5919. (e) Yamazaki, S.; Yanase, Y.; Tanigawa, E.; Yamabe, S.; Tamura, H. J. Org. Chem. 1999, 64, 9521. (3) Yamazaki, S.; Yamabe, S. J. Chem. Soc., Perkin Trans. 2 2001, 164.
With the goal of broadening the applicability of this novel chemistry, our interest is currently directed toward expanding this new type of reaction toward other heteroatoms. Substitution of selenium by sulfur and comparison of the reactivities of the corresponding analogues is one possible approach to this goal; however, sulfur is wellknown to stabilize R-cations more strongly than selenium, suggesting that the planned silicon migration should not be as facile as that with selenium.4 Previously, we examined the reactivity of (E)-1-(phenylthio)-2-(trimethylsilyl)ethene (2), the sulfur analogue of 1; however, all reactions only afforded highly complex mixtures.2a In the literature, the combination of sulfur and silicon has been examined for the reaction of cyclohexenone and 1-(isopropylthio)-2-(trimethylsilyl)ethene in the presence of Lewis acids,5 and the reaction with BF3-etherate afforded [2 + 2] cycloaddition accompanied by desilylation to give a cyclobutane product. This suggested to us that a detailed examination of the combination of substrates and conditions would be required in order to achieve cyclopropanation. Herein, we report the first example of a Lewis acid-promoted [2 + 1] cycloaddition of a 1-thio2-silylethene, and we demonstrate clearly that the general Scheme 1 is not restricted only to the Se-Si combination hitherto described. Results and Discussion Reaction of (E)-1-(phenylthio)-2-(trimethylsilyl)ethene (2) with trimethyl 2-phosphonoacrylate (3) was examined (eq 2), because the highly electrophilic olefin 3 was
previously shown to be the best substrate for 1, affording a cyclopropane in extremely high yield (96%).2d The same (4) (a) McClelland, R. A.; Leung, M. J. Org. Chem. 1980, 45, 187. (b) Hevesi, L.; Piquard, J.-L.; Wautier, H. J. Am. Chem. Soc. 1981, 103, 870. (c) Heveshi, L. Phosphorus, Sulfur Silicon Relat. Elem. 1992, 67, 155.
10.1021/jo0101555 CCC: $20.00 © 2001 American Chemical Society Published on Web 07/27/2001
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Notes
Table 1. [2 + 2] and [2 + 1] Cycloadditions of 2 and 3a entry Lewis acid temp, time 1 2 3 4 5 6 7 8 9 10 11 12
SnCl4 BF3‚ether ZnCl2 ZnBr2 ZnI2 ZnI2 ZnI2 ZnI2 ZnI2 ZnI2 ZnI2 ZnI2
-78 °C, 3 h -40 °C, 3 h -30 °C, 4 h -30 °C, 2 h -30 °C, 2 h 0 °C, 2 h 0 °C, 4 h 0 °C, 8 h 15 °C, 2 h 15 °C, 4 h 15 °C, 15 h 40 °C, 4 h
4
5
12%b 51%b 59%b 49%b 35%b 24%c 16%c 11%c 2%c 1%c
76
6 d
1%c 12%c 9%c 6%c 20%c 24%c 29%c 22%c 14%c 3%c
d 1%c 7%c 4%c 3%c 19%c 24%c 31%c 32%c 54%c 11%c 61%c 3%c
recovered 2 48% e 31% 26% 11% 3% 5% 4% 3% 4% 3% 4%
a All reactions were carried out using 1 mmol of 2, 1.3 equiv of 3, and 1.5 equiv of Lewis acid at 0.4 M for 1 in CH2Cl2. b Isolated yields for 4. c Obtained as a mixture. The yields were calculated by 1H NMR. d The reaction gave a complex mixture including cyclobutane 5 and cyclopropane 6. Purification of the mixture failed. e No reaction.
conditions as for the reaction of 1 and 3 (SnCl4, -78 °C, 3 h, in CH2Cl2) gave only a complex mixture possibly including cyclobutanes and cyclopropanes, along with recovered 2 (48%) (Table 1, entry 1). Purification of the products failed to produce an identifiable compound. Next, reactions in the presence of zinc halides were examined. In the case of 1 and 3, reactions do not proceed when zinc halides (ZnBr2) are used, because zinc halides are significantly weaker Lewis acids than SnCl4. However, the reaction of 2 and 3 in CH2Cl2 with ZnX2 proceeded smoothly to give a mixture of cyclobutanes and cyclopropanes, as shown in Table 1. This result follows from the nucleophilicity of sulfur-substituted olefins, which is higher than that of selenium-substituted olefins.4 In these reactions, separation of the cycloadducts was difficult because of similar Rf values; however, at -30 °C for 2 h, cyclobutane 4 was the major product (59%) (entry 5). On the other hand, at +40 °C for 4 h, cyclopropane 6 was the major product (61%) (entry 12). Thus, in the reactions using ZnI2, selective cyclopropane or cyclobutane formation was found to be critically dependent on temperature and time. At higher temperatures, cyclopropane formation is preferred. However, reaction at 80 °C using 1,2-dichloroethane instead of dichloromethane gave a decomposed mixture, including traces of unreacted 2. Without the Lewis acid, thermal reactions of 2 and 3 in 1,2-dichloroethane or acetonitrile at 80 °C did not proceed. The structures of cyclopropanes and cyclobutanes were clearly distinguished by NMR spectra. The major product at +40 °C, cyclopropane 6, shows similar chemical shifts and coupling patterns to those of its selenium analogue obtained previously.2d The structures of cyclopropanes 6 and 76 were assigned by characteristic 1JCH values (166168 Hz) for the cyclopropane ring carbons. The presence of a CH(SPh)(SiMe3) group in 6 was also confirmed by HMBC correlations (H13-C4, H4-C13, H4-C9), which indicated that S and Si reside on the same carbon C4 (see Figure 1 for numbering). The cis stereochemistry of CH(SPh)(SiMe3) and CO2Me/PO(OMe)2 in 6 was determined by the observed NOE (CO2Me and SPh) (Figure 1). The relative configuration at C2 and C4 of 6 was deduced as (R,R) or (S,S), assuming the similar heteroatom-coordi(5) Bonini, B. F.; Comes-Franchini, M.; Fochi, M.; Mazzanti, G.: Ricci, A. Synlett 1997, 681. (6) The minor product 7 was not completely purified. Therefore, the structure assignment is tentative. Nevertherless, the major peaks in the NMR spectra (including HMBC and NOESY) agree with the structure in eq 2.
Figure 1. Selected NOEs for 6.
nated ring closure mechanism as shown in Scheme 1. The combination of the large vicinal coupling constants JH2-H4 (12.0 Hz), which indicate that H2-C2-C4-H4 is close to 180°, the previously mentioned observed NOE, and also the NOE between SiMe3 and H3a supports the assignment.2b-d A distinguishing difference between cyclopropanes and cyclobutanes is the chemical shifts of the methylene protons: H3a,3b in cyclopropanes 6 and 76 appear at characteristic high fields (δ 1.57-1.90 ppm). On the other hand, H4a,4b in cyclobutanes 4 and 5 appear at slightly lower fields (δ 2.18-2.65). The cis and trans stereochemistry of SPh and CO2Me/PO(OMe)2 in 4 and 5 was suggested by the observed NOE between SPh and PO(OMe)2 for 4, and between SPh and CO2Me for 5.7 The potential for isomerization of a cyclobutane product to a cyclopropane was also examined. When isolated cyclobutane 4 was treated with ZnI2 (1.5 equiv) in CH2Cl2 at 15 °C for 2 h, 2 (9%), 4 (25%), and an unseparated mixture of 5 (25%) and 6 (29%) were obtained. Such an isomerization was also seen between selenium analogue 1 and di-tert-butyl methylenemalonate in the presence of ZnBr2.2b The mechanism of these [2 + 2] and [2 + 1] cycloadditions can be explained in a manner similar to that proposed for (E)-1-(phenylseleno)-2-(trimethylsilyl)ethene (1).3 Formation of cyclopropane 6 involves a silicon migration step, and the cycloaddition processes are reversible. Furthermore, cyclobutane 4 formation is kinetically more favored than cyclopropane 6 formation. The detailed factors controlling the product ratios are currently under further investigation. The reactivity of the cyclopropane product 6 in comparison to the corresponding selenium analogue was next examined. Oxidation of 6 with NaIO4 in THF-H2O did not proceed. Exposure of the selenium cyclopropane analogues to the same conditions gave aldehydes through a seleno-sila-Pummerer reaction.2 Oxidation of 6 with NaIO4-RuCl4 in CCl4/CH3CN/H2O gave sulfone 8 in 79% yield (eq 3): the reaction of the selenium analogue (triethyl ester) of 6 under the same one-step oxidation conditions gave the corresponding cyclopropane carboxylic acid (91%).8 Further transformations of highly substituted cyclopropane 8 are under investigation.
Notes
J. Org. Chem., Vol. 66, No. 17, 2001 5917
While cyclopropanation using 2 was less effective than with the corresponding selenium analogue 1, the first example of cyclopropane formation using a 1-thio-2silylethene 2 has been discovered. When the combination of an electron-donating heteroatom, a Lewis acid, an electrophilic olefin, and the other reaction conditions was identified, it was shown that cyclopropanation accompanied by atom migration can occur: this example is the combination of a ) S, d ) Si, and Lewis acid (LA) ) ZnI2 in Scheme 1. Experimental Section General Methods. Melting points are uncorrected. IR spectra were recorded in the FT mode. 1H NMR spectra were recorded at 400 MHz. 13C NMR spectra were recorded at 100.6 MHz. Chemical shifts are reported in ppm relative to Me4Si or residual nondeuterated solvent. 13C mutiplicities were determined by DEPT and HSQC. 13C-1H coupling constants were determined by HET2J. Mass spectra were recorded at an ionizing voltage of 70 eV by EI or FAB. All reactions were carried out under a nitrogen atmosphere. Typical Experimental Procedure for 4-7 (Entry 12, Table 1). To a solution of 2 (202 mg, 1.0 mmol) in dichloromethane (2.5 mL) was added ZnI2 (479 mg, 1.5 mmol), followed by 3 (0.202 mL, 252 mg, 1.3 mmol) at 0 °C. The bath temperature was then adjusted to 40 °C, and the mixture was stirred for 4 h. After the mixture was cooled to room temperature, the reaction mixture was quenched by triethylamine (0.32 mL, 232 mg, 2.3 mmol) and then saturated aq NaHCO3. The mixture was extracted with dichloromethane, and the organic phase was washed with water, dried (Na2SO4), and evaporated in vacuo. The residue was purified by column chromatography over silica gel, eluting with CH2Cl2-ether (2:1) to give a mixture (271 mg, total yield 67%) containing 4 and 7 (Rf ) 0.45) and 5 and 6 (Rf ) 0.3). The yields in Table 1 were calculated by 1H NMR. Pure 6 was isolated by column chromatography (SiO2 and CH2Cl2ether ) 2:1; COSMOSIL 75C18-OPN and CH3CN-H2O ) 6:4). Compound 4 was separated by SiO2 and CH2Cl2-ether (2:1) in entries 1-7. Compound 5 was isolated by column chromatography (SiO2 and CH2Cl2-ether ) 2:1; COSMOSIL 75C18-PREP and CH3CN-H2O ) 6:4). Compound 7 (slightly impure) was separated in entry 11. Methyl r-1-(Dimethoxyphosphoryl)-t-2-(phenylthio)-c3-(trimethylsilyl)-1-cyclobutanecarboxylate (4). Rf ) 0.45 (CH2Cl2-ether ) 2:1); colorless oil. 1H NMR (400 MHz, CDCl3): δ -0.030 (s, 9H), 2.18-2.33 (m, 2H), 2.53-2.65 (m, 1H), 3.71 (d, JPH ) 0.5 Hz, 3H), 3.85 (d, JPH ) 10.8 Hz, 3H), 3.88 (d, JPH ) 11.0 Hz, 3H), 4.01-4.12 (m, 1H), 7.19-7.23 (m, 1H), 7.267.31 (m, 2H), 7.53-7.56 (m, 2H). Selected NOE is between δ 3.58, 3.88 (PO(OMe)2) and 7.53-7.56 (H of o-Ph). 13C NMR (100.6 MHz, CDCl3): δ -3.38 (CH3), 26.15 (d, JPC ) 6.9 Hz, 1JCH ) 143 Hz, CH2), 28.22 (d, JPC ) 1.5 Hz, 1JCH ) 129 Hz, CH), 51.74 (d, JPC ) 7.6 Hz, 1JCH ) 148 Hz, CH), 52.72 (CH3), 53.42 (d, JPC ) 6.9 Hz, CH3), 53.62 (d, JPC ) 6.9 Hz, CH3), 56.05 (d, JPC ) 142 Hz, C), 126.94 (CH), 128.77 (CH), 131.40 (CH), 137.11 (C), 171.60 (C). 31P NMR (161.9 MHz, benzene-d6): δ 4.46. IR (neat): 2956, 1734, 1251 cm-1. MS (EI): m/z 402, exact mass M+ 402.1047 (calcd for C17H27O5PSSi 402.1083). (7) In the strict sense, the NOE between SPh and PO(OMe)2 is larger than that between SPh and CO2Me for 4. On the other hand, the NOE between SPh and CO2Me is larger than that between SPh and CO2Me for 6. The stereochemistry of 4 was further supported by the following observation. Cyclobutane 4 was reduced to alcohol 9 quantitatively. The clearly observed NOE between H2 and CH2OH, which are not overlapped in benzene-d6, supported the assignment of the stereochemisty of 4.
(8) Unpublished results from these laboratories.
Methyl r-1-(Dimethoxyphosphoryl)-c-2-(phenylthio)-t3-(trimethylsilyl)-1-cyclobutanecarboxylate (5). Rf ) 0.3 (CH2Cl2-ether ) 2:1); colorless oil. 1H NMR (400 MHz, CDCl3): δ 0.039 (s, 9H), 2.12 (dddd, J ) 11.2, 11.0, 11.0, 2.1 Hz, 1H), 2.31 (ddd, J ) 14.4, 11.1, 11.0 Hz, 1H), 2.57 (dddd, J ) 11.1, 11.1, 11.0, 0.8 Hz, 1H), 3.55 (d, JPH ) 10.8 Hz, 3H), 3.61 (d, JPH ) 10.8 Hz, 3H), 3.88 (s, 3H), 4.24 (ddd, J ) 14.0, 11.2, 0.6 Hz, 1H), 7.21-7.30 (m, 3H), 7.43-7.46 (m, 2H). Selected NOE is between δ 3.88 (CO2Me) and 7.43-7.46 (H of o-Ph). 13C NMR (100.6 MHz, CDCl3): δ -3.21 (CH3), 24.04 (d, JPC ) 3.8 Hz, CH2), 28.91 (d, JPC ) 13.0 Hz, CH), 49.85 (d, JPC ) 6.9 Hz, CH), 52.47 (CH3), 52.55 (d, JPC ) 6.9 Hz, CH3), 53.81 (d, JPC ) 6.9 Hz, CH3), 56.06 (d, JPC ) 143 Hz, C), 127.39 (CH), 128.75 (CH), 132.23 (CH), 135.28 (C), 169.41 (d, JPC ) 1.5 Hz, C). 31P NMR (161.9 MHz, CDCl3): δ 4.75. IR (neat): 2956, 1734, 1255 cm-1. MS (EI): m/z 402, exact mass M+ 402.1056 (calcd for C17H27O5PSSi 402.1083). Methyl r-1-(Dimethoxyphosphoryl)-c-2-[(phenylthio)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (6). Rf ) 0.3 (CH2Cl2-ether ) 2:1); colorless oil. 1H NMR (400 MHz, CDCl3): δ 0.124 (s, 9H), 1.57 (ddd, J ) 9.7, 7.9, 4.6 Hz, 1H), 1.78 (ddd, J ) 13.9, 9.2, 4.6 Hz, 1H), 2.19 (dddd, J ) 14.1, 12.0, 9.2, 7.9 Hz, 1H), 2.64 (d, J ) 12.0 Hz, 1H), 3.33 (s, 3H), 3.77 (d, JPH ) 11.0 Hz, 3H), 3.86 (d, JPH ) 10.8 Hz, 3H), 7.14-7.18 (m, 1H), 7.21-7.29 (m, 2H), 7.34-7.37 (m, 2H). Selected NOEs were between δ 0.124 (H13) and 1.57 (H3a), δ 1.57 (H3a) and 1.78 (H3b), δ 1.57 (H3a) and 2.64 (H4), δ 1.78 (H3b) and 2.19 (H2), δ 2.19 (H2) and 3.77 (H7 or H8), δ 2.64 (H4) and 7.34-7.37 (H10), δ 3.33 (H6) and 7.21-7.29 (H11), and δ 3.33 (H6) and 7.34-7.37 (H10). For atom numbering, see Figure 1. 13C NMR (100.6 MHz, CDCl3): δ -2.19 (1JCH ) 120 Hz, CH3), 22.28 (d, JPC ) 3.1 Hz, 1JCH ) 167 Hz, CH2), 24.34 (d, JPC ) 190 Hz, C), 33.44 (1JCH ) 136 Hz, CH), 33.54 (d, JPC ) 3.1 Hz, 1JCH ) 166 Hz, CH), 52.69 (1JCH ) 148 Hz, CH3), 53.57 (d, JPC ) 6.1 Hz, 1JCH ) 149 Hz, CH3), 53.62 (d, JPC ) 6.1 Hz, 1JCH ) 149 Hz, CH3), 126.69 (1JCH ) 162 Hz, CH), 128.68 (1JCH ) 161 Hz, CH), 131.60 (1JCH ) 163 Hz, CH), 136.68 (C), 168.96 (d, JCP ) 6.9 Hz, C). Selected HMBC peaks were between δ 0.124 (H13) and 33.44 (C4) and δ 2.64 (H4) and 136.68 (C9). 31P NMR (161.9 MHz, CDCl3): δ 6.01. IR (neat): 2956, 1723, 1253 cm-1. MS (EI): m/z 402, exact mass M+ 402.1057 (calcd for C17H27O5PSSi 402.1083). Methyl r-1-(Dimethoxyphosphoryl)-t-2-[(phenylthio)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (7). Rf ) 0.45 (CH2Cl2-ether ) 2:1); colorless oil. 1H NMR (400 MHz, CDCl3): δ 0.015 (s, 9H), 1.68-1.75 (m, 1H), 1.85-1.90 (m, 2H), 3.23 (d, J ) 11.7 Hz, 1H), 3.69 (d, J ) 11.4 Hz, 3H), 3.73 (s, 3H), 3.76 (d, J ) 11.0 Hz, 3H), 7.10-7.15 (m, 1H), 7.19-7.23 (m, 2H), 7.45-7.48 (m, 2H). Selected NOEs were between δ 0.015 (H13) and 1.68-1.75 (H3b), δ 1.68-1.75 (H3b) and 1.85-1.90 (H3a), δ 1.68-1.75 (H3b) and 3.23 (H4), δ 3.23 (H4) and 7.45-7.48 (H10), and δ 3.69 (H8) and 7.45-7.48 (H10). Atom numbering uses that corresponding to 6. 13C NMR (100.6 MHz, CDCl3): δ -2.15 (1JCH ) 120 Hz, CH3), 23.03 (d, JPC ) 1.5 Hz, 1JCH ) 168 Hz, CH2), 24.31 (d, JPC ) 197 Hz, C), 32.29 (d, JPC ) 4.6 Hz, 1JCH ) 134 Hz, CH), 33.49 (d, JPC ) 2.3 Hz, 1JCH ) 164 Hz, CH), 52.91 (1JCH ) 148 Hz, CH3), 53.14 (d, JPC ) 6.1 Hz, 1JCH ) 148 Hz, CH3), 53.66 (d, JPC ) 6.9 Hz, 1JCH ) 149 Hz, CH3), 126.17 (1JCH ) 162 Hz, CH), 128.64 (1JCH ) 160 Hz, CH), 130.90 (1JCH ) 162 Hz, CH), 136.35 (C), 170.63 (d, JCP ) 6.9 Hz, C). Selected HMBC peaks were between δ 0.015 (H13) and 32.29 (C4) and δ 3.23 (H4) and 130.90 (C9). 31P NMR (161.9 MHz, CDCl3): δ 5.84. IR (neat): 2956, 1723, 1251 cm-1. MS (EI): m/z 402, exact mass M+ 402.1136 (calcd for C17H27O5PSSi 402.1083). Methyl r-1-(Dimethoxyphosphoryl)-c-2-[(phenylsulfonyl)(trimethylsilyl)methyl]-1-cyclopropanecarboxylate (8). A flask was charged with CCl4 (3.1 mL), MeCN (3.1 mL), water (1.5 mL), compound 6 (163 mg, 0.41 mmol), and NaIO4 (678 mg, 3.17 mmol). To the mixture was added ruthenium trichloride hydrate (6.2 mg, ∼0.03 mmol), and the reaction mixture was stirred vigorously for 4 h at room temperature. Water was added, and the mixture was extracted two times with CH2Cl2. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was filtered through Celite, washing with ether. The ether solution was concentrated. The crude product was purified by crystallization with ethyl acetate to give 8 (139 mg, 79% yield). 8: colorless crystals, mp 102-103 °C. 1H NMR (400 MHz, CDCl3): δ 0.188 (s, 9H), 1.35 (ddd, J ) 10.1, 7.9, 4.6
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Hz, 1H), 1.80 (ddd, J ) 15.0, 9.4, 4.6 Hz, 1H), 2.35 (dddd, J ) 13.0, 11.7, 9.4, 7.9 Hz, 1H), 3.42 (d, J ) 11.7 Hz, 1H), 3.52 (s, 3H), 3.81 (d, J ) 11.0 Hz, 3H), 3.86 (d, J ) 10.8 Hz, 3H), 7.507.62 (m, 3H), 7.87-7.89 (m, 2H). Selected NOEs were between δ 0.188 and 1.35, δ 1.35 and 1.85, δ 1.85 and 2.35, δ 1.35 and 3.42, and δ 3.52 and 7.87-7.89. 13C NMR (100.6 MHz, CDCl3): δ -0.728 (CH3), 20.23 (d, JPC ) 3.9 Hz, CH2), 24.45 (d, JPC ) 192 Hz, C), 25.08 (CH), 52.88 (CH), 52.92 (CH3), 53.65 (d, JPC ) 6.1 Hz, CH3), 53.87 (d, JPC ) 6.9 Hz, CH3), 128.46 (CH), 128.98 (CH), 133.20 (CH), 141.12 (C), 169.27 (d, JCP ) 6.9 Hz, C). Selected HMBC peaks were between δH 0.188 and δC 52.88 and δH 3.42 and δC -0.728. IR (KBr): 2960, 1719, 1301, 1267, 1145 cm-1. MS (EI): m/z 434, exact mass M+ 434.1005 (calcd for C17H27O7PSSi 434.0984). Anal. Calcd for C17H27O7PSSi: C, 46.99; H, 6.26; S, 7.38. Found: C, 46.93; H, 6.17; S, 7.32. r-1-(Dimethoxyphosphoryl)-1-hydroxymethyl-c-2-(phenylthio)-t-3-(trimethylsilyl)cyclobutane (9). 4 (141 mg, 0.38 mmol) was dissolved in THF (5.5 mL), and anhydrous lithium chloride (323 mg, 7.6 mmol) and NaBH4 (288 mg, 7.6 mmol) were added. After addition of ethanol (11 mL), the mixture was stirred at room temperature overnight. The mixture was cooled with ice-water, adjusted to pH 4 by the gradual addition of 10% aq citric acid (3.8 mL), and concentrated in vacuo. Water (70 mL) was added to the residue, which was extracted with methylene chloride three times and dried (Na2SO4). Removal of the solvent and purification by column chromatography over silica gel eluting with CH2Cl2-ether (1:4) gave 9 (126 mg, 100%) (Rf ) 0.3). 9: colorless crystals, mp 125 °C. 1H NMR (400 MHz, CDCl3): δ -0.020 (s, 9H), 1.77 (ddd, J ) 11.1, 11.1, 11.1 Hz, 1H), 2.11 (ddd, J ) 11.1, 11.1, 1.3 Hz, 1H), 2.29 (ddd, J ) 18.9,
Notes 11.1, 11.1 Hz, 1H), 2.65 (dd, J ) 7.0, 5.3 Hz, 1H), 3.65-3.83 (m, 3H), 3.83 (d, JPH ) 10.6 Hz, 3H), 3.86 (d, JPH ) 10.6 Hz, 3H), 7.15-7.20 (m, 1H), 7.24-7.28 (m, 2H), 7.43-7.46 (m, 2H). 1H NMR (400 MHz, benzene-d6): δ -0.017 (s, 9H, SiMe3), 1.761.88 (m, 1H, H4b), 2.28-2.42 (m, 2H, H3,4a), 2.96 (br s, 1H, OH), 3.50 (d, JPH ) 10.6 Hz, 3H, OMe), 3.53 (d, JPH ) 10.8 Hz, 3H), 3.68-3.76 (m, 1H, CHHO), 3.90 (td, J ) 11.0, 3.7 Hz, 1H, CHHO), 4.16 (dd, J ) 24.3, 10.7 Hz, 1H, H2), 6.93 (t-like, J ) 7.4 Hz, 1H, H of p-Ph), 7.07 (t-like, J ) 7.7 Hz, 2H, 1H, H of m-Ph), 7.68 (d-like, J ) 7.1 Hz, 2H, 1H, H of o-Ph). For atom numbering, see eq 4. Selected NOEs were observed between δ 3.68-3.76 and 4.16 and between δ 3.90 and 4.16. 13C NMR (100.6 MHz, CDCl3): δ -3.23 (CH3), 23.81 (d, JPC ) 6.1 Hz, CH2), 27.79 (d, JPC ) 1.5 Hz, CH), 49.22 (d, JPC ) 6.1 Hz, CH), 51.44 (C), 52.88 (d, JPC ) 7.6 Hz, CH3), 52.92 (d, JPC ) 7.6 Hz, CH3), 66.45 (CH2), 126.63 (CH), 128.89 (CH), 130.60 (CH), 137.49 (C). 31P NMR (161.9 MHz, CDCl3): δ 12.69. IR (neat): 3404, 2958, 1243 cm-1. MS (EI): m/z 374, exact mass M+ 374.1141 (calcd for C16H27O4PSSi 374.1137). Anal. Calcd for C16H27O4PSSi: C, 51.31; H, 7.50. Found: C, 51.18; H, 7.19.
Acknowledgment. This work was supported by the Ministry of Education, Science, Sports and Culture of the Japanese Government. Supporting Information Available: 1H and 13C NMR spectra for compounds 4-9. This information is available free of charge via the Internet at http://pubs.acs.org. JO0101555
