Desymmetrization of meso-Hydrobenzoin Using Chiral, Nucleophilic Phosphine Catalysts E. Vedejs,*,† O. Daugulis,‡ and N. Tuttle† Chemistry Department, University of Wisconsin, Madison, Wisconsin 53706, and Department of Chemistry, University of Michigan Ann Arbor, Michigan 48109
[email protected] Received September 2, 2003
we have investigated several substituted analogues 8b-d that are available by the same approach. The only new challenge was to prepare the necessary ArPH2 without contamination by the diarylphosphines. This was accomplished by reaction of the corresponding arylzinc chlorides with PCl3, followed by reduction with lithium aluminum hydride (see Experimental Section). A comparison of the new phospholanes with our recently optimized phosphabicyclooctane (PBO) catalysts 9-119-11 has now been carried out for the desymmetrization of 4, as summarized in Table 1 and outlined below.
Abstract: The desymmetrization of meso-hydrobenzoin is described using chiral phosphine catalysts 8b-d and 9-11. The best enantioselectivity at room temperature was obtained with the newly synthesized phospholane 8c and benzoic anhydride, but the reaction is very slow. Much faster reactions, but somewhat lower enantioselectivities were observed using the bicyclic phosphine catalyst 9. To obtain product 5a with >90% ee required conditions where the ee is upgraded due to the formation of the dibenzoate 6a. Among the new phospholane catalysts, 8b has the best selectivity in the kinetic resolution of benzylic alcohols, but not at the level observed previously with catalyst 11.
An intensive effort has been made to develop enantioselective acylation catalysts, and much progress has been recorded in the kinetic resolution of secondary alcohols.1 The desymmetrization of diols has also been explored,2-6 and promising methodology has been reported using heavy metal-free catalytic conditions.2-5 So far, the most widely applicable catalyst appears to be Oriyama’s diamine 1.2 This catalyst promotes the desymmetrization of aliphatic meso-diols with exceptional selectivity at -78 °C, as illustrated for the conversion of 2 to 3 (96% ee). The analogous benzoylation of 4 was less effective (60% ee). Desymmetrization of a meso-1,5-diol using a chiral DMAP catalyst has also been reported to occur with excellent selectivity.5 Some years ago, we had demonstrated the desymmetrization of 4 using Burk’s phospholane 8a as the catalyst for activation of benzoic anhydride.7 A moderate level of enantioselectivity was observed in the benzoate ester 5a at room temperature (69% ee). Because 8a is easy to prepare from the sulfate ester 7 by reaction with PhPH2,8 †
University of Michigan. University of Wisconsin. (1) Reviews: Spivey, A. C.; Maddaford, A.; Redgrave, A. J. Org. Prep. Proced. Int. 2000, 32, 331. Fu, G. C. Acc. Chem. Res. 2000, 33, 412. (2) (a) Oriyama, T.; Imai, K.; Sano, T.; Hosoya, T. Tetrahedron Lett. 1998, 39, 3529. (b) Oriyama, T.; Taguchi, H.; Terakado, D.; Sano, T. Chem. Lett. 2002, 1, 26. (3) (a) Kawabata, T.; Stragies, R.; Fukaya, T.; Nagaoka, Y.; Schedel, H.; Fuji, K. Tetrahedron Lett. 2003, 44, 1545. (b) Trost, B. M.; Takashi, M. J. Am. Chem. Soc. 2003, 125, 2410. (c) Mizuta, S.; Sadamori, M.; Fujimoto, T.; Yamamoto, I. Angew. Chem, Int. Ed. 2003, 42, 3383. (4) (a) Yamada, S.; Katsumata, H. J. Org. Chem. 1999, 64, 9365. (b) Yamada, S.; Katsumata, H. Chem. Lett. 1998, 10, 995. (5) Ruble, J. C.; Tweddell, J.; Fu, G. C. J. Org. Chem. 1998, 63, 2794. (6) Matsumura, Y.; Maki, T.; Murakami, S.; Onomura, O. J. Am. Chem. Soc. 2003, 125, 2052. (7) Vedejs, E.; Daugulis, O.; Diver, S. T. J. Org. Chem. 1996, 61, 430. (8) Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1993, 115, 10125. ‡
All of the experiments in Table 1 were conducted using 2.5 equiv of benzoic or isobutyric anhydride, a 0.06 M solution of 4, and an amount of catalyst sufficient to promote partial conversion at a convenient reaction rate in dichloromethane or acetone. Heptane or toluene had given optimal results with the PBO catalysts for acylation of secondary alcohols,10 but these solvents could not be used because of limited solubility for the substrate 4. In typical experiments, conversion was monitored by integration of NMR signals for the methine proton of 4, the monobenzoate 5a, and in some experiments at higher conversion, also for the dibenzoate 6a. The monobenzoate 5a was then purified by chromatography prior to ee assay by HPLC. In the case of phospholanes 8b-d (entries 1-3), 40-50 mol % of catalyst was necessary to achieve reasonable rates. For the initial comparisons of enantioselectivity (entries 1-11), conversions were limited to ca. 60% or less to minimize contributions to ee by kinetic resolution due to the formation of meso-dibenzoate 6a from the chiral monobenzoate 5a. However, the kinetic (9) (a) Vedejs, E.; Daugulis, O. J. Am. Chem. Soc. 1999, 121, 5813. (b) Vedejs, E.; MacKay, J. A. Org. Lett. 2001, 3, 535. (c) Vedejs, E.; Rozners, E. J. Am. Chem. Soc. 2001, 123, 2428. (10) Vedejs, E.; Daugulis, O. J. Am. Chem. Soc. 2003, 125, 4166. (11) Vedejs, E.; Daugulis, O.; Harper, L. A.; MacKay, J. A.; Powell, D. R. J. Org. Chem. 2003, 68, 5020.
10.1021/jo030279c CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/27/2004
J. Org. Chem. 2004, 69, 1389-1392
1389
TABLE 1. Desymmetrization of 4 Using (RCO)2O and Chiral Phosphines 8-11 entry
catalyst
amount
R
solvent
temp
time
conversion
(5 + ent-5):6
product (ee)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
8b 8c 10 10 11 11 9 9 9 9 9 9 9 9 9 9 9
38% 41% 35% 5.5% 6% 4.1% 12.4% 12% 6.7% 6.9% 12% 5% 9% 9% 14% 10% 10%
C6H5 C6H5 C6H5 C6H5 i-Pr C6H5 i-Pr C6H5 i-Pr i-Pr i-Pr C6H5 C6H5 C6H5 C6H5 C6H5 C6H5
CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 acetone CH2Cl2 acetone CH2Cl2 CH2Cl2 acetone acetone acetone acetone acetone acetone CH2Cl2 CH2Cl2
rt rt rt rt rt rt rt rt rt rt -78 rt rt rt -30 -30 -30
4h 1.5 h 17 h 10 min 9.5 h 5 min 2.2 h 17 min 45 min 2.5 h 26 h 1.5 h 7h 72 h 24 h 8h 22 h
20% 20% 32% 61% 43% 64% 40% 58% 53% 52% 8% 31% 82% 98% 50% 73% 97%
>20:1 >20:1 >20:1 9:1 >20:1 5:1 NA 33:1 NA NA >20:1 15:1 2.9:1 1:1.1 8:1 7:1 2.6:1
5a (77.5%) 5a (87.2%) 5a (86.7%) ent-5a (65.3%) ent-5b (73%) ent-5 (60.7%) ent-5b (80.6%) ent-5a (68.6%) ent-5b (79.5%) ent-5b (81.2%) ent-5b (88.4%) ent-5a (68-71%)a ent-5a (80.9%) ent-5a (93.0%) ent-5a (82.6%) ent-5a (83.1%) ent-5a (93.7%)
TABLE 2. Kinetic Resolutions of PhCH(OH)R′ Using (RCO)2O/Catalyst at Room Temperature entry
R′
R
1 2 3 4 5 6 7 8
tert-C4H9 tert-C4H9 tert-C4H9 tert-C4H9 iso-C3H7 iso-C3H7 iso-C3H7 iso-C3H7
m-ClC6H4 m-ClC6H4 m-ClC6H4 C6H5 C6H5 C6H5 C6H5 C6H5
a
catalyst (%)
solvent
time
conversion
configuration; sa
8a (16%) 8b (20%) 8c (20%) 11 (4%) 8b (37%) 8b (20%) 8c (10%) 11 (5%)
CH2Cl2 CH2Cl2 CH2Cl2 heptane CH2Cl2 benzene toluene toluene
13 days 4 days 6 days 12 h 3 days 5 days 6 days 1h
24% 20% 27% 53% 22% 23% 17% 66%
(S); 12b (S); 17 (S); 4.5 (R); 24c (S); 14 (S); 11d (S); 6d (R); 6.9c
Configuration of fast-reacting enantiomer; enantioselectivity s ) kfast/kslow. b Ref 7 data. c Ref 10 data.
resolution effect could be used to advantage at >80% conversion to increase the enantiomeric purity of 5a, as discussed later. Benzoylations catalyzed by the phosphabicyclooctane (PBO) derivatives 9-11 were faster than the corresponding phospholane-catalyzed reactions and gave ent-5 as the major enantiomer. Bicyclic catalysts 10 and 11, having the more highly substituted P-aryl groups, were the most reactive (entries 4-6), as expected from similar trends seen in our studies with benzylic secondary alcohol substrates.10,11 The amount of catalyst could be decreased to 4-5% in these examples, resulting in reaction times of less than 1 h for preparative benzoylations at room temperature and enantioselectivities in the range of 6080% (entries 4-7). The reactivity of catalysts 9-11 was lower for the activation of iso-butyric anhydride. Even though these reactions were marginally more enantioselective than the benzoylations (entries 6, 8-10), they were too slow for convenient use and were not studied extensively. The P-phenyl PBO derivative 9 was less reactive compared to 10 or 11, and more of the catalyst (7-14%) was generally used in the benzoylations because room-temperature reactions taken to partial conversion over many hours gave somewhat variable results, especially in acetone solution (entry 12). The reasons for the variation in ee are not fully understood, but the reactions were more repeatable using higher catalyst loading. The phospholanes 8c and 8d proved to have the highest enantioselectivity for benzoylation of 4 among the catalysts tested (entries 2, 3). However, the reactions required impractical amounts of the catalyst to achieve preparatively useful conversions. The bicyclic catalysts 9-11 gave a better compromise of enantioselectivity and 1390 J. Org. Chem., Vol. 69, No. 4, 2004
d
Experiment by E. Rozners.
reactivity, and the most easily accessible P-phenyl derivative 9 generally performed as well as 10 or 11.9 We therefore focused on catalyst 9 for a closer look at reaction variables, preparative potential, and enantioselectivity using benzoic anhydride as the reagent. The effect of increased conversion on enantioselectivity was probed at room temperature using the bicyclic catalyst 9. Substantially improved ee was observed at room temperature in acetone when conversion of 4 was taken to 98% (entry 14). Under these conditions, kinetic resolution of the monobenzoate 5a occurs as a consequence of >50% conversion to the dibenzoate 6a. An attempt to improve efficiency by carrying out the benzoylation at -30 °C was unsuccessful due to a significant decrease in reactivity (entry 15; 50% conversion after 24 h). However, the corresponding process was faster in dichloromethane, and 97% conversion could be achieved in 22 h (entry 17). Although ca. 30% of the material was consumed by formation of the dibenzoate 6a, it was possible to recover 70% of 5a with 93.7% ee. This is the result of a modest increase in enantioselectivity at -30 °C (see entry 16), combined with improved selectivity in the kinetic resolution of 5a by conversion to 6a. A similar experiment was attempted using the more highly selective iso-butyric anhydride reaction (entry 11). Good enantioselectivity for 5b was observed, but the process was too slow for the intended purpose.12 (12) Extension of the desymmetrization procedure to the hindered 1,3-diphenyl-2,2-dimethylpropane-1,3-diol was briefly explored. Reaction of the diol with benzoic anhydride and catalyst 9 gave the monobenzoate with promising enantioselectivity (86.6% ee). However, the reaction was slow even at room temperature (22% conversion after 8 h). Experiments at lower temperatures were precluded by the limited solubility of the diol as well as by the low reactivity.
The newly prepared phospholanes 8b-d have also been evaluated briefly for the kinetic resolution of representative benzylic alcohols following procedures described previously10 (Table 2). Somewhat improved selectivities were seen in the case of 8b compared to 8a with the hindered substrate tert-butylphenyl carbinol. The 3,5-dimethylphenyl derivative 8b was also more reactive (ca. 3-fold more reactive than 8a), but the benzoylation still required several days at room temperature, much slower than the analogous reactions using 11 as the catalyst. Furthermore, the 3,5-diphenylphenyl analogue 8d gave no conversion at room temperature on a similar time scale. Although 8b has some potential in view of the improved selectivity, none of the new phospholane catalysts matches the best bicyclic phosphine 11 in terms of both reactivity and selectivity for kinetic resolutions. To summarize the above studies, improved enantioselectivities have been observed for the desymmetrization of meso-hydrobenzoin (4) using catalysts 8c, 8d, and 9-11. Benzoylations catalyzed by 9 offer the best compromise of catalyst accessibility, reactivity, and enantioselectivity. At the current stage of development, the method is not as effective as the recently reported CuCl2catalyzed6 or cinchona phosphinite-catalyzed3c processes. However, the meso-hydrobenzoin desymmetrization results reported above with the phosphine 9 are the best so far for activation of an anhydride by a nucleophilic catalyst. Experimental (2S,5S)-2,5-Dimethyl-1-(3′,5′-di-tert-butylphenyl)phospholane-Borane (8c-BH3). By analogy to the method of Burk et al.8 to a solution of 3,5-di-tert-butylphenylphosphine10 (ca. 90% pure, 252 mg, 1.02 mmol) in THF (10 mL) was added BuLi (0.66 mL of a 1.6 M solution in hexanes, 1.05 mmol) at 0 °C. The yellow solution was stirred at 0 °C for 10 min and then cooled to -78 °C. Next, cyclic sulfate 78 (180 mg, 1.0 mmol) was added as a solution in THF (5 mL) in 1 min. The pale yellow solution was warmed to rt (ca. 30 min) and stirred for 30 min. After the mixture was cooled to -78 °C, additional BuLi (0.66 mL of a 1.6 M solution in hexanes, 1.05 mmol) was added and the yellow solution was allowed to warm to rt (ca. 30 min) and stirred for 3 h. After the addition of borane-THF complex (3 mL of 1 M solution in THF, 3 mmol) the colorless solution was stirred at rt for 2 h; then, solvent was evaporated (N2 stream), and 5% HCl (4 mL) was added. The mixture was extracted with CH2Cl2, and the organic extracts were dried (MgSO4) and evaporated (aspirator); the residue was then purified by flash chromatography on EM silica gel 60 (11 × 1.8 cm), 3:2 hexane/toluene eluent. The first 20 mL were blank; the next 10 mL contained impurity, and the next 10 mL were blank. The product eluted in the next 80 mL. Fractions containing 8c-BH3 were evaporated to give 222 mg (70%) of colorless crystals. Analytical TLC on EM silica gel 60 F254, 4:3 hexane/toluene, Rf ) 0.31. Pure material was obtained by crystallization from methanol-water, mp 101-102 °C. RD ) +28.1 (c 1.17, EtOAc). The structure was verified by X-ray crystallography. HRMS for C20H36BP: m/z 318.2673. IR (KBr, cm-1): 2369, B-H. 250 MHz 1H NMR (CDCl3, ppm): δ 7.55 (1H, s), 7.52 (2H, dd, J ) 1.8, 7.8 Hz), 2.68-2.46 (1H, m), 2.42-2.05 (3H, m), 1.65-1.39 (2H, m), 1.4-0.1 (3H, br m), 1.32 (3H, dd, J ) 7.0, 16.1 Hz), 1.35 (18H, s), 0.83 (3H, dd, J ) 6.8, 14.3 Hz). 31P NMR (121.4 MHz, {H}, CDCl3, ppm): δ 39.6-37.1 br m. (2S,5S)-2,5-Dimethyl-1-(3′,5′-dimethylphenyl)phospholane-Borane Complex (8b-BH3). The same method was used as described for 8c-BH3, starting from 3,5-dimethyl-phenylphosphine (ca. 85% pure, 170 mg, 1.05 mmol; CAUTION!
STENCH!)10 and cyclic sulfate 78 (187 mg, 1.04 mmol). After the addition of borane-THF complex, workup, and chromatography, 141 mg (58%) of 8b-BH3 as colorless crystals was obtained. Analytical TLC on EM silica gel 60 F254, 1:1 hexane/ toluene, gave Rf ) 0.31. Pure material was obtained by crystallization from hexane, mp 123-124 EC, RD ) +42.4 (c 0.54, EtOAc). HRMS for C14H24BP-BH3: 220.1366. IR (KBr, cm-1): 2366, B-H. 300 MHz 1H NMR (CDCl3, ppm): δ 7.29 (2H, br d, J ) 10.0 Hz), 7.13 (1H, br s), 2.68-2.51 (1H, m) 2.36 (6H, s), 2.39-2.09 (3H, m), 1.63-1.42 (2H, m), 1.3 (3H, dd, J ) 7.0, 16.2 Hz), 1.24-0.05 (3H, br m), 0.86 (3H, dd, J ) 7.0, 14.4 Hz). 31P NMR (121.4 MHz, {H}, CDCl3, ppm): δ 39.5-37.7, br m. (2S,5S)-2,5-Dimethyl-1-(3′,5′-diphenylphenyl)phospholane-Borane Complex (8d-BH3). 3,5-Diphenylphenylphosphine was prepared according to the lithium-halogen exchange method from 3,5-diphenylbromobenzene13 as described for preparation of 3,5-di-tert-butylphenyl phosphine in ref 10, but the crude phosphine was used without distillation (ca. 80% pure, 233 mg, 0.71 mmol). The same method was then used for conversion to 8d-BH3 as described above for 8c-BH3 and cyclic sulfate 78 (116 mg, 0.64 mmol). After addition of borane-THF complex, workup, and chromatography, 177 mg of 8d-BH3 was obtained (77%) as colorless crystals. Analytical TLC on EM silica gel 60 F254, 1:1 hexane/toluene, gave Rf ) 0.29. Pure material was obtained by crystallization from hexane, mp 177-179 EC, RD ) +35.8 (c 0.98, EtOAc). HRMS for C24H28BP: 358.20220; m/z ) 358.2014. IR (KBr, cm-1): 2377, B-H. 300 MHz 1H NMR (CDCl3, ppm): δ 7.94-7.85 (3H, m), 7.68-7.61 (4H, m), 7.537.38 (6H, m), 2.80-2.62 (1H, m), 2.43-2.15 (3H, m), 1.69-1.49 (2H, m), 1.45-0.16 (3H, br m), 1.36 (3H, dd, J ) 7.1, 16.3 Hz), 0.97 (3H, dd, J ) 6.9, 14.4 Hz). 31P NMR (121.4 MHz {H}, CDCl3, ppm): δ 40.1-37.8 br m. Deprotection of Phosphine-Boranes: (2S,5S)-2,5-Dimethyl-1-(3′,5′-diphenylphenyl)phospholane (8d). Following a Livinghouse precedent,14 to a N2-purged flask equipped with a reflux condenser and containing phosphine-borane 8d-BH3 (60 mg, 0.168 mmol) was added pyrrolidine (6 mL). The resulting solution was refluxed for 4 min. The solution was cooled to rt (20 min); pyrrolidine was evaporated with a N2 stream, and the residue was filtered through a 4.5 × 1.2 cm pad of deareated silica gel (the flask and the column were previously purged with N2 for 1 h) in benzene (25 mL) under N2. The solvent was evaporated (N2 stream) to give 48 mg (83%) of a 8d as a thick oil; RD ) +40.3 (c 3.1, THF). HRMS for C24H25P: 344.16940; m/z ) 344.1693. 300 MHz 1H NMR (CDCl3, ppm): δ 7.87 (2H, dd, J ) 1.8, 6.7 Hz), 7.76 (1H, dt, J ) 0.7, 1.8 Hz), 7.55-7.50 (4H, m), 7.26-7.12 (6H, m), 2.75-2.57 (1H, m), 2.25-1.97 (2H, m), 1.84-1.70 (1H, m), 1.43 (1H, ddq, J ) 2.6, 6.3, 12.0 Hz), 1.33 (3H, dd, J ) 7.2, 18.8 Hz), 1.24-1.08 (1H, m), 0.88 (3H, dd, J ) 7.0, 10.7 Hz). 31P NMR (121.4 MHz {H}, CDCl3, ppm): δ 11.4. (2S,5S)-2,5-Dimethyl-1-(3′,5′-dimethylphenyl)phospholane (8b). The above procedure was followed from 8b-BH3 to give 8b as a colorless oil, 68% yield (0.08 mmol scale). RD ) +58.0 (c 0.9, THF). HRMS for C14H21P: 220.13810; m/z ) 220.1377. 300 MHz 1H NMR (C6D6, ppm): δ 7.24 (2H, br d, J ) 7.0 Hz), 6.78 (1H, br s), 2.71-2.55 (1H, m), 2.23-2.01 (2H, m), 2.13 (6H, s), 1.86-1.73 (1H, m), 1.45 (1H, ddq, J ) 2.5, 5.9, 12.5 Hz), 1.32 (3H, dd, J ) 7.2, 18.6 Hz), 1.25-1.10 (1H, m), 0.87 (3H, dd, J ) 7.0, 10.5 Hz). 31P NMR (121.4 MHz, {H}, C6D6, ppm): δ 10.0. (2S,5S)-2,5-Dimethyl-1-(3′,5′-di-t-butylphenyl)phospholane (8c). The above procedure was followed from 8c-BH3 to give 8c as a colorless oil, 94% yield (0.02 mmol scale). HRMS for C20H33P: 304.23210; m/z ) 304.2308; RD ) +30.4 (c 0.47, THF). 300 MHz 1H NMR (C6D6, ppm): δ 7.60 (2H, dd, J ) 1.8, 7.4 Hz), 7.51 (1H, dt, J ) 0.7, 1.8 Hz), 2.84-2.66 (1H, m), 2.282.07 (2H, m), 1.91-1.78 (1H, m), 1.53 (1H, ddq, J ) 2.4, 6.1, 12.2 Hz), 1.34 (3H, dd, J ) 7.3, 18.7 Hz), 1.31-1.16 (1H, m), 1.29 (18H, s), 0.88 (3H, dd, J ) 7.0, 10.5 Hz). 31P NMR (121.4 MHz, {H}, C6D6, ppm): δ 11.4. (13) Du, C.-J. F.; Hart, H.; Ng, K.-K. D. J. Org. Chem. 1986, 51, 3162. (14) Wolfe, B.; Livinghouse, T. J. Am. Chem. Soc. 1998, 120, 5116.
J. Org. Chem, Vol. 69, No. 4, 2004 1391
Desymmetrization of Hydrobenzoin: Benzoylation. mesoHydrobenzoin (21.5 mg, 0.1 mmol) in the desired solvent (0.5 mL) was stirred with benzoic anhydride (0.056 g, 0.25 mmol), and the phosphine catalyst was added under nitrogen. The reaction mixture was stirred under N2 and quenched at the times indicated in Table 1 by the addition of 20:L of MeI followed by chromatography on silica gel. The crude product mixture was assayed by NMR to establish the ratio of recovered 4, monobenzoate 5a, and dibenzoate 6a by integration of the methine signals. The monobenzoate 5a was then isolated by flash chromatography and assayed for ee as previously described.7 iso-Butyroylation: (1R,2S)-2-Isobutyroyloxy-1,2-diphenylethanol 5b. To a solution of meso-hydrobenzoin (429 mg, 2.0 mmol) and 10 (3.3 mg, 0.012 mmol) in acetone (20 mL) was added iso-butyric anhydride (0.83 mL, 5 mmol) via syringe. The reaction was kept at rt for 9 h 30 min and then quenched with MeI (100 µL). The NMR assay showed that the reaction mixture consisted of 57.0% starting material, 42.5% product, and 0.5% 6b. After removal of solvent (aspirator), the residue was purified by flash chromatography on EM silica gel 60 (15 × 2.4 cm), 17:3 hexane/EtOAc eluent. The first 100 mL were blank, followed by 140 mL containing the product. After evaporation, 231 mg (41% based on starting material or 96% based on conversion; 73% ee) of the product was obtained as colorless crystals; after a single recrystallization from hexane 120 mg (52% recovery; 98% ee) of
1392 J. Org. Chem., Vol. 69, No. 4, 2004
product was obtained as colorless needles with mp 97-98 °C. Analytical TLC on EM silica gel 60 F254, 17:3 hexane/EtOAc, gave Rf ) 0.16; analytical HPLC, CHIRALCEL OD (5% IPA/ hex, 1 mL/min), gave TR ) 14.5, 18.0 min (major). RD ) +27.2 (c 0.85, EtOAc; 98% ee material). Molecular ion calcd for C18H20O3: 284.1412; found m/z ) 284.1424, error ) 4 ppm; base peak ) 107 amu. IR (KBr, cm-1): 1720, CdO; 3126, br, O-H; 3526, O-H. 300 MHz 1H NMR (CDCl3, ppm): δ 7.37-7.25 (10H, m), 5.89 (1H, d, J ) 6.6 Hz), 4.96 (1H, dd, J ) 3.6, 6.6 Hz), 2.48 (1H, sept, J ) 7.0 Hz), 2.1 (1H, d, J ) 3.6 Hz), 1.05 (3H, d, J ) 7.0 Hz), 1.01 (3H, d, J ) 7.0 Hz).
Acknowledgment. This work was supported by the National Science Foundation and by an Eli Lilly and Co. Undergraduate Research Fellowship (N.T.). The authors thank Dr. E. Rozners for the experiments of Table 2, entries 6 and 7. Supporting Information Available: NMR spectra for phospholanes 8a-d and the corresponding borane compexes. This material is available free of charge via the Internet at http://pubs.acs.org. JO030279C
