K.A. Monk et al. / Tetrahedron 64 (2008) 8605–8609
8609
3.5.4. 2-Isopropoxy-2-phenylpropanoic acid (1d)
Isolated as a colorless oil (0.836 g, 72% yield), which slowly
crystallized (mp 57–61 ꢃC). IR (KBr): 2990, 1695, 1282 cmꢀ1 1H
ether gave the free acid (R)-(ꢀ)-1a in w99% purity, [
a
]
ꢀ34.0 (c
D
1.08, MeOH) (lit.4a
[
a]
D ꢀ31.5 (c 0.8, MeOH)).4a
.
NMR:
d
1.07 (d, 3H, J¼6.3 Hz, CH3), 1.22 (d, 3H, J¼6.3 Hz, CH3), 1.86
3.7. Preparation of (S)-(L)-a-methylbenzylamides 6a–i
(s, 3H, CH3), 3.75 (sept, 1H, J¼6.3 Hz, CH), 7.38 (m, 5H, ArH). 13C
NMR:
d 22.1, 24.2, 24.3, 67.9, 81.3, 126.3, 128.4, 128.4, 140.1, 175.9.
Racemic acid 1a (22 mg, 0.12 mmol) was dissolved in 1 mL of
anhydrous dichloromethane and treated with a catalytic amount of
DMF (2 mL) and oxalyl chloride (31 mL, 0.36 mmol, 3 equiv). Gas
GC–MS: 207 (Mꢀ1), 121 (base peak). Calcd for C12H16O3: C, 69.21;
H, 7.74; found: C, 69.09; H. 7.66.
evolution was evident and the mixture was stirred at room temper-
ature for 20 min. Vacuum (20 mmHg) was applied to remove all
volatiles and 1 mL of fresh anhydrous dichloromethane was added,
3.5.5. 2-n-Butoxy-2-phenylpropanoic acid (1e)
Isolated as a colorless oil (1.985 g, 86% yield). IR (neat): 2959,
1713, 1226 cmꢀ1. 1H NMR:
d
0.91 (t, 3H, J¼7.2 Hz, CH3), 1.41 (dpent,
followed by (S)-(ꢀ)-a-methylbenzylamine (60 mL, 0.47 mmol,
2H, J¼9.3, 6.6 Hz, CH2), 1.63 (dpent, 2H, J¼9.3, 6.6 Hz, CH2), 1.85 (s,
3H, CH3), 3.31 (dt, 1H, J¼8.7, 6.6 Hz, CHa), 3.41 (dt, 1H, J¼8.7, 6.6 Hz,
3.9 equiv). After 10 min, the mixture was transferred to a separatory
funnel using dichloromethane. After extraction with 1 M HCl, the
organic phase was dried with anhydrous Na2SO4 and analyzed by
capillary GC (200–240 ꢃC at 2 ꢃC per min). The RS diastereomer
eluted at 6.13 min, and the SS diastereomer at 6.54 min. This pro-
cedure was repeated with brucine-resolved (R)-(ꢀ)-1a and gave an
RS/SS ratio of 98.8ꢂ0.15:1.2ꢂ0.15 (97.5ꢂ0.3% ee). This procedure was
repeated witheach of theother racemicacids 1b–i; averageretention
times and chromatographic resolution values are given in Table 1.
CHb), 7.37 (m, 5H, ArH). 13C NMR:
d 13.8, 19.3, 21.2, 32.0, 63.9, 81.0,
126.1, 128.4, 128.6, 139.4, 175.3. GC–MS: 177 (Mꢀ45), 121 (base
peak). HRMS: calcd for C13H18O3$NHþ4 ¼240.1599; found: 240.1605.
3.5.6. 2-Isobutoxy-2-phenylpropanoic acid (1f)
Isolated as a colorless oil (2.57 g, 85% yield), which slowly
crystallized (mp 48–50 ꢃC). IR (KBr): 2964, 1703, 1281 cmꢀ1 1H
.
NMR:
d
0.93 (d, 3H, J¼6.9 Hz, CH3), 0.95 (d, 3H, J¼7.2 Hz, CH3), 1.83
(s, 3H, CH3), 1.92 (nonet, 1H, J¼6.6 Hz, CH), 3.10 (dd, 1H, J¼8.4, 6.6H,
Acknowledgements
CHa), 3.17 (dd, 1H, J¼8.4, 6.6 Hz, CHb), 7.37 (m, 5H, ArH). 13C NMR:
d
19.4, 21.3, 28.7, 70.6, 80.9, 126.1, 128.3, 128.5, 139.6, 175.7. GC–MS:
We thank theRobert A. Welch Foundation (grant numberAA-1395)
for support of this work, and the National Science Foundation (Award
#CHE-0420802) for funding the purchase of our 500 MHz NMR.
177 (Mꢀ45), 121 (base peak). Calcd for C13H18O3: C, 70.24; H, 8.16;
found: C, 70.39; H. 8.30.
3.5.7. 2-Cyclohexyloxy-2-phenylpropanoic acid (1h)
References and notes
Isolated as a crystalline solid (0.859 g, 86% yield), mp 104.5–
105.2 ꢃC. IR (KBr): 2943, 1704, 1073 cmꢀ1. 1H NMR:
d
1.41 (m, 10H,
CH2), 1.86 (s, 3H, CH3), 3.42 (dpent, 1H, J¼7.5, 3.9 Hz, CH), 7.38 (m,
5H, ArH), 9.95 (br s, 1H, COOH). 13C NMR:
22.2, 24.3, 25.3, 34.2,
1. Trost, B. M.; Belletire, J. L.; Godleski, S.; McDougal, P. G.; Balkovek, J. M.; Bald-
win, J. J.; Christy, M. E.; Ponticello, G. S.; Varga, S. L.; Springer, J. P. J. Org. Chem.
1986, 51, 2370–2374.
d
34.3, 73.7, 81.2, 126.3, 128.4, 140.2, 176.2. GC–MS: 231 (Mꢀ17), 203
(Mꢀ45), 121 (base peak). Anal. Calcd for C15H20O3: C, 72.55; H, 8.12.
Found: C, 72.42; H, 8.10.
2. For example, a pyrazolylpyridine ligand incorporating an atrolactic methyl
ether group has recently been reported: Kowalczyk, R.; Skarzewski, J. Tetra-
hedron 2005, 61, 623–628.
3. (a) Eliel, E. L.; Frazee, W. J. J. Org. Chem. 1979, 44, 3598–3599; (b) Eliel, E. L.;
Koskimies, J. K.; Lohri, B. J. Am. Chem. Soc. 1978, 100, 1614–1616; (c) Kasai, Y.;
Sugio, A.; Sekiguchi, S.; Kuwahara, S.; Matsumoto, T.; Wantanabe, M.; Ichikawa,
A.; Harada, N. Eur. J. Org. Chem. 2007, 1811–1826.
4. (a) Aoyama, Y.; Urabe, H.; Sato, F. Tetrahedron Lett. 1991, 32, 6731–6734; (b)
Bach, R. D.; Domagala, J. M. J. Org. Chem. 1984, 49, 4181–4189; (c) Meyers, A. I.;
Slade, J. Synth. Commun. 1976, 6, 601–608; (d) Prasad, K. R.; Chandrakumar, A.;
Anbarasan, P. Tetrahedron: Asymmetry 2006, 17, 1979–1984.
5. Yabuuchi, T.; Kusumi, T. Chem. Pharm. Bull. 1999, 47, 684–686.
6. Fristrup, P.; Dideriksen, B. B.; Tanner, D.; Norrby, P.-O. J. Am. Chem. Soc. 2005,
127, 13672–13679.
3.5.8. 2-Benzyloxy-2-phenylpropanoic acid (1i)
Isolated as an off-white solid (0.206 g, 25% yield), mp 86–88 ꢃC.
IR (KBr): 2982, 1698, 1128 cmꢀ1. 1H NMR:
d 1.97 (s, 3H, CH3), 4.42 (d,
1H, J¼10.8 Hz, CHa), 4.46 (d, 1H, J¼10.8 Hz, CHb), 7.22–7.44 (m, 8H,
ArH), 7.56 (d, 2H, J¼6.8 Hz, ArH), 9.2 (v br s, 1H, CO2H). 13C NMR:
d
21.8, 66.6, 81.6, 126.2,127.7,127.9, 128.4,128.55, 128.6,137.5, 139.2,
176.1. GC–MS: 211(Mꢀ45), 177 (Mꢀ79), 150, 105. Anal. Calcd for
7. Camps, F.; Coll, J.; Messeguer, A.; Pujol, F. J. Org. Chem. 1982, 47, 5402–5404.
8. Yamazaki, S. Org. Biomol. Chem. 2007, 5, 2109–2113.
C
16H16O3: C, 74.98; H, 6.29. Found: C, 74.86; H, 6.36.
9. (a) Yu, K.; Gu, Z.; Ji, R.; Lou, L.-L.; Ding, F.; Zhang, C.; Liu, S. J. Catal. 2007, 252, 312–
320; (b) Yu, K.; Lou, L.-L.; Lai, C.; Wang, S.; Ding, F.; Liu, S. Catal. Commun. 2006, 7,
1057–1060; (c) Sun, Y.; Tang, N. J. Mol. Catal. A: Chem. 2006, 255, 171–179.
10. (a) Meinwald, J.; Labana, S. S.; Chadha, M. S. J. Am. Chem. Soc. 1963, 85, 582–585;
(b) Larock, R. C. Comprehensive Organic Transformations; VCH: New York, NY,
1989; p 628.
3.5.9. 2-Neopentoxy-2-phenylpropanoic acid (1j)
Isolated as a white solid (0.581 g, 57% yield), mp 61–63 ꢃC. IR
(KBr): 2958 (v br), 1710, 1152 cmꢀ1. 1H NMR:
d
0.97 (s, 9H, 3CH3),
1.84 (s, 3H, CH3), 3.01 (d, 1H, J¼8.2 Hz, CHa), 3.08 (d, 1H, J¼8.2 Hz,
CHb), 7.38 (m, 5H, ArH). 13C NMR:
21.1, 26.8, 31.8, 73.8, 80.9, 126.1,
11. Sonawane, H. R.; Sethi, S. C.; Merchant, S. N. Indian J. Chem., Sect. B 1984, 23,
940–943.
d
128.5, 128.6, 139.4, 175.0. GC–MS: 191 (Mꢀ45), 121 (base peak).
12. Mahesh, M.; Murphy, J. A.; Wessel, H. P. J. Org. Chem. 2005, 70, 4118–4123.
13. Preparations of the ethoxy (4b) and butoxy (4e) alcohols have not been reported,
but Scifinder erroneously attributes their synthesis to: Takeuchi, H.; Kitajima, K.;
Yamamoto, Y.; Mizuno, K. J. Chem. Soc., Perkin Trans. 2 1993, 199–203.
14. Heyns, K.; Trautwein, W. P.; Paulsen, H. Chem. Ber. 1963, 96, 3195–3199.
15. Bennani, Y. L.; Vanhessche, K.; Sharpless, K. B. Tetrahedron: Asymmetry 1994, 5,
1473–1476.
Calcd for C14H20O3: C, 71.16; H, 8.53; found: C, 71.09; H. 8.34.
3.6. Resolution of 2-methoxy-2-phenylpropanoic acid (1a)
16. Ref. 3c provides IR, 1H and 13C NMR data for methoxy acid 1a but failed to
Racemic acid 1a (5.05 g, 28 mmol) was dissolved in 75 mL of
acetone and treated with (ꢀ)-brucine (11.95 g, 30.3 mmol). A white
precipitate formed within 10 min. After stirring at room tempera-
ture for 1 h, the suspension was heated to 60 ꢃC and the solid was
isolated by filtration. This material was suspended in additional
acetone (50 mL) at 60 ꢃC and again isolated by filtration. After
drying under vacuum, this gave the (ꢀ)-brucine salt as a white
include the C]O 13C resonance at
d 175.6 (CDCl3).
17. Bonner, W. A.; Grimm, R. A. J. Org. Chem. 1967, 32, 3022–3027.
18. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John
Wiley and Sons: New York, NY, 1999; pp 26–66.
19. Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81, 2748–2755.
20. Angiolini, L.; Costa-Bizzari, P.; Tramontini, M. Tetrahedron 1969, 25, 4211–4216.
21. The chiral stationary phase GC column we used was a CycloSil-B column (30%
heptakis-(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)-b-cyclodextrin in DB-
1701), 30 mꢁ0.25 mm, from J&W Scientific.
powder (6.43 g, 40%), [
1.00, MeOH)). Treatment of this with 1 M HCl and extraction into
a
]
ꢀ18 (c 1.05, MeOH) (lit.20
[
a]
ꢀ11 (c
D
D
22. Miller, J. M. Chromatography: Concepts and Contrasts; John Wiley and Sons: New
York, NY, 1988; pp 17–18.