E. Maerten et al. / Tetrahedron 64 (2008) 8700–8708
8707
(s, 1H, CHO), 5.4–5.2 (br s, 1H, OH). 13C{1H} NMR (CDCl3)
d
¼159.7,
4.2.10. (7-Chloroquinolin-4-yl)(phenyl)methanol 11a
147.5, 144.8, 136.5, 134.0, 129.3, 127.4, 126.6, 124.7, 122.2, 120.8, 73.9
(C7). Optical purity was determined by chiral HPLC on a Chiralpack
AD column (i-PrOH/hexane: 7:93; flow rate: 0.7 mL/min; detection
UV at 215 nm; tR¼14 and 19 min). The major enantiomer (S)
obtained with precatalyst 1 was the second one to be eluted.
Oil, 1H NMR (CDCl3)
d
¼8.83 (d, 1H, J¼4.2 Hz, H2), 8.03 (d, 1H,
J¼2.0 Hz, H8), 7.85 (d,0 1H, J¼9.1 Hz, H5), 7.69 (m, 1H, H6), 7.38–7.26
0
(m, 6H, H3, Ho,o , Hm,m , Hp), 6.42 (s, 1H, CHO), 3.9–3.4 (br s, 1H, OH).
MS (EI): m/z¼268 (Mþ, 12), 253 (100), 196 (12), 91 (Tolþ, 8). Optical
purity was determined by chiral HPLC on a Chiralpack AS column
(i-PrOH/hexane: 5:95; flow rate: 0.7 mL/min; detection UV at
215 nm; tR¼32 and 38 min). The major enantiomer (R) obtained
with precatalyst 1 was the second one to be eluted.
4.2.5. Phenyl(pyridin-3-yl)methanol 9a
White solid, mp¼66 ꢀC, 1H NMR (CDCl3)
d
¼8.43 (s, 1H, H2), 8.29
(d, 1H, J¼3.9 Hz, H6), 7.67 (d, 1H, J¼7.3 Hz, H4), 7.35–7.20 (m, 5H,
0
0
Ho,o , Hm,m , Hp), 7.18 (m, 1H, H5), 5.8 (s, 1H, CHO), 5.3–4.0 (br s, 1H,
4.2.11. (7-Chloroquinolin-4-yl)(o-tolyl)methanol 11b
OH). 13C{1H} NMR (CDCl3)
d
¼148.0, 147.8, 143.2, 139.9, 134.5, 128.6,
Oil, 1H NMR (CDCl3)
d
¼8.91 (d, 1H, J¼4.4 Hz, H2), 8.13 (d, 1H,
127.8, 126.5, 123.5, 73.7 (C7). Optical purity was determined by
chiral HPLC on a Chiralpack AS column (i-PrOH/hexane: 8:92; flow
rate: 0.7 mL/min; detection UV at 215 nm; tR¼21 and 25 min). The
major enantiomer (R) obtained with precatalyst 1 was the second
one to be eluted.
J¼1.95 Hz, H8), 7.70 (d, J¼9.0 Hz, 1H, H5), 7.58 (d, 1H, J¼4.4 Hz, H3),
0
7.41 (dd, 1H, J¼7.1 and 2.2 Hz, H6), 7.26–7.02 (m, 4H, Ho, Hm,m , Hp),
2.51 (s, 3H, CH3). 13C{1H} NMR (CDCl3)
d¼151.4, 136.0, 131.1, 129.1,
128.6, 127.7, 127.1, 126.6, 125.1, 119.1, 64.4, 41.4 (CH3). Optical purity
was determined by chiral HPLC on a Chiralpack AS column (i-PrOH/
hexane: 5:95; flow rate: 0.7 mL/min; detection UV at 215 nm; tR¼24
and 31 min). The major enantiomer (S) obtained with precatalyst 1
was the first one to be eluted.
4.2.6. Pyridin-3-yl(o-tolyl)methanol 9b
Yellow oil, 1H NMR (CDCl3)
d
¼8.42 (s, 1H, H2), 8.33 (d, 1H,
J¼3.9 Hz, H6), 7.60 (d, 1H, J¼7.8 Hz, H4), 7.45 (m, 1H, H5), 7.25–7.12
0
(m, 4H, Ho, Hm,m , Hp), 5.98 (s, 1H, CHO), 4.20–4.00 (br s, 1H, OH),
4.2.12. (7-Chloroquinolin-4-yl)(p-tolyl)methanol 11c
2.20 (s, 3H, CH3). 13C{1H} NMR (CDCl3)
d
¼148.5, 148.2, 140.8, 138.8,
1H NMR (CDCl3)
d
¼8.77 (d, 1H, J¼4.1 Hz, H2), 7.97 (d, 1H,
135.2, 134.8, 130.7, 127.8, 126.4, 126.3, 123.4, 70.9 (C7), 19.3 (CH3).
MS (EI): m/z¼199 (Mþ, 3),180 (100),108 (MþꢁTol, 21), 91 (Tolþ, 36),
78 (Pyþ, 17), 77 (Phþ, 11), 51 (C4Hþ3 , 11). Optical purity was de-
termined by chiral HPLC on a Chiralpack AS column (i-PrOH/hex-
ane: 5:95; flow rate: 0.7 mL/min; detection UV at 215 nm; tR¼28
and 32 min). The major enantiomer (S) obtained with precatalyst 1
was the first one to be eluted.
J¼1.5 Hz, H8), 7.80 (d, J¼9.0 Hz, 1H, H5), 7.70 (d, 1H, J¼4.40 Hz, H30),
7.32 (dd, 1H, J¼9.3 and 1.7 Hz, H6), 7.27–7.17 (m, 4H, Ho,o , Hm,m ),
6.37 (s, 1H, CHO), 3.5–3.3 (s, 1H, OH), 2.29 (s, 3H, CH3). 13C{1H} NMR
0
(CDCl3)
d
¼151.1, 149.2, 148.3, 138.9, 138.3, 135.0, 129.6 (Co,o ), 128.5,
0
127.5, 127.2 (Cm,m ), 125.4, 124.1, 118.5, 72.4 (C11), 21.1 (CH3). Optical
purity was determined by chiral HPLC on a Chiralpack AS column
(i-PrOH/hexane: 5:95; flow rate: 0.7 mL/min; detection UV at
215 nm; tR¼29 and 41 min). The major enantiomer (R) obtained
with precatalyst 1 was the second one to be eluted.
4.2.7. Pyridin-3-yl(p-tolyl)methanol 9c
Yellow pale solid, mp¼132 ꢀC, 1H NMR (CDCl3)
¼8.45 (s, 1H,
d
H2), 8.32 (d, 1H, J¼3.9 Hz, H6), 7.67 (d, 1H, J¼7.3 Hz, H4), 7.19–7.13
4.3. Representative procedure for esterification
0
0
(m, 5H, H5, Ho,o , Hm,m ), 5.77 (s,1H, CHO), 4.2–3.6 (br s,1H, OH), 2.32
(s, 3H, CH3). 13C{1H} NMR (CDCl3)
d
¼148.0, 147.7, 140.2, 137.65,
In a typical experiment, the alcohol (0.1 mmol) was dissolved in
dichloromethane (3 mL) along with (R)-MPA (0.183 g, 0.11 mmol),
DMAP (0.0021 g, 0.012 mmol), and DCC (0.0416 g, 0.2 mmol) in
a Schelnk tube under nitrogen. The mixture is stirred for 15 h at
room temperature. Then, the solvent was removed under reduced
pressure. The residue was then either directly analysed by NMR or
purified by silica gel chromatography (pentane/ether) to give the
analytically pure ester products.
134.4, 129.6, 129.3, 126.5, 123.4, 73.6 (C7), 21.0 (CH3). MS (EI):
m/z¼199 (Mþ, 64), 184 (MþꢁMe, 82), 167 (MþꢁMeꢁOH, 35), 119
(23), 108 (MþꢁTol, 37), 106 (100), 93 (49), 91 (Tolþ, 99), 80, 78 (Pyþ,
58), 77 (Phþ, 36), 51 (C4Hþ3 , 28). Optical purity was determined by
chiral HPLC on a Chiralpack AS column (i-PrOH/hexane: 4:96; flow
rate: 0.7 mL/min; detection UV at 215 nm; tR¼48 and 55 min). The
major enantiomer (R) obtained with precatalyst 1 was the second
one to be eluted.
Acknowledgements
4.2.8. (3-Chlorophenyl)(pyridin-3-yl)methanol 9d
Yellow oil, 1H NMR (CDCl3)
d
¼8.5 (s, 1H, H2), 8.42 (d, 1H,
`
The authors thank the ‘Ministere de la Recherche et de la
Technologie’ (grant to E.M.) and the ‘Centre National de la
Recherche Scientifique’ for financial support.
J¼4.8 Hz, H60), 7.67 (d, 1H, J¼7.9 Hz, H4), 7.38 (br s, 1H, H5), 7.26–7.22
(m, 4H, Ho,o , Hm, Hp), 5.81 (s, 1H, CHO), 5.27 (br s, 1H, OH). 13C{1H}
NMR (CDCl3)
d
¼148.4, 147.7, 145.1, 139.3, 134.6, 134.5, 129.9, 128.0,
126.6, 124.6, 123.7, 73.2 (C7). Optical purity was determined by
chiral HPLC on a Chiralpack AS column (i-PrOH/hexane: 10:90; flow
rate: 0.7 mL/min; detection UV at 215 nm; tR¼20 and 24 min). The
major enantiomer (R) obtained with precatalyst 1 was the second
one to be eluted.
References and notes
1. Selected examples: (a) Tilford, C. H.; Shelton, R. S.; Van Campen, M. G., Jr. J. Am.
Chem. Soc. 1948, 70, 4001–4009; (b) Perry, D. J.; Le Van, P. J. Allergy 1950, 21, 73–
77; (c) Papa, D.; Sperber, N.; Sherlock, M. J. Am. Chem. Soc. 1951, 73, 1279–1280;
(d) Roszkowski, A. P. J. Pharmacol. Exp. Ther. 1965, 1, 288–299; (e) Barbieri, E. J.;
Rossi, G. V.; Orzechowski, R. F. J. Pharm. Sci. 1973, 62, 648–651; (f) Simons, F. E.;
Roberts, J. R.; Gu, X.; Kapur, S.; Simons, K. J. J. Allergy Clin. Immunol. 1999, 103,
223–226; (g) Rennison, D.; Bova, S.; Cavalli, M.; Ricchelli, F.; Zulian, A.; Hopkins,
B.; Brimble, M. A. Bioorg. Med. Chem. 2007, 15, 2963–2974.
2. (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109, 5551–5553;
(b) Hayashi, T.; Matsumoto, Y.; Ito, Y. J. Am. Chem. Soc. 1989, 111, 3426–3428; (c)
Brown, J. M.; Hulmes, D. I.; Layzell, T. P. J. Chem. Soc., Chem. Commun. 1993,
1673–1674.
3. (a) Brunner, H.; Nishiyama, H.; Itoh, K. Catalytic Asymmetric Synthesis; Ojima, I.,
Ed.; VCH: New York, NY, 1993; Chapter 6; (b) Sun, J.; Buchwald, S. L. J. Am. Chem.
Soc. 1999, 121, 5640–5644; (c) Bette, V.; Mortreux, A.; Savoia, D.; Carpentier, J.-F.
Adv. Synth. Catal. 2005, 347, 289–302.
4. (a) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97–102 and references
therein; (b) Jiang, Y.; Jiang, Q.; Zhang, X. J. Am. Chem. Soc. 1998, 120, 3817–3818;
4.2.9. Phenyl(pyridin-4-yl)methanol 10a
White solid, mp¼125 ꢀC, 1H NMR (CDCl3)
d
¼8.21 (d, 2H,
0
0
J¼4.9 Hz, H2, H6), 7.29–7.25 (m, 7H, H3, H5, Ho,i , Hm,m , Hp), 5.8–5.3
(br s, 1H, OH). 13C{1H} NMR (CDCl3)
d
¼153.7, 148.9, 147.0, 143.0,
128.9, 128.6, 127.9, 126.8, 126.7, 122.6, 121.4, 74.5 (C7). MS (EI):
m/z¼185 (Mþ, 64), 167 (16), 105 (35), 79 (Pyþ, 100), 77 (Phþ, 72), 51
(C4Hþ3 , 35). Optical purity was determined by chiral HPLC on
a Chiralpack AD column (i-PrOH/hexane: 3:97; flow rate: 0.7 mL/
min; detection UV at 215 nm; tR¼86 and 94 min). The major enan-
tiomer (R) obtained with precatalyst 1 was the first one to be eluted.