Communications
erosion of the stereochemical integrity (R,R/S,R 94:6). When
Experimental Section
the same experiments were carried out with the diastereomer
of 22 obtained from the opposite enantiomer of the Mosher
acid chloride (R,S/S,S 99:1), the results were similar but not
identical (conditions of Table 3, entry 1: d.r. = 97:3; condi-
tions of Table 3, entry 2: d.r. = 64:36; conditions of Table 3,
entry 3: d.r. = 69:31).
With these final results standing as a powerful testament
to the mildness of the presently introduced method, we
anticipate its applicability and usefulness in chemical syn-
thesis to be widespread.
General procedure: The carboxylic ester (0.01–0.15 mmol) was
dissolved in 1,2-dichloroethane and after addition of trimethyltin
hydroxide (1–10 equiv), the mixture was heated at 60–808C until TLC
analysis indicated a complete reaction. After completion of the
reaction, the mixture was concentrated in vacuo, and the residue was
taken up in ethyl acetate (ꢀ 15 mL). The organic layer was washed
with aqueous KHSO4 (0.01n) or HCl (5%) (3 ꢀ 5–15 mL). The
organic layer was then washed with brine (5–15 mL) and dried over
sodium sulfate. Removal of the solvent in vacuo afforded the
1
carboxylic acid, often in > 98% purity (by H NMR spectroscopy).
Received: October 5, 2004
Published online: January 26, 2005
Keywords: epimerization · hydrolysis · synthetic methods · tin
Table 4: Selected physical properties for compounds 9a, 10a, 14a, 17a,
and 22a.
.
9a: Rf =0.12 (silica gel, EtOAc/hexanes 1:1); [a]3D2 =ꢂ32.5 (CH2Cl2,
c=1.20); IR (film): n˜max =3323, 3060, 2978, 2931, 1696, 1665, 1519,
1368, 1249, 1166, 1070, 737 cmꢂ1; 1H NMR (600 MHz, CDCl3): d=7.56–
7.54 (m, 2H), 7.26–7.25 (m, 3H), 7.09 (br d, J=7.4 Hz, 1H), 4.89 (m,
2H), 3.48 (dd, J=13.1, 4.4 Hz, 1H), 3.34 (m, 1H), 1.46 (br s, 9H),
1.25 ppm (m, 3H); 13C NMR (150 MHz, CDCl3): d=173.4, 172.9, 133.2,
129.4, 129.2, 127.4, 53.1, 50.0, 29.6, 29.2, 28.3, 18.1 ppm; HRMS (ESI-
TOF): calcd for C17H24N2O5SeNa+ [M+Na]+: 439.0743; found: 439.0743
10a: Rf =0.10 (silica gel, EtOAc/hexanes 1:1); IR (film): n˜max =3406,
2917, 1629, 1527, 1352, 1095, 1038, 718 cmꢂ1; 1H NMR (600 MHz,
CD3OD): d=8.03–7.99 (m, 2H), 7.51–7.48 (m, 1H), 6.89 (s, 1H),
6.22 ppm (s, 1H); 13C NMR (150 MHz, CD3OD): d=194.6, 171.0, 152.0,
144.3, 138.9, 135.4, 134.7, 131.8, 127.2, 124.8 ppm; HRMS (ESI-TOF):
calcd for C10H6BrNO5Hꢂ [MꢂH]ꢂ: 297.9357; found: 297.9354
14a: Rf =0.30 (silica gel, EtOAc/hexanes 7:3); IR (film): n˜max =3460,
2980, 2934, 2859, 1731, 1714, 1467, 1374, 1181, 1109 cmꢂ1; 1H NMR
(400 MHz, CDCl3): d=5.00 (septet, J=6.2 Hz, 1H), 2.37–2.24 (m, 4H),
1.65–1.60 (m, 4H), 1.36–1.33 (m, 4H), 1.22 ppm (d, J=6.2 Hz, 6H);
13C NMR (150 MHz, CDCl3): d=173.3, 67.4, 34.5, 28.6, 28.6, 24.7, 24.7,
24.6, 21.7 ppm; HRMS (ESI-TOF): calcd for C11H20O4Na+ [M+Na]+:
239.1254; found: 239.1255
[1] a) K. C. Nicolaou, B. S. Safina, M. Zak, A. A. Estrada, S. H. Lee,
Angew. Chem. 2004, 116, 5197 – 5202; Angew. Chem. Int. Ed.
2004, 43, 5087 – 5092; b) K. C. Nicolaou, M. Zak, B. S. Safina,
S. H. Lee, A. A. Estrada, Angew. Chem. 2004, 116, 5202 – 5207;
Angew. Chem. Int. Ed. 2004, 43, 5092 – 5097.
[2] a) R. L. E. Furlan, E. G. Mata, O. A. Mascaretti, J. Chem. Soc.
Perkin Trans. 1 1998, 355 – 358; b) R. L. E. Furlan, E. G. Mata,
O. A. Mascaretti, C. Pena, M. P. Coba, Tetrahedron 1998, 54,
13023 – 13034; c) R. L. E. Furlan, O. A. Mascaretti, Aldrichi-
mica Acta 1997, 30, 55 – 69; d) R. L. E. Furlan, E. G. Mata, O. A.
Mascaretti, Tetrahedron Lett. 1996, 37, 5229 – 5232.
[3] For a related process that employs dibutyltin oxide to induce
transesterifications, see: P. Baumhof, R. Mazitschek, A. Giannis,
Angew. Chem. 2001, 113, 3784 – 3786; Angew. Chem. Int. Ed.
2001, 40, 3672 – 3674.
[4] K. C. Nicolaou, M. Nevalainen, M. Zak, S. Bulat, M. Bella, B. S.
Safina, Angew. Chem. 2003, 115, 3540 – 3546; Angew. Chem. Int.
Ed. 2003, 42, 3418 – 3424.
[5] D. A. Evans, J. Bartroli, T. L. Shih, J. Am. Chem. Soc. 1981, 103,
2127 – 2129.
[6] C. J. Salomon, G. O. Danelon, O. A. Mascaretti, J. Org. Chem.
2000, 65, 9220 – 9222.
17a: Inseparable mixture of ꢀ1:1 diastereomers: Rf =0.34 (silica gel,
EtOAc/hexanes 7:3); [a]D32 =ꢂ22.3 (CH2Cl2, c=0.60); IR (film):
[7] Arylglycine derivatives such as 22 are known to be extremely
prone to racemization; for examples, see: a) H. Deng, J.-K. Jung,
T. Liu, K. Kuntz, M. L. Snapper, A. H. Hoveyda, J. Am. Chem.
Soc. 2003, 125, 9032 – 9034; b) F. A. Davis, D. L. Fanelli, J. Org.
Chem. 1998, 63, 1981 – 1985; c) A. J. Pearson, G. Bignan, P.
Zhang, M. Chelliah, J. Org. Chem. 1996, 61, 3940 – 3941; d) A. J.
Pearson, H. Shin, J. Org. Chem. 1994, 59, 2314 – 2323.
[8] a) A. J. Pearson, M. V. Chelliah, G. C. Bignan, Synthesis 1997, 5,
536 – 540; b) L. B. Crast, US Patent 3489750, 1970 [Chem.
Abstr. 1970, 72, 100725].
[9] a) J. A. Dale, D. L. Dull, H. S. Mosher, J. Org. Chem. 1969, 34,
2543 – 2549; b) J. A. Dale, H. S. Mosher, J. Am. Chem. Soc. 1973,
95, 512 – 519.
[10] a) I. A. Motorina, C. Huel, E. Quiniou, J. Mispelter, E. Adjadj,
D. S. Grierson, J. Am. Chem. Soc. 2001, 123, 8 – 17; b) F. Polyak,
W. D. Lubell, J. Org. Chem. 2001, 66, 1171 – 1180.
n˜max =3380, 2925, 2854, 1737, 1719, 1460, 1375, 1252, 1094, 836 cmꢂ1
;
1H NMR (600 MHz, CDCl3): d=8.37 (s, 2ꢀ1H), 6.05 (m, 2ꢀ1H), 5.06–
5.03 (m, 2ꢀ1H), 2.94–2.84 (m, 2ꢀ1H), 2.79–2.74 (m, 2ꢀ1H), 2.69–
2.65 (m, 2ꢀ1H), 2.14 (s, 2ꢀ3H), 2.10–2.02 (m, 2ꢀ2H), 1.95 (m,
2ꢀ1H), 1.39 (d, J=6.12 Hz, 3H), 1.36 (d, J=6.18 Hz, 3H), 0.92 (s, 9H),
0.90 (s, 9H), 0.09 (s, 3H), 0.07 (s, 3H), 0.00 (s, 3H), ꢂ0.02 ppm (s,
3H); 13C NMR (150 MHz, CDCl3): d=178.3, 170.6, 157.8, 152.4, 144.5,
134.0, 120.2, 70.3, 66.6, 66.5, 32.1, 29.9, 25.9, 25.9, 25.2, 25.0, 22.9, 21.5,
18.1, ꢂ4.6, ꢂ4.6, ꢂ4.7 ppm; HRMS (ESI-TOF): calcd for C20H31NO5SiH+
[M+H]+: 394.2044; found: 394.2049
22a: Rf =0.34 (silica gel, MeOH/CH2Cl2 1:9); [a]3D2 =ꢂ62.6 (MeOH,
c=0.67); IR (film): n˜max =3381, 2920, 2856, 1732, 1649, 1454, 1270,
1
1164, 1106 cmꢂ1; H NMR (600 MHz, CD3OD): d=7.59–7.57 (m, 2H),
7.45–7.44 (m, 5H), 5.48 (br s, 1H), 3.88 (s, 3H), 3.40 ppm (m, 3H);
13C NMR (150 MHz, CD3OD): d=168.1, 153.4, 137.0, 133.7, 131.0,
130.5, 129.8, 129.5, 129.4, 126.5, 124.6, 61.3, 56.1, 55.7, 30.9 ppm;
HRMS (ESI-TOF): calcd for C19H16Cl2F3NO5H+ [M+H]+: 466.0430;
found: 466.0429
(R,S)-22a: Rf =0.34 (silica gel, MeOH/CH2Cl2 1:9); [a]3D2 =ꢂ34.1
(MeOH, c=0.27); IR (film): n˜max =3377, 2917, 2851, 1730, 1694, 1479,
1268, 1166, 1105 cmꢂ1; 1H NMR (600 MHz, CD3OD): d=7.46–7.44 (m,
2H), 7.41–7.37 (m, 3H), 7.29 (s, 2H), 5.52 (br s, 1H), 3.85 (s, 3H),
3.62 ppm (m, 3H); 13C NMR (150 MHz, CD3OD): d=168.1, 153.5,
136.3, 134.6, 130.9, 130.4, 129.6, 129.5, 128.5, 126.2, 124.3, 61.3, 56.6,
56.1, 30.9 ppm; HRMS (ESI-TOF): calcd for C19H16Cl2F3NO5Na+
[M+Na]+: 488.025; found: 488.0246
1382
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 1378 –1382