K. Linn et al. / Tetrahedron Letters 49 (2008) 3762–3765
3765
(b) Schuricht, U.; Endler, K.; Hennig, L.; Findeisen, M.; Welzel, P. J.
Prakt. Chem. 2000, 342, 761–772; (c) Mukaiyama, T.; Shiina, I.;
Iwadare, H.; Saitoh, M.; Nishimura, T.; Ohkawa, N.; Sakoh, H.;
Nishimura, K.; Tani, Y.; Hasegawa, M.; Yamada, K.; Saitoh, K.
Chem. Eur. J. 1999, 5, 121–161. For procedures utilizing sodium metal
and bromoacetic acid 4b for the preparation of 2, see: (d) Tietze, L.
F.; Geriche, K. M.; Guentner, C. Eur. J. Org. Chem. 2006, 21, 4910–
4915.
References and notes
1. For leading references, see: (a) Coppola, G. M.; Shuster, H. F.
Hydroxy Acids in Enantioselective Synthesis; Wiley-VCH: Weinheim,
1997; (b) Hanessian, S. Total Synthesis of Natural Products. The
Chiron Approach; Pergamon: New York, 1983 Chapter 2; (c) Bunte, J.
O.; Cuzzupe, A. N.; Daly, A. M.; Rizzacasa, M. A. Angew. Chem.,
Int. Ed. 2006, 45, 6376–6380.
7. Benzyloxyacetic acid
Chemical Co.
2 is commercially available from Aldrich
2. For the synthesis of secondary a-hydroxy acids, see: (a) Seebach, D.;
Naef, R. Helv. Chim. Acta 1981, 64, 2704–2708; (b) Enomoto, M.; Ito,
Y.; Katsuki, T.; Yamaguchi, M. Tetrahedron Lett. 1985, 26, 1343–
1344; (c) Evans, D. A.; Morrissey, M. M.; Dorow, R. L. J. Am. Chem.
Soc. 1985, 107, 4346–4348; (d) Adam, W.; Lazarus, M.; Boss, B.;
Saha-Mo¨ller, C. R.; Humpf, H. U.; Schreier, P. J. Org. Chem. 1997,
62, 7841–7843; (e) Burk, M. J.; Kalberg, C. S.; Pizzano, A. J. Am.
Chem. Soc. 1998, 120, 4345–4353; (f) Pansare, S. V.; Ravi, R. G.
Tetrahedron 1998, 54, 14549–14564; (g) Pansare, S. V.; Ravi, R. G.;
Jain, R. P. J. Org. Chem. 1998, 63, 4120–4124; (h) Andrus, M. B.;
Soma Sekhar, B. B. V.; Meredith, E. L.; Dally, N. K. Org. Lett. 2000,
2, 3035–3037; (i) Crimkmins, M. T.; Emmitte, K. A.; Katz, J. D. Org.
Lett. 2000, 2, 2165–2167; (j) Jung, J. E.; Ho, H.; Kim, H.-D.
Tetrahedron Lett. 2000, 41, 1793–1796; (k) He, L.; Byun, H.-S.;
Bittman, R. J. Org. Chem. 2000, 65, 7627–7633; (l) Tbag, L.; Deng, L.
J. Am. Chem. Soc. 2002, 124, 2870–2871; (m) Yu, H.; Ballard, E.;
Boyle, P. D.; Wang, G. Tetrahedron 2002, 58, 7663–7679; (n) Nam, J.;
Lee, S. K.; Park, Y. S. Tetrahedron 2003, 59, 2397–2401; Deechongkit,
S.; Yoou, S.-L.; Kelly, J. W. Org. Lett. 2004, 6, 497–500 and
references cited therein.
8. For a procedure describing the use of NaO–tBu in the preparation of
benzyloxyacetic acid, see: Meurs, J. H. H.; De Jong, F. U.S. Patent
5,378,797, 1995.
9. HPLC assay yield refers to quantitative HPLC analysis of reaction
mixtures using an analytically pure standard.
10. The use of NaOEt for this transformation has been reported, but
acceptable results were not obtained in our hands, see: Kovacˇ, V.;
ˇ
´
ˇ
Rapic, V.; Susnik, I.; Suprina, M. J. Organomet. Chem. 1997, 530,
149–158.
11. The use of NaOH for the preparation of 2 has been reported to occur
in 86% yield; however, no experimental details were provided, see:
Solladie, G.; Hutt, J. Tetrahedron Lett. 1987, 28, 797–800; See also:
Ishiwata, A.; Sakamoto, S.; Noda, T.; Hirama, M. Synlett 1999,
692–694.
12. 85% Powdered KOH is available from Fluka and was used as
received.
13. General procedure for the preparation of 2: In a 3 L, 4necked round-
bottomed flask equipped with a condenser, thermocouple, nitrogen
inlet, and mechanical stirrer were added 459 g (4.23 mol) of benzyl
alcohol and 500 mL of THF. To the homogeneous solution was
added 210 g (3.18 mol) of 85% KOH portion-wise in four 52.5 g
aliquots over 4 h while maintaining the internal temperature <40 °C.
The bright orange slurry was cooled to 10 °C in an acetone/ice bath
and 100 g (1.06 mol) of chloroacetic acid 4a was added over 35 min in
four 25 g aliquots. The solution was heated to 70 °C and stirred for
1.5 h. The mixture was cooled to rt and 400 mL of water and 400 mL
of MTBE were added. The layers were separated and the aqueous
layer was washed with MTBE (4 Â 400 mL). The HPLC analysis of
the organic extracts indicated the presence of 330 g (3.04 mol) of
BnOH. The aqueous layer was acidified with 250 mL of concentrated
hydrochloric acid and extracted with MTBE (2 Â 400 mL). The
organic extracts were concentrated under reduced pressure to afford
130.1 g (65%) of 2 which was sufficiently pure for use in the
subsequent reactions without any further purification.
´
3. For the synthesis of tertiary a-hydroxy acids, see: (a) Frater, G.;
Mu¨ller, U.; Gu¨nther, W. Tetrahedron Lett. 1981, 22, 4221–4224; (b)
Seebach, D.; Naef, R.; Calderari, G. Tetrahedron 1984, 40, 1313–
1324; (c) Chang, J.-W.; Jang, D.-P.; Unag, B.-J.; Liao, F.-L.; Wang,
S.-L. Org. Lett. 1999, 1, 2061–2063; (d) Picoul, W.; Urchegui, R.;
Haudrechy, A.; Langlois, Y. Tetrahedron Lett. 1999, 40, 4797–4800;
´
(e) Dıez, E.; Dixon, D. J.; Ley, S. V. Angew. Chem., Int. Ed. 2001, 40,
2906–2909; (f) Hutchinson, J. M.; Lindsay, H. A.; Dormi, S. S.; Jones,
G. D.; Vicic, D. A.; McIntosh, M. C. Org. Lett. 2006, 8, 3663–3665;
(g) Howard, B. E.; Woerpel, K. A. Org. Lett. 2007, 9, 4651–4653.
4. Green, T. W.; Wutts, P. G. M. Protective Groups in Organic Synthesis,
3rd ed.; Wiley: New York, 1999. p 86.
5. (a) For representative procedures utilizing NaH and chloroacetic acid
4a for the preparation of 2, see: (a) Ref. 2m; (b) Refs. 13a and 13b; (c)
May, J. A.; Stoltz, B. M. J. Am. Chem. Soc. 2002, 124, 12426–12427;
(d) Glover, S. A.; Golding, S. L.; Goosen, A.; McCleland, C. W. J.
Chem. Soc., Perkin Trans. 1 1983, 2479–2483; For procedures utilizing
NaH and bromoacetic acid 4b for the preparation of 2, see: (e)
Enomoto, M.; Ito, Y.; Katsuki, T.; Yamaguchi, M. Tetrahedron Lett.
1985, 26, 1343–1344.
14. Complete degassing of the reaction mixture has no effect on the level
of benzoic acid formed, lending further support for the proposed
mechanism in Scheme 4.
15. (a) Abraham, D. J.; Mehanna, A. S.; Williams, F. L. J. Med. Chem.
1982, 25, 1015–1017; (b) Abraham, D. J.; Kennedy, P. E.; Mehanna,
A. S.; Patwa, D. C.; Williams, F. L. J. Med. Chem. 1984, 27, 967–
978.
6. For representative procedures utilizing sodium metal and chloroacetic
acid 4a for the preparation of 2, see: (a) Yamashita, Y.; Saito, S.;
Ishitani, H.; Kobayashi, S. J. Am. Chem. Soc. 2003, 125, 3793–3798;