Roussel et al.
TABLE 3. Results of the DFT Calculations (angles in degrees,
barriers in kJ/mol)
hydrogen bonding (in the case of the hydroxy group), MeO and
OH exhibit the same steric requirement and are smaller than a
CH3. This is clearly recognized in various steric scales derived
from conformational equilibrium20 or rotational barrier studies.
In the Sternhell’VdW scale derived from barrier to rotation in
the biphenyl framework, the following order in size was
(18) Examples of plateau during HPLC on chiral support: (a)
Chankvetadze, B.; Kartozia, I.; Yamamoto, C.; Okamoto, Y. J. Pharm.
Biomed. Anal. 2002, 27, 467-478. (b) Pinkerton, T. C.; Howe, W. J.; Ulrich,
E. L.; Comisky, J. P.; Haginaka, J.; Murashima, T.; Walkenhorst, W. F.;
Westler, W. M.; Markley, J. L. Anal. Chem. 1995, 67, 2354-2367. (c)
Cabrera, K.; Jung, M.; Fluck, M.; Schurig, V. J. Chromatogr. A 1996, 731,
315-321. (d) Cabrera, K.; Jung, M.; Kempter, C.; Schurig, V. Fresenius’
J. Anal. Chem. 1995, 352, 676-678. (e) Lo¨tter, J.; Krieg, H. M.; Keizer,
K.; Breytenbach, J. C. Drug DeV. Ind. Pharm. 1999, 25, 879-884. (f) Krieg,
H. M.; Lotter, J.; Keizer, K.; Breytenbach, J. C. J. Membr. Sci. 2000, 167,
33-45. (g) Ute, K.; Hirose, K.; Kashimoto, H.; Nakayama, H.; Hatada,
K.; Vogl, O. Polym. J. 1993, 25, 1175-1186. (h) Fischer, C.; Modler, A.;
Moinet, C.; Fiaud, J. C. J. Chromatogr. A 1996, 728, 433-439. (i) Haglund,
P. J. Chromatogr. A 1996, 724, 219-228. (j) Friary, R. J.; Spangler, M.;
Osterman, R.; Schulman, L.; Schwerdt, J. H. Chirality 1996, 8, 364-371.
(k) Oxelbark, J.; Allenmark, S. J. Chem. Soc., Perkin Trans. 2 1999, 1587-
1589. (l) Oswald, P.; Desmet, K.; Sandra, P.; Krupcik, J.; Armstrong, D.
W. Chirality 2002, 14, 334-339. (m) Kanazawa, H.; Kunito, Y.; Mat-
sushima, Y.; Okubo, S.; Mashige, F. Chromatography 1999, 20, 81-87.
(n) Shimizu, T.; Yamazaki, Y.; Taka, H.; Kamigata, N. J. Am. Chem. Soc.
1997, 119, 5966-5967. (o) Taka, H.; Yamazaki, Y.; Shimizu, T.; Kamigata,
N. J. Org. Chem. 2000, 65, 2127-2133. (p) Kamigata, N. Phosphorus Sulfur
Silicon 2001, 171, 207-229. (q) Bringmann, G.; Scho¨ner, B.; Schupp, O.;
Peters, K.; Peters, E.-M.; von Schnering, H. G. Liebigs Ann. Chem. 1994,
91-97. (r) Bo¨hmer, V.; Caccamese, S.; Principato, G.; Schmidt, C.
Tetrahedron Lett. 1999, 40, 5927-5930. (s) Lorenz, K.; Yashima, E.;
Okamoto, Y. Angew. Chem., Int. Ed. 1998, 37, 1922-1925. (t) Stara, I.
G.; Stary, I.; Kollarovic, A.; Teply, F.; Saman, D.; Tichy, M. J. Org. Chem.
1998, 63, 4046-4050. (u) Wolf, C.; Pirkle, W. H.; Welch, C. J.; Hochmuth,
D. H.; Ko¨nig, W. A.; Chee, G.-L.; Charlton, J. L. J. Org. Chem. 1997, 62,
5208-5210. (v) Thede, R.; Haberland, D.; Fischer, C.; Below, E.; Langer,
S. H. J. Liq. Chromatogr. Relat. Technol. 1998, 21, 2089-2102. (w) Spivey,
A. C.; Fekner, T.; Spey, S. E.; Adams, H. J. Org. Chem. 1999, 64, 9430-
9443. (x) Spivey, A. C.; Charbonneau, P.; Fekner, T.; Hochmuth, D. H.;
Maddaford, A.; Malardier-Jugroot, C.; Redgrave, A. J.; Whitehead, M. A.
J. Org. Chem. 2001, 66, 7394-7401. (y) Taka, H.; Yamazaki, Y.; Shimizu,
T.; Kamigata, N. J. Org. Chem. 2000, 65, 2127-2133. (z) Cannazza, G.;
Braghiroli, D.; Tait, A.; Baraldi, M.; Parenti, C.; Lindner, W. Chirality 2001,
13, 94-101. (aa) Oxelbark, J.; Claeson, S.; Allenmark, S. Enantiomer 2000,
5, 413-419. (ab) Blanca, M. B.-D.; Yamamoto, C.; Okamoto, Y.; Biali, S.
E.; Kost, D. J. Org. Chem. 2000, 65, 8613-8620. (ac) Gasparrini, F.; Grilli,
S.; Leardini, R.; Lunazzi, L.; Mazzanti, A.; Nanni, D.; Pierini, M.;
Pinamonti, M. J. Org. Chem. 2002, 67, 3089-3095. (ad) Dai, W. M.; Lau,
C. W. Tetrahedron Lett. 2001, 42, 2541-2544. (ae) Cirilli, R.; Costi, R.;
Di Santo, R.; Artico, M.; Roux, A.; Gallinella, B.; Zanitti, L.; La Torre, F.
J. Chromatogr. A 2003, 993, 17-28. (af) Abatangelo, A.; Zanetti, F.;
Navarini, L.; Kontrec, D.; Vinkovic, V.; Sunjic, V. Chirality 2002, 14, 12-
17. (ag) Shimizu, T.; Watanabe, I.; Kamigata, N. Angew. Chem., Int. Ed.
2001, 40, 2460-2462. (ah) Andreani, R.; Bombelli, C.; Borocci, S.; Lah,
J.; Mancini, G.; Mencarelli, P.; Vesnaver, G.; Villani, C. Tetrahedron:
Asymmetry 2004, 15, 987-994. (ai) Ceccacci, F.; Mancini, G.; Mencarelli,
P.; Villani, C. Tetrahedron: Asymmetry 2003, 14, 3117-3122. (aj) Dai,
W. M.; Zhang, Y.; Zhang, Y. Tetrahedron: Asymmetry 2004, 15, 525-
535. (ak) Trapp, O.; Trapp, G.; Schurig, V. J. Biochem. Biophys. Methods
2002, 54, 301-313. (al) Pham-Huy, C.; Villain-Pautet, G.; Hua, H.; Chikhi-
Chorfi, N.; Galons, H.; Thevenin, M.; Claude, J. R.; Warnet, J. M. J.
Biochem. Biophys. Methods 2002, 54, 287-299. (am) Nakashima, Y.;
Shimizu, T.; Hirabayashi, K.; Kamigata, N. J. Org. Chem. 2005, 70, 868-
873. (an) Watanabe, M.; Suzuki, H.; Tanaka, Y.; Ishida, T.; Oshikawa, T.;
Tori-i, A. J. Org. Chem. 2004, 69, 7794-7801. (ao) Dalla Cort, A.;
Gasparrini, F.; Lunazzi, L.; Mandolini, L.; Mazzanti, A.; Pasquani, C.;
Pierini, M.; Rompietti, R.; Schiaffino, L. J. Org. Chem. 2005, 70, 8877-
8883. (ap) Nakashima, Y.; Shimizu, T.; Hirabayashi, K.; Iwasaki, F.;
Yamasaki, M.; Kamigata, N. J. Org. Chem. 2005, 70, 5020-5027. (aq)
Benincori, T.; Celentano, G.; Pilati, T.; Ponti, A.; Rizzo, S.; Sannicolo, F.
Angew. Chem., Int. Ed. 2006, 45, 6193-6196. (ar) Wolf, C.; Xu, H.
Tetrahedron Lett. 2007, 48, 6886-6889. (as) Trapp, O. Chirality 2006,
18, 489-497. (at) Wolf, C. Chem. Soc. ReV. 2005, 35, 595-609.
calcd
barrier
exptl
barrier
compound
X
Y
θ min
θ TS
1a
1c
average
1e
1h
CH3
CH3
CH3
OCH3
78.4
78.8
78.6
59.8
60.2
60.0
9.7
8.3
9.0
1.5
1.3
1.4
114.3
112.8
113.5
81.7
82.7
82.2
122.3
121.8
122.0
84.6
87.8
86.2
OH
OH
CH3
OCH3
average
obtained: Me(1.8) > OH(1.53) ) MeO(1.52).21 The same holds
true for Taft’s steric scale where Me(-1.24) > OH(-0.55) )
MeO(-0.55).22 In the iminothiazoline 1 model, substituents X
rank in the following order: Me(122.1) > MeO(109.6) > OH-
(85.3). The values in parentheses are the mean values of the
experimental barriers. It is obvious that the contribution to the
barrier is much lower for the OH group than for the methoxy
group, contrary to what was expected on pure steric grounds.
The barrier gap (∆∆Gq, ca. 24 kJ/mol) between MeO and OH
demonstrates that an extra stabilization occurs in the quasi-planar
transition state when X ) OH. The OH group develops a
stabilizing hydrogen bond with the imino group throughout the
rotation process, the stabilizing effect being maximal in the near-
planar transition state. The observed barrier gap due to the
presence or the absence of hydrogen bonding is very similar to
the one we have already observed when comparing the barriers
in thiazolin-2-ones 2a and 2b (∆∆Gq ) 23.2 kJ/mol).11
To evaluate the hydrogen bond hypothesis, calculations were
performed on compounds 1a, 1c, 1e, and 1h. The calculations
were carried out at the B3LYP/6-31G* level23 using the facilities
of the Gaussian 03 package.24 The structures have been
characterized as minima or transition state based on the number
of imaginary frequencies (0 or 1). The results are gathered in
Table 3 where the calculated barriers correspond to the rotation
through the imino group. The torsion angles θ are defined by
the 2-1-1′-2′ atoms; one corresponds to the energy minimum,
θ min, and the other to the TS, θ TS.
The calculated values reproduce quite well the experimental
values, both are linearly related (eq 1).
exptl barrier ) -(7.8 ( 3.9) + (1.14 ( 0.04) ×
calcd barrier, n ) 4, r2 ) 0.998 (1)
The calculated barriers are related to the torsion angle of the
minimum θ min defined as 2-1-1′-2′ by eq 2.
(21) Bott, G.; Field, L. D.; Sternhell, S. J. Am. Chem. Soc. 1980, 102,
5618-5626.
(22) Gallo, R.; Roussel, C.; Berg, U. AdV. Heterocycl. Chem. 1988, 43,
173-299.
(23) (a) Becke, A. D. Phys. ReV. A 1988, 38, 3098-3100. (b) Becke, A.
D. J. Chem. Phys. 1993, 98, 5648-5652. (c) Lee, C.; Yang, W.; Parr, R.
G. Phys. ReV. B 1988, 37, 785-789. (d) Hariharan, P. A.; Pople, J. A.
Theor. Chim. Acta 1973, 28, 213-222.
(19) Trapp, O.; Schurig, V. Chirality 2002, 14, 465-470.
(20) Rajoharison, H. G.; Roussel, C.; Berg, U. Tetrahedron Lett. 1983,
24, 2259-2262.
408 J. Org. Chem., Vol. 73, No. 2, 2008