3474
J . Org. Chem. 1998, 63, 3474-3477
Li+, are collected in Table 1. It is important to note that
all the derivatives retained their chair structures on
complexation as well. Whereas the enlargements in the
torsion angles D2 and D3 on carbonyl protonation are
some 17° at the 6-31G level and 13° at the 6-31G* level
for the 4-ax-Cl-derivative, the related 4-eq-Cl-derivative
computed, on protonation, for much smaller 5 and 6.4°
changes, respectively. Likewise, whereas the 4-ax-F-
cyclohexanone shows an enlargement of about 15° at the
6-31G level and 11° at the 6-31G* level in D2 and D3 on
carbonyl protonation, these enlargements in the proto-
nated 4-eq-F-cyclohexanone are about 9 and 6°, respec-
tively. Both the 4-ax-Cl- and 4-ax-F-cyclohexanones
must, therefore, exhibit larger axial selectivity than the
corresponding 4-eq-derivatives. The slightly smaller D2
and D3 changes in protonated 4-ax-F-cyclohexanone in
comparison to the protonated 4-ax-Cl-cyclohexanone
indicate that an axial chlorine may be a slightly better
axial-director than an axial fluorine. All these observa-
tions are in excellent accord with the experimental
results.5 Further, the relatively larger torsion-angle
changes in the 4-eq-F-derivative in comparison to the
4-eq-Cl-species may be predictive of slightly better axial
diastereoselection with the former. Unfortunately, no
such experimental results have been reported to allow
us to confirm this observation.
Since good experimental results are reported for the
4-OH-trans-1-decalones,5 we have computed 4-OH-cyclo-
hexanones as well. The results are revealing. Better
axial diastereoselectivity must be predicted for 4-ax-OH-
cyclohexanone than that for the corresponding equatorial
derivative. Accordingly, trans-1-decalone exhibits 85%
and 61% axial diastereoselection for the 4-ax- and 4-eq-
OH substituents, respectively. The related mercapto
derivatives were also computed. For both of the 4-SH-
derivatives, axial nucleophilic attack appears to be
favored for the enhancements in the said torsion angles.
These selectivities appear to be slightly lower than those
for the respective Cl-derivatives for the slightly lower
torsion angles changes. We ourselves have determined
the selectivity of 4-eq-SPh-cyclohexanone in reductions
with LAH in Et2O, NaBH4 in methanol, and Na(CN)BH4
in MeOH at pH 1.0. The axial attacks, computed from
1H NMR integrals, were 55, 61, and 64%, respectively.
As against the 61% axial selectivity of 4-eq-SPh-cyclo-
hexanone in reduction with NaBH4 in MeOH, the axial
selectivity of 4-eq-Cl-trans-1-decalone is reported at 71%.5
The slightly larger selectivity with Na(CN)BH4 may be
a consequence of tighter cation-carbonyl complexation,
protonation in this case. Otherwise symmetric to a plane,
the molecules must lose this symmetry on cation-com-
plexation and, hence, the differences in the bond angles
A1 and A2.
4-Su bstitu ted Cycloh exa n on es. P r ed ictin g
th e F a cia l Selectivity of Nu cleop h ilic
Atta ck s fr om th e Geom etr ica l Ch a n ges on
Ca tion -Ca r bon yl Com p lexa tion : An a b
In itio In vestiga tion
Veejendra K. Yadav* and Duraiswamy A. J eyaraj
Department of Chemistry, Indian Institute of Technology,
Kanpur 208 016, India
Received November 3, 1997
In tr od u ction
We have conceptualized1 the view that in reactions of
substituted cyclohexanones with nucleophiles there is
first a complexation of the carbonyl oxygen with the
nucleophile’s cation component and that the resulting
changes in the torsion angles about the carbonyl carbon
must depend on the nature, location, and orientation of
a ring substituent. An increase in the torsion angles of
the carbonyl oxygen with the ring positions 3 and 5 on
the axial face that leads to ring flattening indicates a
preferred axial orientation of the electron-deficient p
orbital on the carbonyl carbon and, hence, a propensity
for axial attack. On the contrary, a reduction in the said
torsion angles leads to ring puckering and, hence, a
propensity for equatorial attack. The theory of stereo-
electronic effects2 dictates that an electron-deficient
orbital, such as the above p orbital in the present case,
must orient, respectively, antiperiplanar and orthogonal
to an adjacent electron-donating and electron-attracting
bond. Under forces of electrostatic attraction, a nucleo-
phile is drawn to this orbital on whichever face it is to
result in the predominant product.
The present approach avoids not only the often bother-
some transition-state (TS) calculations but also takes care
of the iminent fact that unlike the hitherto reported TS
models the cationic (Lewis acid) species is retained in the
carbonyl σ plane, which is of higher electron density.3 We
present herein the results of our calculations on 4-sub-
stituted cyclohexanones to show that our approach is not
only stereoelectronically rational but also that it does a
qualitatively decent job at facial prediction4 and dif-
ferential reaction rates.
Resu lts a n d Discu ssion
The relevant geometrical parameters, both before and
after complexation with selected cations such as H+ and
* To whom correspondence should be addressed. Fax: Int. code +
(91) 512-590260. E-mail: vijendra@iitk.ernet.in.
(1) J eyaraj, D. A.; Yadav, A.; Yadav, V. K. Tetrahedron Lett. 1997,
38, 4483. J eyaraj, D. A.; Yadav, V. K. Tetrahedron Lett. 1997, 38, 6095.
For an excellent review giving decent description of several prominent
theoretical models and the related experimental results, see: Gung,
The 4-eq-SPh-cyclohexanone was prepared from cyclo-
hexane-1,4-dione as shown in Scheme 1. The spectral
B. W. Tetrahedron 1996, 52, 5263. For
a very recent work, see:
Tomada, S.; Senju, T. Tetrahedron 1997, 53, 9057.
(2) Deslongchamps, P. in Stereoelectronic Effects in Organic Chem-
istry, Baldwin, J . E., Ed.; Pergamon Press: New York, 1983; Vol. 4,
Chapters 2-3.
(3) Fraser, R. R.; Faibish, N. C.; Kong, F.; Bednarski, K. J . Org.
Chem. 1997, 62, 6164. Power, M. B.; Bott, S. G.; Atwood, J . L.; Barron,
A. R. J . Am. Chem. Soc. 1990, 112, 3446.
(4) For a recent comprehensive work on 4-halocyclohexanones and
other references in the area, see: Shi, Z.; Boyd, R. J . J . Am. Chem.
Soc. 1993, 115, 9614.
(5) Wu, Y. D.; Tucker, J . A.; Houk, K. N. J . Am. Chem. Soc. 1991,
113, 5018. Monson, R. S.; Przybycien, D.; Baraze, A. J . Org. Chem.
1970, 35, 1700. le Noble, W. J .; Chiou, D.-M.; Okaya, Y. Tetrahedron
Lett. 1978, 1961; J . Am. Chem. Soc. 1979, 101, 3244. Cheung, C. K.;
Tseng, L. T.; Lin, M. H.; Srivastava, S.; le Noble, W. J . J . Am. Chem.
Soc. 1986, 108, 1598; 1987, 109, 7239. Xie, M.; le Noble, W. J . J . Org.
Chem. 1989, 54, 3836.
(6) Haslanger, M.; Lawton, R. G. Synth. Commun. 1974, 4, 155.
S0022-3263(97)02006-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/17/1998
Yadav, Veejendra K.
