Page 1161 - Advanced Organic Chemistry Part B - Reactions & Synthesis

CF 3 1137
O
O O SECTION 12.5
b a
Oxidation of Ketones
O H and Aldehydes
R 1
R 2
1 2
CP1, TS1: R = CF , R = H, a
3
1 2
CP2, TS2: R = CF , R = H, b
3
2
1
CP3, TS3: R = H, R = CF , a
3
2
1
CP4, TS4: R = H, R = CF , b
3
TS3(28.3)
27.0
Type /
TS2(26.2)
path a : 22.8
25.0 path b :
TS1(24.8)
TS4(23.7)
22.3
E rel / kcal /mol CP2(3.4)

CP4(1.4) 24.8
CP3(1.3)
0.0 CP1(0.0)

CP TS
Fig. 12.15. Computational comparison of
reactants (adducts) and transition struc-
tures for Baeyer-Villiger oxidation of 2-
(trifluoromethyl)cyclohexanone by peroxytrifluo-
roacetic acid. Reproduced from Org. Lett., 5, 4803
(2003), by permission of the American Chemical
Society.

This intermediate has the oxygenation and pattern and trans-disubstitution pattern
found in the prostaglandins. Several syntheses of similar intermediates have been
developed. 239
In the synthesis of Travoprost, an antiglaucoma agent, a bicyclo[2.2.1]heptan-2-
one is converted to a lactone. 240 The commercial process uses peroxyacetic acid as
the oxidant and gives a 40% yield. The regioselectivity in this case is only 3:1 but the
unwanted isomer can be removed by selective hydrolysis.

239 I. Vesely, V. Kozmik, V. Dedek, J. Palecek, J. Mostecky, and I. Stibor, Coll. Czech. Chem. Commun.,
54, 1683 (1989); J. S. Bindra, A. Grodski, T. K. Schaaf, and E. J. Corey, J. Am. Chem. Soc., 95,
7522 (1973).
240
L. T. Boulton, D. Brick, M. E. Fox, M. Jackson, I. C. Lennon, R. McCague, N. Parkin, D. Rhodes, and
G. Ruecroft, Org. Proc. Res. Dev., 6, 128 (2002).