Chemospecific chromium[VI] catalyzed oxidation of C-H bonds at -40 °C

Article abstract of DOI:10.1021/ja026734o

H₅IO₆ in the presence of catalytic chromoyl diacetate is a powerful method for oxidation of C-H bonds. Tertiary and oxygen activated C-H bonds are oxidized to tertiary alcohols or ketones at temperatures as low as -40 °C. The putative reagent is neutral dioxoperoxy chromium[VI] which undergoes C-H oxidation with retention of stereochemistry. This reagent appears to be the first reagent capable of oxidation of a C-H bond in the presence of an olefin without concomitant epoxidation. Copyright

Full text of DOI:10.1021/ja026734o

Published on Web 11/02/2002
Chemospecific Chromium[VI] Catalyzed Oxidation of C-H Bonds at -40 °C1
Seongmin Lee and P. L. Fuchs*
Department of Chemistry, Purdue UniVersity, West Lafayette, Indiana 47907
Received April 30, 2002
Scheme 1
In the course of our research involving hyperactive analogues
of the cephalostatin2/ritterazine3 family of marine natural products,
we wished to effect sequential allylic oxidation of olefin 1 to
hemiacetal 2 followed by directed epoxidation to epoxide 3r. While
dioxiranes have been shown to smoothly oxidize tertiary C-H
bonds of saturated spiroketals,4 reaction of 1 with DMDO or TFDO
(methyl(trifluoromethyl)dioxirane) produces complex mixtures.
Furthermore, neither of the epoxy isomers of 4 undergoes additional
C-H oxidation under extended reaction times with the dioxirane
reagents (Scheme 1).
The search for a reagent capable of C-H oxidation in the
presence of olefins avoided reagents that produce alkoxy radicals.5
Instead, we employ a metallic peroxide to pursue oxidative C-H
Table 1. Cr[VI] Catalyzed Oxidation of Ethylbenzene
insertion akin to the dioxiranes.6 Our study was strongly influenced
by a pair of excellent reviews by Dickman and Pope,7 and Shilov
and Shul’pin8 in conjunction with a recent theoretical paper by
Ro¨sch.9 Calculations by the latter group indicated that the unknown10
bisoxo, monoperoxo Cr[VI] species were less prone to epoxidation
than similar Mo or W complexes.9 Moreover, inclusion of additional
basic ligands is calculated to further increase the activation barrier
for oxidation by all three metals.9,10 A smattering of references offers
encouragement that Cr[VI] can effect certain C-H oxidations,11
but because bis and trisperoxo complexes of Cr are known to be
only weak C-H oxidizing agents,12 we elected to initially seek
preparation of a monoperoxo, bisoxo Cr[VI] species associated with
weak donor ligands.13 Therefore, our beginning studies employed
acetic acid, acetonitrile, and dichloromethane as solvents. Initial
oxidations were carried out with excess CrO3, but the more soluble
chromoyl diacetate is superior. Other chromium[VI] substrates
including chromoyl chloride, chromoyl bistrifluoroacetate, chromoyl
bistriflate, and chromoyl bis tert-butylester were far inferior. The
premier co-oxidant is periodic acid (or tetrabutylammonium pe-
riodate), while hydrogen peroxide, tert-butyl hydroperoxide, TM-
SOOTMS, peroxydisulfate, and persulfate are poor.
run
1
2
3
4
5
6
Ac2O (equiv)
yield (%)
0a
85
1b
89
2b
96
3b
92
5b
79
6c
25
a Light yellow mixture. b Light orange mixture. c Dark brown mixture.
Attempts at trapping secondary alcohol intermediates using excess
trifluoroacetic anhydride15 were not successful. Reaction of sub-
strates bearing tertiary amide or lactam functionality revealed that
amides prevented the oxidation, possibly due to their serving as
nondissociable ligands. Trichloroacetonitrile and benzonitrile do not
facilitate the reaction, but this may be a result of their inability to
dissolve the periodic acid. All of the yields reported herein are based
upon 1 equiv of C-H substrate.
Of considerable significance is that C-H oxidations occur at
about -40 °C, and the reaction is catalytic in chromium. Reactions
deficient in co-oxidant begin as brownish-orange, but rapidly turn
green and cease oxidation. Addition of excess periodic acid
reestablishes both the brown-orange color and the oxidative process.
Both excess periodic acid and acetic anhydride are required for
optimal yield of acetophenone from ethyl benzene (Table 1).
An expanded series of substrates (Table 2) reveals several
generalities. The reaction is stereospecific with the retention of
stereochemistry of the C-H bond oxidized (entries 6-9, 10). Where
a second oxidation can give a cis-diol, periodate effects rapid
oxidative cleavage (entries 5, 10). While substantially preferred,
the oxidation is not restricted to tertiary C-H bonds. Cyclohexane
and its perdeuterio analogue are oxidized to cyclohexanone (kH/kD
) 2.5, similar to the TFDO oxidation of cyclohexane kH/kD ) 2.214).
While much remains to be done to define the mechanism, scope,
and limitations of this amazing reaction, we have returned to the
oxidation of the spiroketals shown in Scheme 1. It is very rewarding
that stoichiometric oxidation of 1 produces the desired epoxyalcohol
3r in 66% yield along with 26% of the C-22 spiroketal isomer,
due to acid-catalyzed isomerization. Monitoring the reaction by
NMR provides no evidence of intermediates 2 or 4r (see Scheme
1). Evidence in support of C-H oxidation preceding epoxidation
is seen in the Cr oxidation of 4â which requires more forcing
conditions (-10 °C, 1 h) to stereospecifically generate lactol
epoxide 3â. Related noteworthy reactions are the unprecedented
chemospecific oxidations of 5 to hemiacetal 6 and allylic oxidations
of enol ethers 7 and 9 (Scheme 2).16
We postulate intermediacy of chromoylperiodate17 A1 (or
analogue A2) formed from reaction of CrO3 SM1 (or chromoyl
diacetate SM2) via addition of “anhydrous” HIO4. Formation of
the putative peroxy intermediates R1,2 (IR shows a Cr peroxy stretch
* To whom correspondence should be addressed. E-mail: pfuchs@purdue.edu.
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J. AM. CHEM. SOC. 2002, 124, 13978-13979
10.1021/ja026734o CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Cr[VI] Mediated C-H Oxidation
Scheme 2
Scheme 3
(2) Pettit, G. R.; Tan, R.; Xu, J.-P.; Ichihara, Y.; Williams, M. D.; Boyd, M.
R. J. Nat. Prod. 1998, 61, 953 and references therein.
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and references therein.
(4) Arnone, A.; Cavicchioli, M.; Montanari, V.; Resnati, G. J. Org. Chem.
1994, 59, 5511.
(5) Kojima, T.; Matsuo, H.; Matsuda, Y. Inorg. Chim. Acta 2000, 300, 661.
Barton, D. H. R. Chem. Soc. ReV. 1996, 237. Perkins, M. J. Chem. Soc.
ReV. 1996, 229.
(6) Denmark, S. E.; Wu, Z. Synlett 1999, 847. Curci, R.; Dinoi, A.; Rubino,
M. F. Pure Appl. Chem. 1995, 67, 811. Adam, W.; Curci, R.; Edwards,
J. O. Acc. Chem. Res. 1989, 22, 205. Murray, R. W. Chem. ReV. 1989,
89, 1187.
(7) Dickman, M. H.; Pope, M. T. Chem. ReV. 1994, 94, 569.
(8) Shilov, A. E.; Shul’pin, G. B. Chem. ReV. 1997, 97, 2879.
(9) Di Valentin, C.; Gisdakis, P.; Yudanov, I. V.; Ro¨sch, N. J. Org. Chem.
2000, 65, 2996.
(10) Complexes of Cr(O2)O2L (L ) tridentate amine ligands) are reported to
be essentially inert as oxidants: Tarafder, M. T. H.; Bhattacharjee, P.;
Sarkar, A. K. Polyhedron 1992, 11, 795.
(11) Shul’pin, G. B.; Su¨ss-Fink, G.; Shul’pina, L. S. J. Chem. Res. 2000, 576.
Muzart, J. Chem. ReV. 1992, 92, 113. Parish, E. J.; Aksara, N.; Boos, T.
L.; Kaneshiro, E. S. J. Chem. Res., Synop. 1999, 708. Samsel, E. G.;
Srinivasan, K.; Kochi, J. K. J. Am. Chem. Soc. 1985, 107, 7606. Parish,
E. J.; Aksara, N.; Boos, T. L. Lipids 1997, 32, 1325. Kunkely, H.; Vogler,
A. Inorg. Chim. Acta 1997, 256, 169.
(12) Shul’pin, G. B.; Su¨ss-Fink, G.; Shul’pina, L. S. J. Chem. Res. 2000, 576.
Curci, R.; Giannattasio, S.; Sciacovelli, O.; Troisi, L. Tetrahedron 1984,
40, 2763. Ciminale, F.; Camporeale, M.; Mello, R.; Troisi, L.; Curci, R.
J. Chem. Soc., Perkin Trans. 2 1989, 417.
a Isolated yield. b CrO3 (3 equiv), Bu4NIO4 (3 equiv), -40 °C, 10 min.
c CrO2(OAc)2 (5 mol %), H5IO6 (3 equiv), -40 to 0 °C, 2 h. d -20 °C, 1
h. e Prolonged reaction 12 h gave tertiary acetamide (82%, X ) NHAc).
f Amide (19%, X ) NHAc) and acetophenone (10%) isolated. g Amide (4%,
X ) NHAc) and acetophenone (3%) formed. h H5IO6 (10 equiv), 2 h.
(O-O); 945 cm-1), followed by insertion to the hydrocarbon C-H
bond, may afford Cr[VI] compounds C1 and C2 which decompose
to SM1 and SM2, the precatalysts (Scheme 3). The major decrease
in yield with 6 equiv of acetic anhydride (Table 1) seems to indicate
a role for water in the oxidative process.
(13) Catalytic chromium[VI] has been employed with periodate for oxidation
of alcohols: Schmieder-van de Voondervoort, L.; Bouttemy, S.; Padro´n,
J. M.; Le Bras, J.; Muzart, J.; Alsters, P. L. Synlett 2002, 243. Zhao, M.;
Li, J.; Song, Z.; Desmond, R.; Tschaen, D. M.; Grabowski, E. J. J.; Reider,
P. J. Tetrahedron Lett. 1998, 39, 5323.
Acknowledgment. We thank the National Institute of Health
(CA 60548) for funding.
(14) Mello, R.; Fiorentino, M.; Fusco, C.; Curci, R. J. Am. Chem. Soc. 1989,
Supporting Information Available: Representative experimental
procedures, and 1H, 13C NMR of all new compounds (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
111, 6749.
(15) Moody, C. J.; O’Connell, J. L. Chem. Commun. 2000, 1311.
(16) See: Luzzio, F. A.; Moore, W. J. J. Org. Chem. 1993, 58, 2966. Jeong,
J. U.; Fuchs, P. L. J. Am. Chem. Soc. 1994, 116, 773.
(17) Chromoyl iodate, the stable iodine[V] analogue of this reagent, is well-
known: Kebir, A.; Vast, P. C. R. Acad. Sc. Paris 1973, 276, 503-506.
Balicheva. Res. 1973, 5, 507. Dupuis, T. Mikrochim. Acta 1967, 461.
References
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