Solvent-dependent chemoselectivities in Ce(IV)-mediated oxidative coupling reactions

Article abstract of DOI:10.1021/ol034763d

(Matrix presented) The oxidative coupling of 1,3-diketones, β-keto esters, and β-keto silyl enol ethers with allyl trimethylsilane in the presence of CTAN was investigated. In the case of acyclic diketones and esters, different chemoselectivities were observed in CH₃CN and CH ₂Cl₂ leading to good yields of allylation and dihydrofuran products, respectively.

Full text of DOI:10.1021/ol034763d

ORGANIC
LETTERS
2003
Vol. 5, No. 13
2363-2365
Solvent-Dependent Chemoselectivities in
Ce(IV)-Mediated Oxidative Coupling
Reactions
Yang Zhang, Andrew J. Raines, and Robert A. Flowers, II*
Department of Chemistry and Biochemistry, Texas Tech UniVersity, Box 41061,
Lubbock, Texas 79423-1061
robert.flowers@ttu.edu
Received May 6, 2003
ABSTRACT
The oxidative coupling of 1,3-diketones, â-keto esters, and â-keto silyl enol ethers with allyl trimethylsilane in the presence of CTAN was
investigated. In the case of acyclic diketones and esters, different chemoselectivities were observed in CH CN and CH Cl2 leading to good
3
2
yields of allylation and dihydrofuran products, respectively.
Ceric ammonium nitrate (CAN) has been utilized extensively
for oxidative bond-forming reactions including the oxidative
addition of carbonyls,1-3 silyl enol ethers,4,5 and diones6,7 to
alkenes, arenes, and dienes. While CAN is useful in the
aforementioned reactions, its use is limited to polar organic
and aqueous solvents. The poor solubility of Ce(IV) in less
polar solvents can be circumvented by the preparation of
ceric tetra-n-butylammonium nitrate (CTAN).8,9 Recent work
in our group has revealed that while CTAN oxidizes
substrates more slowly than CAN by a factor of 2, they
behave in a mechanistically analogous manner.10
The solubility of CTAN in a number of solvents provides
an opportunity to determine the impact of solvation on both
substrates and Ce-based oxidants. During our initial studies
we decided to examine the influence of solvent on the
reaction between allyl trimethylsilane and 1,3-dicarbonyls.
This particular reaction, previously reported by Hwu and co-
workers, has a number of advantages including relatively
fast reaction times and the absence of competing side
reactions such as internal ligand transfer.11
Scheme 1
(1) Baciocchi, E.; Ruzziconi, R. J. Org. Chem. 1986, 51, 1645.
(2) Paolobelli, A. B.; Ceccherelli, P.; Pizzo, F.; Ruzziconi, R. J. Org.
Chem. 1995, 60, 4954.
(3) Baciocchi, E.; Ruzziconi, R. Gazz. Chim. Ital. 1986, 116, 671.
(4) Nair, V. J.; Mathew, J. J. Chem. Soc., Perkin Trans. 1 1995, 187.
(5) Paolobelli, A. B.; Latini, D.; Ruzziconi, R. Tetrahedron Lett. 1993,
34, 721.
(6) Nair, V.; Mathew, J.; Alexander, S. Synth. Commun. 1995, 25, 3981.
(7) Paolobelli, A. B.; Gioacchini, R.; Ruzziconi, R. Tetrahedron Lett.
1993, 34, 6333.
(8) Muathen, H. A. Ind. J. Chem. 1991, 30B, 522.
(9) Chen, C.; Mariano, P. S. J. Org. Chem. 2000, 65, 3252.
(10) Zhang, Y.; Flowers, R. A., II J. Org. Chem. 2003, 68, 4560.
10.1021/ol034763d CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/03/2003

Table 1. Results of Oxidative Addition of 1,3-Dioxo Compounds with CTANa
a Conditions: (A) 2 equiv of CTAN, 1 equiv of substrate in CH3CN, 4 h; (B) 2 equiv of CTAN, 1 equiv of substrate in CH2Cl2, 4 h. b Isolated yield. c GC
yields.
In an initial experiment, equimolar amounts of methyl-
acetoacetate and allyltrimethylsilane were treated with 2
equiv of CTAN in CH3CN and CH2Cl2 at room temperature.
It was expected that the allylation would occur in both
solvents so that the influence of solvent polarity on rate could
be examined in further kinetic studies. Surprisingly, a totally
different chemoselectivity was observed in both solvents
(Scheme 1). The products 1A and 1B were generated
exclusively in CH3CN and CH2Cl2, respectively. To probe
the generality of this finding, the investigation was extended
to a number of substrates and the results are summarized in
Table 1.
Examination of the results in Table 1 clearly shows that
cyclized dihydrofuran products or allyl addition products are
obtained as primary products in CH2Cl2 or CH3CN, respec-
tively. The â-keto silylenol ether (6) and 1,3-cyclohexadione
(4) provided only the furan products under both sets of
conditions.
Previous work of Hwu described the reaction of 1,3-di-
carbonyls and allyl trimethylsilane with CAN and Mn(OAc)3.11
Allylation products were obtained when the reaction was
carried out with CAN in CH3OH at room temperature
(11) Hwu, J. R.; Chen, C. N.; Shiao, S.-S. J. Org. Chem. 1995, 60, 856.
2364
Org. Lett., Vol. 5, No. 13, 2003

whereas dihydrofuran products were obtained with Mn(OAc)3
in acetic acid at 80 oC. While Hwu and co-workers examined
a number of variables in these reactions one point in their
discussion proposed that the diversity of the reactions came
from the reactivity difference between CAN and Mn(OAc)3,
where the latter is a weaker oxidant.
Scheme 2
The redox potentials of lanthanides are known to be
sensitive to the solvent milieu.12-14 Cyclic voltammetry (CV)
was utilized to determine the redox potential of CTAN in
CH3CN and CH2Cl2 to establish whether the chemoselectivity
was possibly due to different redox potentials of CTAN in
those two solvents. Figure 1 shows the CV data for CTAN
supposition that the more polar CH3CN stabilizes the â-silyl
cation through solvation providing a pathway to elimination.
Upon oxidation of the radical in the less polar CH2Cl2,
cyclization is favored through the proximity of a carbonyl
(in the absence of solvent stabilization) producing an oxo
stabilized cation.
The discussion in the preceding paragraphs focuses on the
effect of solvent on allylation vs addition-cyclization in
acyclic substrates 1-3 and 5 but does not address the absence
of this phenomenon in substrates 4 and 6. In the case of
substrate 4, addition of the allyltrimethylsilane and subse-
quent oxidation places the â-silyl cation in close proximity
to the carbonyls due to the restricted conformational flex-
ibility of the cyclic system. In this more ordered system it is
reasonable to expect less solvent dependence on the product
distribution. On the other hand, dihydrofuran formation after
addition of allyltrimethylsilane to oxidized 6 in both solvents
is somewhat more surprising. Initial rate studies on the
CTAN-mediated oxidative addition to 6 indicate an ordered
transition state, consistent with recent reported work,10 but
further studies are necessary to determine the underlying
mechanistic nuances of this reaction.
Figure 1. Cyclic voltammograms of CTAN at a glassy carbon
electrode in acetonitrile and CH2Cl2 vs Ag/AgNO3 reference
electrode.
in CH2Cl2 and CH3CN. The potentials (vs Ag/AgNO3) are
510 (20 and 540 (10 mV, respectively. While the CV of
CTAN in acetonitrile is nearly ideal (∆E of 67 mV),
inspection of the voltammogram for CTAN in CH2Cl2 is
clearly quasireversible with a ∆E of 180 mV. While the low
polarity of CH2Cl2 made the experiment somewhat more
difficult, the results of numerous determinations were
consistent and repeatable. The redox potential of CTAN in
CH2Cl2 was indeed lower by 30 mV (0.7 kcal/mol), but it is
unlikely that this small difference is responsible for the
change in chemoselectivity.
In conclusion, we have unraveled some interesting solvent-
dependent chemoselectivities of the CTAN-mediated oxida-
tive coupling of 1,3-dicarbonyl compounds and allyltri-
methylsilane. Further work on the discreet mechanistic details
of the oxidation process in various solvents and the general
synthetic utility of this approach is currently being explored.
Since the oxidizing power of Ce(IV) is nearly the same
in CH3CN and CH2Cl2, the chemoselectivity does not arise
from solvent-induced changes in the thermodynamic redox
potential of the oxidant. Nonetheless, solvent must play a
role in determining the product distribution. During the
course of the reaction, the dicarbonyl substrate is oxidized
to produce a radical cation, which attacks the allyl trimethyl-
silane forming a â-silyl radical. Further oxidation of the
â-silyl radical produces a carbocation (Scheme 2). It is our
Acknowledgment. R.A.F. is grateful to the National
Science Foundation (CHE-0196163) for support of this work.
The Robert A. Welch Foundation is also acknowledged for
providing research support for Y.Z. We also thank Dr.
Rebecca S. Miller for her useful comments on the manu-
script.
Supporting Information Available: General methods,
electrochemical data, experimental protocols, and spectro-
scopic data. This material is available free of charge via the
Internet at http://pubs.acs.org.
(12) Shabangi, M.; Flowers, R. A., II Tetrahderon Lett. 1997, 38,
1137.
(13) Shabangi, M.; Sealy, J. M.; Fuchs, J. R.; Flowers, R. A., II
Tetrahedron Lett. 1998 39, 4429.
(14) Kuhlman, M. L.; Flowers, R. A., II Tetrahedron Lett. 2000, 41,
8049.
OL034763D
Org. Lett., Vol. 5, No. 13, 2003
2365