New reactivity of oxaziridine: Pd(II)-catalyzed aromatic C-H ethoxycarbonylation via C-C bond cleavage

Article abstract of DOI:10.1021/ol2021252

A novel Pd(II)-catalyzed aromatic C-H ethoxycarbonylation with oxaziridine involving C-C bond cleavage is described. Various aromatic 2-phenylpyridines and related compounds as well as aryl ureas can be effectively ethoxycarbonylated. A catalytic cycle in

Full text of DOI:10.1021/ol2021252

ORGANIC
LETTERS
2011
Vol. 13, No. 19
5244–5247
New Reactivity of Oxaziridine: Pd(II)-Catalyzed
Aromatic CÀH Ethoxycarbonylation via
CÀC Bond Cleavage
Xingao Peng, Yingguang Zhu, Thomas A. Ramirez, Baoguo Zhao, and Yian Shi*
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523,
United States
yian@lamar.colostate.edu
Received August 5, 2011
ABSTRACT
A novel Pd(II)-catalyzed aromatic CÀH ethoxycarbonylation with oxaziridine involving CÀC bond cleavage is described. Various aromatic
2-phenylpyridines and related compounds as well as aryl ureas can be effectively ethoxycarbonylated. A catalytic cycle involving Pd(II) and Pd(IV)
is proposed.
Three-membered ring compounds containing two het-
eroatoms are highly versatile oxidation reagents.1À3 As
part of our general interest in the reactivity and selectivity
of dioxirane1g and its nitrogen analogues, we have ex-
plored various metal-catalyzed transformations of diazir-
idinone and related compounds, including Pd(0)- and
Cu(I)-catalyzed diamination of dienes,4 Pd(0)-catalyzed
allylic and homoallylic CÀH amination of terminal olefins,5
and Cu(I)-catalyzed CÀH R-amination of esters6 using di-
(7) For leading reviews on Pd-catalyzed CÀH activations, see: (a)
Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1698. (b) Godula, K.; Sames,
D. Science 2006, 312, 67. (c) Alberico, D.; Scott, M. E.; Lautens, M.
Chem. Rev. 2007, 107, 174. (d) Hartwig, J. F. Nature 2008, 455, 314. (e)
Catellani, M.; Motti, E.; Della Ca’, N. Acc. Chem. Res. 2008, 41, 1512. (f)
Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42, 1074.
(g) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int.
(1) For general leading reviews on dioxiranes, see: (a) Murray, R. W.
Chem. Rev. 1989, 89, 1187. (b) Adam, W.; Curci, R.; Edwards, J. O. Acc.
Chem. Res. 1989, 22, 205. (c) Curci, R.; Dinoi, A.; Rubino, M. F. Pure
Appl. Chem. 1995, 67, 811. (d) Denmark, S. E.; Wu, Z. Synlett 1999, 847.
~
Ed. 2009, 48, 5094. (h) Muniz, K. Angew. Chem., Int. Ed. 2009, 48, 9412.
(i) Xu, L.-M.; Li, B.-J.; Yang, Z.; Shi, Z.-J. Chem. Soc. Rev. 2010, 39,
712. (j) Sehnal, P.; Taylor, R. J. K.; Fairlamb, I. J. S. Chem. Rev. 2010,
110, 824. (k) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(8) For recent examples of C-H functionalization of 2-phenylpyri-
dines and related compounds, see: (a) Dick, A. R.; Hull, K. L.; Sanford,
M. S. J. Am. Chem. Soc. 2004, 129, 2300. (b) Hull, K. L.; Anani, W. Q.;
Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 7134. (c) Chen, X.; Hao, X.-
S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 6790.
(d) Cheng, K.; Yao, B.; Zhao, J.; Zhang, Y. Org. Lett. 2008, 10, 5309.
€
(e) Frohn, M.; Shi, Y. Synthesis 2000, 1979. (f) Adam, W.; Saha-Moller,
C. R.; Zhao, C.-G. Org. React. 2002, 61, 219. (g) Shi, Y. Acc. Chem. Res.
2004, 37, 488. (h) Yang, D. Acc. Chem. Res. 2004, 37, 497. (i) Wang,
O. A.; Shi, Y. Chem. Rev. 2008, 108, 3958. (j) Adam, W.; Zhao, C.-G.;
Jakka, K. Org. Rect. 2007, 69, 1.
(2) For leading reviews on oxaziridines see: (a) Davis, F. A.;Sheppard,
A. C. Tetrahedron 1989, 45, 5703. (b) Andreae, S.; Schmitz, E. Synthesis
ꢀ
(e) Zhao, X.; Dimitrijevic, E.; Dong, V. M. J. Am. Chem. Soc. 2009, 131,
ꢀ
1991, 327. (c) Davis, F. A.; Chen, B. C. Chem. Rev. 1992, 92, 919. (d) Aube,
3466. (f) Jin, W.; Yu, Z.; He, W.; Ye, W.; Xiao, W.-J. Org. Lett. 2009, 11,
1317. (g) Jia, X.; Zhang, S.; Wang, W.; Luo, F.; Cheng, J. Org. Lett.
2009, 11, 3120. (h) Wang, X.; Truesdale, L.; Yu, J.-Q. J. Am. Chem. Soc.
2010, 132, 3648. (i) Gao, K.; Lee, P.-S.; Fujita, T.; Yoshikai, N. J. Am.
Chem. Soc. 2010, 132, 12249.
J. Chem. Soc. Rev. 1997, 26, 269.
(3) For a leading review on diaziridines and related compounds, see:
Heine, H. W. In The Chemistry of Heterocyclic Compounds; Wiley: New
York, 1983; p 547.
(4) (a) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 762. (b)
Yuan, W.; Du, H.; Zhao, B.; Shi, Y. Org. Lett. 2007, 9, 2589. (c) Du, H.;
Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007, 129, 11688.
(d) Zhao, B.; Du, H.; Cui, S.; Shi, Y. J. Am. Chem. Soc. 2010, 132, 3523.
(e) Zhao, B.; Peng, X.; Cui, S.; Shi, Y. J. Am. Chem. Soc. 2010, 132,
11009.
(5) (a) Du, H.; Yuan, W.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2007,
129, 7496. (b) Du, H.; Zhao, B.; Shi, Y. J. Am. Chem. Soc. 2008, 130,
8590. (c) Wang, B.; Du, H.; Shi, Y. Angew. Chem., Int. Ed. 2008, 47, 8224.
(6) Zhao, B.; Du, H.; Shi, Y. J. Am. Chem. Soc. 2008, 130, 7220.
(9) For recent examples of synthetic transformations with oxazi-
dines, see: (a) Brodsky, B. H.; Du Bois, J. J. Am. Chem. Soc. 2005,
127, 15391. (b) Armstrong, A.; Jones, L. H.; Knight, J. D.; Kelsey, R. D.
Org. Lett. 2005, 7, 713. (c) Armstrong, A.; Challinor, L.; Moir, J. H.
Angew. Chem., Int. Ed. 2007, 46, 5369. (d) Michaelis, D. J.; Shaffer, C. J.;
Yoon, T. P. J. Am. Chem. Soc. 2007, 129, 1866. (e) Allen, C. P.;
Benkovics, T.; Turek, A. K.; Yoon, T. R. J. Am. Chem. Soc. 2009,
131, 12560. (f) Partridge, K. M.; Guzei, I. A.; Yoon, T. P. Angew. Chem.,
Int. Ed. 2010, 49, 930. (g) Benkovics, T.; Guzei, I. A.; Yoon, T. P. Angew.
Chem., Int. Ed. 2010, 49, 9153.
r
10.1021/ol2021252
Published on Web 08/29/2011
2011 American Chemical Society

tert-butyldiaziridinone or N,N-di-tert-butylthiadiaziridine
1,1-dioxide as nitrogen source. During our ongoing studies
on the reactivity of diaziridine and its analogues, we have
found that aromatics such as 2-phenylpyridines and re-
lated compounds can be ethoxycarbonylated with certain
oxaziridines via a process involving CÀC bond cleavage in
the presence of Pd catalyst (Scheme 1).7À10 The aromatic
CÀH alkoxycarbonylation11À16 process described herein
introduces a novel reactivity of oxaziridines.
2-phenylpyridine (1a), but aziridine 2g was ineffective for
the reaction (Table 1, entries 13À18).
Table 1. Reactivity Studies with Various Three-membered
Heterocyclic Compoundsa
Scheme 1
Reactivity studies of three-membered heterocyclic com-
pounds were carried out with 2-phenylpyridine (1a) as test
substrate and with various Pd-sources as catalysts. As
shown in Table 1 (entries 1À4), no reaction occurred when
2-phenylpyridine (1a) was treated with di-tert-butyldiazir-
idinone (2a) or N,N-di-tert-butylthiadiaziridine 1,1-diox-
ide (2b) in the presence of 10 mol % PdCl2 or 5 mol %
Pd2(dba)3 in CHCl3 at 100 °C for 24 h. However, a small
amount of methoxycarbonylation product 3aa was iso-
lated when diaziridine 2c was used with 10 mol % PdCl2
(Table 1, entry 5). Interestingly, ethoxycarbonylation
product 3a was formed in 94% conversion along with
amide 4a when oxaziridine 2d was used (Table 1, entry 7).
Good conversions were also obtained with other Pd
catalysts (Table 1, entries 8À12). Oxaziridines 2e and 2f
were also found to be capable of ethoxycarbonylating
(10) For recent reviews on CÀC activations, see: (a) Crabtree, R. H.
Chem. Rev. 1985, 85, 245. (b) Horino, Y. Angew. Chem., Int. Ed. 2007,
46, 2144. (c) Jun, C.-H.; Park, J.-W. Top. Organomet. Chem. 2007, 24,
117. (d) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008, 41,
222. (e) Najera, C.; Sansano, J. M. Angew. Chem., Int. Ed. 2009, 48, 2452.
(f) Winter, C.; Krause, N. Angew. Chem., Int. Ed. 2009, 48, 2460. (g)
Murakami, M.; Matsuda, T. Chem. Commun. 2011, 47, 1100.
a All reactions were carried out with 2-phenylpyridine (1a) (0.2mmol), 2
(0.4 mmol), Pd catalyst (0.02 mmol) in CHCl3 (0.5 mL) at 100 °C for 24
h. b The conversion was based on 2-phenylpyridine (1a) and determined
by analysis of the 1H NMR spectrum of the crude reaction mixture.
ꢀ
(11) For Pd(II)-catalyzed alkoxycarbonylation with CO/ROH and
oxidant [benzoquinone or Cu(OAc)2], see: (a) Horino, H.; Inoue, N. J.
Org. Chem. 1981, 46, 4416. (b) Houlden, C. E.; Hutchby, M.; Bailey,
ꢀ
C. D.; Ford, J. G.; Tyler, S. N. G.; Gagne, M. R.; Lloyd-Jones, G. C.;
The PdCl2-catalyzed ethoxycarbonylation with oxazir-
idine 2d can be extended to a variety of substituted
2-phenylpyridines. As shown in Table 2, various sub-
stituents including electron-donating and electron-
withdrawing groups are tolerable under the reaction
conditions. Somewhat lower yields obtained for entries
2, 10, and 11 could be attributed to the steric effect of the
o-methyl substituent. Pyrimidine and benzo[h]quinoline
Booker-Milburn, K. I. Angew. Chem., Int. Ed. 2009, 48, 1830. (c) Li, H.;
Cai, G.-X.; Shi, Z.-J. Dalton Trans. 2010, 39, 10442.
(12) For Pd(II)-catalyzed carboxylation with CO and oxidant
(K2S2O8, O2, or Ag2CO3), see: (a) Lu, W.; Yamaoka, Y.; Taniguchi,
Y.; Kitamura, T.; Takaki, K.; Fujiwara, Y. J. Organomet. Chem. 1999,
580, 290. (b) Ohashi, S.; Sakaguchi, S.; Ishii, Y. Chem. Commun. 2005,
486. (c) Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 14082.
(13) For Pd(II)-catalyzed C-H alkoxycarbonylation with diethyl-
azodicarboxylate (DEAD) and oxidant (oxone or K2S2O8), see: Yu,
W.-Y.; Sit, W. N.; Lai, K.-M.; Zhou, Z.; Chan, A. S. C. J. Am. Chem.
Soc. 2008, 130, 3304.
(14) For Pd(II)-catalyzed aromatic CÀH carbonylation with CO and
oxidant [Cu(OAc)2] to form benzolactams, see: Orito, K.; Horibata, A.;
Nakamura, T.; Ushito, H.; Nagasaki, H.; Yuguchi, M.; Yamashita, S.;
Tokuda, M. J. Am. Chem. Soc. 2004, 126, 14342.
(17) For recent examples of CÀH functionalization of aryl ureas, see:
ꢀ
(a) Houlden, C. E.; Bailey, C. D.; Ford, J. G.; Gagne, M. R.; Lloyd-Jones,
(15) For Ru(II)-catalyzed CÀH alkoxycarbonylation with ClCO2R,
see: Kochi, T.; Urano, S.; Seki, H.; Mizushima, E.; Sato, M.; Kakiuchi,
F. J. Am. Chem. Soc. 2009, 131, 2792.
(16) For Rh(I)-catalyzed CÀH alkoxycarbonylation with CO/ROH,
and oxone, see: Guan, Z.-H.; Ren, Z.-H.; Spinella, S. M.; Yu, S.; Liang,
Y.-M.; Zhang, X. J. Am. Chem. Soc. 2009, 131, 729.
G. C.; Booker-Milburn, K. I. J. Am. Chem. Soc. 2008, 130, 10066. (b) Rauf,
W.; Thompson, A. L.; Brown, J. M. Chem. Commun. 2009, 3874. (c)
Nishikata, T.; Abela, A. R.; Lipshutz, B. H. Angew. Chem., Int. Ed. 2010,
49, 781. (d) Nishikata, T.; Abela, A. R.; Huang, S.; Lipshutz, B. H. J. Am.
Chem. Soc. 2010, 132, 4978. (e) Wei, Y.; Ding, H.; Lin, S.; Liang, F. Org.
Lett. 2011, 13, 1674.
Org. Lett., Vol. 13, No. 19, 2011
5245

were also found to be effective substrates (Table 2, entries
13 and 14).
Table 3. Pd(CH3CN)4(BF4)2-catalyzed CÀH Ethoxycarbony-
lation of Aryl Urea Derivatives with 2da
Table 2. PdCl2-catalyzed CÀH Ethoxycarbonylation of Aryl
Pyridine Derivatives with 2da
a All reactions were carried out with substrate 5 (0.2 mmol), 2d
(0.6 mmol), Pd(CH3CN)4(BF4)2 (0.03 mmol) in toluene (0.8 mL) at 100
°C for 20 h. b Isolated yield based on substrate 5.
When 2-phenylpyridine (1a) was treated with PdCl2 in
CHCl3 at 100 °C for 24 h, a yellow solid likely to be
palladacycle 7 was obtained in 85% yield (Scheme 2).18,19
Scheme 2
a All reactions were carried out with substrate 1 (0.2 mmol), 2d
(0.4 mmol), PdCl2 (0.02 mmol) in CHCl3 (0.5 mL) at 100 °C for 24 h.
b Isolated yield based on substrate 1.
Besides aryl pyridines, the ethoxycarbonylation can also
be applied to aryl ureas 5 using Pd(CH3CN)4(BF4)2 as
catalyst.17 As shown in Table 3, various substituted aryl
ureas were ethoxycarbonylated at the positions ortho to
the ureas to give anthranilates 6, and essentially only one
isomer was isolated.
Compound 7 was insoluble in CHCl3, and no product
was obtained when it was treated with oxaziridine 2d at
(19) For leading references on the formation of dimeric palladacycles
from 2-phenylpyridine and M2PdCl4 or Pd(OAc)2, see: (a) Craig, C. A.;
Watts, R. J. Inorg. Chem. 1989, 28, 309. (b) Constable, E. C.; Thompson,
A. M. W. C.; Leese, T. A.; Reese, D. G. F.; Tocher, D. A. Inorg. Chim.
Acta 1991, 182, 93. (c) Racowski, J. M.; Dick, A. R.; Sanford, M. S. J.
Am. Chem. Soc. 2009, 131, 10974.
(18) For leading reviews on palladacycles, see: (a) Ryabov, A. D.
Synthesis 1985, 233. (b) Dupont, J.; Consorti, C. S.; Spencer, J. Chem.
Rev. 2005, 105, 2527.
5246
Org. Lett., Vol. 13, No. 19, 2011

100 °C for 24 h (Scheme 2). However, compound 7
dissolved immediately in CHCl3 when 2.0 equiv of
pyridine was added. When the resulting solution was
treated with oxaziridine 2d at 100 °C for 24 h, ethox-
ycarbonylation product 3a was isolated in 42% yield
(Scheme 2). It is likely that the pyridine first converts
dimeric 7 into a monomeric Pd species, which then reacts
with oxaziridine 2d to form the ethoxycabonylation pro-
duct. Palladacycle 7 was also shown to be catalytically
active. Compound 3a was isolated in 68% yield when
2-phenylpyridine (1a) was treated with oxaziridine 2d in
the presence of 5 mol % 7 (Scheme 3). In this case, in
addition to being a substrate, 2-phenylpyridine (1a) could
also act as a ligand to break the dimeric structure of 7 like
pyridine did in the earlier case.20
Scheme 4. Proposed Catalytic Cycle for the Ethoxycarbonylation
Scheme 3
In summary, a novel Pd(II)-catalyzed aromatic CÀH
ethoxycarbonylation with oxaziridine has been ob-
served. Various 2-phenylpyridines and related com-
pounds as well as aryl ureas can be effectively
ethoxycarbonylated. The reaction process likely pro-
ceeds via a Pd(II)/Pd(IV) catalytic cycle and involves a
CÀC bond cleavage of oxaziridines.2d Oxaziridines act
as a CO2Et group donor as well as an oxidant, which
illustrates a new type of reactivity for this class of three-
membered heterocyclic compounds. Further mechan-
istic studies and development of other reaction pro-
cesses with oxaziridines and related compounds are
currently underway.
On the basis of the above results, a tentative catalytic
pathway involving Pd(II) and Pd(IV) is shown in Scheme
4. PdCl2 reacts with 2-phenylpyridine to generate Pd(II)
intermediate A via CÀH activation.7,21,22 The Pd(II) then
inserts into the NÀO bond of oxaziridine 2d to form
Pd(IV) species B, which rearranges to Pd(IV) species C
by a shift of CO2Et from the carbon to the Pd via a CÀC
bond cleavage process. The reductive elimination of com-
pound C forms ethoxycarbonylation product 3a and Pd-
(II) species D. Pd(II) species A is then regenerated from D
along with the formation of amide 4a. At this moment,
other alternative pathways cannot be excluded. Better
understanding of the reaction mechanism awaits further
study.
Acknowledgment. We are grateful to the financial sup-
port from the ACS Arthur C. Cope Fund.
(20) (a) Constable, A. G.; McDonald, W. S.; Sawkins, L. C.; Shaw,
B. L. J. Chem. Soc., Chem. Commun. 1978, 1061. (b) Deprez, N. R.;
Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 11234.
(21) (a) Hull, K. L.; Lanni, E. L.; Sanford, M. S. J. Am. Chem. Soc.
2006, 128, 14047. (b) Whitfield, S. R.; Sanford, M. S. J. Am. Chem. Soc.
2007, 129, 15142.
Supporting Information Available. Experimental pro-
cedures and characterization data along with 1H NMR
and 13C NMR spectra of 2cÀg, 3, 4 and 6. This material
is available free of charge via the Internet at http://
pubs.acs.org.
(22) Addition of bases such as pyridine, NEt3 or Na2CO3 lowered the
reaction yield.
Org. Lett., Vol. 13, No. 19, 2011
5247