Palladium-catalyzed 1,1-aryloxygenation of terminal olefins

Article abstract of DOI:10.1021/ol103121r

This paper describes the 1,1-arylacetoxylation of diverse α-olefins using organostannanes and hypervalent iodine oxidants. The reaction provides a convergent approach for generating a C-C and a C-O bond as well as a new stereocenter in a single catalytic transformation.(Figure Presented)

Full text of DOI:10.1021/ol103121r

ORGANIC
LETTERS
2011
Vol. 13, No. 5
1076–1079
Palladium-Catalyzed 1,1-Aryloxygenation
of Terminal Olefins
Andrew D. Satterfield, Asako Kubota, and Melanie S. Sanford*
University of Michigan, Department of Chemistry, 930 North University Avenue,
Ann Arbor, Michigan 48109-1055, United States
mssanfor@umich.edu
Received December 23, 2010
ABSTRACT
This paper describes the 1,1-arylacetoxylation of diverse R-olefins using organostannanes and hypervalent iodine oxidants. The reaction
provides a convergent approach for generating a C-C and a C-O bond as well as a new stereocenter in a single catalytic transformation.
The coupling of olefins with aryl-metal species in the
presence of a terminal oxidant (the oxidative Heck
reaction) is an important method for the formation of
Scheme 1. Oxidatively Intecepting Heck Intermediates
substituted alkenes.1 This reaction proceeds via a pathway
involving transmetalation, olefin insertion (to generate
intermediate C, Scheme 1), β-hydride elimination/olefin
dissociation (to release G), and finally oxidation of Pd0 to
regenerate the PdII catalyst.1 Work from our group2 and
others3-6 has shown that oxidative Heck intermediate C
(or the related species D) can be intercepted to form 1,2-
and 1,1-difunctionalized products such as F and H, respec-
tively. These arylfunctionalization reactions combine the
(1) (a) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100,
3009. (b) The Mizoroki-Heck Reaction; Oestreich, M., Ed.; John Wiley &
C-C bond-forming step of the oxidative Heck reaction
with the generation of an additional bond and a new
stereocenter. As such, they provide an attractive means
for the convergent coupling of three components (A, B,
and E) in a single transformation.7
We have recently utilized this approach for the Pd-
catalyzed 1,2- and 1,1-arylhalogenation of unactivated
olefins using arylstannanes in conjunction with halide-
based oxidants.2 We sought to expand this methodology
Sons Ltd: Chichester, UK, 2009. (c) Gligorich, K. M.; Sigman, M. S.
Chem. Commun. 2009, 3854. (d) Karimi, B.; Behzadnia, H.; Elhamifar,
D.; Akhavan, P. F.; Esfahani, F. K.; Zamani, A. Synthesis 2010, 1399.
(2) (a) Kalyani, D.; Sanford, M. S. J. Am. Chem. Soc. 2008, 130, 2150.
(b) Kalyani, D.; Satterfield, A. D.; Sanford, M. S. J. Am. Chem. Soc.
2010, 132, 8419.
(3) (a) Tamaru, Y.; Hojo, M.; Higashimura, H.; Yoshida, Z. Angew.
Chem., Int. Ed. 1986, 25, 735. (b) Tamaru, Y.; Hojo, M.; Kawamura, S.;
Yoshida, Z. J. Org. Chem. 1986, 51, 4089.
(4) Parrish, J. P.; Jung, Y. C.; Shin, S. I.; Jung, K. W. J. Org. Chem.
2002, 67, 7127.
(5) (a) Urkalan, K. B.; Sigman, M. S. Angew. Chem., Int. Ed. 2009, 48,
3146. (b) Werner, E. W.; Urkalan, K. B.; Sigman, M. S. Org. Lett. 2010,
12, 2848.
(7) For recent reviews on other approaches to the Pd-catalyzed 1,2-
difunctionalization of olefins, see: (a) Minatti, A.; Muniz, K. Chem. Soc.
Rev. 2007, 36, 1142. (b) Wolfe, J. P. Synlett 2008, 2913.
(6) Rodriguez, A.; Moran, W. J. Eur. J. Org. Chem. 2009, 1313.
r
10.1021/ol103121r
Published on Web 02/03/2011
2011 American Chemical Society

to analogous aryloxygenations of diverse alkene substrates.8
We report herein the development and scope of a Pd-
catalyzed reaction for the 1,1-aryloxygenation of olefins
using organostannane transmetallating reagents and hyper-
valent iodine oxidants.
Table 1. Optimization of 1,1-Arylacetoxylation Reaction
Iodobenzene diacetate [PhI(OAc)2] has been widely
used to oxidatively functionalize PdII alkyl intermediates
formed in catalytic sp3 C-H activation,9 olefin nucleo-
palladation10,11 and Pd-catalyzed cascade reactions.12 We
reasoned that this reagent could promote a similar trans-
formation in the context ofoxidative Heckintermediates C
and/or D (Scheme 1). Thus, the reaction of 2-(hex-3-en-1-
yl)isoindoline 1,3-dione (1) with PhSnBu3 was examined in
the presence of 2 equiv of PhI(OAc)2. Gratifyingly, the PdII
catalyst PdCl2(PhCN)2 provided 1,1-phenylacetoxylated
product 2 in 50% yield in diethyl ether at rt (Table 1, entry
1). None of the corresponding 1,2-arylacetoxylated isomer
was detected; however, a significant quantity (21% yield)
of the Heck product 3 was formed under these conditions.
Several strategies were examined to limit formation of 3.
First, we used LiBr as an additive, since this salt has been
shown to suppress β-hydride elimination/alkene dissocia-
tion pathways in other Pd-catalyzed transformations.13
Gratifyingly, the addition of 1 equiv of LiBr to the room
temperature reaction in Et2O increased the yield of 2 (to
59%), while decreasing that of 3 (to 16%) (Table 1, entry
3). A similar improvement was also observed in toluene
(entries 2 and 4).
entry
solvent
temp (°C)
rt
additivea
yield 2b
yield 3b
1
2
3
4
5
6
7
8
Et2O
none
none
LiBr
LiBr
none
LiBr
none
LiBr
50%
22%
59%
35%
51%
25%
66%
62%
21%
34%
16%
29%
13%
7%
PhMec
Et2O
rt
rt
PhMec
Et2O
rt
-78 °C to rt
-78 °C to rt
-78 °C to rt
-78 °C to rt
Et2O
PhMec
PhMec
19%
12%
a One equivalent of additive. b Yield of products determined by H
NMR spectroscopic analysis of crude reaction mixture. In most reac-
tions, the mass balance was 5-20% of the 1,1-arylchlorinated product.
The chloride is presumably derived from the Pd catalyst. When LiBr was
present, 5-17% of the 1,1-arylbrominated product was observed. See
Supporting Information for complete optimization table. c Degassed
toluene was used.
1
did not improve, due to the generation of significant
quantities of the corresponding arylbrominated product.14
With these optimized conditions in hand (Table 1, entry 7),
we next explored the scope of this reaction. A number of
electronically different arylstannanes were effective arylat-
ing reagents (Table 2). For example, ArSnBu3 derivatives
containing both electron-donating (entries 3, 4) and elec-
tron withdrawing (entries 6-8) para-substituents provided
reasonable to good yields. In comparison, ortho-substituted
arylstannanes showed modest reactivity. For example, p-
MeOC6H4SnBu3 afforded 75% yield of 1,1-arylacetoxyla-
tion (entry 4), while the analogous o-MeO-substituted
stannane provided 35% yield of the corresponding product
(entry 5).
Iodine(III) reagents of general structure PhI(O2CR0)2
could be used to introduce diverse carboxylates. These
oxidants are readily prepared by reacting commercially
available PhI(OAc)2 with 2 equiv of R0CO2H in chloro-
benzene.15 As shown in Table 2, acetate, trifluoroacetate,
pivalate, and benzoate-containing products could be ac-
cessed in moderate to good yields (entries 4, 9, 10, and 11).
Furthermore, substituted benzoate derivatives (containing
both electron withdrawing and electron donating para-
substituents) afforded comparable results (entries 12 and 13).
This 1,1-arylacetoxylation reaction was also effective
across a wide range of terminal olefin substrates. For
example, alkenes containing remote protected alcohol
derivatives (Table 3, entries 1-3, 6-7) as well as alkyl
bromides (entry 4) and aryl iodides (entry 5) were effective
Lowering the temperature of the toluene reaction also
decreased formation of Heck product 3. For example,
when the reaction mixture was stirred for 4 h at -78 °C
and then slowly warmed to rt, product 2 was formed in
66% yield along with only 19% of 3 (entry 7). The
combination of LiBr and low temperature further mini-
mized the formation of 3 (entry 8); however, the yield of 2
(8) A related strategy for the aryloxygenation of R,β-unsaturated
olefins is reported in ref 6.
(9) (a) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc.
2004, 126, 2300. (b) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am.
Chem. Soc. 2004, 126, 9542. (c) Lyons, T. W.; Sanford, M. S. Chem. Rev.
2010, 110, 1147. (d) Neufeldt, S. R.; Sanford, M. S. Org. Lett. 2010, 12,
532. (e) Zhang, S.; Luo, F.; Wang, W.; Jia, X.; Hu, M.; Cheng, J.
Tetrahedron Lett. 2010, 51, 3317.
(10) (a) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am. Chem. Soc.
2005, 127, 7690. (b) Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128,
7179. (c) Desai, L. V.; Sanford, M. S. Angew. Chem., Int. Ed. 2007, 46,
5737. (d) Li, Y.; Song, D.; Dong, V. M. J. Am. Chem. Soc. 2008, 130,
2962. (e) Wang, W.; Wang, F.; Shi, M. Organometallics 2010, 29, 928.
(11) (a) Streuff, J; Hovelmann, C. H.; Nieger, M.; Muniz, K. J. Am.
Chem. Soc. 2005, 127, 14586. (b) Muniz, K. J. Am. Chem. Soc. 2007, 129,
14542. (c) Muniz, K.; Hovelmann, C. H.; Streuff, J. J. Am. Chem. Soc.
2008, 130, 763. (d) Muniz, K.; Hovelmann, C. H.; Streuff, J.; Campos-
Gomez, E. Pure Appl. Chem. 2008, 80, 1089. (e) Iglesias, A.; Perez, E. G.;
Muniz, K. Angew. Chem., Int. Ed. 2010, 49, 8109.
(12) (a) Tong, X.; Beller, M.; Tse, M. K. J. Am. Chem. Soc. 2007, 129,
4906. (b) Welbes, L. L.; Lyons, T. W.; Cychosz, K. A.; Sanford, M. S.
J. Am. Soc. 2007, 129, 5836. (c) Liu, H.; Yu, J.; Wang, L.; Tong, X.
Tetrahedron Lett. 2008, 49, 6924. (d) Lyons, T. W.; Sanford, M. S.
Tetrahedron 2009, 65, 3211. (e) Tsujihara, T.; Takenaka, K.; Onitsuka,
K.; Hatanaka, M.; Sasai, H. J. Am. Chem. Soc. 2009, 131, 3452. (f)
Jaegli, S.; Dufour, J.; Wei, H. I.; Piou, T.; Duan, X. H.; Vors, J. P.;
Neuville, L.; Zhu, J. Org. Lett. 2010, 12, 4498. (g) Fujino, D.; Yorimitsu,
H.; Oshima, K. Chem. Asian J. 2010, 5, 1758.
(13) Lu, X. Top. Catal. 2005, 35, 73.
(14) The use of degassed toluene also enhanced the yield of 2. For
example, when the reaction in Table 1, entry 7 was run in nondegassed
toluene, 2 was formed in 42% yield along with 29% of 3.
(15) Stang, P. J.; Boehshar, M.; Wingert, H.; Kitamura, T. J. Am.
Chem. Soc. 1988, 110, 3272.
Org. Lett., Vol. 13, No. 5, 2011
1077

Table 2. Scope of Organostannanes and Iodoarene Dicarbox-
ylates
Table 3. Substrate Scope for 1,1-Arylacetoxylation
entry
aryl
C6H5
R0
isolated (crude) yielda
1
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CF3
t-Bu
66% (66%)b
52% (62%)
59% (68%)
75% (78%)
35% (51%)
56% (63%)
50% (57%)
49% (56%)
41% (49%)c
48% (55%)
60% (72%)
53% (52%)
68% (73%)
2
2-napthyl
3
p-MeC6H4
p-MeOC6H4
o-MeOC6H4
p-ClC6H4
4
5
6
7
p-BrC6H4
8
p-FC6H4
9
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
10
11
12
13
C6H5
p-MeOC6H4
p-FC6H4
a Crude yields of products determined by 1H NMR spectroscopic
analysis of crude reaction mixture. In most reactions, the mass balance
was the Heck product 3 (5-20%) and the 1,1-arylchlorinated product
(5-15%). b Reaction conducted on 0.22 mmol scale. The isolated yield was
68% at 1 mmol scale. c The trifluoroacetate product was observed by
1H NMR analysis of the crude reaction mixture; however, it hydrolyzed
upon chromatographic purification and was isolated as the free alcohol.
a Crude yields of products determined by 1H NMR spectroscopic
analysis of crude reaction mixture. In most reactions, 5-15% of the
corresponding Heck product formation was observed along with <5%
of the 1,1-arylchlorinated product.
substrates in these transformations. Allylic ethers and
acetates (entries 8-9) also afforded 1,1-arylacetoxylated
products in good yield. Interestingly, products derived
from β-acetoxy elimination (which is typically fast at PdII
in the absence of AgI additives)16-18 were not detected in
these latter systems.
formed because intermediate C is a Pd-benzyl complex,
which are known to be highly reactive toward oxidative
functionalization.2,19
All of the substrates in Table 3 reacted with >20:1
selectivity for the 1,1-regioisomer. These results suggest
that the oxidative functionalization of intermediate C
(Scheme 1) with PhI(OAc)2 is significantly slower than β-
hydride elimination/equilibration to form PdII-benzyl
complex D.2 We reasoned that analogous 1,2-arylacetoxy-
lated products might be accessible if the initially formed
PdII alkyl complex C was more reactive toward oxidative
functionalization. Indeed, when p-methoxystyrene was
utilized as the alkene substrate with p-FC6H4SnBu3, the
1,2-arylacetoxylation product 13 was obtained with >20:1
selectivity (Scheme 2). In this case, the 1,2-product is
Scheme 2. 1,2-Arylacetoxylation with p-Methoxystyrene
Vinyl ether substrates were also examined in this con-
text. In these systems, the initially formed R-alkoxy- alkyl
Pd intermediate C-a (Scheme 3) is expected to be highly
electron rich. As such, we anticipated that the relative rate
of oxidative functionalization with PhI(OAc)2 (to form the
(16) Zhu, G.; Lu, X. Organometallics 1995, 14, 4899.
(17) Pan, D.; Jiao, N. Synlett 2010, 1577.
(18) For examples of selective β-H elimination in Heck-typereactions
using allyl acetate substrates see: (a) Pan, D.; Chen, A.; Su, Y.; Zhou, W.;
Li, S.; Jia, W.; Xiao, J.; Liu, Q.; Zhang, L.; Jiao, N. Angew. Chem., Int.
Ed. 2008, 47, 4729. (b) Su, Y.; Jiao, N. Org. Lett. 2009, 11, 2980. (c) Pan,
D.; Yu, M.; Chen, W.; Jiao, N. Chem. Asian J. 2010, 5, 1090. For
examples of selective β-OAc elimination in Heck-type reactions using
allyl acetate substrates see:(d) Mariampillai, B.; Herse, C.; Lautens, M.
Org. Lett. 2005, 7, 4745. (e) Ohmiya, H.; Makida, Y.; Tanaka, T.;
Sawamura, M. J. Am. Chem. Soc. 2008, 130, 17276.
(19) (a) Becker, Y.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 845.
(b) Johns, A. M.; Utsunomiya, M.; Incarvito, C. D.; Hartwig, J. F.
J. Am. Chem. Soc. 2006, 128, 1828. (c) Johns, A. M.; Tye, J. W.; Hartwig,
J. F. J. Am. Chem. Soc. 2006, 128, 16010.
1078
Org. Lett., Vol. 13, No. 5, 2011

byproducts) is a clear limitation. A highly attractive alter-
native would be to use a simple C-H substrate like benzene
as the arene precursor. In this case, intermediate C could be
formed via C-H activation of Ph-H followed by olefin
insertion (the first two steps of the Fujiwara-Moritani
reaction for benzene olefination).1b,6,18c Gratifyingly, a
preliminary screen of conditions showed that Pd(acac)2 is
an effective catalyst for the coupling of allyl acetate with
benzene and PhI(OAc)2. The reaction proceeds efficiently
at60 °C in benzene in the presence of 0.1 equiv of AgOAc to
afford the 1,1-phenylacetoxylation product 18 in 51% yield
(Scheme 5). Further studies of the scope and limitations of
this transformation are underway.
Scheme 3. 1,2-Arylacetoxylation with Vinyl Ether Substratesa
a Yields determined by 1H NMR spectroscopic analysis of crude
reaction mixtures; isolated yields were significantly lower due to decom-
position of the mixed acetal products on silica gel.
Scheme 5. 1,1-Phenylacetoxylation via Benzene C-H
Activation
1,2-product) might be faster than that of β-hydride elim-
ination. Gratifyingly, the use of ethyl, cyclohexyl and
t-butyl vinyl ether under our standard reaction conditions
afforded excellent yields of the 1,2-arylacetoxylated pro-
ducts 14-16, respectively.20 Interestingly, 2,3-dihydrofur-
an afforded a somewhat different result, providing the
arylacetoxylated product 17 in 68% yield as a 1.3: 1
mixture of the cis and trans isomers (Scheme 4). This
latter reaction is believed to proceed via initial carbopalla-
dation to place the aryl group R to oxygen. A series
of β-H elimination/Pd-H reinsertion reactions then
generates an alkyl Pd complex at the 5-position, which
undergoes rapid oxidative cleavage with PhI(OAc)2 to
afford 17.
In summary, this paper describes the 1,1-arylacetoxyla-
tion of diverse R-olefins using organostannanes and hyper-
valent iodine oxidants. The reaction provides a convergent
approach for merging these three components, and it
generates a C-C and a C-O bond as well as a new
stereocenter in a single catalytic transformation. Prelimi-
nary results also indicate that the aryl tin reagents can be
replaced by simple arene derivatives. Ongoing work is
focused on fully exploring the scope of alternative arylat-
ing reagents and oxidants that can be utilized for this and
related alkene functionalization reactions.
Scheme 4. Arylacetoxylation of 2,3-Dihydrofuran
Acknowledgment. We thank Dr. Dipannita Kalyani
for preliminary studies of this transformation. This work
was supported by NIH NIGMS (R01-GM073836).
Supporting Information Available. Experimental de-
tails and spectroscopic and analytical data for new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
See Supporting Information for full details.
(20) For an alternative approach to the 1,2-aryloxygenation of
olefins, see: (a) Heinrich, M. R.; Wetzel, A.; Kirschstein, M. Org. Lett.
2007, 9, 3833. (b) Lazzaroni, S.; Protti, S.; Fagnoni, M.; Albini, A. Org.
Lett. 2009, 11, 349.
The current reaction provides a straightforward route to
products such as 3-17. However, the requirement for toxic
tin reagents (and the generation of toxic Sn-containing
Org. Lett., Vol. 13, No. 5, 2011
1079