Copper-catalyzed regioselective 1,2-alkylesterification of dienes to allylic esters

Article abstract of DOI:10.1021/acs.orglett.5b03399

Copper catalyzed 1,2-alkylesterification of 1,3-dienes with diacyl peroxides affords branched allylic esters in excellent regioselectivity, including products with a newly generated fully substituted carbon center. The only byproduct is CO₂. The reaction proceeds by a radical mechanism as suggested by spin trap and crossover experiments.

Full text of DOI:10.1021/acs.orglett.5b03399

Letter
pubs.acs.org/OrgLett
Copper-Catalyzed Regioselective 1,2-Alkylesterification of Dienes to
Allylic Esters
Yougui Li,† Yulong Han,†,‡ Haigen Xiong,‡ Nengbo Zhu,‡ Bo Qian,‡ Changqing Ye,‡
Eric Assen B. Kantchev,† and Hongli Bao*,‡
†School of Chemistry and Chemical Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, 230009, China
‡Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter,
Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, 350002, P. R. China
S
* Supporting Information
ABSTRACT: Copper catalyzed 1,2-alkylesterification of 1,3-
dienes with diacyl peroxides affords branched allylic esters in
excellent regioselectivity, including products with a newly
generated fully substituted carbon center. The only byproduct is
CO2. The reaction proceeds by a radical mechanism as suggested
by spin trap and crossover experiments.
functionalization of 1,3-butadiene with different functional
groups have been developed.5−11
ranched allylic esters are useful synthetic intermediates
Band can be generated by some elegant methods, including
metal-catalyzed allyllic substitution,1 oxidative C−H esterifica-
tion,2 and copper-catalyzed Kharasch−Sosnovsky reactions.3
Most existing methods use an olefin to generate allylic radicals
or allyl-metal complexes as key intermediates. Despite the many
merits of this strategy, the main drawback is that the structure
of the product is limited by the structure of the olefin
substrates. More often, the generation of a specific olefin
substrate is more difficult than the allylic oxidation step.
Retrosynthetically, the synthesis of allylic esters from olefin
substrates represents a one-group disconnection, in which the
substrate and product have similar molecular complexity.4 A
more efficient strategy would involve a two-group disconnec-
tion in which the desired allylic esters are assembled from
readily available substrates with low molecular complexity that
can incorporate multiple functional groups in a single chemical
step (Scheme 1).4
Although the catalyzed alkylesterification (oxyalkylation) of
styrenes has been done by Wang’s group,12 the efficient
catalyzed alkylesterification of dienes is not known. We
envisioned that 1,3-butadiene would react with a radical to
generate a new allylic radical species, which then could couple
with other reagents in the presence of metal catalysts. In many
cases, such allylic radical species are difficult to obtain from
olefins. It is well-known that, upon heating or in the presence of
metal ions, alkyl diacyl peroxides decompose to acyloxy
radicals, alkyl radicals, and CO2.13 The rate of addition of
alkyl radicals into butadiene to generate allyl radicals is fast.5
We envisioned that, with a suitable catalyst, the newly
generated allyl radical can couple with the acyloxy radicals
already present in the reaction mixture. Herein, we describe a
general method for the synthesis of branched allylic esters,
including such containing a newly generated fully substituted
carbon, by a copper-catalyzed, regioselective 1,2-alkylesterifica-
tion of 1,3-dienes with diacyl peroxides. It is noteworthy that
this reaction is an environmentally benign process and the only
byproduct of this reaction is CO2. Moreover, no other
chemicals than solvent and catalyst are needed in this reaction.
Gratifyingly, when the reaction between 1,3-butadiene (1) and
lauroyl peroxide (2a, LPO) was attempted by bubbling 1 into a
solution of LPO and CuCl (10 mol %) as the catalyst in
CH3CN/H2O/HOAc, 15% of the desired product 3a was
obtained (Table 1, entry 1). Additionally, 20% of 1-undecene
and n-docosane (C22H46; most likely arising from alkyl radical
homodimerization) were isolated.13 An examination of a
number of copper catalysts (entries 3−7, 10) revealed that
CuTc (Tc = thiophene-2-carboxylate) was the most effective.
Under optimized conditions, 3a was obtained in 66% yield of
We hypothesized that 1,3-butadiene would be the ideal
starting material for the development of a more efficient two-
group disconnection to allylic esters (Scheme 1). This four-
carbon feedstock, which is a product of petroleum cracking, is
inexpensive and abundant. Efficient methods for double
Scheme 1. Strategies for Generation of Allylic Esters
Received: November 26, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b03399
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Reaction Conditions Optimization
Table 2. Scope of the Diacyl Peroxides
catalyst
temp
yield of 3a
b
entry
1
(mol %)
solvent
(°C)
(%)
CuCl (10)
CuCl (20)
CuCl (10)
CH3CN/H2O/
HOAc
90
15
2
CH3CN/H2O/
HOAc
90
34
3
1,4-dioxane
80
80
80
80
80
70
60
70
70
70
58
29
56
47
63
67
29
69
66
0
4
Cu(OAc)2 (10) 1,4-dioxane
5
CuBr (10)
CuI (10)
CuCl2 (10)
CuCl (10)
CuCl (10)
CuTc (10)
CuTc (5)
none
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
6
7
8
9
10
11
12
a
1,3-Butadiene was bubbled into a solution of 2a (1 mmol) in solvent
b
(2 mL). Yields of isolated products.
isolated product with CuTc (5 mol %) at 70 °C in dioxane.
Decomposition of LPO leading to lauric acid, 1-undecene, and
n-docosane was the main competing reaction. The above-
mentioned three compounds were observed by GCMS and 1H
NMR. Product 3a was not detected in the absence of Cu
catalyst (entry 12). Notably, the corresponding linear product
4a was not isolated in any of the reaction optimization runs.
Next, other diacyl peroxides were synthesized from
corresponding carboxylic acids (two steps) or acyl chlorides
(one step) in moderate to high yields. Then these diacyl
peroxides were evaluated as substrates (Table 2). Besides
unfunctionalized alkyl diacyl peroxides, ester or olefin-function-
alized analogues also reacted with 1,3-butadiene smoothly to
produce 1,2-difunctionalization products in good to moderate
yields. However, benzoyl peroxide failed to give the anticipated
product.
Substituted 1,3-dienes were also suitable as substrates (Table
3). 2,3-Dimethyl-1,3-butadiene (5a) reacted with LPO (2a),
2g, and 2j to afford 1,2-alkylesterification products (6, 7, 9)
having a newly generated fully substituted carbon in good to
moderate yield (77%, 65%, and 39%, entries 1, 2, 4). No 1,4-
alkylesterification product was observed. This time, benzoyl
peroxide gave the anticipated product in low yield when 2,3-
dimethyl-1,3-butadiene (5a) was applied (11%, entry 3).
Similarly, C-2 monosubstituted dienes (5b−d) and disubsti-
tuted diene 5e gave 1,2-alkylesterification products (10, 12, 13,
14) with LPO or bis(tert-butylacetyl) peroxide. In these cases
(entries 5−8), 1,2-alkylesterification products having a newly
generated fully substituted carbon center were the only (12, 13,
14) or the major (10) isomers. The latter was formed as a 5:1
mixture with the regioisomer (11) containing a secondary
carbon. A free hydroxyl group (diene 5f, entry 9) or TBS (tert-
butyldimethylsilyl) ether group (diene 5g, entry 10) were well
tolerated, and the 1,2-alkylesterification products (15, 16) were
obtained in 59% and 42% yield, respectively. To further
understand the reaction, 4-phenyl-1-butene and styrene were
examined with LPO under the best reaction conditions. Styrene
led to a complex mixture from which no product could be
isolated (entry 11) when 4-phenyl-1-butene showed no
reactivity at all (entry 12). These two experiments suggest
a
1,3-Butadiene was bubbled into a solution of 2 (2 mmol) in dioxane
b
(4 mL). Yields of isolated products.
that this is the copper catalyzed difunctionalization process of
dienes rather than the copper catalyzed difunctionalization of
olefins.14
To explore the reaction mechanism, several experiments
were conducted. First, when TEMPO was added into the
standard reaction, no alkylesterification product was observed
and only the radical coupling product 17 was isolated in 58%
yield (Scheme 2). Second, with NHPI (N-hydroxyphthali-
mide), the anticipated product 6 and an NHPI adduct 18 were
isolated in 18% and 30% yield, respectively. Compound 18
presumably arises from the formation of a nitroxyl radical from
NHPI under the reaction conditions.
To further understand the behavior of alkyl and acyloxy
radicals in the reaction, crossover experiments between two
different diacyl peroxides were performed (Scheme 3). When
equimolar amounts of efficient diacyl peroxides 2c and 2g
(Scheme 3a) were used, four products were obtained. This
result is consistent with the alkylation and esterification being
separate, intermolecular events. On the other hand, the
crossover reaction between an effective (2g) and a noneffective
(2i) diacyl peroxide with 2,3-dimethyl-1,3-butadiene (Scheme
3b) resulted in products 7 and 21 in a 7:10 ratio. Interestingly,
when the hybrid diacyl peroxide 2k was treated with 2,3-
dimethyl-1,3-butadiene, an additional 1,4-alkylesterification
product (22) was observed (Scheme 3c). The ratio of
7:21:22 was 6:10:6. We attribute this result to the different
decomposition rate of the diacyl peroxides and different
dicarboxylation rate of the acyloxy radicals.
B
DOI: 10.1021/acs.orglett.5b03399
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 3. Scope of Substituted 1,3-Dienes
Scheme 2. Radical Trapping Experiments
Scheme 3. Crossover Reactions between Two Symmetrical
(a,b) or One Unsymmetrical Diacyl Peroxides (c)
Scheme 4. Proposed Catalytic Cycle for Alkylesterification of
Butadiene
addition to substituted dienes implies that the alkyl radicals add
to the least sterically hindered position in order to generate the
allylic radical having the greatest degree of substitution, hence
the highest stability. This alkyl radical reacts with the
copper(II) acyl species forming a copper(III) species (V).
And after reductive elimination preferentially at the most
substituted carbon, the final products are formed, and the
copper(I) catalyst is regenerated (path a).14f−h,15 The
alternative possible pathway is depicted in path b, with a
copper(II) species (IV) transferring the acyl group to the allylic
radicals and regenerating the copper(I) catalyst. Further studies
to uncover the nature of active copper species are currently
underway.
a
Diene (1.0 equiv) and diacyl peroxide (1.75 equiv) in dioxane (2
b
mL/mmol). Yields of isolated products.
Considering the results of the mechanistic experiments, a
two-stage, radical mediated catalytic cycle is proposed (Scheme
4). Alkyl diacyl peroxides decompose under heating conditions
(with or without the involvement of the copper catalyst) to
afford alkyl radicals (II), CO2, and copper(II) acyl species (IV).
The alkyl radicals couple with 1,3-dienes to generate new allylic
radicals (III). The regioselectivity pattern observed during the
In summary, we have developed a new method that provides
an efficient access to branched allylic esters from 1,3-dienes
including products with a newly generated fully substituted
carbon, which are difficult to access by other methods. The
regioselectivity of the reaction is excellent, with only 1,2-
alkylesterification products isolated. The reaction conditions are
mild, and no extra reagent is needed in this reaction. A
C
DOI: 10.1021/acs.orglett.5b03399
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(5) Alkylesterification of dienes: Citterio, A.; Arnoldi, A.; Minisci, F.
J. Org. Chem. 1979, 44, 2674.
particular advantage of this reaction is using readily available
difunctionalization reagents (diacyl peroxides) to simultane-
ously generate two different types of radicals, acyloxy and alkyl,
after releasing one CO2 molecule. The idea that 1,3-dienes
combining diacyl peroxides could be a more versatile
replacement for olefins is under investigation in other types
of difunctionalizations.
(6) Alkylamination of dienes: (a) Stakem, F. G.; Heck, R. F. J. Org.
Chem. 1980, 45, 3584. (b) Xing, D.; Yang, D. Org. Lett. 2013, 15, 4370.
(7) For a recent example of alkylvinylation of butadiene, see:
(a) McCammant, M. S.; Liao, L.; Sigman, M. S. J. Am. Chem. Soc.
2013, 135, 4167. (b) Liao, L.; Jana, R.; Urkalan, K. B.; Sigman, M. S. J.
Am. Chem. Soc. 2011, 133, 5784.
(8) Aminoarylation of butadiene: Bao, H.; Bayeh, L.; Tambar, U. K.
Chem. Sci. 2014, 5, 4863.
(9) Hydroarylation of dienes: (a) Liao, L.; Sigman, M. S. J. Am. Chem.
Soc. 2010, 132, 10209. (b) Podhajsky, S. M.; Iwai, Y.; Cook-Sneathen,
A.; Sigman, M. S. Tetrahedron 2011, 67, 4435.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.5b03399.
■
S
(10) Hydrovinylation of dienes: (a) Hilt, G.; du Mesnil, F.-X.; Luers,
̈
S. Angew. Chem., Int. Ed. 2001, 40, 387. (b) Hilt, G.; Danz, M.;
̆
Treutwein, J. Org. Lett. 2009, 11, 3322. (c) Arndt, M.; Dindaroglu, M.;
Experimental details and NMR spectra (PDF)
Schmalz, H.-G.; Hilt, G. Org. Lett. 2011, 13, 6236. (d) Erver, F.;
Kuttner, J. R.; Hilt, G. J. Org. Chem. 2012, 77, 8375. (e) Page, J. P.;
RajanBabu, T. V. J. Am. Chem. Soc. 2012, 134, 6556. (f) Timsina, Y.
N.; Sharma, R. K.; RajanBabu, T. V. Chem. Sci. 2015, 6, 3994.
(11) Other types of difunctionalization: (a) Larock, R. C.; Berrios-
Pena, N.; Narayanan, K. J. Org. Chem. 1990, 55, 3447. (b) Jackstell, R.;
Andreu, G. A.; Frisch, A.; Selvakumar, K.; Zapf, A.; Klein, H.;
Spannenberg, A.; Rottger, D.; Briel, O.; Karch, R.; Beller, M. Angew.
Chem., Int. Ed. 2002, 41, 986. (c) Zbieg, J. R.; Yamaguchi, E.;
McInturff, E. L.; Krische, M. J. Science 2012, 336, 324. (e) Arndt, M.;
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: hlbao@fjirsm.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
̆
Dindaroglu, M.; Schmalz, H.-G.; Hilt, G. Org. Lett. 2011, 13, 6236.
We thank NSFC (Grant No. 21402200), The 100 Talents
Program (The Chinese Academy of Sciences) for financial
support. We also thank Prof. Kuiling Ding, Prof. Guosheng Liu
from Shanghai Institute of Organic Chemistry and Prof. Uttam
Tambar from UT Southwestern Medical Center for exper-
imental and writing suggestions, and graduate student Liang Ge
and Xiaotao Zhu for experimental assistance.
(f) Fang, X.; Li, H.; Jackstell, R.; Beller, M. Angew. Chem., Int. Ed.
2014, 53, 9030. (g) Fang, X.; Li, H.; Jackstell, R.; Beller, M. J. Am.
Chem. Soc. 2014, 136, 16039. (h) Banerjee, D.; Junge, K.; Beller, M.
Angew. Chem., Int. Ed. 2014, 53, 1630.
(12) Wang, Y.; Zhang, L.; Yang, Y.; Zhang, P.; Du, Z.; Wang, C. J.
Am. Chem. Soc. 2013, 135, 18048.
(13) Ryzhkov, L. R. J. Org. Chem. 1996, 61, 2801.
(14) For recent examples of copper catalyzed difunctionalization of
olefins: (a) Sequeira, F. C.; Turnpenny, B. W.; Chemler, S. R. Angew.
Chem., Int. Ed. 2010, 49, 6365. (b) Liwosz, T. W.; Chemler, S. R. J.
Am. Chem. Soc. 2012, 134, 2020. (c) Miller, Y.; Miao, L.; Hosseini, A.
S.; Chemler, S. R. J. Am. Chem. Soc. 2012, 134, 12149. (d) Chemler, S.
R. Science 2013, 341, 624. (e) Bovino, M. T.; Liwosz, T. W.; Kendel,
N. E.; Miller, Y.; Tyminska, N.; Zurek, E.; Chemler, S. R. Angew.
Chem., Int. Ed. 2014, 53, 6383. (f) Wang, F.; Wang, D.; Mu, X.; Chen,
P.; Liu, G. J. Am. Chem. Soc. 2014, 136, 10202. (g) Wang, F.; Qi, X.;
Liang, Z.; Chen, P.; Liu, G. Angew. Chem., Int. Ed. 2014, 53, 1881.
(h) Liang, Z.; Wang, F.; Chen, P.; Liu, G. Org. Lett. 2015, 17, 2438.
(i) Liao, Z.; Yi, H.; Li, Z.; Fan, C.; Zhang, X.; Liu, J.; Deng, Z.; Lei, A.
Chem. - Asian J. 2015, 10, 96−9.
REFERENCES
■
(1) For reviews, see: (a) Yorimitsu, H.; Oshima, K. Angew. Chem., Int.
Ed. 2005, 44, 4435. (b) Alexakis, A.; Backvall, J.-E.; Krause, N.; Pamies,
O.; Dieguez, M. Chem. Rev. 2008, 108, 2796. (c) Lu, Z.; Ma, S. Angew.
Chem., Int. Ed. 2008, 47, 258. (d) Dieguez, M.; Pamies, O. Acc. Chem.
Res. 2010, 43, 312. (e) Hartwig, J. F.; Stanley, L. M. Acc. Chem. Res.
2010, 43, 1461.
(2) For seminal examples, see: (a) Rappoport, Z.; Winstein, S.;
Young, W. G. J. Am. Chem. Soc. 1972, 94, 2320. (b) Shono, T.; Ikeda,
A. J. Am. Chem. Soc. 1972, 94, 7892. (c) Trost, B. M.; Lautens, M. J.
Am. Chem. Soc. 1987, 109, 1469. (d) Chen, M. S.; White, M. C. J. Am.
Chem. Soc. 2004, 126, 1346. (e) Chen, M. S.; Prabagaran, N.; Labenz,
N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970. (f) Mitsudome,
T.; Umetani, T.; Nosaka, N.; Mori, K.; Mizugaki, T.; Ebitani, K.;
Kaneda, K. Angew. Chem., Int. Ed. 2006, 45, 481. (g) Covell, D. J.;
White, M. C. Angew. Chem., Int. Ed. 2008, 47, 6448. (h) Vermeulen, N.
A.; Delcamp, J. H.; White, M. C. J. Am. Chem. Soc. 2010, 132, 11323.
(i) Kondo, H.; Yu, F.; Yamaguchi, J.; Liu, G.; Itami, K. Org. Lett. 2014,
16, 4212.
̈
(15) Yoshikai, N.; Nakamura, E. Chem. Rev. 2012, 112, 2339.
(3) For seminal examples, see: (a) Kharasch, M. S.; Sosnovsky, G. J.
Am. Chem. Soc. 1958, 80, 756. (b) Meyers, A. I.; Tavares, F. X. J. Org.
Chem. 1996, 61, 8207. (c) Eames, J.; Watkinson, M. Angew. Chem., Int.
Ed. 2001, 40, 3567. (d) Mayoral, J. A.; Rodriguez-Rodriguez, S.;
Salvatella, L. Chem. - Eur. J. 2008, 14, 9274. (e) Wei, W.; Zhang, C.;
Xu, Y.; Wan, X. Chem. Commun. 2011, 47, 10827. (f) Aldea, L.; Delso,
I.; Hager, M.; Glos, M.; Garcia, J. I.; Mayoral, J. A.; Reiser, O.
Tetrahedron 2012, 68, 3417. (g) Marin-Barrios, R.; Guerra, F. M.;
Garcia-Cabeza, A. L.; Moreno-Dorado, F. J.; Massanet, G. M.
Tetrahedron 2012, 68, 1105. (h) Zhang, B.; Zhu, S.; Zhou, Q.
Tetrahedron Lett. 2013, 54, 2665.
(4) (a) Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis;
Wiley: 1995. (b) Warren, S., Wyatt, P., Eds. Workbook for Organic
Synthesis: the Disconnection Approach, 2nd ed.; John Wiley & Sons,
Inc.: 2010.
D
DOI: 10.1021/acs.orglett.5b03399
Org. Lett. XXXX, XXX, XXX−XXX