Metal-Free Microwave-Assisted Decarboxylative Elimination for the Synthesis of Olefins

Article abstract of DOI:10.1021/acs.orglett.5b03069

A metal-free efficient synthesis of olefins via microwave-assisted direct decarboxylative elimination of arylacetic acids is described. This reaction, using commercially available reagent PIFA as oxidant, readily provides a variety of desired products in moderate to good yields.

Full text of DOI:10.1021/acs.orglett.5b03069

Letter
pubs.acs.org/OrgLett
Metal-Free Microwave-Assisted Decarboxylative Elimination for the
Synthesis of Olefins
Shu-Wei Wu, Jia-Li Liu, and Feng Liu*
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Department of Medicinal Chemistry,
College of Pharmaceutical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, People’s Republic of China
S
* Supporting Information
ABSTRACT: A metal-free efficient synthesis of olefins via micro-
wave-assisted direct decarboxylative elimination of arylacetic acids is
described. This reaction, using commercially available reagent PIFA as
oxidant, readily provides a variety of desired products in moderate to
good yields.
a
Table 1. Optimization of Reaction Conditions
irect decarboxylative transformations of carboxylic acids,
Dwhich are usually considered as readily available, bench
stable, and inexpensive feedstocks, provide a useful approach
for chemical synthesis. In particular, decarboxylative couplings
using transition-metal catalysts, such as Pd,1 Ag,2 Rh,3 Cu,4 and
Ni,5 have received significant attention. Recently, the utility of
photoredox reagents including iridium complex6 and Fukuzumi
acridinium photooxidant7 has emerged as an alternative strategy
for direct decarboxylative functionalization of carboxylic acids.
Hypervalent iodine reagents are extensively used in organic
synthesis as oxidants mainly due to their benign environmental
quality, commercial availability, and easy handling. Although
the efficient generation of a carbon-centered radical from a
carboxylic acid is not easy, several methods for decarboxylative
coupling reactions have been developed recently using
iodine(III) derivatives, in combination with transition-metal2d,8
or photoredox catalysis,9,10 especially, Ag-catalyzed2d and
photoinduced10 decarboxylative alkynylation. Moreover, the
iodine(III) dicarboxylate intermediates were produced in the
photoredox system,10d followed by the formation of carbon-
centered radicals. However, via a direct decarboxylative
elimination of fatty acids to form olefins, there are only a few
reports in which a transition-metal catalysis was employed.11
Herein, we would like to report on metal-free direct
decarboxylative elimination of arylacetic acids for the synthesis
of olefins using iodine(III) reagents under microwave heat
conditions.
We began by investigating the reaction parameters (Table 1).
In the presence of air, commercially available iodine(III)
reagents and organic solvents were screened under microwave
irradiation conditions. In terms of chemical yield (only E-
isomer found), PIFA (PhI(OCOCF3)2, phenyliodine bis-
(trifluoroacetate)) was determined as the best one with
acetonitrile as the solvent (entries 1−6). The addition of acid
or base did not improve the chemical yields (entries 7−9).
When shortening the reaction time from 30 to 20 min, the
chemical yield did not drop (entry 10). However, microwave
irradiation for 10 min, no microwave heat, lower or higher
reaction temperature, led to lower yields (entries 11−14).
b
entry
iodine(III)
solvent
t (min)
yield (%)
1
2
3
4
5
6
PhIO
PhI(OAc)2
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
PIFA
CH3CN
CH3CN
CH3CN
PhCH3
AcOEt
30
30
30
30
30
30
30
30
30
20
10
30
20
20
<5
<5
85
10
29
52
84
40
<5
85
63
13
<5
DCE
c
7
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
d
8
e
9
10
11
f
12
g
13
h
14
79
a
b
1a (0.20 mmol), iodine(III) (0.24 mmol), solvent (2 mL). Isolated
yield. CF3COOH (0.40 mmol). t-BuOK (0.40 mmol). K2CO3 (0.40
c
d
e
f
g
h
mmol). Oil bath heat. 100 °C. 140 °C.
With the optimized reaction condition established, we first
explored the substrate scope of aryl/diphenylacetic acids. As
depicted in Figure 1, the reaction exhibited a broad generality,
readily affording a variety of different aryl/diphenylvinyls in
moderate to good yields. It should be noted that the direct
decarboxylative elimination generated the sole E-olefins, which
could be the thermodynamic products (2b−2r). Moreover,
substituents or functional groups on the aromatic ring (2b−2i)
or side chain (2o−2r) were well tolerated. We also observed
that thienyl group (2h) or hydroxyl group (2q) led to a sharp
Received: October 22, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b03069
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Proposed Mechanism
radical C and the release of CO2. Subsequent oxidation8 and
elimination give corresponding olefin 2a.
In addition, we conducted the decarboxylative elimination of
substrate 5, which could be subject to proton leaving at the
methyl site or methylene site (Scheme 3, eq 1). As expected,
Scheme 3. Reactions of 5 and 7
this reaction afforded an inseparable mixture of 6a and 6b with
fair regioselectivity. Using phthalimide-protected amino acid
instead of arylacetic acid as the substrate (Scheme 3, eq 2) also
afforded the desired olefin 8.
In conclusion, we have developed the first example of a
metal-free direct decarboxylative elimination for the synthesis
of olefins under microwave irradiation conditions. The reaction,
in the presence of commercially available PIFA, readily afforded
a variety of aryl/diphenylvinyls in moderate to good yields.
Preliminary mechanistic investigations suggested a radical
process could be involved in the decarboxylative elimination
reaction.
Figure 1. Substrate scope of aryl/diphenylacetic acids.
decrease of the yield. Higher reaction temperature was required
to achieve olefin 2i. When treating diphenylacetic acids with the
same reaction condition, it also furnished the desired products
in satisfactory yields (2u−2x).
To probe the mechanism of this decarboxylative elimination,
arylacetic acid 3 with a cyclopropyl group was subjected to the
optimized condition (Scheme 1). This reaction gave a
ASSOCIATED CONTENT
■
S
* Supporting Information
Scheme 1. Reaction of Cyclopropyl Acid 3
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.5b03069.
1
Experimental details, characterizations, and copies of H
and 13C NMR spectra for new compounds (PDF)
cyclopropyl ring opening product 4, suggesting that a radical-
mediated process was involved. On the basis of the above
results, a postulated mechanism is depicted in Scheme 2. The
reaction of 1a and PIFA provides iodine(III) dicarboxylate
intermediate A,9a,10d which is liable to furnishing carboxylic
radical B, followed by generating the corresponding carbon
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: fliu2@suda.edu.cn.
Notes
The authors declare no competing financial interest.
B
DOI: 10.1021/acs.orglett.5b03069
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Commun. 2012, 48, 2552. (e) Maetani, S.; Fukuyama, T.; Suzuki, N.;
Ishihara, D.; Ryu, I. Organometallics 2011, 30, 1389.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (Grant No. 21302134), the Natural
Science Foundation of Jiangsu (Grant No. BK20130338), and
the Priority Academic Program Development of Jiangsu Higher
Education Institutions (PAPD).
REFERENCES
■
(1) For selected examples, see: (a) Xu, Z.; Wang, Q.; Zhu, J. Angew.
Chem., Int. Ed. 2013, 52, 3272. (b) Cornella, J.; Righi, M.; Larrosa, I.
Angew. Chem., Int. Ed. 2011, 50, 9429. (c) Shang, R.; Ji, D.-S.; Chu, L.;
Fu, Y.; Liu, L. Angew. Chem., Int. Ed. 2011, 50, 4470. (d) Shang, R.;
Yang, Z.-W.; Wang, Y.; Zhang, S.-L.; Liu, L. J. Am. Chem. Soc. 2010,
132, 14391. (e) Wang, C. Y.; Piel, I.; Glorius, F. J. Am. Chem. Soc.
2009, 131, 4194. (f) Waetzig, S. R.; Tunge, J. A. J. J. Am. Chem. Soc.
2007, 129, 4138. (g) Rayabarapu, D. K.; Tunge, J. A. J. Am. Chem. Soc.
2005, 127, 13510.
(2) For selected recent examples, see: (a) Liu, C.; Wang, X.; Li, Z.;
Cui, L.; Li, C. J. Am. Chem. Soc. 2015, 137, 9820. (b) Kan, J.; Huang,
S.; Lin, J.; Zhang, M.; Su, W. Angew. Chem., Int. Ed. 2015, 54, 2199.
(c) Hu, F.; Shao, X.; Zhu, D.; Lu, L.; Shen, Q. Angew. Chem., Int. Ed.
2014, 53, 6105. (d) Liu, X.; Wang, Z.; Cheng, X.; Li, C. J. Am. Chem.
Soc. 2012, 134, 14330. (e) Yin, F.; Wang, Z.; Li, Z.; Li, C. J. Am. Chem.
Soc. 2012, 134, 10401. (f) Wang, Z.; Zhu, L.; Yin, F.; Su, Z.; Li, Z.; Li,
C. J. Am. Chem. Soc. 2012, 134, 4258.
(3) For selected examples, see: (a) Zhang, Y.; Zhao, H.; Zhang, M.;
Su, W. Angew. Chem., Int. Ed. 2015, 54, 3817. (b) Neely, J. M.; Rovis,
T. J. Am. Chem. Soc. 2014, 136, 2735. (c) Pan, F.; Lei, Z.-Q.; Wang, H.;
Li, H.; Sun, J.; Shi, Z.-J. Angew. Chem., Int. Ed. 2013, 52, 2063.
(d) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2010, 12,
5776. (e) Sun, Z.-M.; Zhang, J.; Zhao, P. Org. Lett. 2010, 12, 992.
(4) For selected examples, see: (a) Feng, Q.; Song, Q. J. Org. Chem.
2014, 79, 1867. (b) Feng, Y.-S.; Xu, Z.-Q.; Mao, L.; Zhang, F.-F.; Xu,
H.-J. Org. Lett. 2013, 15, 1472. (c) Zhang, Y.; Patel, S.; Mainolfi, N.
Chem. Sci. 2012, 3, 3196.
(5) For selected examples, see: (a) Noble, A.; McCarver, S. J.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2015, 137, 624. (b) Yang, K.;
Zhang, C.; Wang, P.; Zhang, Y.; Ge, H. Chem. - Eur. J. 2014, 20, 7241.
(c) Yoshino, Y.; Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2009,
131, 7494.
(6) For selected recent examples, see: (a) Ventre, S.; Petronijevic, F.
R.; MacMillan, D. W. C. J. Am. Chem. Soc. 2015, 137, 5654. (b) Lang,
S. B.; O’Nele, K. M.; Tunge, J. A. J. Am. Chem. Soc. 2014, 136, 13606.
(c) Noble, A.; MacMillan, D. W. C. J. Am. Chem. Soc. 2014, 136,
11602. (d) Chu, L.; Ohta, C.; Zuo, Z.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2014, 136, 10886. (e) Zuo, Z.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2014, 136, 5257.
(7) (a) Griffin, J. D.; Zeller, M. A.; Nicewicz, D. A. J. Am. Chem. Soc.
2015, 137, 11340. (b) Wu, X.; Meng, C.; Yuan, X.; Jia, X.; Qian, X.;
Ye, J. Chem. Commun. 2015, 51, 11864.
(8) Xu, K.; Wang, Z.; Zhang, J.; Yu, L.; Tan, J. Org. Lett. 2015, 17,
4476.
(9) (a) He, Z.; Bae, M.; Wu, J.; Jamison, T. F. Angew. Chem., Int. Ed.
2014, 53, 14451. (b) Xie, J.; Xu, P.; Li, H.; Xue, Q.; Jin, H.; Cheng, Y.;
Zhu, C. Chem. Commun. 2013, 49, 5672.
(10) (a) Le Vaillant, F.; Courant, T.; Waser, J. Angew. Chem., Int. Ed.
2015, 54, 11200. (b) Zhou, Q.-Q.; Guo, W.; Ding, W.; Wu, X.; Chen,
X.; Lu, L.-Q.; Xiao, W.-J. Angew. Chem., Int. Ed. 2015, 54, 11196.
(c) Tan, H.; Li, H.; Ji, W.; Wang, L. Angew. Chem., Int. Ed. 2015, 54,
8374. (d) Huang, H.; Zhang, G.; Chen, Y. Angew. Chem., Int. Ed. 2015,
54, 7872.
(11) For selected examples, see: (a) Liu, Y.; Virgil, S. C.; Grubbs, R.
H.; Stoltz, B. M. Angew. Chem., Int. Ed. 2015, 54, 11800. (b) Liu, Y.;
Kim, K. E.; Herbert, M. B.; Fedorov, A.; Grubbs, R. H.; Stoltz, B. M.
Adv. Synth. Catal. 2014, 356, 130. (c) Miranda, M. O.; Pietrangelo, A.;
Hillmyer, M. A.; Tolman, W. B. Green Chem. 2012, 14, 490.
(d) Maetani, S.; Fukuyama, T.; Suzuki, N.; Ishihara, D.; Ryu, I. Chem.
C
DOI: 10.1021/acs.orglett.5b03069
Org. Lett. XXXX, XXX, XXX−XXX