Hydroalkylation of terminal aryl alkynes with alkyl diacyl peroxides

Article abstract of DOI:10.1016/j.tetlet.2016.11.020

A photo and nickel co-catalyzed hydroalkylation of terminal aryl alkynes enabled Z-preferred olefin synthesis has been developed under mild conditions. Alkyl diacyl peroxides were utilized as a new type of alkylation reagents and afforded Z-olefins as the major products in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2016.11.020

Accepted Manuscript
Hydroalkylation of terminal aryl alkynes with alkyl diacyl peroxides
Yougui Li, Liang Ge, Bo Qian, Kaki Raveendra Babu, Hongli Bao
PII:
S0040-4039(16)31476-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.11.020
TETL 48306
Reference:
Tetrahedron Letters
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Revised Date:
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16 September 2016
3 November 2016
4 November 2016
Please cite this article as: Li, Y., Ge, L., Qian, B., Raveendra Babu, K., Bao, H., Hydroalkylation of terminal aryl
alkynes with alkyl diacyl peroxides, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.11.020
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Hydroalkylation of terminal aryl alkynes
with alkyl diacyl peroxides
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Yougui Li , Liang Ge, Bo Qian, Kaki Raveendra Babu, and Hongli Bao*

1
Tetrahedron Letters
Hydroalkylation of terminal aryl alkynes with alkyl diacyl peroxides
Yougui Li, a Liang Ge, a Bo Qian, b Kaki Raveendra Babu, b and Hongli Bao*b
a School of Chemistry and Chemical Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, 230009, China.
b Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, University of Chinese
Academy of Science,155 Yangqiao Road West, Fuzhou, 350002, P.R. China. E-mail: hlbao@fjirsm.ac.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A photo and nickel co-catalyzed hydroalkylation of terminal aryl alkynes enabled Z-preferred
olefins synthesis has been developed under mild conditions. Alkyl diacyl peroxides were utilized
as a new type of alkylation reagents and afforded Z-olefins as the major products in moderate to
good yields.
Available online
Keywords:
Hydroalkylation
Aryl alkynes
Alkyl diacyl peroxides
Radicals
Photo catalysis
Alkenes are among the most important organic compounds
and many synthetic methodologies have been developed for
effective olefination such as Wittig reactions,1 Peterson
olefination,2 Julia olefination,3 Heck reactions,4 olefin
metathesis,5 Negishi type addition of organometallic reagents to
alkynes6 and other type of reactions.7 Recently, two classic
examples by Lalic8 and Hu9 revealed that hydroalkylation of
terminal alkynes with alkyl electrophiles is an effective strategy
to generate alkenes from alkynes. Lalic et al. reported the first
hydroalkylation of alkynes with alkyl triflate catalyzed by copper
catalyst (Scheme 1) which generated E-olefins. Hu et al disclosed
the first Z-selective hydroalkylation of alkynes. This iron
catalyzed hydroalkylation of terminal alkynes used alkyl iodides
and alkyl tosylates as the electrophiles.
Alkyl diacyl peroxides are the inexpensive chemicals
commonly used in industry as radical initiators or oxidants and
they are readily accessible from carboxylic acids. Nevertheless,
the utilization of peroxides as alkylation reagents was under
explored and there were very few documented examples so far to
our knowledge.10,11
As part of our ongoing interest in developing new type of al-
kylating reagents for important reactions,11d herein we report the
hydroalkylation of terminal aryl alkynes with alkyl diacyl
peroxides as electrophiles. This is an alternative method for Z-
preferred synthesis of 1,2-disubstituted olefins via photo and
nickel catalysis.
We commenced our study by optimizing the reaction of
phenyl acetylene with lauroyl peroxide (LPO). After a screening
of all reaction parameters, we found that the optimized conditions
involved the merger of photo and metal catalysis.12 The reaction
underwent smoothly in isopropanol in presence of photo catalyst
4a (1 mol%), NiCl2 (10 mol%), salen ligand ((R,R)-N,N'-bis(3,5-
di-tert-butylsalicylidene)-1,2-cyclohexanediamine, 10 mol%),
NHPI (N-hydroxyphthalimide, 100 mol%), and DIPEA (7 eqiuv)
(Table 1, entry 1). The yield was up to 71% with the optimal
conditions. The yield dropped to 51% when the reaction was
heated to 70 oC and without photo catalysis. Seven photo sensors
were applied and the yields range from 0-65% (entries 3-9). 1,4-
Cyclohexanediene and N-hydroxysuccinimide were used to
replace NHPI. 1,4-Cyclohexanediene showed similar reactivity
but worse Z/E ratio (entry 10). Whereas N-hydroxysuccinimide
also deliver product in good yield and good Z/E ratio (entry 11).
Other controlled reactions were examined. The reaction afforded
product in only 9% of product without photo catalyst (entry 12).
Salen ligand is also key factor to this reaction (entries 13 and 14).
NHPI can increase the yield but is not essential (entry 13) to this
o
reaction. The reaction delivered product in a lower yield at 0 C
(entry 16) and much less product in dark (entry 15). Other metal
and solvent screening did not improve the result further (entries
17-21).
Table 1
Scheme 1. Hydroalkylation of alkynes.
Optimization of reaction conditionsa

2
Tetrahedron Letters
1
2
3
4
5
6
7
Change from the optimized
condition
Yieldb % (Z/E)
Entry
No change
71% (3.2:1)
51% (1:1)
1
2
Without 4a, DIPEA, white LED, but
8
reacted at 70 oC
4b instead of 4a
56% (2.8:1)
65% (3.2:1)
trace
3
O
4c instead of 4a
O
4
9
O
4d instead of 4a
O
5
4e instead of 4a
trace
6
10
4f, DCA instead of 4a
4g, EoSin Y instead of 4a
4h, Eosin B instead of 4a
39% (3.0:1)
42% (2.9:1)
60% (3.0:1)
70% (2.3:1)
7
8
aReaction conditions: phenylacetylene 1 (0.5 mmol), alkyl diacyl peroxides
(1.125 mmol), solvent (2.0 mL), 8 h at room temperature, under argon
atmosphere. bYield of isolated products.
9
1,4-cyclohexanediene instead of
NHPI
10
N-Hydroxysuccinimide instead of
NHPI
Without 4a
66% ( 3.3:1)
Next, the scope of aryl alkynes was investigated (Table 3).
Alkyl substituted aryl alkynes afforded the products 8a-c. Further,
halogen substituted aryl alkynes provided the olefins 8d-i.
Furthermore, methoxy substituted aryl alkynes gave products 8j-l
in moderate yields. Ortho-substituents affected the reaction more
than para-substituted groups and delivered products in lower
yields (Table 3, entries 6 and 12).
11
9% (3.4:1)
12
Without NHPI
58% (2.5:1)
23% (2.8:1)
18% (2.0:1)
51% (2.4:1)
25% (1.7:1)
25% (1.9:1)
41% (1.5:1)
39% (1.6:1)
35% (2.0:1)
13
Without salen and NHPI
No light
At 0 oC
14
15c
16c
17c
18c
19c
20c
21c
FeCl2 instead of NiCl2
CoCl2 instead of NiCl2
THF instead of IPA
CH3CN instead of IPA
DME instead of IPA
Table 3
Substrate scope of aryl alkynesa
aReaction conditions: phenylacetylene 1 (0.5 mmol), LPO 2 (1.125 mmol),
b
solvent (2.0 mL), 8 h at room temperature, under argon atmosphere. Yield
of isolated product. c Yields determined by 1H NMR.
With the optimal reaction conditions in hand, we studied the
scope of diacyl peroxides (Table 2), which were synthesized
from the corresponding carboxylic acids or acyl chlorides.
Hydroalkylation of alkynes with primary and secondary alkyl
diacyl peroxides afforded Z-olefins as the major products. The
Z/E ratios were about 2:1 in all the cases. The alkyl dicayl
peroxides which contain long chain alkyl groups and methyl
substituted alkyl groups afforded the corresponding olefins with
moderate yields (6a-f). Methyl cyclopentyl diacyl peroxide gave
compound 6g. Further, alkyl diacyl peroxides which contain
phenyl group furnished 6h. Finally, secondary diacyl peroxides
delivered compound 6i and 6j.
entry
1
Aryl Alkyne
product and yieldb
2c
3
Table 2
4
Substrate scope of alkyl diacyl peroxidesa
5
Entry
Peroxide 5
Product and yieldb

3
delivered products in moderate yields. This reaction offers a
complementary approach to the current methods.
6
7
8e
9
Scheme 3. Proposed catalytic cycle.
10
11
Acknowledgments
We gratefully acknowledge NSFC (grant no. 21402200,
21672213), The 100 Talents Program (The Chinese Academy of
Sciences) for financial support.
References and notes
12
1. Reviews and book on the Wittig reactions: a) Murphy, P. J.;
Brennan, J. Chem. Soc. Rev. 1988, 17, 1; b) Maryanoff, B. E.;
Reitz, A. B. Chem. Rev. 1989, 89, 863; c) Edmonds, M.; Abell, A.;
Wiley-VCH Verlag GmbH & Co. KGaA: 2004, p 1.
aReaction conditions: phenylacetylene 1 (0.5 mmol), alkyl diacyl peroxides
(1.125 mmol), solvent (2.0 mL), 8 h at room temperature, under argon
atmosphere. bYield of isolated products.
2. Review on the Peterson olefination: a) Ager, D. J. Organic
Reactions. (N. Y.) 1990, 38, 1; b) van Staden, L. F.; Gravestock,
D.; Ager, D. J. Chem. Soc. Rev. 2002, 31, 195.
3. Dumeunier, R.; Marko, I. E.; Modern Carbonyl Olefination,
Wiley-VCH Verlag GmbH & Co. KGaA: 2004, p 104.
We performed mechanistic experiments to further understand
the reaction. Firstly, a radical trapping experiment was conducted
with TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy). The
reaction was shut down and there was no desired product
observed, while 9 was observed by GC-MS (Scheme 2). Next,
four experiments were conducted with deuterated reagents, d8-
isopropanol, D2O, 10 and 11. None of these experiments afforded
product bearing deuteron atom at the benzylic carbon.
4. Reviews and book on the Heck reactions: a) Book: M. Oestreich,
The Mizoroki-Heck reaction, Wiley, Hoboken, NJ, 2008; b) Cabri,
W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2; c) Crisp, G. T.
Chem. Soc. Rev. 1998, 27, 427; d) Amatore, C.; Jutand, A. Acc.
Chem. Res. 2000, 33, 314; e) Beletskaya, I. P.; Cheprakov, A. V.
Chem. Rev. 2000, 100, 3009; f) Biffis, A.; Zecca, M.; Basato, M.
J. Mol. Catal. A: Chem. 2001, 173, 249; g) Bedford, R. B. Chem.
Commun. 2003, 1787; h) Dounay, A. B.; Overman, L. E. Chem.
Rev. 2003, 103, 2945; i) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D.
Angew. Chem. Int. Ed. 2005, 44, 4442; j) Phan, N. T. S.; Van Der
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Int. Ed. 2000, 39, 3012; b) Trnka, T. M.; Grubbs, R. H. Acc. Chem.
Res. 2001, 34, 18; c) Connon, S. J.; Blechert, S. Angew. Chem., Int.
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Chem. Rev. 2009, 109, 3708; e) ougioukalakis, G. C.; Grubbs, R.
H. Chem. Rev. 2010, 110, 1746.
6. a) Negishi, E.; Van Horn, D. E.; Yoshida, T.; Rand, C. L.
Organometallics 1983, 2, 563; (b) Stüdemann, T.; Ibrahim-Ouali,
M.; Knochel, P. Tetrahedron 1998, 54, 1299; c) Endo, K.;
Hatakeyama, T.; Nakamura, M.; Nakamura, E. J. Am. Chem. Soc.
2007, 129, 5264; d) Fujii, Y.; Terao, J.; Kambe, N. Chem
Commun 2009, 1115; e) Xie, M.; Gu, X.; Wang, J.; Zhang, J.; Lin,
G.; Wang, S. Applied Organometallic Chem. 2009, 23, 258.
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Molinaro, C.; Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 8076; c)
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137, 1424.
9. Cheung, C. W.; Zhurkin, F. E.; Hu, X. J. Am .Chem. Soc. 2015,
137, 4932.
Scheme 2. Initial mechanistic studies.
Based on our experimental results and previous works,12
a
mechanism involving single electron transfer catalytic and photo
redox catalytic cycle is proposed here (Scheme 3). Ni(II) complex
transfers an electron to the diacyl peroxide to form Ni (III)
compound and an alkyl radical. Then this Ni (III) is reduced by Ru (I)
species to Ni (II). The generated Ru (II) turns back to Ru (I) under
the photo-catalysis condition in presence of DIPEA.
In summary, we have developed the first hydro-alkylation
reaction of aryl alkynes with alkyl diacyl peroxides. This reaction
enabled Z-preferred hydro-alkylation of aryl alkynes and
10. Non-catalyzed reaction with peroxides as alkyl electrophiles: a)
Fieser, L. F. & Oxford, A. E. J. Am. Chem. Soc.1942, 64, 2060; b).
Rueda-Becerril, M.; Chatalova Sazepin, C.; Leung, J. C. T.;
Okbinoglu, T.; Kennepohl, P.; Paquin, J.-F.; Sammis, G. M. J.
Am. Chem. Soc. 2012, 134, 4026; c). Pan, C.; Zhang, H.; Han, J.;
Cheng, Y.; Zhu, C. Chem. Commun. 2015, 51, 3786; d). Liu, X.;
Wang, Z.; Cheng, X.; Li, C. J. Am. Chem. Soc. 2012, 134, 14330.
11. Catalytic reactions with peroxides as alkyl electrophiles: a)
Citterio, A.; Arnoldi, A.; Minisci, F. J. Org. Chem. 1979, 44, 2674;
b) Zhang, Y.; Feng, J.; Li, C.-J. J. Am. Chem. Soc. 2008, 130,

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Tetrahedron Letters
2900; c) Dirocco, D. A.; Dykstra, K.; Krska, S.; Vachal, P.;
12. Reviews on merging of photoredox and transitional metal catalysis,
see: a) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. Chem Rev
2013, 113, 5322. b) Xuan, J.; Zhang, Z. G.; Xiao, W. J. Angew.
Chem., Int. Ed. 2015, 54, 15632.
Conway, D. V.; Tudge, M. Angew. Chem. Int. Ed. 2014, 53, 4802;
d) Li, Y.; Han, Y.; Xiong, H.; Zhu, N.; Qian, B.; Ye, C.;
Kantchev, E. A.; Bao, H. Org. Lett. 2016, 18, 392.
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Highlights
(1) Diacyl peroxides as electrophiles for
hydroalkylation of aryl alkynes.
(2) Z-selective hydroalkylation of alkynes
(3) Mild reaction condition.