One-pot synthesis of α,α-disubstituted Aryl-1-ethanones via the Wittig-Horner reaction

Article abstract of DOI:10.1080/10426507.2017.1415899

A one-pot methodology for the synthesis of α,α-disubstituted aryl-1-ethanones via the Wittig-Horner reaction has been developed and described in this manuscript. Both aryl/alkyl and dialkyl α-branched arylethanone were obtained in high yields (up to 96%) without the use of any metal catalysts. A total of 14 α,α-disubstituted arylethanone derivatives were synthesized based on this simple method that easily converts the carbonyl carbon (sp²) into the sp³ carbon. This versatile method is expected to further promote the use of substituted ketones as synthetic building blocks to construct a variety of α-branched aryl ketones.

Full text of DOI:10.1080/10426507.2017.1415899

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
One-pot synthesis of α,α-disubstituted Aryl-1-
ethanones via the Wittig-Horner reaction
Yunxia Yang, Le Wang, Yuan Chen, Yiru Dai & Zhihua Sun
To cite this article: Yunxia Yang, Le Wang, Yuan Chen, Yiru Dai & Zhihua Sun (2018) One-pot
synthesis of α,α-disubstituted Aryl-1-ethanones via the Wittig-Horner reaction, Phosphorus, Sulfur,
and Silicon and the Related Elements, 193:3, 121-126, DOI: 10.1080/10426507.2017.1415899
To link to this article: https://doi.org/10.1080/10426507.2017.1415899
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PHOSPHORUS, SULFUR, AND SILICON
, VOL. , NO. , –
https://doi.org/./..
One-pot synthesis of α,α-disubstituted Aryl--ethanones via the Wittig-Horner
reaction
Yunxia Yang, Le Wang, Yuan Chen, Yiru Dai, and Zhihua Sun
Department of Chemistry, College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China
ABSTRACT
ARTICLE HISTORY
Received  September 
Accepted  November 
A one-pot methodology for the synthesis of α,α-disubstituted aryl-1-ethanones via the Wittig-Horner
reaction has been developed and described in this manuscript. Both aryl/alkyl and dialkyl α-branched
arylethanone were obtained in high yields (up to 96%) without the use of any metal catalysts. A total of
14 α,α-disubstituted arylethanone derivatives were synthesized based on this simple method that easily
converts the carbonyl carbon (sp2) into the sp3 carbon. This versatile method is expected to further pro-
mote the use of substituted ketones as synthetic building blocks to construct a variety of α-branched aryl
ketones.
KEYWORDS
α,α-disubstituted
aryl--ethanones; active
phosphonates; one-pot
synthesis; Wittig-Horner
reaction
GRAPHICAL ABSTRACT
Introduction
of the ketone moiety usually does not change, which is not
very convenient to construct branched arylketones. Herein, we
demonstrate a one-pot synthesis of α-branched arylketones
based on the Wittig-Horner reaction (Scheme 1c). The car-
bonyl (sp2) moiety of ketones are successfully converted into
the sp3 carbon to afford α,α-branched arylketones. Substi-
tuted ketones are versatile building blocks to construct versatile
α-branched aryl ketones. The well-known Wittig-Horner reac-
tion is widely used in the synthesis of alkenes with active phos-
phonates and aldehydes as the building blocks. However, the
suitability of ketones is limited because of the apparent steric
effect.[28–31] The resulting enol ethers can be readily converted
to branched arylketones in an acid medium.[32] Since there were
quite few examples of such enolethers to form ketone in the
literature,[33–34] we were prompted to develop a systemic and
extensive research to construct a serious of α-branched arylke-
tones via the Wittig-Horner reaction. This manuscript describes
the synthesis of a series of α-branched (aryl/alkyl and dialkyl)
arylketones in high yields under relatively mild conditions in
Aryl ketone moieties are widely found in drugs and medic-
inal intermediates due to their extraordinary biological and
pharmaceutical properties.[1–8] For example, pitofenone and
n-butylphthalide (NBP) are well-known antiplatelet and anti-
spasmodic drugs in the market.[9] Moreover, aryl ketone
derivatives are also pivotal structural motifs in many bio-
logically active natural products.[10–13] Therefore, it is very
important to develop different efficient protocols to construct
aryl carbonyl compounds.
Among various effective methods for the synthesis of
ketones, the Friedel-Crafts acylation[14,15] and transition-
metal catalyzed acylation[16–20] are the most common meth-
ods (Scheme 1a). Although these protocols are effective in
forming arylketones, the synthesis of branched arylketones
remains challenging, and documented examples are rather
limited so far,[21–23] with three elegant examples shown in
Scheme 1b.[24–27] Despite the fact that branched arylketones
could be derived from these ketones, the carbonyl group (sp2)
CONTACT Le Wang
wangle@sues.edu.cn
Science, Shanghai , China.
Department of Chemistry, College of Chemistry and Chemical Engineering, Shanghai University of Engineering
Color versions of one or more of the figures in this article can be found online at www.tandfonline.com/gpss.
Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/./...
©  Taylor & Francis Group, LLC

122
Y. YANG ET AL.
Scheme . The synthesis of arylketones.
one step. Moreover, the strategy described herein also provides a ratio even up to 92:8 (entry 6). Obviously, a higher selectivity
very versatile way to synthesize a variety of α-branched arylke- is obtained at lower temperatures (entries 6–8). Considering
tones, with substituted ketones as starting materials.
that the H2SO4 was too harsh an acid herein, other acids were
used to explore their catalytic efficiency. We found hydrolysis
completed by the use of citric acid or trifluoroacetic acid (TFA).
Considering the previous reports of protonation of enols,[34]
the reaction was modified and performed with n-BuLi at
−78°C in THF and subsequent hydrolysis by TFA. While the
configuration of the intermediate 3a does not affect the final
product, it is important to further confirm its stereochemistry.
3a was isolated and characterized with respect to the E/Z ratio.
Moreover, 1D selective NOE (Nuclear Overhauser Effect)[38,39]
experiment were also used to confirm the E configuration of
3a. A representative 1D selective NOE spectrum is shown in
Fig. S4. (See Supporting Information). Irradiation of the CH3
protons resulted in clear NOE of the OCH3 protons, indicating
that they are in close proximity and thus the E-alkenes was
formed.
Results and discussion
Acetophenone (1a) and diethyl 1-(p-chlorophenyl)-1-methoxy-
methanephosphonate (2a) were used as model compounds to
optimize the reaction conditions (Table 1). Different conditions,
such as the base used, the reaction time, and the temperature,
were explored to optimize the synthesis as listed in Table 1.
The synthesis of the phosphonates followed the literature
reports[35–37] and the details are shown in the Supporting Infor-
mation. It is evident from the data presented in Table 1 that
t-BuONa and n-BuLi produced higher yields of 4a compared to
other bases (e.g. NaNH2 and K2CO3). When t-BuONa was used
as the base, the α,α-disubstituted aryl-1-ethanone 4a could be
obtained under mild conditions with up to 88% yield (entry
5), and various yields by altering the temperature and reaction
time (entries 3–5). The yield of 4a was further improved to 93%
with the much stronger base n-BuLi at −78°C, and the stereo
selectivity of 3a was significantly improved, with an E/Z (3a)
After establishing the optimal reaction conditions (Table 1,
entry 6), different aryl/alkyl ketones (1a-g) were used to test
this method. (Table 2). As we expected, most of the target
compounds were obtained in high yields (90–96%) via hydrol-
ysis without isolating the intermediate compounds 3. Some
Table . Optimization of reaction conditionsa.
Entry
Base
Solvents
Temp. (°C)
Time (h)
Ratio of 3a Z/Ec (%)
Yield of 4ae (%)

NaNH
KCO
t-BuONa
t-BuONa
t-BuONa
n-BuLi
CH
DMF
DMF
DMF
DMF
THF


r.t.


−
−



NDd
NDd
NDd
:
:
:
<
<















b
b
b
n-BuLi
n-BuLi
THF
THF
:

NDd
aGeneral procedure: The base was added dropwise to the diethyl phosphonate dissolved in the relevant solvent at the temperature mentioned. After reacting with ace-
tophenone, the reaction mixture was hydrolyzed by % HSO, r.t.,  h; b− /−/°C, . h.; r.t., . h.; cDetermined by H NMR and NOE; dNot determined; eThe crude
yield of 4a was determined by LC-MS.

PHOSPHORUS, SULFUR, AND SILICON
123
Table . Synthesis of α,α-aryl/alkylaryl--ethanone (4a-k)a.
R1 /R2 = Alkyl or Aryl
R3 = Cl , H, CH3, OCH3 , NO2
4b: 96%
4d: 92%
4a: 93%
4c: 95%
4g: 85%b
4hc: 92%
4f: 91%
4e: 90%
4ic: 93%
4jc: 95%
4kc: NDd
aReaction conditions: n-BuLi (. equiv.), phosphonate (. equiv.), ketone (. equiv.), THF, −°C,  h.; TFA, r.t., h. bThe hydrolysis time was  h. cDiethyl phosphate;
dNot determined.
alkenes intermediates were isolated and characterized with p-nitrophenylphosphonate 2e does not effectively react, perhaps
respect to the ratio of E/Z, while it seems that the one-pot because the strong electron withdrawing effect deactivates the
methodology for the synthesis of α,α-disubstituted arylketones phosphonate.[28]
is more effective. With the same phosphonate 2a, p-nitro-
To further check the applicability of the strategy, the reaction
and p-trifluoromethyl arylketones provided excellent yields was carried out with dialkylketones under optimal condi-
(95–96%, 4b-c), which indicates that electron withdrawing tions. Four symmetric and asymmetric alkylketones (1h-k)
groups increase the activity of arylketones. As pyridine is an were selected and investigated. As shown in Table 3, four
electron-poor arene, substrate 1f also provided high yield of α,α-dialkyl-aryl-aryl-1-ethanones were obtained in high yields
4f (91%). For a substrate with steric hindrance, the yield of (80–91%). Especially, asymmetric dialkyl arylketones (4l-m)
1,2,2-triaryl-1-ethanone 4g is slightly reduced to 85%. Mean- were obtained in the higher yields (88–91%), while similar
while, other 1-aryl-1-alkoxy-methanephosphonates (2a-e) with ketones were only obtained in low or moderated yields (e.g.
different groups were also investigated. As shown in Table 2, 62–72%) by the use of metal catalyst, as described in previous
the phosphonates 2a-d with electron donating groups and weak work.[26] These studies further expanded the scope of substrate
electron withdrawing groups, such as methyl, methoxy, chorine, ketones, which illustrates that both arylketones and alkylketones
can provided excellent yields (92–95%) of 4a,4h-j. However, can provide branched arylketones through this method.
Table . Synthesis of α,α-diarylaryl--ethanones from dialkylketones 1h-ka.
R3/R4 = Alkyl
4m:
4l:
4n: 83%
4o: 80%
88%
91%
aReaction conditions: n-BuLi (. equiv.), phosphonate (. equiv.), ketone (. equiv.), THF, −◦C, h.; TFA, r.t., h.

124
Y. YANG ET AL.
-(-Chlorophenyl)--(-nitrophenyl)--propanone (b)
Conclusion
1
Yellow oil. H NMR: δ 7.27 (m, 1H), 8.19 (d, J = 8.8 Hz, 2H,
In summary, we have developed a very convenient one-pot
method for the synthesis of α-branched arylketones via the
Wittig-Horner reaction from simple ketones, in which both α,α-
aryl/alkyl and dialkyl aryl-1-ethanone were obtained in high
yields (>90%) under various, mostly mild conditions. Therein
the carbonyl (sp2) moiety of ketones is successfully converted
into the sp3 carbon to afford various α-branched aryl ketones.
We believe that the strategy presented in this work will be useful
in the field of synthetic medicinal chemistry.
NO2-ArH), 7.88 (d, J = 8.4 Hz, 2H, ClArH), 7.47 (d, J = 8.8 Hz,
2H, NO2-ArH), 7.41 (d, J = 8.8 Hz, 2H, ClArH), 4.78–4.79
(m, 1H, CH), 1.59 (d, J = 7.2 Hz, 3H, CH3). 13C NMR: δ 197.9,
148.3, 147.1, 139.9, 134.2, 130.1, 129.1, 128.7, 124.6, 47.6, 19.3.
MS: calcd. C15H12ClNO3 m/z 289.05.; found 290.1 [M+H]+.
-(-Chlorophenyl)--(-trifluoromethylphenyl)--
propanone(c)
1
Yellow oil. H NMR: δ 7.89 (d, J = 8.8 Hz, 2H, ClArH), 7.58
(d, J = 8.0 Hz, 2H, ClArH),7.40–7.42 (m,4H, CF3-ArH), 4.70–
4.75 (m, 1H, CH), 1.57 (d, J = 6.8 Hz, 3H, CH3). 13C NMR: δ
198.3, 139.7, 134.4, 130.1, 129.3, 128.9, 128.1, 126.1, 126.0, 125.9,
125.9, 47.7, 19.3. 19F NMR: −62.6. MS: calcd. C16H12ClF3O m/z
312.05.; found 313.0 [M+H]+.
Experimental
Chemicals and apparatus
The solvents were dried as follows. THF was heated at reflux
over sodium benzophenone ketyl. NMR spectra were recorded
in CDCl3 with a Bruker Advance II spectrometer at 400 MHz for
1H, 100 MHz for 13C, 376 MHz for 19F, 162 MHz for 31P. Chem-
ical shifts are given in parts per million. LC-MS (ESI) analyses
was carried out with an Agilent 1100 LC/MSD. The Supplemen-
tal Materials contains sample 1H and 13C NMR spectra of the
products (Figures S 1 – S 37).
-(-Chlorophenyl)--(p-tolyl)--propanone (d)
Yellow oil. 1H NMR: δ 7.90 (d, J = 8.4 Hz, 2H, ClArH),
7.37 (d, J = 8.8 Hz, 2H, CH3ArH), 7.146 (m, 4H, ClArH,
CH3-ArH), 4.59–4.61 (m, 1H, CH), 2.31 (s, 3H, ArCH3), 1.53
(d, J = 6.8 Hz, 3H, CHCH3). 13C NMR: δ 199.2, 139.1, 138.2,
136.7, 134.9, 130.2, 129.8, 128.8, 127.6, 47.7, 20.9, 19.4. MS:
calcd. C16H15ClO: m/z 258.08.; found 259.1 [M+H]+.
General procedure for the preparation of α,α-disubstituted
aryl-1-ethanones
-(-Chlorophenyl)--(-methoxyphenyl)--propanone (e)
n-BuLi (1.1 equiv., 3.3 mmol) was added dropwise to a solution
of 3 mmol of phosphonate 2 in THF (10 mL) at −78°C. The
mixture was kept at this temperature for 10 min. Then ketone
1 (1.5 equiv., 4.5 mmol) was added. The resulting mixture was
stirred for 30 min at −78°C, allowed to warm up to r.t. for 2.5 h
followed by addition of saturated NH4Cl-H2O solution (5 mL);
and extracted with EtOAc (3 × 10 mL). The organic phases were
dried and hydrolyzed by TFA (5 mL, r.t., 12 h), the extracted liq-
uid was subjected to flash chromatography to isolate the desired
products which were characterized with NMR and LC-MS. If
the organic phase was purified directly by column chromatog-
raphy without further hydrolysis, the intermediate 3-E was
obtained.
1
Yellow oil. H NMR: δ 7.89 (d, J = 8.8 Hz, 2H, ClArH), 7.36
(d, J = 8.4 Hz, 2H, ClArH), 7.19 (d, J = 8.8 Hz, 2H, CH3O-ArH),
6.85 (d, J = 8.8 Hz, 2H, CH3O-ArH), 4.58–4.60 (m,1H, CH),
3.78 (s, 3H, OCH3), 1.52 (d, J = 6.8 Hz, 3H, CH3). 13C NMR: δ
199.3, 158.6, 139.1, 134.9, 133.2, 130.1, 128.7, 114.5, 55.2, 47.2,
19.4. MS: calcd.C16H15ClO2: m/z 274.08.; found 275.2 [M+H]+.
-(-Chlorophenyl)--(pyridinyl--yl)--butanone (f)
1
Yellow oil. H NMR: δ 8.61(s,1H, NCH), 8.51(s,1H, NCH),
7.91 (d, J = 8.4Hz, 2H, ClArH), 7.66 (d, J = 8.0 Hz, 1H,
NCH-CH-CH), 7.41 (d, J = 8.8 Hz, 2H, ClArH), 7.26–
7.28 (m, 1H, NCH-CH), 4.46(t, J = 7.2 Hz, 1H, CH),
2.18–2.29 (m, 1H, CH2), 1.84–1.93 (m, 1H, CH2), 0.92–0.96
(t, J = 7.4 Hz, 3H, CH3). 13C NMR: δ 198.20, 148.56, 139.79,
135.48, 135.02, 134.81, 129.96, 129.05, 123.92, 77.31, 76.99,
76.67, 52.43, 27.13, 12.12. MS: calcd. C15H14ClNO: m/z 259.08;
found 260.2 [M+H]+.
(E)--(-Methoxy--phenylpropene--yl)chlorobenzene (a-E)
Yellow oil. 1H NMR: δ 7.13–7.18 (m, 5H, ArH), 7.06
(d, J = 8.8 Hz, 4H, ClArH), 3.45 (s, 3H, OCH3), 2.20 (s, 3H,
CH3). 1D-NOE: Irradiation of 2.20 (s, CH3) found: 7.06 (m,
ClArH), 3.45 (s, OCH3). MS: calcd. C16H15ClO: m/z 258.08;
found: 259.1 [M+H]+.
-(-Chlorophenyl)-,-diphenyl--ethanone (g)
1
Yellow solid, m.p. 106–105°C. H NMR: δ 7.95 (d, J = 8.6
-(-Chlorophenyl)--phenyl--propanone (a)
Hz, 2H, ArH), 7.83 (d, J = 7.2 Hz, 2H, ArH), 7.61 (t, J = 7.4 Hz,
Yellow oil. 1H NMR: δ 7.90 (d, J = 8.8 Hz, 2H, ClArH), 1H, ArH), 7.51 (t, J = 7.6 Hz, 2H, ArH) 7.39 (d, J = 8.6 Hz, 2H,
7.30–7.37 (m, 7H, ClArH, ArH), 4.62–4.64 (m, 1H, CH), 1.55 ArH), 7.33–7.35 (m, 3H, ArH), 7.26–7.28 (m, 2H, ArH), 5.99 (s,
(d, J = 7.2 Hz, 3H, CH3). 13C NMR: δ 199.1, 141.4, 139.2, 1H, CH). 13C NMR: δ 196.9, 139.5, 138.8, 137.7, 135.1, 132.4,
134.8, 130.2, 129.1, 128.8, 127.7, 127.1, 48.1, 19.4. MS: calcd. 130.4, 130.0, 129.1, 128.9, 128.8, 128.3, 127.3, 59.6. MS: calcd.
C15H13ClO m/z 244.07; found 245.1 [M+H]+.
C20H15ClO: m/z 306.08; found 307.1 [M+H]+.

PHOSPHORUS, SULFUR, AND SILICON
125
,-Diphenyl--propanone (h)
Acknowledgments
Yellow solid, m.p.: 78.4–79.7°C. 1H NMR: δ 7.98 (d, J = 10 Hz,
2H, CO-ArH), 7.50–7.52 (m, 1H, CO-ArH), 7.39–7.42 (m, 2H,
CO-ArH), 7.28–7.38 (m, 4H, CH-ArH), 7.21–7.24 (m, 1H, CH-
ArH), 4.71–4.73 (m, 1H, CH), 1.56 (d, J = 6.8 Hz, 3H, CH3).
13C NMR: δ 200.3, 141.5, 136.5, 132.8, 129.5, 128.9, 128.8, 128.5,
127.8, 126.9, 47.9, 19.5. MS: calcd. C15H14O: m/z 210.10.; found
211.1 [M+H]+.
The authors thank Professor Li-June Ming of the University of South
Florida for carefully reading of the manuscript and constructive comments.
We are grateful for financial support from the Natural Science Foundation
of Shanghai. (NO. 17ZR14120 00).
Supplementary material
Experimental procedures and full characterization data for all compounds
are available on the Journal’s website.
-Phenyl--(p-tolyl)--propanone (i)
1
Yellow oil. H NMR: δ 7.88 (d, J = 8.0 Hz, 2H, CO-ArH),
Funding
7.28–7.31 (m, 5H, CH-ArH), 7.20 (d, J = 8.0 Hz, 2H, CO-ArH),
4.68–4.70 (m, 1H, CH), 2.37 (s, 3H, Ar-CH3), 1.55 (d, J = 6.8 Hz
3H, CHCH3). 13C NMR: δ 199.8.3, 141.5, 136.5, 132.8, 129.5,
128.9, 128.8, 128.5, 127.8, 126.9, 47.9, 19.5. MS: calcd. C16H16O:
m/z 224.12.; found 225.1 [M+H]+.
The Natural Science Foundation of Shanghai (NO. 17ZR14120 00).
References
[1] Dallavalle, S.; Ferrari, A.; Biasotti, B.; Merlini, L.; Penco, S.;
Gallo, G.; Marzi, M.; Tinti, M.O.; Martinelli, R.; Pisano, C.;
Carminati, P.; Carenini, N.; Beretta, G.; Perego, P.; De Cesare,
M.; Pratesi, G.; Zunino, F. J. Med. Chem. 2001, 44, 3264–3274.
doi:10.1021/jm0108092.
[2] Gandeepan, P.; Parthasarathy, K.; Cheng, C. H. J. Am. Chem. Soc.
2010, 132, 8569–8571. doi:10.1021/ja1026248.
[3] Karpaviciene, I.; Cikotiene, I.; Padrón, J. M. Eur. J. Med. Chem. 2013,
70, 568–578. doi:10.1016/j.ejmech.2013.10.041.
[4] Bandarugattu, V. B.; Naveen, K. K.; Waro, N.; Satoko, H.; Naseem,
A.; Petar, M. M. Anticancer Agents Med. Chem. 2013, 13, 307–332.
doi:10.2174/1871520611313020017.
-(-Methoxyphenyl)--phenyl--propanone (j)
1
Yellow oil. H NMR: δ 7.97 (d, J = 9.2 Hz, 2H, CO-ArH),
7.30–7.31 (m, 4H, CH-ArH), 7.21–7.22 (m, 1H, CH-ArH), 6.88
(d, J = 8.8 Hz, 2H, CO-ArH), 4.64–4.69 (m, 1H, CH), 3.84
(s, 3H, OCH3), 1.54 (d, J = 6.8 Hz, 3H, CH3). 13C NMR: δ 198.9,
142.3, 135.1, 129.2, 128.9, 127.7, 126.8, 47.7, 29.7, 21.6, 19.5. MS:
calcd .C16H16O2: m/z 240.12.; found 241.1 [M+H]+.
[5] Kapdi, A. R.; Fairlamb, I. J. S. New J. Chem. 2013, 37, 961–964.
doi:10.1039/c3nj40943k.
[6] Gobbi, S.; Cavalli, A.; Negri, M.; Schewe, K. E.; Belluti, F.; Piazzi, L.;
Hartmann, R. W.; Recanatini, M.; Bisi, A. J. Med. Chem. 2007, 50,
3420–3422. doi:10.1021/jm0702938.
[7] Deshpande, S. R.; Pai, K. V. J. Enzyme Inhib. Med. Chem. 2012, 27,
241–248. doi:10.3109/14756366.2011.586345.
[8] Bringmann, G.; Gampe, C. M.; Reichert, Y.; Bruhn, T.; Faber, J. H.;
Mikyna, M.; Reichert, M.; Leippe, M.; Brun, R.; Gelhaus, C. J. Med.
Chem. 2007, 50, 6104–6115. doi:10.1021/jm061464w.
[9] Suchand, B.; Satyanarayana, G. J. Org. Chem. 2016, 81, 6409–6423.
doi:10.1021/acs.joc.6b01064.
[10] Wei, Y.; Deb, I.; Yoshikai, N. J. Am. Chem. Soc. 2012, 134, 9098–9101.
doi:10.1021/ja3030824.
[11] Jung, M. E.; Sun, D. L.; Dwight, T. A.; Yu, P.; Li, W.; Houk, K. N. Org.
Lett. 2016, 18, 5138–5141. doi:10.1021/acs.orglett.6b02588.
[12] Lancianesi, S.; Palmieri, A.; Petrini, M. Chem. Rev. 2014, 114,
7108–7149. doi:10.1021/cr400676v.
-(-Chlorophenyl)--cyclopropyl--propanone (l)
1
Yellow oil. H NMR: δ 7.87 (d, J = 8.4 Hz, 2H, ArH), 7.45
(d, J = 8.4 Hz, 2H, ArH), 2.74–2.78 (m, 1H, CH3-CH), 1.27
(d, J = 6.8 Hz, 3H, CHCH3), 1.05–1.07 (m, 1H, CH2CH), 0.56–
0.57 (m, 2H, CH2), 0.49–0.51 (m, 2H, CH2). 13C NMR: δ 202.8,
139.3, 135.3, 129.7, 128.9, 45.1, 16.9, 14.6, 4.36, 3.41. MS: calcd.
C12H13ClO: m/z 208.07.; found 209.1 [M+H]+.
-(-Chlorophenyl)--methyl--butanone (m)
1
Yellow oil. H NMR: δ 7.91 (d, J = 8.4 Hz, 2H, ArH), 7.46
(d, J = 8.4 Hz, 2H, ArH), 3.34–3.39 (m, 1H, CH), 1.80–1.88
(m, 1H, CH2), 1.48–1.55 (m, 1H, CH2), 1,20–1.28 (m, 3H,
CHCH3), 0.89–0.95 (m, 3H, CH2CH3). 13C NMR: δ 203.1, 139.2,
135.2, 129.6, 128.9, 42.2, 26.6, 16.6, 11.7. MS: calcd. C11H13ClO:
m/z 196.67; found 197.6 [M+H]+.
[13] Mardani, H. R.; Golchoubian, H. Tetrahedron Lett. 2006, 47,
2349–2352. doi:10.1016/j.tetlet.2006.02.007.
[14] Sartori, G.; Maggi, R. Chem. Rev. 2006, 106, 1077–1104.
doi:10.1021/cr040695c.
[15] George, S. R. D.; Frith, T. D. H.; Thomas, D. S.; Harper, J. B. Org.
Biomol. Chem. 2015, 13, 9035–9041. doi:10.1039/C5OB01215E.
[16] Kogan, V.; Aizenshtat, Z.; Neumann, R. New J. Chem. 2002, 26,
272–274. doi:10.1039/b110937p.
[17] Wu, X.-F.; Neumann, H.; Spannenberg, A.; Schulz, T.; Jiao,
H.; Beller, M. J. Am. Chem. Soc. 2010, 132, 14596–14602.
doi:10.1021/ja1059922.
[18] Chen, Z.-W.; Ye, D.-N.; Qian, Y.-P.; Ye, M.; Liu, L.-X. Tetrahedron
2013, 69, 6116–6120. doi:10.1016/j.tet.2013.05.057.
[19] Lee, D.; Ryu, T.; Park, Y.; Lee, P. H. Org. Lett. 2014, 16, 1144–1147.
doi:10.1021/ol500003g.
[20] Hudrlik, P. F.; Chou, D. T. W.; Stephenson, M. A. J. Org. Chem.
1982,47, 2987–2993. doi:10.1021/jo00136a034.
[21] Schlepphorst, C.; Maji, B.; Glorius, F. ACS Catal. 2016, 6, 4184–4188.
doi:10.1021/acscatal.6b01351.
[22] Kim, J.; Yi, C. S. ACS Catal.2016, 6, 3336–3339.
doi:10.1021/acscatal.6b00856.
(-Chlorophenyl)-cyclohexylmethanone (n)
Yellow oil.1H NMR: δ 7. 91 (d, J = 8.8 Hz, 2H, Ar-H), 7.45
(d, J = 6.8 Hz, 2H, ArH), 3.21–3.22 (m, 1H, CO-CH), 1.85–
1.90 (m, 4H, CH2), 1.27 (m, 6H, CH2), 13C NMR: δ 202.6, 139.1,
134.7, 129.7, 128.9, 45.7, 29.4, 26.9, 25.8. MS: calcd. C13H15ClO:
m/z 222.08; found 223.2. [M+H]+.
(-Chlorophenyl)-cycloheptylmethanone (o)
1
Yellow oil. H NMR: δ 7.89 (d, J = 8.4 Hz, 2H, ArH), 7.45
(d, J = 8.8 Hz, 2H, ArH), 3.38–3.40 (m, 1H, CO-CH), 1.83–1.96
(m, 2H, CH2), 1.80–1.82(m, 2H, CH2), 1,70–1.76 (m, 6H, CH2),
1.62–1.68 (m, 2H, CH2). 13C NMR: δ 202.9, 139.0, 134. 8, 129.7,
128.9, 46.7, 30.8, 28.3, 26.7. MS: calcd. C14H17ClO: m/z 236.10;
found: [M+H]+, 237.7 [M+H]+.

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Y. YANG ET AL.
[23] Frost, J. R.; Cheong, C. B.; Akhtar, W. M.; Caputo, D. F. J.;
Stevenson, N. G.; Donohoe, T. J. J. Am. Chem. Soc. 2015, 137,
15664–15667. doi:10.1021/jacs.5b11196.
[24] Kise, N.; Sakurai, T. J. Org. Chem. 2015, 80, 3496–3503.
doi:10.1021/acs.joc.5b00102.
[25] Zhou, L.; Zhang, Y. Tetrahedron 2000, 56, 2953–2960.
doi:10.1016/S0040-4020(00)00077-6.
[26] Simmons, B. J.; Weires, N. A.; Dander, J. E.; Garg, N. K. ACS Catal.
2016, 6, 3176–3179. doi:10.1021/acscatal.6b00793.
[27] Quan, X.; Kerdphon, S.; Andersson, P. G. Chem. Eur. J. 2015, 21,
3576–3579. doi:10.1002/chem.201405990.
[28] Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–927.
doi:10.1021/cr00094a007.
[32] Kanemasa, S.; Tanaka, J.; Nagahama, H.; Tsuge, O. Bull. Chem. Soc.
Jpn. 1985, 58, 3385–3386. doi:10.1246/bcsj.58.3385.
[33] Zimmerman, H. E.; Cheng, J. J. Org. Chem. 2006, 71, 873–882.
doi:10.1021/jo051611i.
[34] Jung, M. E.; Cordova, J.; Murakami, M. Org. Lett. 2009, 11,
3882–3885. doi:10.1021/ol901455q.
[35] Kim, D. Y.; Oh, D. Y. Synth. Commun. 1986, 16, 859–863.
doi:10.1080/00397918608077285.
[36] Burkhouse, D.; Zimmer, H. Synthesis 1984, 4, 330–332. doi:10.1055/s-
3401984-30832.
[37] Jedhe, G. S.; Kotmale, A. S.; Rajamohanan, P. R.; Pasha,
S.; Sanjayan, G. J. Chem. Commun. 2016, 52, 1645–1648.
doi:10.1039/C5CC09687A.
[29] Ianni, A.; Waldvogel, S. R. Synthesis 2006, 2103–2112.
[30] Molander, G. A.; Figueroa, R. J. Org. Chem. 2006, 71, 6135–6140.
doi:10.1021/jo060863w.
[31] Liu, Z.; Gong, Y.; Byun, H.-S.; Bittman, R. New J. Chem. 2010, 34,
470–475. doi:10.1039/b9nj00710e.
[38] Jones, C. R.; Butts, C. P.; Harvey, J. N. Beilstein J. Org. Chem. 2011, 7,
145–150. doi:10.3762/bjoc.7.20.
[39] Butts, C. P.; Jones, C. R.; Towers, E. C.; Flynn, J. L.; Appleby,
L.; Barron, N. J. Org. Biomol. Chem. 2011, 9, 177–184.
doi:10.1039/C0OB00479K.