Acid-catalyzed C-O coupling of styrenes with N-hydroxyphthalimide: Trapping alkenyl radicals by TEMPO

Article abstract of DOI:10.1016/j.tet.2016.04.028

A mild metal-free acid-catalyzed 1,2-dihydroxylaminations of alkenes with N-hydroxyphthalimide and 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) has been demonstrated under air conditions to furnish the dioxygenated products in good to excellent yields. Th

Full text of DOI:10.1016/j.tet.2016.04.028

Accepted Manuscript
Acid-catalyzed C–O coupling of styrenes with N-hydroxyphthalimide: trapping alkenyl
radicals by TEMPO
Xiao-Feng Xia, Su-Li Zhu, Yan-Ning Niu, Danting Zhang, Xiang Liu, Haijun Wang
PII:
S0040-4020(16)30290-3
10.1016/j.tet.2016.04.028
TET 27671
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 February 2016
Revised Date: 9 April 2016
Accepted Date: 11 April 2016
Please cite this article as: Xia X-F, Zhu S-L, Niu Y-N, Zhang D, Liu X, Wang H, Acid-catalyzed C–O
coupling of styrenes with -hydroxyphthalimide: trapping alkenyl radicals by TEMPO, Tetrahedron (2016),
doi: 10.1016/j.tet.2016.04.028.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Leave this area blank for abstract info.
Acid-Catalyzed C-O Coupling of Styrenes with N-hydroxyphthalimide:
Trapping Alkenyl Radicals by TEMPO
Xiao-Feng Xia,*a Su-Li Zhu, a Yan-Ning Niu,b Danting Zhang, a Xiang Liu, a Haijun Wang a
a The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and
Material Engineering, Jiangnan University, Wuxi, Jiangsu, 214122, China.
b Southern College (huai’an) of Nanjing Forestry University, Jiangsu, 223003, China.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Acid-Catalyzed C-O Coupling of Styrenes with N-hydroxyphthalimide:
Trapping Alkenyl Radicals by TEMPO
Xiao-Feng Xia,*a Su-Li Zhu, a Yan-Ning Niu,b Danting Zhang, a Xiang Liu, a Haijun Wang a
a The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi,
Jiangsu, 214122, China.
b Southern College (huai’an) of Nanjing Forestry University, Jiangsu, 223003, China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A
mild metal-free acid-catalyzed 1,2-dihydroxylaminations of alkenes with N-
hydroxyphthalimide and 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) has been demonstrated
under air conditions to furnish the dioxygenated products in good to excellent yields. The
dioxygenated product can be easily transformed into ketone derivative using 3-chloroperbenzoic
acid (m-CPBA) as the oxidant in a high yield.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Acid-catalyzed
C-O coupling
N-hydroxyphthalimide
TEMPO
1,2-dihydroxylaminations
1. Introduction
Alkenes are abundant simple chemical feedstocks and organic
molecules, which have been widely applied in organic synthesis,
and methods for their efficient, selective transformations are
attractive to construct more complex molecules.1 In these
methodologies, direct 1,2-difunctionalization of alkenes has
stimulated chemists’ considerable attention, providing the most
efficient strategy for the synthesis of functionalized organic
compounds.2 1,2-Dioxygenated structures are present in many
natural products and biologically active molecules, such as
Myriocin and related immunosuppressive compounds.3 In this
context, in recent years, a series of metal-catalyzed 1,2-
dioxygenation of alkenes have been developed,4 however, metal-
free conditions have not been seriously studied up to now.5 On
the other hand, as we all know, TEMPO is usually used as a
radical scavenging to trap radicals or inhibit reactions in radical
reactions. At the same time, olefins are undoubtedly one of the
most important radical acceptors. When they are attacked by
radicals, alkyl radicals are formed which can be easily trapped by
TEMPO and give useful aminoxylative products. Indeed, some
significant studies on intermolecular aminoxylative of olefins
have been reported involving Ar, CF3, NO2 and N3 radicals
(Scheme 1-1).6 Recently, our group and others found that N-
hydroxyphthalimide (NHPI) can generate the phthalimide N-oxyl
(PINO) radical under the oxidizing conditions, which is an active
species to realize the radical addition of alkenes.5b, 7 Herein, we
envisioned that the PINO captured alkyl radicals from alkenes
can be also trapped by TEMPO to give the 1,2-dioxygenated
products (Scheme 1-2).
Scheme 1. Trapping alkyl radicals by TEMPO.
2. Results/Discussion
On the basis of our assumption, we began our study using our
previous conditions 5b by reacting styrene 1a with NHPI 2a and
TEMPO using 10% 4-methylbenzenesulfonic acid (TsOH) as a
catalyst, t-butylhydroperoxide (TBHP, 5.0 equiv.) as the oxidant
in 1,2-dichloroethane (DCE) at room temperature, and 3a was
indeed sluggishly produced in 86% yield after 24 hours (Table 1,
entry 1). When the oxidant was omitted, no reaction was
detected, which meant that TEMPO was not the oxidant in this

2
Tetrahedron
ACCEPTED MANUSCRIPT
reaction and TBHP was essential for this transformation. When
peroxide product 3o was separated in 70% yield, which was
oxygen gas (1 atm) was used as the oxidant, only trace amount of
product was observed (entry 3). Interestingly, the loading of
TBHP was decreased to 3 equivalents, and the yield was
increased to 92% within 24 hours (entry 5). Then, the reaction
difficult to be synthesized in our previous work. α-Methyl styrene
did not yield the corresponding product, but an allyl product 3p
(Scheme 3). In our opinion, when NHPI radical added to α-
methyl styrene, a benzyl radical was obtained, which underwent
further oxidation to give benzyl ion. Due to the steric hindrance
of TEMPO, an easily proton elimination was occurred to give the
product 3p.
o
temperature was increased to 60 C, the yield reached up to 98%
in a short time (4 hours). Other acids were also tried, and no
better results were obtained (entries 7 and 8). When the loadings
of 1a and TEMPO were changed to 1.0 equiv., the yield of 3a
was decreased to 57%.
Table 1. Optimization of Reaction Conditions for 3aa
Entry Catalyst
Oxidant
Solvent
T/
Yield
(%)b
86%
(oC)
r.t.
1
10% TsOH
5.0 equiv. DCE
TBHP
2
3
4
10% TsOH
10% TsOH
10% TsOH
DCE
DCE
2.0 equiv. DCE
TBHP
r.t.
r.t.
r.t.
0%
<5%
69%
—
O2
5
6
7
8
10% TsOH
3.0 equiv. DCE
TBHP
r.t.
60
60
60
60
92%
98%c
70% c
68% c
57%
10% TsOH 3.0 equiv. DCE
TBHP
10%
PhCOOH
10%
HOAc
3.0 equiv. DCE
TBHP
3.0 equiv. DCE
TBHP
3.0 equiv. DCE
TBHP
9d
10% TsOH
a
Reaction conditions: 1a (0.45 mmol), N-hydroxyphthalimide
(0.3 mmol), TEMPO (0.6 mmol), catalyst (0.03 mmol, 10%),
b
c
oxidant, and solvent (2.0 mL), 12 h. Isolated yield. 4h.d
1a:NHPI:TEMPO= 1:1:1.
With the optimal reaction condition in hand (Table 1, entry 6), we
subsequently investigated the substrate scope of this highly selective
method (Scheme 2). A series of substituted styrenes including fluoro,
chloro, bromo, methoxyl, ester, cyano and methyl substituents, can
readily be converted into the corresponding products in good to
excellent yields, where 1-methyl-4-vinylbenzene gave the product 3b
in 97% yield. Electron-withdrawing substituents on the para position
gave a slightly lower yield (3c, 3d, 3e, 3f, 3l). When a sterically
demanding ortho substituted Cl was imbedded in styrene, a slightly
lower yield was obtained (3g). 3-Bromostyrene delivered the product
3h in 68% yield, while 3-chlorostyrene gave a higher yield (3i, 86%).
2-Vinylnaphthalene gave a moderate yield (3j, 68%). (E)-Prop-1-
enylbenzene can be well tolerated in this reaction, providing 3k in
50% yield in a single isomer. (E)-1,2-Diphenylethene was also
tolerated, but unfortunately, a very low yield was obtained due to the
steric hindrance (3l, 15%, dr=1.3:1). When norbornene was used as
substrate under the standard conditions, the target product 3m was
obtained in 86% yield. Cyano substituent was also well retained
during the reaction (3n). When the olefin with an expanded pi-
system such as (1E, 3E)-1,4-diphenylbuta-1,3-diene was used in our
reaction conditions, a mixture was obtained. Interestingly, when 4-
methoxylstyrene was submitted to the reaction conditions, a
Scheme 2. The scope of the reaction
Scheme 3. The special scope of the reaction

3
1
In view of the reactive N−O bond, the dioxygenated product can
be easily transformed into the ketone derivative 4a in 90% yield
using m-CPBA as the oxidant at room temperature (Scheme 4).
isoindolin-1,3-dione, 3a, oil, H NMR (400 M HZ, CDCl3):
ACCEPTED MANUSCRIPT
7.67-7.77 (m, 4 H), 7.46-7.47 (m, 2 H), 7.33-7.35 (m, 2 H), 7.25-
7.31 (m, 1 H), 5.13-5.16 (m, 1 H), 4.73-4.75 (m, 1 H), 4.48-4.52
(m, 2 H), 1.20-1.46 (m, 13 H), 1.05 (m, 3 H), 0.72 (m, 2 H); 13C
NMR (100 MHz, CDCl3): 163.0, 140.0, 134.2, 128.3, 127.7,
123.2, 83.2, 80.1, 60.0, 40.3, 33.9, 20.2, 17.0; HRMS (ESI) m/z:
calcd for C25H30N2O4Na+: [M+Na+]= 445.2103; found: 445.2104.
IR (cm-1): 3063, 2972, 2931, 1790, 1732, 1467, 1454, 1375,
1362, 1187, 1132, 1018, 996, 877, 784;
N
O
O
2.0 eq. mCPBA
CH2Cl2, r.t. 12h
O
O
O
N
O
N
O
O
2-(2-(2,2,6,6,-tetramethylpiperidin-1-yloxy)-2-p-tolylethoxy)-
4a, 90% yield
3a, 0.5 mmol
1
isoindoline-1,3-dione, 3b, oil, H NMR (400 M HZ, CDCl3):
7.68-7.78 (m, 4 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.13 (d, J = 8.0 Hz,
2 H), 5.08-5.11 (m, 1 H), 4.71-4.74 (m, 1 H), 4.47-4.51 (m, 1 H),
2.3 (s, 3 H), 1.04-1.46 (m, 16 H), 0.74 (s, 2 H); 13C NMR (100
MHz, CDCl3): 163.1, 137.3, 137.0, 134.2, 128.8, 128.7, 127.8,
123.2, 82.9, 79.9, 59.9, 40.3, 34.1, 33.9, 21.1, 20.2, 17.1; IR (cm-
1): 2972, 2930, 1790, 1731, 1514, 1468, 1375, 1361, 1186, 1131,
1081, 1017, 876, 817, 701; HRMS (ESI) m/z: calcd for
C26H32N2O4Na+: [M+Na+ ]= 459.2260; found:459.2282.
Scheme 4. Transformation of the product 3a
Last, a one-pot two-steps reaction was also tried using the
standard reaction conditions, and the product 4a was obtained in
80% yield (Scheme 5).
2-(2-(4-chlorophenyl)-2-(2,2,6,6-tetramethylpiperidin-1-yloxy)-
ethoxy)isoindoline-1,3-dione, 3c, M.P.= 86-88 oC, 1H NMR (400
M HZ, CDCl3): 7.71-7.79 (m, 4 H), 7.43 (d, J= 8.0 Hz, 2 H), 7.31
(d, J = 8.0 Hz, 2 H), 5.08-5.11 (m, 1 H), 4.69-4.72 (m, 1 H),
4.45-4.49 (m, 1 H), 1.03-1.47 (m, 16 H), 0.73 (m, 2 H); 13C NMR
(100 MHz, CDCl3): 162.9, 138.5, 134.2, 133.3, 129.1, 128.5,
127.9, 123.1, 82.4, 79.5, 59.8, 40.1, 33.9, 33.8, 20.0, 16.8; IR
(cm-1): 2973, 2932, 1791, 1731, 1491, 1467, 1375, 1362, 1187,
1131, 1082, 1015, 876, 830, 701; HRMS (ESI) m/z: calcd for
C25H29ClN2O4Na+: [M+Na+ ]= 479.1714; found: 479.1714.
Scheme 5. One pot reaction
3. Conclusion
In conclusion, we have developed an efficient acid-catalyzed
highly 1,2-dihydroxylation of olefins with N-hydroxyphthalimide
and TEMPO. A radical addition process was involved in this
transformation with the formation of two C-O bonds in one step.
The product can be further easily transformed into ketone
derivative using m-CPBA as the oxidant. Further investigations
on the synthetic application of these reactions are ongoing in our
group.
2-(2-(4-fluorophenyl)-2-(2,2,6,6-tetramethylpiperidin-1-
yloxy)ethoxy)isoindoline-1,3-dione, 3d, M.P.=75-77 oC
,
1H
NMR (400 M HZ, CDCl3): 7.70-7.79 (m, 4 H), 7.45 (d, J = 8.0
Hz, 2 H), 7.01-7.05 (m, 2 H), 5.09-5.12 (m, 1 H), 4.70-4.73 (m, 1
H), 4.45-4.49 (m, 1 H), 1.03-1.47 (m,16 H), 0.71 (m, 2 H); 13C
NMR (100 MHz, CDCl3): 163.5, 163.0, 161.1, 135.9, 134.3,
129.6, 128.7, 123.3, 114.9, 114.7, 82.4, 79.8, 60.1, 59.9, 40.3,
33.9, 20.2, 16.9; IR (cm-1): 2973, 2932, 1791, 1732, 1605, 1509,
1375, 1361, 1187, 1131, 1071, 877, 836; HRMS (ESI) m/z: calcd
for C25H29FN2O4Na+: [M+ Na+ ]= 463.2009; found: 463.2010.
4. Experimental section
4.1 General Remarks:
Column chromatography was carried out on silica gel. Unless
noted, 1H NMR spectra were recorded on 400 MHz in CDCl3, 13C
NMR spectra were recorded on 100 MHz in CDCl3. IR spectra
were recorded on an FT-IR spectrometer and only major peaks
are reported in cm-1. Melting points were determined on a
microscopic apparatus and were uncorrected. All new products
were further characterized by HRMS (high resolution mass
spectra), high resolution mass spectrometry (HRMS) spectra was
obtained on a micrOTOF-Q instrument equipped with an ESI
source; copies of their 1H NMR and 13C NMR spectra are
provided. Commercially available reagents and solvents were
used without further purification.
Methyl
4-(2-(1,3-dioxoisoindolin-2-yloxy)-1-(2,2,6,6-
tetramethylpiperidin-1-yloxy)ethyl)benzoate, 3e, M.P.=100-102
oC, 1H NMR (400 M HZ, CDCl3): 7.70-7.78 (m, 2 H), 7.50 (d, J =
8.0 Hz, 2 H), 7.09 (d, J = 8.0 Hz, 2 H), 5.14-5.17 (m, 1 H), 4.72-
4.74 (m, 1 H), 4.44-4.49 (m, 1 H), 2.3 (s, 3 H), 1.05-1.47 (m, 16
H), 0.74 (m, 2 H); 13C NMR (100 MHz, CDCl3): 169.0, 163.0,
150.1, 137.5, 134.3, 128.8, 128.6, 123.2, 120.9, 82.4, 79.9, 59.9,
40.2, 33.9, 33.8, 20.9, 20.1, 16.9; IR (cm-1): 2973, 2933, 1790,
1731, 1506, 1467, 1372, 1131, 1081, 1017, 877, 701; HRMS
(ESI) m/z: calcd for C27H32N2O6Na+: [M+Na+]= 503.2158; found:
503.2156.
4.2 Typical procedure for the synthesis of products 3
To a solution of N-hydroxyphthalimide (2, 0.3 mmol, 48.9 mg)
and TEMPO (0.6 mmol, 93.6 mg) in DCE (2.0 mL) was added
styrene (1, 0.45 mmol), TsOH (10%, 0.03 mmol, 5.2 mg), TBHP
(3.0 equiv., 150 uL, 5-6 M in decane). The reaction mixture was
then stirred for 4 h at 60 oC in air. After the reaction, the resulting
mixture was quenched with water and extracted twice with
EtOAc (10 mL). The combined organic extracts were washed
with brine (10 mL), dried over Na2SO4 and concentrated.
Purification of the crude product by flash column
chromatography afforded the product 3 (petroleum ether/ethyl
acetate as eluent (10:1)).
2-(2-(4-bromophenyl)-2-(2,2,6,6-tetramethylpiperidin-1-yloxy)
o
1
ethoxy)isoindoline-1,3-dione, 3f, M.P.= 95-97 C, H NMR (400
M HZ, CDCl3): 7.70-7.79 (m, 4 H), 7.45 (d, J = 8.0 Hz, 2 H), 7.37
(d, J = 8.0 Hz, 2 H), 5.06-5.09 (m, 1 H), 4.69-4.71 (m, 1 H),
4.44-4.49 (m, 1 H), 1.03-1.47 (m, 16 H), 0.73 (m, 2 H); 13C NMR
(100 MHz, CDCl3): 163.0, 139.2, 134.4, 128.7, 123.3, 121.7,
82.6, 79.6, 60.0, 40.3, 34.1, 33.9, 20.2, 17.0; IR (cm-1): 2973,
2932, 1790, 1731, 1487, 1468, 1374, 1361, 1186, 1131, 1081,
1072, 876, 826; HRMS (ESI) m/z: calcd for C25H29BrN2O4Na+:
[M+Na+]= 523.1208; found: 523.1239.
2-(2-phenyl-2-(2,2,6,6-tetramethylpiperidin-1-yloxy)ethoxy)-
2-(2-(2-chlorophenyl)-2-(2,2,6,6-tetramethylpiperidin-1-yloxy)

4
Tetrahedron
o
1
ethoxy)isoindoline-1,3-dione, 3g, M.P.= 85-87 C, H NMR
(400 M HZ, CDCl3): 7.80-7.82 (m, 2 H), 7.73-7.75 (m, 2 H),
4.35-4.46 (m, 1 H), 4.10-4.23 (m, 1 H), 2.65 (m, 1 H), 2.25-2.26
(m, 1 H), 1.98-2.00 (m, 1 H), 1.81-1.83 (m, 1 H), 1.53-1.60 (m, 2
H), 1.44 (m, 7 H), 1.26-1.34 (m, 3 H), 1.11-1.19 (m, 10 H); 13C
NMR (100 MHz, CDCl3): 163.8, 134.1, 128.9, 123.1, 94.9, 90.8,
89.8, 59.9, 59.1, 40.4, 40.2, 39.9, 39.5, 33.9, 33.7, 33.6, 32.7,
25.4, 24.0, 23.5, 20.0, 17.0; IR (cm-1): 2971, 2933, 1790, 1731,
1461, 1374, 1361, 1185, 1131, 1082, 1045, 876, 733; HRMS
(ESI) m/z: calcd for C24H32N2O4Na+: [M+Na+]= 435.2260; found:
435.2263.
ACCEPTED MANUSCRIPT
(400 M HZ, CDCl3): 7.68-7.77 (m,5 H), 7.21-7.34 (m, 3 H), 5.50-
5.52 (m, 1 H), 4.70-4.74 (m, 1 H), 4.57-4.60 (m, 1 H), 1.06-1.49
(m, 16 H), 0.78 (m, 2 H); 13C NMR (100 MHz, CDCl3): 162.9,
137.7, 134.2, 132.3, 128.6, 126.4, 123.2, 81.3, 78.7, 60.0, 40.3,
34.0, 33.1, 20.2, 17.0; IR (cm-1): 3062, 2973, 2932, 1791, 1732,
1468, 1187, 1131, 1081, 1034, 876, 759; HRMS (ESI) m/z: calcd
for C25H29ClN2O4Na+: [M+Na+]= 479.1714; found: 479.1710.
2-(2-(3-bromophenyl)-2-(2,2,6,6-tetramethylpiperidin-1-yloxy)
ethoxy)isoindoline-1,3-dione, 3h, oil, 1H NMR (400 M HZ,
CDCl3): 7.70-7.80 (m, 4 H), 7.63 (s, 1 H), 7.38-7.44 (m, 2 H),
7.20-7.24 (m, 1 H), 5.07-5.10 (m, 1 H), 4.69-4.71 (m, 1 H), 4.45-
4.49 (m, 1 H), 1.05-1.47 (m, 16 H), 0.74 (m, 2 H); 13C NMR (100
MHz, CDCl3): 163.0, 142.5, 134.3, 130.9, 130.7, 129.6, 128.7,
126.5, 123.3, 122.1, 82.6, 79.6, 60.1, 40.3, 33.9, 20.2, 17.0; IR
(cm-1): 3070, 2972, 1790, 1730, 1570, 1374, 1361, 1186, 1131,
1081, 876, 785; HRMS (ESI) m/z: calcd for C25H29BrN2O4Na+:
[M+Na+]= 523.1208; found: 523.1230.
4-(2-((1,3-dioxoisoindolin-2-yl)oxy-1-((2,2,6,6-tetramethyl-
o
1
piperidin-1-yl)oxy)ethyl)benzonitrile, 3n, M.P.=119-120 C, H
NMR (400 M HZ, CDCl3): 7.79-7.81 (m, 4 H), 7.63-7.75 (m, 4
H), 5.14-5.17 (m, 1 H), 4.70-4.73 (m, 1 H), 4.47-4.52 (m, 1 H),
1.43-1.49 (m, 5 H), 1.05-1.40 (m, 10 H), 0.73 (m, 3 H); 13C NMR
(100 MHz, CDCl3): 162.9, 145.4, 134.4, 131.7, 128.4, 123.3,
118.7, 111.3, 82.6, 79.2, 60.0, 40.1, 33.8, 20.1, 16.8; IR(cm-1):
2937, 2229, 1791, 1733, 1467, 1374, 1187, 1130, 1020, 996, 877,
840; HRMS (ESI) m/z: calcd for C26H29N3O4Na+: [M+Na+]=
470.2056; found: 470.2086.
2-(2-(3-chlorophenyl)-2-((2,2,6,6-tetramethylpiperidin-1-yl)oxy)
ethoxy)isoindoline-1,3-dione, 3i, oil, 1H NMR (400 MHZ,
CDCl3): 7.72-7.79 (m, 4 H), 7.48 (s, 1 H), 7.37-7.39 (m, 1 H),
7.23-7.30 (m, 2 H), 5.08-5.11 (m, 1 H), 4.69-4.71 (m, 1 H), 4.45-
4.49 (m, 1 H), 1.05-1.47 (m, 16 H), 0.74 (m, 2 H); 13C NMR (100
MHz, CDCl3): 163.1, 142.2, 134.4, 133.8, 129.3, 128.7, 128.0,
127.8, 126.1, 123.3, 82.7, 79.7, 65.8, 60.1, 40.3, 34.0, 20.2, 17.0,
15.2; IR (cm-1): 2973, 2932, 1791, 1732, 1468, 1362, 1187, 1131,
1081, 1018, 998, 876, 786, 699; HRMS (ESI) m/z: calcd for
C25H29ClN2O4H+: [M+H+]=457.1894; found: 457.1896.
2-(2-(tert-butylperoxy)-2-(4-methoxyphenyl)ethoxy)isoindoline-
1,3-dione, 3o, oil, H NMR (400 M HZ, CDCl3): 7.71-7.81 (m, 4
1
H), 7.35-7.38 (m, 2 H), 6.87 (d, J = 8.0 Hz, 2 H), 5.30-5.33 (m, 1
H), 4.62-4.65 (m, 1 H), 4.44-4.48 (m, 1 H), 3.77 (s, 3 H), 1.17 (s,
9 H); 13C NMR (100 MHz, CDCl3): 163.1, 159.7, 134.3, 128.9,
128.8, 123.3, 113.7, 82.8, 80.6, 78.2, 55.1, 28.5, 26.2; IR (cm-1):
2977, 2933, 1790, 1731, 1612, 1407, 1364, 1249, 1186, 1130,
1018, 996, 877, 830, 701; HRMS (ESI) m/z: calcd for
C21H23NO6Na+: [M+ Na+]= 408.1423; found: 408.1415.
2-(2-(naphthalen-2-yl)-2-((2,2,6,6-tetramethylpiperidin-1-yl)oxy)
2-(2-phenylallyloxy)isoindoline-1,3-dione, 3p, oil, 1H NMR (400
M HZ, CDCl3): 7.81-7.83 (m, 2 H), 7.72-7.75 (m, 2 H), 7.66-7.68
(m, 2 H), 7.38-7.40 (m, 2 H), 7.33-7.37 (m, 1 H), 5.73 (s, 1 H),
5.51 (s, 1 H), 5.09 (s, 2 H); 13C NMR (100 MHz, CDCl3): 163.4,
141.2, 137.8, 134.4, 128.4, 127.9, 126.2, 123.4, 119.6, 79.7; IR
(cm-1): 3060, 2970, 1790, 1731, 1645, 1465, 1180, 1130, 1080,
1034, 876.
ethoxy)isoindoline-1,3-dione, 3j, M.P.=108-109 oC, 1H NMR
(400 MHZ, CDCl3): 7.92 (s, 1 H), 7.76-7.86 (m, 3 H), 7.68-7.71
(m, 2 H), 7.58-7.62 (m, 3 H), 7.39-7.46 (m, 2 H), 5.28-5.31 (m, 1
H), 4.80-4.84 (m, 1 H), 4.58-4.62 (m, 1 H), 1.05-1.49 (m, 16 H),
0.69 (m, 2 H); 13C NMR (100 MHz, CDCl3): 163.0, 137.4, 132.9,
128.0, 127.7, 127.5, 127.3, 125.7, 125.6, 125.4, 123.1, 83.5, 79.7,
40.3, 17.0; IR (cm-1): 3058, 2976, 2932, 1788, 1734, 1465, 1369,
1183, 1129, 994, 874, 818, 742; HRMS (ESI) m/z: calcd for
C29H32N2O4H+:[M+H+]=473.2440; found: 473.2440.
Acknowledgments
2-(1-phenyl-1-(2,2,6,6-tetramethylpiperidin-1-yloxy)propan-2-
yloxy)isoindoline-1,3-dione, 3k, oil, 1H NMR (400 M HZ,
CDCl3): 7.79-7.82 (m, 2 H), 7.71-7.74 (m, 2 H), 7.62-7.64 (m, 2
H), 7.28-7.35 (m, 3 H), 5.05-5.11 (m, 1 H), 4.83 (d, J = 3.2 Hz, 1
H), 1.27-1.40 (m, 15 H), 1.10 (m, 2 H), 1.00 (m, 2 H), 0.46 (m, 2
H); 13C NMR (100 MHz, CDCl3): 163.7, 138.6, 134.2, 129.8,
129.0, 127.5, 123.1, 89.8, 85.4, 60.4, 59.5, 40.6, 34.4, 33.9, 20.2,
17.0, 16.4; IR (cm-1): 3070, 2932, 1791, 1731, 1467, 1455, 1376,
1362, 1187, 1131, 1081, 1016, 878; HRMS (ESI) m/z: calcd for
C26H32N2O4Na+: [M+Na+]= 459.2260; found: 459.2260.
We thank the National Science Foundation of China NSF
21402066, Natural Science Foundation of Jiangsu Province
(BK20140139) and the Fundamental Research Funds for the
Central Universities (JUSRP11419) for financial support.
Financial support from MOE&SAFEA for the 111 project
(B13025) is also gratefully acknowledged
.
References and notes
1. For selected reviews, see: (a) The Chemistry of Double Bonded Functional
Groups; Patai, S., Ed.; Wiley: Chichester, U.K., 1997. (b) Takacs, J. M.;
Jiang, X. Curr. Org. Chem. 2003, 7, 369. (c) Cornell, C. N.; Sigman, M. S.
Inorg. Chem. 2007, 46, 1903. (d) Muzart, J. Tetrahedron 2007, 63, 7505.
(e) Flynn, A. B.; Ogilvie, W. W. Chem.Rev. 2007, 107, 4698. (f) Tang, S.;
Liu, K.; Liu, C.; Lei, A. Chem. Soc. Rev. 2015, 44, 1070.
2-(1,2-diphenyl-2-(2,2,6,6-tetramethylpiperidin-1-yloxy)ethoxy)
1
isoindoline-1,3-dione, 3l, dr=1.3:1, oil, H NMR (400 M HZ,
CDCl3): 7.61-7.73 (m, 4 H), 7.06-7.34 (m, 10 H), 6.01-6.20 (d, J
= 5.2, 6.8 Hz, 1 H), 5.04-5.45 (d, J = 6.8, 5.2 Hz, 1 H), 1.26-1.67
(m, 15 H), 1.01-1.02 (m, 3 H); 13C NMR (100 MHz, CDCl3):
163.5, 138.9, 137.3, 136.1, 135.3, 134.1, 128.2, 127.1, 123.2,
123.1, 89.8, 88.8, 88.6, 88.0, 60.7, 40.9, 34.5, 33.8, 31.5, 30.1,
29.7, 22.7, 20.4, 17.1; IR (cm-1): 2930, 1790, 1737, 1455, 1374,
1187, 1132, 976, 876, 699; HRMS (ESI) m/z: calcd for
C31H34N2O4Na+: [M+Na+] = 521.2416; found: 521.2417.
2. For selected reviews, see: (a) Sibbald, P. A. Palladium-catalyzed oxidative
difunctionalization of alkenes: New reactivity and new mechanisms,
ProQuest, UMI Dissertation Publishing, 2011. (b) Jacques, B.; Muinz K.
Catalyzed carbon-heteroatom bond formation (Ed.: A. K. Yudin), Wiley,
VCH, 2011. (c) McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev. 2011,
111, 2981. (d) Jensen, K. H.; Sigman, M, S. Org. Biomol Chem. 2008, 6,
4083. (e) Schultz, D. M.; Wolfe, J. P. Synthesis. 2012, 44, 351. (f) Mai, W.;
2-(3-(2,2,6,6-tetramethylpiperidin-1-yloxy)bicycle[2.2.1]heptan-
o
1
2-yloxy)isoindoline-1,3-dione, 3m, M.P.= 104-106 C, H NMR

5
Wang, J.; Yang, L.; Yuan, J.; Mao, P.; Xiao, Y.; Qu, L. Chin. J. Org.
Chem. 2014, 34, 1958.
Liang, Y.-M. J. Org. Chem. 2015, 80, 5572. (c) Xue, Q.; Xie, J.; Xu, P.;
ACCEPTED MANUSCRIPT
Hu, K.; Cheng, Y.; Zhu, C. ACS Catal. 2013, 3, 1365. (d) Chen, J.; Shao,
Y.; Zheng, H.; Cheng, J.; Wan, X. J. Org. Chem. 2015, 80, 10734.
3. (a) Kiuchi, M.; Adachi, K.; Kohara, T.; Minoguchi, M.; Hanano, T.; Aoki,
Y.; Mishina, T.; Arita, M.; Nakao, N.; Ohtsuki, M.; Hoshino, Y.; Teshima,
K.; Chiba, K.; Sasaki, S.; Fujita, T. J. Med. Chem. 2000, 43, 2946. (b)
Zhou, S.; Drach, J. C.; Prichard, M. N.; Zemlicka, J. J. Med. Chem.
2009, 52, 3397. (c) Ardashov, O. V.; Pavlova, A. V.; Il’ina, I.
V.; Morozova, E. A.; Korchagina, D. V.; Karpova, E. V.; Volcho, K. P.;
Tolstikova, T. G.; Salakhutdinov, N. F. J. Med. Chem., 2011, 54, 3866.
6. (a) Heinrich, M. R.; Wetzel, A.; Kirschstein, M. Org. Lett. 2007, 9, 3833.
(b) Hartmann, M.; Li, Y.; Studer, A. J. Am. Chem. Soc. 2012, 134,16516.
(c) Li, Y.; Studer, A. Angew. Chem., Int. Ed. 2012, 51, 8221. (d) Zhang, B.;
Studer, A. Org. Lett. 2013, 15, 4548. (e) Pradhan, P. P.; Bobbitt, J. M.;
Bailey, W. F. Org. Lett. 2006, 8, 5485. (f) Yan, H.; Rong, G.; Liu, D.;
Zheng, Y.; Chen, J.; Mao, J. Org. Lett. 2014, 16, 6306. (g) Hartmann, M.;
Li, Y.; Mück-Lichtenfeld, C.; Studer, A. Chem. Eur. J. 2016, 22, DOI :
10.1002/chem.201504852. (h) Dutta, U.; Maity, S.; Kancherla, R.; Maiti, D.
Org. Lett. 2014, 16, 6302.
4. For selected dioxygenation, see: (a) Bataille, C. J. R.; Donohoe, T. J.
Chem. Soc. Rev. 2011, 40, 114. (b) Schmidt, V. A.; Alexanian, E. J.
Angew. Chem., Int. Ed. 2010, 49, 4491. (c) Zhang, Y.; Shen, Z.; Tang, J.;
Zhang, Y.; Kong, L.; Zhang, Y. Org. Biomol. Chem. 2006, 4, 1478. (d)
Plietker, B. J. Org. Chem. 2003, 68, 7123. (e) Plietker, B. Eur. J. Org.
Chem. 2005, 9, 1919. (f) Plietker, B. J. Org. Chem. 2004, 69, 8287. (g)
Cornell, C. N.; Sigman, M. S. J. Am. Chem. Soc. 2005, 127, 2796. (h)
Abeykoon, G. A.; Chatterjee, S.; Chen, J. S. Org. Lett. 2014, 16, 3248. (i)
Plietker, B. Org. Lett. 2004, 6, 289. (j) Lu, Q.; Liu, Z.; Luo, Y.; Zhang, G.;
Huang, Z.; Wang, H.; Liu, C.; Miller, J. T.; Lei, A. Org. Lett. 2015, 17,
3402. (k) Bag, R.; Sar, D.; Punniyamurthy, T. Org. Lett. 2015, 17, 2010. (l)
Andia, A. A.; Miner, M. R.; Woerpel, K. A. Org. Lett. 2015, 17, 2704. (m)
Li, W.; Jia, P.; Han, B.; Li, D.; Yu, W. Tetrahedron. 2013, 69, 3274.
7. (a) Xia, X.-F.; Gu, Z.; Liu, W.; Wang, H.; Xia, Y.; Gao, H.; Liu, X.; Liang,
Y.-M. J. Org. Chem. 2015, 80, 290. (b) Xia, X.-F.; Zhu, S.-L.; Zhang, D.
Tetrahedron, 2015, 71, 8517.
Click here to remove instruction text...
5. (a) Giglio, B. C.; Schmidt, V. A.; Alexanian, E. J. J. Am. Chem. Soc. 2011,
133, 13320. (b) Xia, X.-F.; Zhu, S.-L.; Gu, Z.; Wang, H.; Li, W.; Liu, X.;