Benzyl C–O and C–N Bond Construction via C–C Bond Dissociation of Oxime Ester under Visible Light Irradiation

Article abstract of DOI:10.1002/ejoc.201901060

A photoredox benzyl activation was developed via formidable C(sp³)–C(sp³) bond dissociation of 1-aryl acetone oxime esters, which were easily prepared from benzyl ketones. Further coupling with O- and N- nucleophiles successfully forged important benzyl ether and amines derivatives in one pot. In this process, different substitutions on oxime esters were found compatible and various primary and secondary alcohols and amines, as well as amides showed good performance as nucleophiles. Mechanistic studies by control experiments, electrochemical measurements and in-situ NMR spectra proposed a N–O bond interruption/C–C bond fragmentation/oxidation sequence to provide the key cation intermediate for the next electrophilic S_N process. The features of mild condition, short reaction time and broad substrate scope made this new strategy much promising in the transformation of benzyl compounds, which might be valuable in last-stage functionalizations.

Full text of DOI:10.1002/ejoc.201901060

A Journal of
Accepted Article
Title: Benzyl C-O and C-N Bond Construction via C-C Bond
Dissociation of Oxime Ester under Visible Light Irradiation
Authors: Xiuwei Fan, Tao Lei, Zan Liu, Xiu-Long Yang, Bin Chen,
Chen-Ho Tung, Li-Zhu Wu, Yuan-Yuan Cheng, and Ge Liang
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901060
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901060
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10.1002/ejoc.201901060
European Journal of Organic Chemistry
FULL PAPER
Benzyl C-O and C-N Bond Construction via C-C Bond
Dissociation of Oxime Ester under Visible Light Irradiation
Xiuwei Fan,[a, b] Tao Lei,[a, b] Zan Liu,[a, b] Xiu-Long Yang,[a, b] Yuan-Yuan Cheng,[a, b] Ge Liang,[a, b] Bin
Chen,[a, b] Chen-Ho Tung[a, b] and Li-Zhu Wu*[a, b]
Abstract:
A
photoredox benzyl activation was developed via
always needs much higher active energy and is a hitherto
formidable challenge.
formidable C(sp3)-C(sp3) bond dissociation of 1-aryl acetone oxime
esters, which were easily perapared from benzyl ketones. Further
coupling with O- and N- nucleophiles successfully forged important
benzyl ether and amines derivatives in one pot. In this process,
different substitutions on oxime esters were found compatible and
various primary, secondary alcohols and amines as well as amides
showed good performance as nucleophiles. Mechanistic studies via
control experiments, electrochemical measurements and in-situ
Here, we report that 1-aryl acetone oxime ester is able to
efficiently construct benzyl C-O and C-N bonds via C-C bond
dissociation (Scheme 1c). In contrast to the previous reports on
oxime esters with photocatalytic radical addition process,[9-10] 1-
aryl acetone oxime esters were found to experience sequential
N-O bond interruption/β-fragmentation of C(sp3)-C(sp3)
bond/oxidation to provide benzyl cation, which further rapidly
reacted with nucleophilic O- and N-atoms to construct benzyl
C−Het bond efficiently. Although many elegant works based on
fragmentation of iminyl radicals have been established to realize
the bond cleavage from cyclic iminyl radicals and then to react
with radical acceptors, only two examples by Zhou[10a] and
Shi[10e] realized the benzyl C-C bond dissociation via ring
opening of cyclic reactant to provide the benzyl C-O bond with
remote CN substitution. Especially, Shi and co-workers[10e] found
the intramolecular fragmentation-rearrangement sequence of
cycloketoxime esters, leading to the carbon ring opening and the
carboxylic group migration. Jiang and co-workers[10h] reported
the benzyl C-C single bond cleavage using CuI and O2 at
heating condition to yield aryl nitriles and ketones. Our work,
however, is to develop a general activation strategy of common
benzyl carbonyl compound via the C-C bond dissociation and
intermolecular nucleophilic addition with various exotic
nucleophiles including primary, secondary alcohols and amines
even H2O is established to construct benzyl ethers and benzyl
amines. Through our method, various 1-aryl acetone oxime
esters have been established as potential precursors to react
with different alcohols and amines. Electron and steric properties
on both oxime esters and nucleophiles showed great compatible
for the construction of benzyl C-O and C-N bonds in an effective
manner, which represented a general method to construct
significant benzyl ether especially amine via the activation of
benzyl substrate C-C bond.
NMR spectra proposed
a N-O bond interruption /C-C bond
fragmentation /oxidation sequence to provide the key cation
intermediate for the next electrophilic SN process. The features of
mild condition, short reaction time and broad substrate scope made
this new strategy much promising in the transformation of benzyl
compounds, which might be valuable in last-stage functionlizations.
Introduction
The construction of benzyl carbon-heteroatom (Bn-Het) bonds,
especially Bn-O and Bn-N bonds, are always an attractive and
significant research topic in modern organic chemistry.[1] Due to
the wide existence of benzyl ethers and amines derivatives in
natural products and medical compounds,[2] numerous synthetic
strategies have been developed.[3-8] Among them, one
straightforward access is to couple O-, N-nucleophiles with
benzyl carbon atom generated from available precursors. In this
context, active benzyl species with good leaving groups (Bn-X)
such as alcohol derivatives (X = OH, OAc, OPT etc.)[3-4] and
halides (X = Cl, Br, I)[5] have been well exploited via SN2
substitution mechanism, which had established efficient way for
benzyl C-O and C-N bond formation. Recently, more stable Bn-
H bond as an available alternative has received increasing
attentions. With the assistance of thermochemical oxidation [7] or
visible light catalysis,[8] the formation of benzyl C-Het bond via C-
H bond activation has been achieved. Contrast to above
mentioned Bn-X and Bn-H precursors, however, direct Bn-C
bond dissociation to provide benzyl ether and amine derivatives
[a]
X.-W. Fan, Dr. T. Lei , Z. Liu, Dr X.-L. Yang, Y.-Y. Cheng, G. Liang,
Dr. B. Chen, Prof. Dr. C.-H. Tung, Prof. Dr. L.-Z. Wu
Key Laboratory of Photochemical Conversion and optoelectronic
Materials, Technical Institute of Physics and Chemistry, The
Chinese Academy of Sciences
Beijing, 100190, PR China
E-mail: lzwu@mail.ipc.ac.cn
Homepage: http://lsp.ipc.ac.cn/
[b]
X.-W. Fan, Dr. T. Lei , Z. Liu, Dr X.-L. Yang, Y.-Y. Cheng, G. Liang,
Dr. B. Chen, Prof. Dr. C.-H. Tung, Prof. Dr. L.-Z. Wu
School of Future Technology, University of Chinese Academy of
Sciences
Beijing, 100049, PR China
Scheme 1. Visible-light-promoted benzyl C-O and C-N bond construction.
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201901060
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Results and Discussion
Initially, oxime ester 1a and methanol 2a were selected as
model substrates to explore the feasibility of this transformation.
To our delight, after irradiation of CH3CN solution of 1a (0.1
mmol), 2a (0.1 mmol), and fac-Ir(ppy)3 (2 mol %) for 2 h, the
desired (methoxymethylene)dibenzene 3a was obtained in 73%
yield (Table 1, entry 1). This good result stimulated us to further
optimize the reaction conditions. Firstly, a brief evaluation on the
dosage of 2a demonstrated that 2 equiv. of 2a was appropriate
to give the desired product in 92% yield (Table 1, entries 2−3).
Contrast to the good performance of CH3CN, CH2Cl2 led to a
moderate yield and only 6% yield was obtained in THF (Table 1,
entries 4−5). With respect to photocatalyst, other photocatalysts
like Ru(bpy)3Cl2·6H2O, Acr+-Mes ClO4- and eosin Y exhibited no
catalytic activities at all on this reaction (Table 1, entries 6-8).
Control experiments showed that omitting any component
including photocatalyst and visible light resulted in no reaction.
When this reaction was carried out in air, almost quantitative
benzophenone was detected. Thus, the optimized reaction
condition was achieved, 0.1 mmol of 1a, 0.2 mmol of 2a, 2
mol % fac-Ir(ppy)3 in 2 mL of CH3CN with irradiation of blue
LEDs under Ar atmosphere for 2 h.
Scheme 2. Scope of alcohols. Standard conditions: 1a (0.1 mmol), 2 (0.2
mmol), fac-Ir(ppy)3 (2 mol %), CH3CN (2 mL), 3 W blue LEDs, argon
atmosphere, rt. PG = 4-(trifluoromethyl)benzoyl.
With the optimum condition in hand, we explored alcohol
scope with oxime 1a as reaction partner. The results were
summarized in Scheme
2 and several conclusions were
obtained as follow: a) Various primary and sencondary alcohols
showed good activity to react with oxime 1a and to construct
benzyl C-O bond smoothly (3a-3l). b) The length of carbon chain
and the steric hinderance of alcohols had little influence on
reaction conversion. For example, octan-1-ol with eight carbon
atom was well tolerant to provide 74% yield of product (3b) and
adamantan-2-ol enabled to produce bulky ether in 81% yield (3j).
c) Different substitutions on the terminus of alchols including
phenyl group (3c, 3e, 3j), naphthalene (3d) and acyclic ring
were all compatible. The corresponding products were isolated
with good to excellent yields. Notably, cinnamyl alcohol and 3-
butyn-1-ol were both smoothly converted into desired products
with the unsaturated bond intact respectively (3f-3g). Even
enantioenriched alpha-substituted alcohol like L-menthol was
compatiable to give target product 3m in 44% yield. d) Through
this method, we could construct tetrabenzyl substituted ether
with moderate yield (3k). e) Besides alcohol, water was also
competent to deliever diphenylmethanol in 85% yield (3l).
Having confirmed the generality of benzyl C-O bond
formation, more effort was trend to investigate the scope of
important benzyl C-N bond construction. To our delight, both aryl
and alkyl amines were well capable to provide diverse benzyl
aza-compounds in good to excellent yields. As shown in
Scheme 3, primary and secondary aryl amines with electron-
withdrawing groups afforded corresponding products with ≥ 80%
yields (5a-5b, 5d-5f). N-methyl aniline without substitution only
gave 65% yield (5c), suggesting a negative electron effect for
aryl N-atom nucleophiles. Besides aniline, alkyl amine like N-
methyl-1-phenylmethanamine, dibenzylamine, morpholine and
1,2,3,4-tetrahydroisoquinoline all worked well to achieve relative
products with 69%-81% yields (5g-5j). As less active nucleophile,
benzamides were also found to work smoothly (5k-5m).
Moreover, heteroarene as nucleophile was well tolerated. 1-
Table 1. Optimization of Reaction Condition.[a]
Entry
Photocatalyst
fac-Ir(ppy)3
Solvent
CH3CN
CH3CN
CH3CN
CH2Cl2
THF
n2a (eq.)
1.0
Yield (%)[b]
1
73
2
fac-Ir(ppy)3
2.0
92 (84)[c]
3
fac-Ir(ppy)3
2.5
93
57
6
4
fac-Ir(ppy)3
2.0
5
fac-Ir(ppy)3
2.0
6
Ru(bpy)3Cl2·6H2O
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
2.0
---
---
---
---
---
---
-
7
Acr+–Mes ClO4
2.0
8
Eosin Y
---
2.0
9
2.0
10[d]
11[e]
fac-Ir(ppy)3
fac-Ir(ppy)3
2.0
2.0
[a] Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), photocatalyst (2
mol %), solvent (2 mL), 3 W blue LEDs, argon atmosphere, rt. PG = 4-
(trifluoromethyl)benzoyl. [b] Yields were determined by 1H NMR using
diphenylacetonitrile as the internal standard. [c] Isolated yield in parentheses.
[d] In dark. [e] In air atmosphere.
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10.1002/ejoc.201901060
European Journal of Organic Chemistry
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Scheme 5. Radical trapping Experiments.
importance of benzyl moiety.
In order to get more details about the mechanism, several
control experiments were carried out. Under optimal condition,
84% yield of benzyl ether 3a was obtained for the template
reaction. However, when 2 equiv 2,2,6,6-tetramethyl piperidin-1-
oxyl (TEMPO) was added as a radical capture, the yield was
sharply decreased into 12% (Scheme 5), accompanying with an
addition product of benzhydryl radical and TEMPO in 78% yield.
This result demonstrated a possible radical procedure in this
reaction. Furthermore, electrochemical data showed that excited
Scheme 3. Scope of amines. Standard conditions: 1a (0.1 mmol), 4 (0.2
mmol), fac-Ir(ppy)3 (2 mol %), CH3CN (2 mL), 3 W blue LEDs, argon
atmosphere, rt. PG = 4-(trifluoromethyl)benzoyl.
V/*III
*III/II
*fac-Ir(ppy)3 (E1/2
= -1.84V vs. SCE, E1/2
= 0.31V vs.
SCE)[10a] enabled to transfer one electron to oxime 1a (Ered
=
Benzhydryl substituted pyrazole, benzimidazole and carbazole
were successfully synthesized in yields of 83-87% (5n-5p).
Then different variations on benzyl reactants were tested via
reaction with N-methyl-p-chloroaniline, to examine the generality
of O-acyl oximes esters (Scheme 4). It was found that 1-aryl and
1-alkyl substitutions on benzyl position were both capable.
Specifically, 1,1-diaryl substrates with electron-donating group
showed a higher reactivity than electron-withdrawing ones (6a-
6d). Replacing the methoxy group (1b) by halide (1c) decreased
the yield from 86% (6b) to 55% (6c). As for alkyl substituents (R
in Scheme 4), expected products 6e-6h in moderate yields were
obtained for tested methyl (6e, 6h), ethyl (6f) and phenylmethyl
(6g) oxime esters. It should be noted that, 1,1-dialkyl substituted
substrate were unsuitable in this reaction, suggesting the
−1.69 V vs SCE, Eox > +2.00 V vs SCE), revealing an oxidative
quenching pathway. As for other three photocatalysts,
.
IV/*III
Ru(bpy)3Cl2 6H2O (E1/2
= -0.81 V vs. SCE),[11a] Acr+–Mes
ClO4- (E1/2M+/*M = -0.51 V vs. SCE)[11b] and eosin Y (E1/2EY•+/EY* = -
1.11 V vs. SCE)[11c], they had much lower reductive abilities and
could not initiate this electron transfer process, and thus
resulting in no products at all (Table 1, entries 6-8). Besides, in-
1
situ H NMR and GC-HRMS spectra were selected to confirm
the release of CH3CN molecule in the step of C-C bond
interruption. Through comparing the spectra before and after
irradiation, a clear signal of CH3CN was detected, which directly
proved the β-fragmentation process to eliminate a CH3CN
molecule (for more details, see Supporting Information).
Based on the above results, a proposed mechanism was
Scheme 6. Proposed reaction pathway.
Scheme 4. Scope of O-acyl oximes. Standard conditions: 1 (0.1 mmol), 4q
(0.2 mmol), fac-Ir(ppy)3 (2 mol %), CH3CN (2 mL), 3 W blue LEDs, argon
atmosphere, rt. PG = 4-(trifluoromethyl)benzoyl.
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10.1002/ejoc.201901060
European Journal of Organic Chemistry
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concentrated in vacuum. The crude product was purified by flash column
chromatography.[13]
depicted shown in Scheme 6. Under the visible light irradiation,
*
fac-Ir(ppy)3 was excited to its triplet state fac-Ir(ppy)3. A single
*
electron transfer from fac-Ir(ppy)3 to oxime ester 1a generated
+
General Procedure for the Synthesis of Oxime Esters: To a solution
of 10 mmol ketone in 30 mL MeOH was added 1.2 eq. hydroxylamine
hydrochloride (0.863 g) and 1.2 eq. pyridine (1.2 mL). The reaction
mixture was heated at reflux for 5 h. After removal of solvent in vacuum,
20 mL DCM and 15 mmol triethylamine (2.08 mL) were added at 0 °C. To
this cooled solution was slowly added a solution of 12 mmol 4-
(trifluoromethyl) benzoyl chloride (1.78 mL) in dry DCM (5 mL). The
mixture was stirred at r.t. for 2 h. After completion, the reaction was
quenched with 50 mL NaHCO3 saturated solution and extracted with 50
mL DCE for three times. The extract was washed with brine and dried
over Na2SO4 and concentrated in vacuum. The crude product was
purified by flash column chromatography.[14]
iminyl radical A along with oxidative fac-Ir(ppy)3 . Sequential β-
fragmentation with CH3CN elimination provided benzyl radical B
+
via C-C bond dissociation. Further oxidation of B by fac-Ir(ppy)3
produced benzyl cation C with the concomitant regeneration of
photocatalyst. Finally, the intermediate C coupled with O- and N-
nucleophiles to yield the desired products.
Conclusions
In summary, we have disclosed 1-aryl acetone oxime esters as
readily accessible and highly efficient precursors for the
construction of benzyl C-O and C-N bonds. Under visible light
catalysis, substrates showed good activity to realize the Bn-C
bond dissociation and to couple with diverse primary and
secondary alcohols, amines and amides in one pot. We believe
that this C-C bond activation strategy will provide a general and
novel method for the Bn-O and Bn-N compounds constructions
and might be of great potential in last-stage functionalization of
benzyl ketones.
(E)-1,1-diphenylpropan-2-one O-(4-(trifluoromethyl)benzoyl) oxime
(1a): The product 1a (white solid, mp: 96–98 °C ) was synthesized by the
procedure of oxime esters; 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.2
Hz, 2H), 7.73 (d, J = 8.2 Hz, 2H), 7.39 – 7.34 (m, 4H), 7.33-7.27 (m, 6H),
5.38 (s, 1H), 2.12 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 168.99, 162.75,
138.94, 134.87 (q, J = 32.3 Hz), 132.68, 130.13, 129.22, 128.86, 127.52,
126.42 (q, J = 273.7 Hz) 125.73 (q, J = 3.7 Hz), 56.72, 15.44; HRMS
(ESI): [M+Na]+ calcd for C23H18NaF3NO2+, 420.1182, found, 420.1171.
(E)-1,1-bis(4-methoxyphenyl)propan-2-one O-(4-(trifluoromethyl)be-
nzoyl) oxime (1b): The reaction was run following the procedure A for
the synthesis of the corresponding 1,1-diketone. Then the product 1b
(viscous oil) was synthesized by the procedure of oxime esters; 1H NMR
(400 MHz, CDCl3) δ 8.18 (d, J = 8.2 Hz, 2H), 7.73 (d, J = 8.3 Hz, 2H),
7.21 (d, J = 8.7 Hz, 4H), 6.89 (d, J = 8.7 Hz, 4H), 5.26 (s, 1H), 3.81 (s,
6H), 2.09 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 169.46, 162.83, 158.93,
134.84 (q, J = 33.3 Hz), 132.72, 131.15, 130.18, 130.11, 125.71 (q, J =
4.0 Hz), 123.70 (q, J = 273.7 Hz), 114.22, 55.40, 55.19, 15.27; HRMS
(ESI): [M+H]+ calcd for C25H23F3NO4+, 480.1393, found, 480.1374.
Experimental Section
General Information 1H and 13C NMR spectra were recorded with 400
and 100 MHz NMR instruments. Chemical shifts (δ, parts per million) are
given with tetramethylsilane (TMS) as an internal standard. The following
abbreviations are used to describe peak patterns where appropriate: s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet or unresolved
and brs = broad signal. All coupling constants (J) are given in Hz and
chemical shifts in ppm. 13C NMR spectra were referenced to CDCl3 at
(E)-1,1-bis(4-chlorophenyl)propan-2-one O-(4-(trifluoromethyl)benz-
oyl) oxime (1c): The reaction was run following the Procedure A for the
synthesis of the corresponding 1,1-diketone. Then the product 1c
(viscous oil) was synthesized by the procedure of oxime esters; 1H NMR
(400 MHz, CDCl3) δ 8.18 (d, J = 8.1 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H),
7.34 (d, J = 8.3 Hz, 4H), 7.21 (d, J = 8.3 Hz, 4H), 5.27 (s, 1H), 2.10 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 168.14, 162.65, 136.98, 135.04 (q, J
= 32.3 Hz), 133.80, 132.42, 130.46, 130.15, 129.20, 125.80 (q, J = 4.0
Hz), 123.66 (q, J = 272.7 Hz), 55.80, 15.59; HRMS (ESI): [M+Na]+ calcd
9
77.16 ppm. F NMR were recorded at 282 MHz using CDCl3 as solvent.
Flash column chromatography was performed over silica gel 200−300
mesh, and the eluent was a mixture of ethyl acetate (EA) and petroleum
ether (PE). Analytical TLC was performed on silica gel plates, and the
spots were visualized under UV light (λ = 254 nm). High-resolution mass
spectra (HRMS) were recorded on a Q-TOF mass spectrometer. All
commercially available reagents and solvents were used without further
purification.
+
for C23H16Cl2F3NNaO2 , 488.0402, found, 488.0385.
General procedure for the Synthesis of 1,1-Disubstituted Ketones:
Method A: To a solution of 10 mmol aryl bromide in 10 mL THF/toluene
(1:1) was added 1 mol % Pd(dba)2 (57.5 mg), 1 mol % PtBu3, 1 eq.
Cs2CO3 (3.25 g) and 1.1 eq. α-aryl ketone. The reaction mixture was
stirred at 80-85 °C for 12 h. After the reaction was finished, the reaction
mixture was diluted with EtOAc (100 mL). The mixture was washed with
a saturated aqueous solution of NH4Cl (25 mL x 3), water (50 mL) and
brine (50 mL). The organic layer was dried over Na2SO4 and
concentrated in vacuum. The crude product was purified by flash column
chromatography.[12] Method B: To a solution of 10 mmol α-aryl ketone
and 3.5 mol % benzyltrimethylammonium chloride in 5 mL 50 wt %
aqueous solution of NaOH was slowly added a solution of 1.5 eq. alkyl
iodide in 2 mL DCM at 0 °C . After 1 h, 40 mL of H2O and 60 mL of ethyl
acetate were added to the reaction mixture. The organic layer was
separated, and was washed with H2O until its pH became neutral. The
resulting organic phase was washed with 30 mL of brine. The organic
layer was separated and dried over Na2SO4, filtrated, and the filtrate was
(E)-1-(4-methoxyphenyl)-1-(p-tolyl)propan-2-one O-(4-(trifluorometh-
yl)benzoyl) oxime (1d): The reaction was run following the Procedure A
for the synthesis of the corresponding 1,1-diketone. Then the product 1d
(viscous oil) was synthesized by the procedure of oxime esters; 1H NMR
(400 MHz, CDCl3) δ 8.19 (d, J = 8.1 Hz, 2H), 7.73 (d, J = 8.2 Hz, 2H),
7.24 – 7.14 (m, 6H), 6.89 (d, J = 8.5 Hz, 2H), 5.28 (s, 1H), 3.81 (s, 3H),
2.35 (s, 3H), 2.10 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.37, 162.80,
158.93, 137.09, 136.14, 134.82 (q, J = 33.3 Hz), 132.72, 131.03, 130.26,
130.10, 129.50, 128.97, 125.70 (q, J = 4.0 Hz), 123.69 (q, J = 272.7 Hz),
114.21, 55.58, 55.39, 21.16, 15.31; HRMS (ESI): [M+Na]+ calcd for
C25H22F3NNaO3+, 464.1444, found, 464.1426.
(E)-3-(4-methoxyphenyl)butan-2-one O-(4-(trifluoromethyl)benzoyl)
oxime (1e): The reaction was run following the procedure B for the
synthesis of the corresponding 1,1-diketone. Then the product 1e (white
solid, mp: 61–65 °C ) was synthesized by the procedure of oxime esters;
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1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.1 Hz, 2H), 7.73 (d, J = 8.1 Hz,
2H), 7.26 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H), 3.96 (q, J = 7.1 Hz,
1H), 3.80 (s, 3H), 1.92 (s, 3H), 1.57 (d, J = 7.1 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 170.39, 162.93, 158.94, 134.72 (q, J = 32.3 Hz), 132.80,
132.45, 130.03, 128.72, 125.64 (q, J = 4.0 Hz), 123.67 (q, J = 273.7 Hz),
114.27, 55.34, 44.51, 17.34, 13.64; HRMS (ESI): [M+Na]+ calcd for
C19H18F3NNaO3+, 388.1131, found, 388.1125.
(methoxymethylene)dibenzene (3a): Colorless oil, 16.6 mg (84%); 1H
NMR (400 MHz, CDCl3) δ 7.37 – 7.29 (m, 8H), 7.24 (t, J = 6.8 Hz, 2H),
5.24 (s, 1H), 3.38 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 142.23, 128.53,
127.59, 127.06, 85.58, 57.15; MS-EI+: [M]+ calcd for C14H14O+, 198.1040,
found, 198.1046.
1
((octyloxy)methylene)dibenzene (3b): Colorless oil, 21.9 mg (74%); H
NMR (400 MHz, CDCl3) δ 7.37 – 7.27 (m, 8H), 7.25 – 7.19 (m, 2H), 5.32
(s, 1H), 3.44 (t, J = 6.6 Hz, 2H), 1.67 – 1.59 (m, 2H), 1.42-1.32 (m, 2H),
1.31 – 1.22 (m, 8H), 0.87 (t, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3)
δ 142.84, 128.45, 127.42, 127.11, 83.74, 69.41, 32.00, 30.04, 29.59,
29.41, 26.41, 22.81, 14.24; MS-EI+: [M]+ calcd for C14H14O+, 296.2135,
found, 296.2138.
(E)-3-(4-methoxyphenyl)pentan-2-one O-(4-(trifluoromethyl)benzoyl)
oxime (1f): The reaction was run following the procedure B for the
synthesis of the corresponding 1,1-diketone. Then the product 1f (white
solid, mp: 71–75 °C ) was synthesized by the procedure of oxime esters.
1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 8.1 Hz,
2H), 7.26 (d, J = 7.8 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 3.80 (s, 3H), 3.67
(t, J = 7.7 Hz, 1H), 2.12 - 1.95 (m, 2H), 1.91 (s, 3H), 0.97 (t, J = 7.3 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 169.55, 162.81, 158.86, 134.60 (q, J
= 32.3 Hz), 132.74, 131.11, 129.93, 129.15, 125.53 (q, J = 4.0 Hz),
123.58 (q, J = 273.7 Hz), 114.14, 55.24, 52.08, 24.22, 13.58, 12.04;
HRMS (ESI): [M+Na]+ calcd for C20H20F3NNaO3+, 402.1287, found,
402.1282.
((benzyloxy)methylene)dibenzene (3c): Colorless oil, 21.9 mg (80%);
1H NMR (400 MHz, CDCl3) δ 7.39 – 7.22 (m, 15H), 5.44 (s, 1H), 4.54 (s,
2H); 13C NMR (101 MHz, CDCl3) δ 142.30, 138.55, 128.54, 128.50,
127.84, 127.67, 127.60, 127.28, 82.64, 70.64; HRMS (ESI): [M+Na]+
calcd for C20H18ONa+, 297.1250, found. 297.1241.
2-((benzhydryloxy)methyl)naphthalene (3d): Colorless oil, 25.3 mg
(78%); 1H NMR (400 MHz, CDCl3) δ 7.84 – 7.76 (m, 4H), 7.52-7.44 (m,
3H), 7.42 – 7.37 (m, 4H), 7.33 (t, J = 7.5 Hz, 4H), 7.28 – 7.21 (m, 2H),
5.48 (s, 1H), 4.70 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 142.26, 135.98,
133.43, 133.11, 128.55, 128.25, 128.01, 127.82, 127.62, 127.29, 126.55,
126.17, 125.98, 125.93, 82.60, 70.75; MS-EI+: [M]+ calcd for C24H20O+,
324.1509, found, 324.1505.
(E)-3-(4-methoxyphenyl)-4-phenylbutan-2-one O-(4-(trifluoromethyl)-
benzoyl) oxime (1g): The reaction was run following the procedure B for
the synthesis of the corresponding 1,1-diketone. Then the product 1g
(viscous oil) was synthesized by the procedure of oxime esters; 1H NMR
(400 MHz, CDCl3) δ 8.16 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 8.2 Hz, 2H),
7.24-7.10 (m, 7H), 6.84 (d, J = 8.4 Hz, 2H), 3.97 (t, J = 7.7 Hz, 1H), 3.77
(s, 3H), 3.47 (dd, J = 13.9, 7.0 Hz, 1H), 3.18 (dd, J = 13.9, 8.5 Hz, 1H),
1.96 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 168.60, 162.68, 158.94,
139.23, 135.64 (q, J = 33.33 Hz), 132.72, 130.76, 129.96, 129.40, 129.23,
128.24, 126.21, 125.56 (q, J = 4.0 Hz), 123.59 (q, J = 273.3 Hz), 114.15,
55.23, 53.06, 38.19, 15.15; HRMS (ESI): [M+Na]+ calcd for
C25H22F3NNaO3+, 464.1444, found, 464.1425.
((3-phenylpropoxy)methylene)dibenzene (3e): Colorless oil, 25.7 mg
1
(85%); H NMR (400 MHz, CDCl3) δ 7.37-7.27 (m, 8H), 7.27 – 7.20 (m,
4H), 7.19 – 7.13 (m, 3H), 5.32 (s, 1H), 3.47 (t, J = 6.3 Hz, 2H), 2.74 (t, J
= 6.3 Hz, 2H), 2.00-1.91 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 142.71,
142.22, 128.61, 128.47, 128.42, 127.48, 127.12, 125.85, 83.78, 68.42,
32.64, 31.66; MS-EI+: [M]+ calcd for C22H22O+, 302.1666, found,
302.1669.
(E)-3-(p-tolyl)butan-2-one O-(4-(trifluoromethyl)benzoyl) oxime (1h):
The reaction was run following the procedure B for the synthesis of the
corresponding 1,1-diketone. Then the product 1h(white solid, mp: 62–
67 °C ) was synthesized by the procedure of oxime esters; 1H NMR (400
MHz, CDCl3) δ 8.18 (d, J = 8.2 Hz, 2H), 7.73 (d, J = 8.3 Hz, 2H), 7.23 (d,
J = 8.1 Hz, 2H), 7.17 (d, J = 7.1 Hz, 2H), 3.97 (q, J = 7.1 Hz, 1H), 2.34 (s,
3H), 1.91 (s, 3H), 1.57 (d, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
170.33, 162.94, 137.52, 137.08, 134.78 (q, J = 32.3 Hz), 132.86, 130.07,
(E)-((cinnamyloxy)methylene)dibenzene (3f): Colorless oil, 22.8 mg
1
(76%, E/Z=1.5:1); H NMR (400 MHz, CDCl3) δ 7.39 – 7.19 (m, 14H),
7.14 (d, J = 7.4 Hz, 1H), 6.60 (d, J = 12.5 Hz, 1H), 6.33/5.95 (m, 1H),
6.00 – 5.89 (m, 1H), 5.48/5.40 (s, 1H), 4.28/4.17 (d, J = 4.0 Hz, 2H); 13
C
NMR (101 MHz, CDCl3) δ 142.32, 142.22, 136.93, 136.77, 132.42,
131.89, 129.07, 128.85, 128.66, 128.55, 128.47, 128.29, 127.75, 127.59,
127.56, 127.24, 127.20, 126.62, 126.34, 83.24, 82.80, 69.51, 65.84;
HRMS (ESI): [M+Na]+ calcd for C22H20ONa+, 323.1406, found. 323.1395.
129.61, 127.63, 125.68 (q, J = 3.7 Hz), 123.71 (q, J = 273.3 Hz), 45.02,
+
21.14, 17.35, 13.82; HRMS (ESI): [M+Na]+ calcd for C19H18NaF3NO2
,
372.1182, found, 372.1176.
((but-3-yn-1-yloxy)methylene)dibenzene (3g): Colorless oil, 12.3 mg
(52%); 1H NMR (400 MHz, CDCl3) δ 7.42-7.30 (m, 8H), 7.29-7.24 (m, 2H),
5.43 (s, 1H), 3.62 (t, J = 7.1 Hz, 2H), 2.56 (td, J = 7.0, 2.5 Hz, 2H), 1.99 (t,
J = 2.5 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 142.23, 128.53, 127.65,
127.19, 83.99, 83.97, 81.52, 69.41, 69.39, 67.32; HRMS (ESI): [M+Na]+
calcd for C17H16ONa+, 259.1093, found. 259.1085.
(E)-3-methylbutan-2-one O-(4-(trifluoromethyl)benzoyl) oxime (1i):
The product 1i (oil) was synthesized by the procedure of oxime esters; 1H
NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.1 Hz, 2H), 7.74 (d, J = 8.2 Hz,
2H), 2.92 – 2.80 (m, 1H), 2.07 (s, 3H), 1.21 (d, J = 6.9 Hz, 6H); 13C NMR
(101 MHz, CDCl3) δ 172.22, 162.95, 134.75 (q, J=33.3Hz), 132.90,
130.04, 125.66 (q J = 4.0 Hz), 123.70 (q, J=273.7Hz), 34.6, 19.69, 12.46;
HRMS (ESI): [M+Na]+ calcd for C13H14F3NNaO2+, 296.0869, found,
296.0862.
((cyclohexyloxy)methylene)dibenzene (3h): Colorless oil, 22.6 mg
1
(85%); H NMR (400 MHz, CDCl3) δ 7.37 – 7.26 (m, 8H), 7.25-7.18 (m,
2H), 5.54 (s, 1H), 3.39 – 3.31 (m, 1H), 1.91 (dd, J = 9.2, 3.3 Hz, 2H), 1.74
(dd, J = 9.4, 4.5 Hz, 2H), 1.51 – 1.38 (m, 3H), 1.26 – 1.17 (m, 3H); 13C
NMR (101 MHz, CDCl3) δ 143.32, 128.39, 127.31, 127.71, 80.12, 75.18,
32.52, 26.01, 24.24; MS-EI+: [M]+ calcd for C19H22O+, 266.1666, found,
266.1671.
General procedure for the construction of benzyl C-O and C-N
bonds: O-acyl oxime esters (0.1 mmol, 1 eq.), nucleophilic reagent (0.2
mmol, 2 eq.), and fac-Ir(ppy)3 (2 μmol, 0.02 eq.) were dissolved in
CH3CN (2 mL) in a 10 mL Pyrex tube equipped with a magnetic stir bar
and a rubber septum, then the argon-purged solution was irradiated with
blue LEDs (λmax = 450 nm) at room temperature for 4 h. The solvent was
removed under reduced pressure. The crude product was purified by
flash column chromatography.
(1r,3r,5r,7r)-2-(benzhydryloxy)adamantine (3i): White solid, mp: 71–
74 °C , 25.8 mg (81%); 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J = 7.4 Hz,
4H), 7.22 (t, J = 7.5 Hz, 4H), 7.18 – 7.11 (m, 2H), 5.45 (s, 1H), 3.44 (s,
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10.1002/ejoc.201901060
European Journal of Organic Chemistry
FULL PAPER
1H), 2.15 (d, J = 12.1 Hz, 2H), 1.97 (s, 2H), 1.72 (d, J = 13.3 Hz, 4H),
1.63 (s, 2H), 1.45 (dd, J = 20.4, 12.0 Hz, 4H); 13C NMR (101 MHz,
CDCl3) δ 143.48, 128.21, 127.13, 127.09, 79.44, 79.03, 37.70, 36.58,
32.05, 31.89, 27.61, 27.52; MS-EI+: [M]+ calcd for C23H26O+, 318.1979,
found, 318.1984.
51.62, 34.79; HRMS (ESI): [M+Na]+ calcd for C22H21NNaO2+, 354.1465,
found, 354.1462.
4-(benzhydryl(methyl)amino)benzonitrile(5e): White solid, mp: 62–
66 °C , 25.3 mg (85%); 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.0 Hz,
2H), 7.41 – 7.27 (m, 6H), 7.14 (d, J = 7.2 Hz, 4H), 6.75 (d, J = 8.1 Hz,
2H), 6.21 (s, 1H), 2.80 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 152.48,
139.39, 133.52, 128.73, 128.62, 127.78, 120.50, 112.27, 98.36, 66.59,
34.71; HRMS (ESI): [M+Na]+ calcd for C21H18N2Na+, 321.1362, found,
321.1354.
(((4-phenylbutan-2-yl)oxy)methylene)dibenzene (3j): Colorless oil,
24.1 mg (71%);1H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 7.2 Hz, 4H),
7.30 (dd, J = 13.0, 7.2 Hz, 4H), 7.26 – 7.19 (m, 4H), 7.14 (t, J = 7.2 Hz,
1H), 7.09 (d, J = 7.5 Hz, 2H), 5.47 (s, 1H), 3.63 – 3.50 (m, 1H), 2.79 –
2.68 (m, 1H), 2.63 – 2.53 (m, 1H), 2.02-1.89 (m, 1H), 1.83-1.72 (m, 1H),
1.21 (d, J = 6.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 143.43, 142.88,
142.62, 128.47, 128.41, 128.37, 127.59, 127.52, 127.28, 127.06, 125.76,
80.79, 72.45, 38.73, 31.93, 19.92; HRMS (ESI): [M+Na]+ calcd for
C23H24ONa+, 339.1719, found, 339.1712.
ethyl 2-(benzhydryl(4-chlorophenyl)amino)acetate (5f): Colorless oil,
1
34.5 mg (91%); H NMR (400 MHz, CDCl3) δ 7.32 – 7.21 (m, 10H), 7.10
(d, J = 9.1 Hz, 2H), 6.63 (d, J = 9.1 Hz, 2H), 6.12 (s, 1H), 4.01-3.94 (m,
4H), 1.11 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 170.92,
147.46, 140.29, 129.16, 128.91, 128.68, 127.69, 123.19, 115.74, 67.69,
+
(oxybis(methanetriyl))tetrabenzene (3k): Colorless oil, 20.3 mg (58%);
1H NMR (400 MHz, CDCl3) δ 7.31 – 7.27 (m, 8H), 7.24 (t, J = 7.3 Hz, 8H),
7.20 – 7.17 (m, 4H), 5.32 (s, 2H); 13C NMR (101 MHz, CDCl3) δ 142.36,
128.52, 127.56, 127.41, 80.15; HRMS (ESI): [M+Na]+ calcd for
C26H22ONa+, 373.1563, found, 373.1552.
60.90, 50.73, 14.23; HRMS (ESI): [M+Na]+ calcd for C23H22ClNNaO2
402.1231, found, 402.1230.
,
N-benzyl-N-methyl-1,1-diphenylmethanamine (5g): Colorless oil, 23.2
mg (81%);1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 7.4 Hz, 4H), 7.44 (d,
J = 7.3 Hz, 2H), 7.39 – 7.30 (m, 6H), 7.28 (d, J = 7.9 Hz, 1H), 7.22 (t, J =
7.3 Hz, 2H), 4.51 (s, 1H), 3.54 (s, 2H), 2.11 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 143.16, 140.06, 128.73, 128.58, 128.34, 128.19, 127.04,
126.99, 75.61, 59.88, 40.42; HRMS (ESI): [M+H]+ calcd for C21H22N+,
288.1747, found, 288.1744.
diphenylmethanol (3l): White solid, mp: 65–68 °C , 15.6 mg (85%); 1H
NMR (400 MHz, CDCl3) δ 7.53-7.43 (m, 8H), 7.43-7.37 (m, 2H), 5.95 (s,
1H); 13C NMR (101 MHz, CDCl3) δ 143.94, 128.63, 127.70, 126.68,
76.40; MS-EI+: [M+] calcd for C13H12O+, 184.0883, found, 184.0879.
((((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)methylene)dibenz-
ene (3m): Colorless solid, , mp: 58–62 °C, 13.6 mg (44%); H NMR (400
N,N-dibenzyl-1,1-diphenylmethanamine (5h): Colorless oil, 25.0 mg
(69%); 1H NMR (400 MHz, CDCl3) δ 7.58 (t, J = 8.5 Hz, 8H), 7.52 – 7.33
(m, 12H), 5.14 (s, 1H), 3.74 (s, 4H); 13C NMR (101 MHz, CDCl3) δ 140.51,
139.69, 129.40, 128.79, 128.45, 128.25, 127.11, 126.97, 67.28, 53.81;
HRMS (ESI): [M+H]+ calcd for C27H26N+, 364.2060, found, 364.2058.
1
MHz, CDCl3) δ 7.48 – 7.13 (m, 10H), 5.52 (s, 1H), 3.14 (td, J = 10.4, 4.1
Hz, 1H), 2.43 – 2.30 (m, 1H), 2.24 – 2.09 (m, 1H), 1.66 – 1.53 (m, 2H),
1.41 – 1.30 (m, 1H), 1.28 – 1.18 (m, 1H), 0.98 – 0.82 (m, 9H), 0.44 (d, J
= 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 143.89, 142.61, 128.25,
128.12, 127.98, 127.44, 126.92, 126.74, 79.96, 75.94, 48.78, 40.46,
34.59, 31.52, 25.10, 22.93, 22.44, 21.36, 15.68; HRMS (ESI): [M+Na]+
calcd for C23H30ONaO+, 345.2189, found. 345.2178.
4-benzhydrylmorpholine (5i): Colorless oil, 17.5 mg (69%); 1H NMR
(400 MHz, CDCl3) δ 7.42 (d, J = 7.3 Hz, 4H), 7.26 (t, J = 7.6 Hz, 4H),
7.17 (t, J = 7.3 Hz, 2H), 4.19 (s, 1H), 3.73 – 3.66 (m, 4H), 2.42 – 2.33 (m,
4H);13C NMR (101 MHz, CDCl3) δ 142.45, 128.64, 128.06, 127.14, 79.62,
67.32, 52.79; HRMS (ESI): [M+H]+ calcd for C17H20NO+, 254.1539, found,
254.1536.
N-benzhydryl-4-chloroaniline (5a): Colorless oil, 23.4 mg (80%); 1H
NMR (400 MHz, CDCl3) δ 7.36 – 7.21 (m, 10H), 7.04 (d, J = 8.8 Hz, 2H),
6.45 (d, J = 8.8 Hz, 2H), 5.44 (s, 1H), 4.27 (s, 1H); 13C NMR (101 MHz,
CDCl3) δ 145.91, 142.57, 129.09, 128.96, 127.66, 127.54, 122.53,
114.78, 63.28; HRMS (ESI): [M+H]+ calcd for C19H17ClN+, 294.1044,
found, 294.1035.
2-benzhydryl-1,2,3,4-tetrahydroisoquinoline (5j): White solid, mp: 80–
84 °C , 21.8 mg (73%); 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 7.5 Hz,
4H), 7.45 (t, J = 7.5 Hz, 4H), 7.35 (t, J = 7.4 Hz, 2H), 7.31 – 7.19 (m, 3H),
7.04 (d, J = 7.4 Hz, 1H), 4.58 (s, 1H), 3.74 (s, 2H), 3.05 (t, J = 5.7 Hz,
2H), 2.89 (t, J = 5.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 142.40,
134.78, 134.18, 128.02, 127.96, 127.34, 126.42, 126.18, 125.46, 124.94,
75.32, 54.55, 48.63, 28.75; HRMS (ESI): [M+H]+ calcd for C22H22N+,
300.1747, found, 300.1744.
methyl 4-(benzhydrylamino)benzoate (5b): White solid, mp: 66–71 °C ,
27.2 mg (80%); 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.7 Hz, 2H),
7.37 – 7.24 (m, 10H), 6.50 (d, J = 8.7 Hz, 2H), 5.58 (s, 1H), 4.67 (brs,
1H), 3.80 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 167.33, 150.95, 142.04,
131.51, 129.00, 127.78, 127.54, 119.06, 112.57, 62.53, 51.64; HRMS
(ESI): [M+Na]+ calcd for C21H19NNaO2+, 340.1308, found, 340.1303.
N-benzhydrylbenzamide (5k): White solid, mp: 158–163 °C , 16.1 mg
(56%); 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.4 Hz, 2H), 7.50 (t, J =
7.3 Hz, 1H), 7.43 (t, J = 7.5 Hz, 2H), 7.38 – 7.24 (m, 10H), 6.69 (d, J =
7.2 Hz, 1H), 6.45 (d, J = 7.8 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ
166.48, 141.48, 134.28, 131.69, 128.76, 128.64, 127.58, 127.51, 127.05,
57.47; HRMS (ESI): [M+Na]+ calcd for C20H17NaNO+, 310.1202, found,
310.1188.
N-benzhydryl-N-methylaniline (5c): Colorless oil, 17.7 mg (65%); 1H
NMR (400 MHz, CDCl3) δ 7.40 – 7.16 (m, 12H), 6.79 (d, J = 7.9 Hz, 2H),
6.72 (t, J = 7.2 Hz, 1H), 6.18 (s, 1H), 2.73 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 150.26, 140.79, 129.23, 128.86, 128.49, 127.30, 116.93,
113.11, 67.18, 34.63; HRMS (ESI): [M+H]+ calcd for C20H20N+, 274.1590,
found, 274.1576.
N-benzhydryl-4-methylbenzamide (5l): White solid, mp: 137–141 °C ,
18.4 mg (61%); 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H),
7.39 – 7.18 (m, 12H), 6.66 (d, J = 7.4 Hz, 1H), 6.44 (d, J = 7.8 Hz, 1H),
2.39 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 166.41, 142.14, 141.59,
131.41, 129.27, 128.73, 127.52, 127.06, 57.39, 21.46; HRMS (ESI):
[M+Na]+ calcd for C21H19NNaO+, 324.1359, found, 324.1345.
methyl 4-(benzhydryl(methyl)amino)benzoate (5d): White solid, mp:
102–105 °C , 29.5 mg (89%); 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J =
9.0 Hz, 2H), 7.36 – 7.27 (m, 6H), 7.19 – 7.12 (m, 4H), 6.76 (d, J = 9.0 Hz,
2H), 6.27 (s, 1H), 3.83 (s, 3H), 2.80 (s, 3H); 13C NMR (101 MHz, CDCl3)
δ 167.44, 139.90, 131.45, 128.79, 128.71, 127.68, 117.96, 111.65, 66.72,
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10.1002/ejoc.201901060
European Journal of Organic Chemistry
FULL PAPER
N-benzhydryl-4-methoxybenzamide (5m): White solid, mp: 192–197 °C ,
23.1 mg (73%); 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.5 Hz, 2H),
7.37 – 7.25 (m, 10H), 6.92 (d, J = 8.6 Hz, 2H), 6.59 (d, J = 7.3 Hz, 1H),
6.44 (d, J = 7.6 Hz, 1H), 3.84 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
166.12, 162.51, 141.79, 129.01, 128.86, 127.65, 126.65, 113.96, 57.54,
55.57; HRMS (ESI): [M+H]+ calcd for C21H20NO2+, 318.1489, found,
318.1474.
114.60, 114.01, 56.66, 55.42, 32.07, 16.52; HRMS (ESI): [M+H]+ calcd
for C14H18NO2+, 232.1332, found, 232.1322.
4-chloro-N-(1-(4-methoxyphenyl)propyl)-N-methylaniline
(6f):
1
Colorless oil, 22.8 mg (79%); H NMR (400 MHz, CDCl3) δ 7.14 (dd, J =
8.0, 5.1 Hz, 4H), 6.83 (d, J = 8.3 Hz, 2H), 6.72 (d, J = 8.7 Hz, 2H), 4.73
(dd, J = 9.0, 6.1 Hz, 1H), 3.77 (s, 3H), 2.63 (s, 3H), 2.08 – 1.86 (m, 2H),
0.95 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 158.71, 149.69,
133.32, 129.02, 128.33, 121.16, 114.19, 113.86, 62.97, 55.34, 31.70,
24.99, 11.77; MS-EI+: [M]+ calcd for C17H20ClNO+, 289.1228, found,
289.1233.
1-benzhydryl-1H-pyrazole (5n): White solid, mp: 65–69 °C , 20.4 mg
(87%); 1H NMR (400 MHz, CDCl3) δ 7.60 (s, 1H), 7.35 – 7.25 (m, 7H),
7.09 (d, J = 6.7 Hz, 4H), 6.79 (s, 1H), 6.27 (s, 1H); 13C NMR (101 MHz,
CDCl3) δ 139.86, 139.71, 129.53, 128.75, 128.35, 128.13, 105.53, 69.56;
HRMS (ESI): [M+H]+ calcd for C16H15N2+, 235.1230, found, 235.1228.
4-chloro-N-(1-(4-methoxyphenyl)-2-phenylethyl)-N-methylaniline (6g):
Colorless oil, 29.1 mg (83%); 1H NMR (400 MHz, CDCl3) δ 7.24 – 7.13
(m, 7H), 7.05 (d, J = 8.6 Hz, 2H), 6.83 (d, J = 8.3 Hz, 2H), 6.52 (d, J = 8.6
Hz, 2H), 5.16 – 5.08 (m, 1H), 3.77 (s, 3H), 3.33 – 3.18 (m, 2H), 2.65 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 158.84, 149.18, 139.16, 132.75,
129.07, 128.85, 128.48, 128.42, 126.41, 121.60, 114.70, 113.91, 63.59,
55.36, 37.84, 32.56; HRMS (ESI): [M+Na]+ calcd for C22H22ClNNaO+,
374.1282, found, 374.1270.
1-benzhydryl-1H-benzo[d]imidazole (5o): Brown solid, mp: 106–111 °C ,
23.6 mg (83%); 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.0 Hz, 1H),
7.71 (s, 1H), 7.39 – 7.33 (m, 6H), 7.26 – 7.09 (m, 7H), 6.75 (s, 1H); 13C
NMR (101 MHz, CDCl3) δ 142.90, 137.95, 134.08, 129.19, 128.74,
128.31, 123.38, 122.90, 120.30, 111.06, 63.96; HRMS (ESI): [M+H]+
calcd for C20H17N2+, 285.1386, found, 285.1382.
9-benzhydryl-9H-carbazole (5p): White solid, mp: 165–170 °C , 27.6 mg
(83%); 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 7.4 Hz, 2H), 7.30 – 7.27
(m, 6H), 7.24 – 7.16 (m, 8H), 7.07 (s, 1H), 7.05 (s, 1H); 13C NMR (101
MHz, CDCl3) δ 140.82, 139.03, 128.77, 128.52, 127.98, 125.67, 123.64,
120.26, 119.32, 110.82, 62.45; HRMS (ESI): [M+Na]+ calcd for
C25H19NNa+, 356.1410, found, 356.1398.
4-chloro-N-methyl-N-(1-(p-tolyl)ethyl)aniline (6h): Colorless oil, 14.2
mg (55%); H NMR (400 MHz, CDCl3) δ 7.21-7.10 (m, 6H), 6.72 (d, J =
1
8.7 Hz, 2H), 5.01 (q, J = 6.7 Hz, 1H), 2.64 (s, 3H), 2.33 (s, 3H), 1.51 (d, J
= 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 148.98, 139.42, 136.71,
129.27, 129.05, 126.87, 121.43, 114.35, 56.77, 32.13, 21.15, 16.63;
HRMS (ESI): [M+Na]+ calcd for C16H18ClNNa+, 282.1020, found,
282.1011.
N-benzhydryl-4-chloro-N-methylaniline (6a): Colorless oil, 25.5 mg
1
(83%); H NMR (400 MHz, CDCl3) δ 7.35 – 7.26 (m, 5H), 7.19-7.11 (m,
(((2,2,6,6-tetramethylcyclohexyl)oxy)methylene)dibenzene: Colorless
oil,; 1H NMR (400 MHz, Chloroform-d) δ 7.49 (d, J = 7.5 Hz, 4H), 7.38 (t,
J = 7.5 Hz, 4H), 7.27 (t, J = 7.3 Hz, 2H), 5.76 (s, 1H), 1.78 – 1.61 (m, 2H),
1.54 (d, J = 5.0 Hz, 4H), 1.27 (s, 7H), 0.86 (s, 7H); 13C NMR (101 MHz,
Chloroform-d) δ 144.85, 128.13, 126.70, 126.54, 90.75, 59.88, 40.42,
33.92, 20.42, 17.15. HRMS (ESI): [M+H]+ calcd for C22H30NO+, 324.2322,
found, 324.2315.
5H), 6.69 (d, J = 8.9 Hz, 2H), 6.10 (s, 1H), 2.71 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 148.88, 140.42, 129.03, 128.81, 128.61, 127.50, 121.84,
114.33, 67.50, 34.88; MS-EI+: [M+] calcd for C20H18ClN+, 307.1122, found,
307.1129.
N-(bis(4-methoxyphenyl)methyl)-4-chloro-N-methylaniline
(6b):
Colorless oil, 31.6 mg (86%); 1H NMR (400 MHz, CDCl3) δ 7.12 (d, J =
8.6 Hz, 2H), 7.07 (d, J = 8.3 Hz, 4H), 6.85 (d, J = 8.3 Hz, 4H), 6.67 (d, J =
8.7 Hz, 2H), 5.99 (s, 1H), 3.79 (s, 6H), 2.68 (s, 3H); HRMS (ESI):
[M+Na]+ calcd for C22H22ClNNaO2+, 390.1231, found, 390.1222.
Acknowledgements
This work was supported by the Ministry of Science and
Technology of China (2017YFA0206903), the National Natural
Science Foundation of China (91427303 and 21861132004), the
Strategic Priority Research Program of the Chinese Academy of
Science (XDB17000000), Key Research Program of Frontier
Sciences of the Chinese Academy of Science (QYZDY-SSW-
JSC029), and K. C. Wong Education Foundation.
N-(bis(4-chlorophenyl)methyl)-4-chloro-N-methylaniline
(6c):
Colorless oil, 20.6 mg (55%); 1H NMR (400 MHz, CDCl3) δ 7.21 (d, J =
8.4 Hz, 4H), 7.06 (d, J = 8.9 Hz, 2H), 7.00 (d, J = 8.3 Hz, 4H), 6.58 (d, J =
8.9 Hz, 2H), 5.92 (s, 1H), 2.58 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
148.58, 138.42, 133.58, 130.02, 129.15, 128.93, 122.64, 114.79, 66.70,
34.81; HRMS (ESI): [M+Na]+ calcd for C20H16Cl3NNa+, 398.0241, found,
398.0229.
4-chloro-N-((4-methoxyphenyl)(phenyl)methyl)-N-methylaniline (6d):
Colorless oil, 31.9 mg (91%); 1H NMR (400 MHz, CDCl3) δ 7.12 (d, J =
8.7 Hz, 4H), 7.05 (t, J = 8.0 Hz, 4H), 6.84 (d, J = 8.6 Hz, 2H), 6.67 (d, J =
8.9 Hz, 2H), 6.01 (s, 1H), 3.79 (s, 3H), 2.69 (s, 3H), 2.34 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 158.92, 148.90, 137.69, 137.03, 132.68,
129.95, 129.27, 128.97, 128.59, 121.55, 114.19, 113.91, 66.58, 55.38,
34.61, 21.21; HRMS (ESI): [M+Na]+ calcd for C22H22ClNNaO+, 374.1282,
found, 374.1271.
Keywords: Photocatalysis • Oxime esters • C-C Interruption •
Benzyl radical • Single electron transfer.
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C-C bond dissociation*
X. Fan, T. Lei, Z. Liu, X.-L. Yang, Y.-Y.
Cheng, G. Liang, B. Chen, C.-H. Tung
and L.-Z. Wu*
Page No. – Page No.
A photoredox benzyl activation was developed via formidable C(sp3)-C(sp3) bond
dissociation of 1-aryl acetone oxime esters, easily perapared from benzyl ketones.
The generated benzyl cation coupling with diverse O- and N- nucleophiles
successfully forged important benzyl ether and amines derivatives that are valuable
in last-stage functionlizations.
Benzyl C-O and C-N Bond
Construction via C-C Bond
Dissociation of Oxime Ester under
Visible Light Irradiation
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