Benzylic C(sp3)-H Functionalization for C-N and C-O Bond Formation via Visible Light Photoredox Catalysis

Article abstract of DOI:10.1021/acs.joc.6b00970

A visible light mediated highly selective benzylic C-H bond functionalization for intermolecular C-N and C-O bond formation is reported. This cross-dehydrogenative coupling reaction demonstrates a straightforward protocol for incorporating the heteroaromatics to the benzylic position. Benzylic oxidation of various alkyl aryls to corresponding carbonyl compounds has also been reported.

Full text of DOI:10.1021/acs.joc.6b00970

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Article
Benzylic C(sp3)–H Functionalization for C-N and C-O
Bond Formation Via Visible-Light-Photoredox Catalysis
Ganesh Pandey, Ramkrishna Laha, and Deepak Singh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00970 • Publication Date (Web): 06 Jun 2016
Downloaded from http://pubs.acs.org on June 11, 2016
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Benzylic C(sp3)–H Functionalization for C–N and C–O
Bond Formation Via Visible-Light-Photoredox Catalysis
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Ganesh Pandey*, Ramkrishna Laha and Deepak Singh
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Molecular Synthesis and Drug Discovery Laboratory, Centre of Biomedical Research, SGPGIMS Campus,
Lucknow – 226014, India.
Corresponding author email: gp.pandey@cbmr.res.in
Table of contents:
Abstract: A visible light mediated highly selective benzylic C–H bond functionalization for inter
molecular C–N and C–O bond formation is reported. This cross-dehydrogenative coupling
reaction demonstrates a straightforward protocol for incorporating the heteroaromatics to benzylic
position. Benzylic oxidation of various alkyl aryls to corresponding carbonyl compounds has also
been reported.
Introduction:
Catalytic functionalization of un-activated C(sp3)–H in a selective and efficient manner remains
most exciting and challenging topic in modern organic chemistry.1 Assortment of C–H bonds with
different electronic and steric environment in a molecule with high bond dissociation energy
(BDE) makes this protocol more delicate and difficult.2 Extensive research in this area have led to
discoveries of few precious methods for saturated C–H bond functionalization for halogenation,3
oxidation4 and amination5 reactions using metal catalysis. Functionalization of hydrocarbon for
C–C bond formation using carbon centered radical, generated through TBHP, DTBP, K2S2O8 and
hypervalent iodine are also known in literature.6 Directed aliphatic C–H functionalization for C–
X (X=O, N, I) bond formation is achieved with remarkable success.7,8
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Functionalization of comparatively reactive benzylic C(sp3)–H over aromatic C(sp2)–H bond is
relatively not so well studied, hence, there is a fundamental research interest in this area. Although
significant advances have been made in this area by directing group strategy using transition metal
catalysis,9 major limitation remains the choice of appropriate directing group and its removal.10
Another popular approach in this area has been the oxidative non-directed C(sp3)–H bond
functionalization using transition metal11,12 PhI(OAc)2,13 DDQ14 and iodoarene15 as an oxidant,
however, this protocol requires an adjacent heteroatom. Recently, oxidative cross-dehydrogenative
couplings (CDC) under metal free conditions using oxidants such as DDQ, hypervalent iodine, n-
Bu4NI/TBHP have also been reported for C–C and C–N bond forming reactions (Scheme 1).16,17
However, owing to the requirement of strong oxidizing agent, selectivity and applicability have
to be compromised. The redox-neutral approach for C–H functionalization via internal hydride
transfer has also attracted much attention recently.18
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An interesting and emerging strategy for the functionalization of C(sp3)–H bond via visible-light
photoredox catalysis is gaining importance in organic synthesis.19 This atom and step economic
strategy with resource efficiency has shifted the routine functional group transformation chemistry
towards ideal reactions. During last decade, considerable success has been made in this area to
functionalize the α-C(sp3)–H bond in t-amines, alcohols, ethers and used as main streamline
reactions in synthetic chemistry.20 Although, reports on simple C(sp3)–H functionalization is
infrequent in literature,21 we had reported earlier a protocol for C–O bond formation using DCN
(1,4-dicyanonaphthalene) as a light harvesting photocatalyst (Scheme 1).22 However, when same
protocol was extended for C–N bond formatiom, this reaction did not succeed possibly because of
competetive electron transfer. To overcome this problem, another concept for benzylic C–N bond
formation was developed to produce benzyl cation and its trapping by an amine by employing a
captodative amine radical, generated by DCA (9-10 dicyanoanthracene, 410 nm) photocatalysis of
N-methoxyacetamide23 followed by another electron transfer (Scheme 1). Very recently, visible
light induced protocol for benzylic oxidation using RFT (Rivoflavin tetraacetate )/Fe catalyst and
molecular oxygen has also appeared (Scheme 1).24 Therefore, it was felt necessary to develop a
highly selective benzylic C(sp3)–H functionalization for C–N as well as C–O bond formation via
visible-light-photoredox catalysis. We report herein a simple and common strategy for the benzylic
C–H functionalization for the C–O as well as C–N bond
formations using
Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1) as a visible light absorbing photoredox catalyst.
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Scheme 1: Benzylic C(sp3)–H Functionalization Reaction:
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Concept: Excited state of Ir[dF(CF3)ppy]2(dtbbpy)PF6 [(Ir(III)*] (1) catalyst, achieved by visible
light excitation, was designed to transfer an electron to BrCCl3 (2) to produce an strong oxidant
[Ir(IV)] as well as trichloromethyl radical (∙CCl3).25 SET (single electron transfer) reaction between
highly electron deficient Ir(IV) and electron rich aromatics 3 was expected to generate
corresponding arene radical cation 4. H-abstraction from benzylic C–H of 4 by trichloromethyl
radical (∙CCl3) was envisioned to produce reactive intermediate 5 which was expected to react with
an amine nucleophile 9 to give 6. Furthermore, it was also envisioned that the reaction of 5 with
moisture could also produce 8 via corresponding alcohol 7 following the 2nd catalytic cycle as
shown in Fig. 1.
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Figure 1: Concept of Benzylic C(sp3)–H Functionalization for C–N and C–O Bond Formation Via Visible-
Light-Photoredox Catalysis.
Results and Discussions:
In order to evaluate this proposed concept, initially a reaction between 4-methoxy ethyl benzene
3a (1 mmol) and diffrent amines (such as pyrrolidine, tosylamine and (Boc)2NH) were carried out
by irridiating with blue LED in the presence of [Ir(III)] (1, 1 mol%) as a photocatalyst, BrCCl3
(2, 1.5 mmol ) and lutidine (1.5 mmol) as a base in CH3CN. Lutidine was used to neutralize HBr
if formed during the course of the reaction. However, no product formation 11 was observed ,
albeit some degradation of amines were noted (Scheme 2). Therefore, we attempted this reaction
using more nucleophlic N-heterocyclic amine 9a (1.5 mmol). After 14 h of irradiation, when ~80
% 3a was disappeared, reaction was stopped and cocentrated. Column chromatography of the
crude reaction mixture delightfully gave 6a in 80 % yield (based on recovery of starting material)
along with minor amount of 8a (15%) (Table 1, entry 1).
Scheme 2: Study of Diffrent Amine
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Comparative study with Ru(II) [Ru(bpy)3Cl2] suggested that [Ir(III)] catalyst was more efficient
(Table 1, entry 2) than Ru (II). Optimisation experments using different bases (Table 1, entry 1, 5,
6), oxidative quenchers (Table 1, entry 5, 7, 8) and solvents established that K2CO3 is better base,
CBr4 and BrCCl3 are comparable oxidants whereas sodiumpersulphate salt diminished overall
yield (Table 1, entry 8) and acetonitrile is the most effective solvent for this reaction (Table 1,
entry 1, 3, 4).
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Table 1: Optimization of Reaction Conditions.a
Entry
Catalyst
Solvent
Base
Time(h) Oxidative Product 6a Ketone 8a
Yieldb (%)
Quencher
Yield(%)
Ir[dF(CF3)ppy]2(dtbbpy)PF6
Ru(bpy)3Cl2
MeCN Lutidine
MeCN Lutidine
12 h
20 h
20 h
18 h
16 h
16 h
16 h
16 h
12 h
12 h
16 h
BrCCl3
BrCCl3
BrCCl3
BrCCl3
BrCCl3
BrCCl3
CCBr4
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40
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50
75
70
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35
0
15
10
12
15
5
1
2
Ir[dF(CF3)ppy]2(dtbbpy)PF6
Ir[dF(CF3)ppy]2(dtbbpy)PF6
DMF
Lutidine
3
DMSO Lutidine
4
Ir[dF(CF3)ppy]2(dtbbpy)PF6 MeCN K2CO3
5
Ir[dF(CF3)ppy]2(dtbbpy)PF6
Ir[dF(CF3)ppy]2(dtbbpy)PF6
Ir[dF(CF3)ppy]2(dtbbpy)PF6
------------
MeCN Cs2CO3
5
6
MeCN
MeCN
MeCN
MeCN
MeCN
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
15
20
0
7
Na2S2O8
BrCCl3
---------
BrCCl3
8
9
Ir[dF(CF3)ppy]2(dtbbpy)PF6
Ir[dF(CF3)ppy]2(dtbbpy)PF6
0
0
10
11c
0
0
aReaction conditions: 4-methoxyethylbenzene (3a, 1.0 mmol), benzotrizole (9a, 1.5 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol%),
oxidative quencher (1.5 mmol) base (1.5 mmol) in CH3CN (5 mL) were irradiated under degassed condition at rt using blue LED
for 12–20 h; bIsolated yield of the product 6a; c Reaction was carried out in the dark.
A control experiment confirmed that there was no product formation in the absence of light,
photocatalyst or oxidative quencher (Table 1, entry 9, 10, 11). Our effort towards complete
elimination 8a did not succeded. A control experiment, in identical manner (Table 1,entry 5), but
without 9a also led the formation of 8a (~10-15%). Therefore, in the presence of 9a, 6a is formed
along with 8a due to the presence of moisture.
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Table 2: Scope of Alkyl Aryls Partnera,b
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aReaction conditions: alkyl aryl (3, 1.0 mmol), benzotrizole (9a, 1.5 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol%) , BrCCl3 (1.5 mmol)
and K2CO3 (1.5 mmol) in CH3CN (5 mL) were irradiated under degassed condition at rt using blue LED for 10-16 h. bIsolated yield
of the product 6.
Generality of this reaction (Table 1 entry 8) was established using various benzylic hydrocarbons
and results are shown in Table 2. To our delight, diphenylmethane, a relatively less electron rich
substrate also reacted as well (Table 2, entry 6e) and electron rich diphenylmethane and biphenyl
gave corresponding products in excellent yields (Table 2, entry 6f and 6g). Furthermore, functional
group tolerance of this methodology was also demonstrated through the preparation of 6h-6l.
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Table 3: Regioselectivity in Benzylic Aminationa,b
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aReaction conditions: alkyl aryl (3, 1.0 mmol), benzotrizole (9a, 1.5 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol%) , BrCCl3 (1.5 eq,
1.5 mmol) and K2CO3 (1.5 eq, 1.5 mmol) in CH3CN (5 mL) were irradiated under degassed condition at rt using blue LED for 16 h.
bIsolated yield of the product 6.
This interesting result encouraged us to establish the regioselectivity of this reaction by studying
substrates having two different benzylic positions. For example, reaction with 6-methoxytetralene
gave 6m (Table 3) exclusively in excellent yield. Similar selectivity was also observed with the
substrates having electronically different benzylic position (Table 3, entry 6n-6r). This
regioselectivity could be explained by the relative resonance stabilization of preferred benzylic
carbocation by –OMe group. Substrates bearing electron withdrawing groups such as –NO2 and –
CO2Me were unable to react (entry 6s and 6t). Simple di-alkylated substrate such as p-xylene was
also found to un-react under this reaction conditions (entry 6u).
Furthermore, the scope of this reaction was explored with a range of nitrogen heterocycles. For
example, reaction with 5-methoxyindane with different heterocyclic amine nucleophiles is
summarized in Table 4. The electron withdrawing and electron donating substituent at 5-position
of benzotriazole ring gave corresponding products in comparative yields (Table 4, entry 10a,
10c).26 Thus, this protocol can be used directly to incorporate potential biologically active groups
such as imidazole, benzimidazole and tetrazole moiety to the benzylic C–H bond (Table 4, entry
10h-10j) of aromatic hydroarbons.
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Table 4: Scope of Nucleophilesa,b
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aReaction conditions: 5-methoxyindane 3o (1.0 mmol), nitrogen nucleophile (9, 1.5 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 1 (1
mol%) , BrCCl3 2 (1.5 mmol) and K2CO3 ( 1.5 mmol) in CH3CN (5 mL) were irradiated under degassed condition at rt using blue
LED for 12-18 h. bIsolated yield of the product 10.
After demonstrating successfully benzylic C–N bond formation through this protocol, we
anticipated that this reaction could as well be used for the oxidation of benzylic position because
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small quantity of 8a was formed during the reaction of 3a with benzotriazole. Direct oxidation of
benzylic (sp3)C–H into ketone or aldehyde has been a hot topic of research where many
methodologies ranging from stoichiometric use of traditional oxidants27 to metal catalysis either
in the presence of THBP28 or molecular oxygen29,30 are reported. Several other oxidants31 have
also been evaluated for this oxidation reaction.
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Table 5: Benzylic Oxidation
aReaction conditions: alkyl-aryl (3, 1.0 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol%) , BrCCl3 (2.2 mmol) and K2CO3 (2.2 mmol) in
CH3CN:H2O ( 20:1, 10 mL) were irradiated under degassed condition at rt using blue LED for 22-24 h. bIsolated yields of the product
8.
Photoredox catalyzed benzylic oxidation is also reported using 10-methyl-9-phenylacridinium
derivatives32 as light absorbing species in the presence of fluorous-tagged decatungstate,33 metal
porphyrin34 and riboflavin tetraacetate (RFT, a vitamin B2 derivative)24,35 and oxygen. Recently,
we have also reported a photoredox protocol for the regio- and chemoselective benzylic oxidation
using DCN (1,4-dicyanonaphthalene) as a photocataloyst and H2O as an oxygen source.29
However, the use of high intensity UV light (>300 nm) somewhat dwarfs this strategy. Therefore,
we contemplated to use this present protocol for the benzylic oxidation reaction. Irradiation (22-
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24 h) of a mixture containing 3a (1 mmol), [Ir(III)] 1 (1 mol%), BrCCl3 (2.2 mmol) and K2CO3
(2.2 mmol) in moist CH3CN, under identical reaction condition as described above, provided
corresponding 4-methoxy acetophenone (8a) in 62 % yield. The strategy was found to be general
as exmplefied with the number of substrates as shown in Table-5, entry 8a-8r. There was no
reaction observed with arenes having electron deficient substituents (entry 8p and 8q) as well as
with p-xylene as mentioned above (entry 8r). Regio-and chemoselectivity was also established by
isolating selectively 8i, 8j and 8l in good yields. It may be worthy to mention that oxidation of 4-
methylanisole produced para-anisaldehye (Table 5, entry 8b), used as a fragnance and favouring
agent in food industry36 in good yields. Potential use of this reaction could be found in the
preparation of 8a by this simple reaction which is of high commercial values as a fragnance, food
favouring agent36 and as a antimycobacterial agent.37
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Scheme 3: Oxidation of Benzylic Alcohol
To implicate corresponding alcohol as an intermediate (Fig. 1) in these oxidations, authentic
samples of 1-(4-methoxyphenyl)ethan-1-ol (7a) and 4-methoxybenzylalcohol (7b) were exposed
to the identical reaction conditon as described above which gave 8a and 8b, respectively, in 82%,
85% yields (Scheme 3). To provide compelling evidence of 7a as an intermediate, 3a was
irradiated for a very short period of time (1-2 h) and analysis photolysate by GC showed the
formation of 7a.
Conclusion: A visible-light- photoredox catalyzed reaction using 1 [Ir(III)] is developed for the
highly selective benzylic C(sp3)–H amination as well as oxidation. This method incorporates
potent bioactive azole moiety such as imidazole, benzotriazole, benzimidazole and tetrazole
directly at benzylic position. Furthermore, same protocol is extended for the selective benzylic
oxidation to prepare industrially and academically important molecules. This straight forward,
atom-economy procedure is a new addition to benzylic C–H functionalization for C–N as well as
C–O bond forming reactions.
EXRERIMENTAL SECTION
General information:
All glass wares were washed with detergent, rinsed with acetone and dried in an oven at 125 °C
prior to use. Moisture sensitive reactions were carried out in argon atmosphere and sensitive
reagents were added via syringe and cannula techniques. Commercial reagents and solvents were
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purified and stored according to procedures prescribed in literature. TLC (Thin Layer
Chromatography) was performed on silica gel coated aluminium plates which were visualized by
UV fluorescence and/or by staining with iodine, alcoholic solution of phosphomolybodic acid. CC
(Column Chromatography) was performed on silica gel 60–120/, 100–200/, 230–400 mesh. NMR
(Nuclear Magnetic Resonance) spectra were recorded on a 400 MHz for 1H and 101 MHz for 13C,
1
respectively and/or 800 MHz and 202 MHz for H and 13C, respectively instruments using
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deuteriated solvent. Chemical shifts are reported in ppm. Proton coupling constants (J) are reported
as absolute values in Hz and multiplicity (s, singlet; d, doublet; t, triplet; dd, doublet of doublet;
m, multiplet). Data for NMR spectra are described in terms of chemical shift (δ in ppm) relative
13
to TMS δ (0.00) for proton NMR and the central line of CDCl3 (δ 77.0) for C NMR. HRMS
(High resolution mass spectra) were performed on Q-TOF using electron spray ionization (ESI)
technique. GCMS (Gas chromatography) was performed with a split-mode capillary injection
system and mass detectors using an Agilent HP-1 column (30 m, 0.32 mm ID). Melting point of
the products were uncorrected.
General procedure for visible light photoredox reactions:
Benzylic C–N bod forming reaction: An oven dry 25 mL round bottom flask, equipped with a
rubber septum and magnetic stir bar was charged with alkyl aryls 3 (1.0 mmol), BrCCl3 2 (1.5
mmol), MeCN (10 mL), K2CO3 (1.5 mmol), Ir(dF(CF3)ppy)2(dtbbpy)PF6, (1, 1 mol%) and
nucleophlic N-heterocyclic amine 9 (1.5 mmol) under argon atmosphere. The flask was degassed
3 times using freeze-pump-thaw method. The round bottom flask was stirred at room temperature
at a distance of approximately 2.0 cm from a blue light-emitting diodes (LED, max = 445 ±10
nm, 700 mA, 3.0 W) for 16 h. After reaction was completed (progress of the reaction monitored
by TLC), the mixture was poured into a separatory funnel containing 20 mL of EtOAc and 10 mL
of H2O, layers were separated and the aqueous layer extracted with ethyl acetate (2×10 mL). The
combined organic phases were washed with water, brine (10 mL) and dried over anhydrous
Na2SO4, filtered, and concentrated in vacuo. The crude reaction mixture was purified by silica gel
chromatography using pet-ether /ethyl acetate to afford pure product 6.
1-(1-(4-methoxyphenyl)ethyl)-1H-benzo[d][1,2,3]triazole (6a). (189.8 mg, 75%); Thick liquid; 1H
NMR (400 MHz, Chloroform-d) δ 7.96 – 7.90 (m, 1H), 7.26 – 7.20 (m, 2H), 7.19 – 7.11 (m, 3H),
6.75 (m, 2H), 5.93 (q, J = 7.1 Hz, 1H), 3.67 (s, 3H), 2.05 (d, J = 7.1 Hz, 3H). 13C NMR (101 MHz,
Chloroform-d) δ 159.3, 146.3, 132.2, 132.0, 127.6, 126.9, 123.7, 119.8, 114.1, 110.2, 58.5, 55.2,
21.0. HRMS (ESI, QTOF) calculated for C15H15N3O, [M+Na]+: 276.1107; found: 276.1098.
1-(4-methoxybenzyl)-1H-benzo[d][1,2,3]triazole (6b). (138.6 mg, 58%); Thick liquid; 1H NMR
(400 MHz, Chloroform-d) δ 7.97 (d, J = 8.2 Hz, 1H), 7.35 – 7.22 (m, 3H), 7.16 (d, J = 8.3 Hz,
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2H), 6.78 (d, J = 8.4 Hz, 2H), 5.70 (s, 2H), 3.69 (s, 3H). C NMR (101 MHz, Chloroform-d) δ
159.6, 146.3, 129.1, 127.3, 126.7, 123.8, 120.0, 114.3, 109.8, 55.2, 51.9. HRMS (ESI, QTOF)
calculated for C14H13N3O, [M+Na]+: 262.0951; found: 262.0944.
1-(1-(4-methoxyphenyl)propyl)-1H-benzo[d][1,2,3]triazole (6c). (213.6 mg, 80%); Thick liquid;
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1H NMR (400 MHz, Chloroform-d) δ 7.95 (d, J = 8.2 Hz, 1H), 7.34 – 7.12 (m, 5H), 6.82 – 6.66
(m, 2H), 5.58 (t, J = 7.7 Hz, 1H), 3.66 (s, 3H), 2.65 (m, 1H), 2.41 (m, 1H), 0.86 (t, J = 7.3 Hz,
3H). 13C NMR (101 MHz, Chloroform-d) δ 159.3, 146.2, 132.6, 131.1, 128.1, 126.9, 123.7, 119.8,
114.0, 109.9, 64.8, 55.2, 27.9, 11.2. HRMS (ESI, QTOF) calculated for C16H17N3O, [M+Na]+:
290.1264; found: 290.1258.
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1-(2-(4-methoxyphenyl)propan-2-yl)-1H-benzo[d][1,2,3]triazole (6d). (197.7 mg, 74%); Thick
liquid; 1H NMR (400 MHz, Chloroform-d) δ 7.96 (m, 1H), 7.21 – 7.14 (m, 1H), 7.07 (m, 3H), 6.77
(m, 2H), 6.64 (m, 1H), 3.71 (s, 3H), 2.07 (s, 6H). C NMR (101 MHz, Chloroform-d) δ 158.9,
146.9, 136.1, 132.0, 126.6, 126.3, 123.4, 119.8, 114.0, 112.2, 64.3, 55.2, 29.7. HRMS (ESI, QTOF)
calculated for C16H17N3O, [M+Na]+: 290.1264; found: 290.1259.
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1-benzhydryl-1H-benzo[d][1,2,3]triazole (6e). (197.7 mg, 68%); White solid, Mp. 155-157 0C; 1H
NMR (400 MHz, Chloroform-d) δ 8.13 – 8.05 (m, 1H), 7.39 (s, 1H), 7.38 – 7.31 (m, 8H), 7.25 –
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7.19 (m, 4H), 7.12 – 7.05 (m, 1H). C NMR (101 MHz, Chloroform-d) δ 146.3, 137.7, 133.0,
128.8, 128.4, 128.3, 127.3, 123.9, 120.2, 110.6, 67.2. HRMS (ESI, QTOF) calculated for
C19H15N3, [M+Na]+: 308.1158; found: 308.1153.
1-((4-methoxyphenyl)(phenyl)methyl)-1H-benzo[d][1,2,3]triazole (6f). (245.8 mg, 78%); White
solid, Mp. 163-164 0C; 1H NMR (400 MHz, Chloroform-d) δ 8.04 – 7.98 (m, 1H), 7.29 – 7.24 (m,
6H), 7.19 (s, 1H), 7.14 – 7.06 (m, 4H), 7.02 (dd, J = 6.9, 2.6 Hz, 1H), 6.80 (d, J = 8.7 Hz, 2H),
3.73 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 159.6, 146.3, 138.1, 133.0, 129.8, 129.7, 128.8,
128.3, 128.0, 127.3, 123.8, 120.2, 114.1, 110.6, 66.7, 55.3. HRMS (ESI, QTOF) calculated for
C20H17N3O, [M+H]+ 316.1444; found: 316.1464.
1-([1,1'-biphenyl]-4-yl(phenyl)methyl)-1H-benzo[d][1,2,3]triazole (6g). (245.6 mg, 68%); White
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solid, Mp. 179-180 C; H NMR (400 MHz, Chloroform-d) δ 8.08 – 8.01 (m, 1H), 7.51 (m, 2.7
Hz, 4H), 7.41 – 7.34 (m, 3H), 7.30 (m, 6H), 7.25 (s, 1H), 7.23 – 7.17 (m, 3H), 7.13 – 7.08 (m, 1H).
13C NMR (101 MHz, Chloroform-d) δ 146.3, 141.3, 140.2, 137.6, 136.6, 133.0, 128.8, 128.8,
128.8, 128.5, 128.3, 127.6, 127.5, 127.4, 127.1, 123.9, 120.2, 110.5, 66.9. HRMS (ESI, QTOF)
calculated for C25H19N3, [M+H]+: 362.1652; found: 362.1666.
3-(1H-benzo[d][1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)propan-1-ol (6h). (164.2 mg, 58%);
Thick liquid; 1H NMR (400 MHz, Chloroform-d) δ 8.02 (d, J = 8.2 Hz, 1H), 7.42 – 7.36 (m, 2H),
7.32 (d, J = 8.2 Hz, 3H), 6.84 (d, J = 8.3 Hz, 2H), 6.11 (dd, J = 9.0, 6.3 Hz, 1H), 3.76 (s, 3H), 3.69
(m, 1H), 3.63 – 3.52 (m, 1H), 2.97 (m, 1H), 2.75 – 2.61 (m, 1H), 2.01 (s, 1H). 13C NMR (101
MHz, Chloroform-d) δ 159.4, 145.9, 132.8, 130.8, 128.2, 127.1, 124.0, 119.7, 114.2, 110.0, 59.2,
58.6, 55.2, 37.4. HRMS (ESI, QTOF) calculated for C16H17N3O2, [M+Na]+: 306.1213; found:
306.1206.
Methyl 2-(1H-benzo[d][1,2,3]triazol-1-yl)-2-(4-methoxyphenyl)acetate (6i). (208.0 mg, 70%);
Thick liquid; 1H NMR (400 MHz, Chloroform-d) δ 8.10 – 8.00 (m, 1H), 7.37 – 7.29 (m, 4H), 7.21
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– 7.16 (m, 1H), 6.92 (d, J = 8.4 Hz, 2H), 6.87 (s, 1H), 3.86 (s, 3H), 3.81 (s, 3H). C NMR (101
MHz, Chloroform-d) δ 168.4, 160.3, 146.4, 132.5, 129.7, 127.5, 124.2, 123.9, 120.0, 114.4, 111.1,
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65.2, 55.3, 53.1. HRMS (ESI, QTOF) calculated for C16H15N3O3, [M+Na]+: 320.1006; found:
320.1001.
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Methyl 3-(1H-benzo[d][1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)propanoate (6j). (230.2 mg,
74%); Thick liquid; H NMR (400 MHz, Chloroform-d) δ 7.96 (d, J = 8.3 Hz, 1H), 7.36 – 7.28
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(m, 2H), 7.23 – 7.18 (m, 2H), 6.81 – 6.70 (m, 2H), 6.17 (dd, J = 9.0, 5.9 Hz, 1H), 3.89 (dd, J =
16.7, 9.0 Hz, 1H), 3.68 (s, 3H), 3.56 (s, 3H), 3.30 (dd, J = 16.8, 5.9 Hz, 1H). 13C NMR (101 MHz,
Chloroform-d) δ 170.6, 159.7, 146.2, 132.75, 130.11, 128.00, 127.29, 124.01, 119.89, 114.36,
109.86, 58.92, 55.25, 52.10, 40.18. HRMS (ESI, QTOF) calculated for C17H17N3O3, [M+Na]+:
334.1162; found: 334.1159.
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1-(1-(4-methoxyphenyl)allyl)-1H-benzo[d][1,2,3]triazole (6k). (198.8 mg, 75%); Thick liquid; 1H
NMR (400 MHz, Chloroform-d) δ 8.00 (d, J = 7.8 Hz, 1H), 7.27 (t, J = 7.0 Hz, 2H), 7.22 – 7.13
(m, 3H), 6.88 – 6.73 (m, 2H), 6.62 – 6.44 (m, 2H), 5.40 (d, J = 9.3 Hz, 1H), 5.10 (d, J = 15.9 Hz,
1H), 3.72 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 159.6, 146.4, 134.5, 132.3, 129.2, 128.8,
127.1, 123.8, 120.1, 119.3, 114.2, 110.5, 65.3, 55.3. HRMS (ESI, QTOF) calculated for
C16H15N3O, [M+Na]+: 288.1107; found: 288.1111.
Ethyl (2E,4E)-6-(1H-benzo[d][1,2,3]triazol-1-yl)-6-(4-methoxyphenyl)hexa-2,4-dienoate (6l).
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(262.9 mg, 72%); Thick liquid; H NMR (800 MHz, Chloroform-d) δ 8.05 (dd, J = 8.3, 1.0 Hz,
1H), 7.38 (dd, J = 6.8, 1.2 Hz, 1H), 7.35 – 7.31 (m, 2H), 7.30 – 7.27 (m, 2H), 6.94 (d, J = 15.7 Hz,
1H), 6.87 – 6.82 (m, 2H), 5.85 – 5.68 (m, 2H), 4.18 (m, 2H), 3.76 (s, 3H), 3.04 – 2.89 (m, 1H),
2.61 (m, 1H), 2.23 (m, 2H), 1.28 (t, J = 7.04 Hz, 3H). 13C NMR (201 MHz, Chloroform-d) δ 166.3,
159.6, 146.7, 146.2, 132.6, 130.6, 128.0, 127.2, 124.0, 122.6, 120.0, 114.3, 109.7, 62.2, 60.3, 55.3,
33.1, 29.0, 14.2. HRMS (ESI, QTOF) calculated for C21H23N3O3, [M+Na]+: 388.1632; found:
388.1615.
1-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-1H-benzo[d][1,2,3]triazole (6m). (189.8 mg,
0
68%); White solid, Mp. 136-138 C;; 1H NMR (400 MHz, Chloroform-d): 8.05 (dd, J = 8.3, 1.1
Hz, 1H), 7.32 – 7.23 (m, 2H), 6.86 (m, 1H), 6.78 (d, J = 2.6 Hz, 1H), 6.70 (d, J = 8.6 Hz, 1H), 6.61
(dd, J = 8.6, 2.7 Hz, 1H), 6.30 (dd, J = 8.3, 6.0 Hz, 1H), 3.79 (s, 3H), 3.03 (dd, J = 8.9, 5.4 Hz,
1H), 2.95 – 2.90 (m, 1H), 2.42 – 2.31 (m, 2H), 2.02 (m, 1H), 1.97 – 1.90 (m, 1H). 13C NMR (201
MHz, Chloroform-d) δ 159.2, 146.5, 139.3, 132.1, 129.7, 126.8, 124.9, 123.6, 120.0, 113.8, 112.9,
110.9, 58.7, 55.2, 31.0, 29.6, 20.9. HRMS (ESI, QTOF) calculated for C17H17N3O, [M+Na]+
302.1264; found: 302.1262.
1-(5-methoxy-2, 3-dihydro-1H-inden-1-yl)-1H-benzo[d][1,2,3]triazole (6n). (212.1mg, 80%);
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Thick liquid; H NMR (400 MHz, Chloroform-d): δ 8.10 – 7.98 (m, 1H), 7.35 – 7.22 (m, 2H),
6.97 – 6.87 (m, 3H), 6.72 (dd, J = 8.5, 2.4 Hz, 1H), 6.59 (dd, J = 8.4, 6.1 Hz, 1H), 3.82 (s, 3H),
3.29 (m, 1H), 3.16 – 3.05 (m, 1H), 2.94 – 2.80 (m, 1H), 2.51 (dd, J = 8.0, 5.8 Hz, 1H); 13C NMR
(101 MHz, Chloroform-d) δ 160.7, 146.7, 145.5, 131.6, 131.3, 126.9, 125.6, 123.7, 120.1, 113.5,
110.5, 110.0, 64.4, 55.4, 33.0, 31.0; HRMS (ESI, QTOF) calculated for C16H15N3O, [M+Na]+
288.1107; found: 288.1109.
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1-(1-(2-ethyl-4-methoxyphenyl)propyl)-1H-benzo[d][1,2,3]triazole (6o). (224.3 mg, 76%); Thick
liquid; 1H NMR (800 MHz, Chloroform-d) 1H NMR (800 MHz, Chloroform-d) δ 8.08 – 7.97 (m,
1H), 7.45 – 7.41 (m, 1H), 7.35 – 7.32 (m, 1H), 7.31 – 7.28 (m, 2H), 6.75 (d, J = 7.6 Hz, 2H), 5.99
(dd, J = 9.2, 5.8 Hz, 1H), 3.77 (s, 3H), 2.84 – 2.71 (m, 2H), 2.66 (dd, J = 14.8, 7.5 Hz, 1H), 2.42
– 2.35 (m, 1H), 1.15 (t, J = 7.6 Hz, 3H), 0.98 (t, J = 7.4 Hz, 3H). 13C NMR (201 MHz, Chloroform-
d) δ 159.3, 146.2, 143.6, 132.6, 128.2, 128.0, 126.9, 123.6, 119.9, 114.6, 111.2, 110.0, 61.1, 55.1,
28.3, 25.3, 15.1, 11.5. HRMS (ESI, QTOF) calculated for C18H21N3O, [M+Na]+ 318.1577; found:
318.1570.
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1-(6-methoxy-1-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)-1H-benzo[d][1,2,3]triazole
(6p).
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(181.6 mg, 62%); Thick liquid; H NMR (800 MHz, Chloroform-d) δ 8.02 (d, J = 8.3 Hz, 1H),
7.24 – 7.20 (m, 1H), 7.11 (m, 1H), 6.85 (d, J = 8.7 Hz, 1H), 6.77 (d, J = 2.7 Hz, 1H), 6.64 (dd, J
= 8.7, 2.7 Hz, 1H), 6.36 (d, J = 8.5 Hz, 1H), 3.81 (s, 3H), 3.02 – 2.91 (m, 2H), 2.42 (m, 1H), 2.33
(s, 3H), 2.18 (m, 1H), 2.02 – 1.95 (m, 1H), 1.89 – 1.82 (m, 1H). 13C NMR (201 MHz, Chloroform-
d) δ 158.9, 138.4, 130.5, 129.0, 126.4, 123.2, 119.8, 113.5, 113.2, 112.2, 64.0, 55.2, 38.6, 30.3,
30.1, 20.3. HRMS (ESI, QTOF) calculated for C18H19N3O, [M+Na]+ 316.1420; found: 316.1416.
1-(5-methoxy-1-methyl-2,3-dihydro-1H-inden-1-yl)-1H-benzo[d][1,2,3]triazole (6q). (178.6 mg,
64%); Thick liquid; 1H NMR (800 MHz, Chloroform-d) δ 8.03 (m, 1H), 7.26 – 7.23 (m, 1H), 7.15
(m, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.92 (d, J = 2.4 Hz, 1H), 6.78 (dd, J = 8.4, 2.5 Hz, 1H), 6.46 (d,
J = 8.5 Hz, 1H), 3.85 (s, 3H), 3.09 (t, J = 7.2 Hz, 2H), 2.71 (d, J = 13.5 Hz, 1H), 2.60 – 2.45 (m,
1H), 2.27 (s, 3H). 13C NMR (201 MHz, Chloroform-d) δ 159.2, 146.5, 139.3, 132.1, 129.7, 126.8,
124.9, 123.6, 120.0, 113.8, 112.9, 110.9, 58.7, 55.2, 31.0, 29.6, 21.0. HRMS (ESI, QTOF)
calculated for C17H17N3O, [M+Na]+ 302.1264; found: 302.1267.
1-(1-(4-methoxyphenyl)-2-phenylethyl)-1H-benzo[d][1,2,3]triazole (6r). (197.5 mg, 60%); White
solid, Mp. 139-141 0C; 1H NMR (800 MHz, Chloroform-d) δ 8.05 – 7.96 (m, 1H), 7.34 – 7.26 (m,
5H), 7.17 – 7.10 (m, 3H), 7.07 – 7.03 (m, 2H), 6.87 – 6.77 (m, 2H), 5.91 (t, J = 7.8 Hz, 1H), 4.09
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(dd, J = 14.0, 8.7 Hz, 1H), 3.75 (s, 3H), 3.72 (dd, J = 14.0, 6.8 Hz, 1H). C NMR (201 MHz,
Chloroform-d) δ 159.4, 146.0, 137.2, 132.8, 130.8, 129.1, 128.4, 128.2, 127.0, 126.7, 123.7, 119.9,
114.1, 109.6, 64.8, 55.2, 41.4. HRMS (ESI, QTOF) calculated for C21H19N3O, [M+Na]+ 352.1420;
found: 352.1414.
1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-5-methyl-1H-benzo[d][1,2,3]triazole (10a-1); (10a-2).
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(201.0 mg, 72%); Thick liquid; H NMR (400 MHz, Chloroform-d) H NMR (400 MHz,
Chloroform-d) δ 7.88 – 7.66 (m, 2H), 7.04 (dd, J = 13.8, 8.5 Hz, 2H), 6.93 – 6.78 (m, 4H), 6.75 –
6.60 (m, 4H), 6.55 – 6.38 (m, 2H), 3.76 (s, 6H), 3.20 (dd, J = 10.5, 5.0 Hz, 2H), 3.03 (m, 2H), 2.78
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(m, 2H), 2.48 – 2.41 (m, 2H), 2.39 (s, 3H), 2.32 (s, 3H). C NMR (101 MHz, Chloroform-d) δ
160.7, 160.6, 147.3, 145.5, 145.3, 137.4, 133.7, 132.1, 131.5, 131.4, 130.1, 129.0, 126.0, 125.6,
125.5, 119.5, 118.9, 113.48, 113.45, 110.0, 109.9, 109.5, 64.4, 64.1, 55.4, 33.0, 32.8, 30.99, 30.96,
22.0, 21.4. HRMS (ESI, QTOF) calculated for C17H17N3O, [M+Na]+ 302.1264; found: 302.1253.
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1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-5,6-dimethyl-1H-benzo[d][1,2,3]triazole (10b). (293.5
mg, 66%); Thick liquid; 1H NMR (400 MHz, Chloroform-d): δ 7.76 (s, 1H), 6.97 – 6.84 (m, 2H),
6.77 – 6.63 (m, 2H), 6.50 (t, J = 7.4 Hz, 1H), 3.80 (s, 3H), 3.28 (m, 1H), 3.07 (m, 1H), 2.82 (m,
1H), 2.50 (m, 1H), 2.33 (s, 3H), 2.27 (s, 3H). 13C NMR (101 MHz, Chloroform-d): δ 160.4, 145.7,
145.1, 136.9, 133.3, 131.5, 130.5, 125.3, 118.8, 113.3, 109.8, 109.6, 63.9, 55.2, 32.6, 30.8, 20.8,
20.2. HRMS (ESI, QTOF) calculated for C18H19N3O, [M+H]+ 294.1601; found: 294.1604.
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5-chloro-1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-1H-benzo[d][1,2,3]triazole (10c-1); (10c-2).
(215.3 mg, 72%); Thick liquid; 1H NMR (400 MHz, Chloroform-d) δ 7.92-7.86 (m, 2H), 7.15 (m,
2H), 6.86 – 6.80 (m, 4H), 6.75 – 6.59 (m, 4H), 6.47 (m, 2H), 3.74 (s, 6H), 3.19 (m, 2H), 3.01 (m,
2H), 2.86 – 2.71 (m, 2H), 2.46 – 2.28 (m, 2H). 13C NMR (101 MHz, Chloroform-d) δ 160.8, 147.2,
145.5, 145.3, 145.1, 133.1, 132.1, 130.70, 130.67, 130.2, 129.5, 127.7, 125.5, 125.4, 124.8, 120.9,
119.2, 113.6, 113.6, 111.3, 110.04, 110.01, 110.0, 64.6, 64.4, 55.3, 55.3, 33.0, 32.9, 30.89, 30.85.
HRMS (ESI, QTOF) calculated for C16H14ClN3O, [M+Na]+ 322.0718; found: 322.0714.
1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-1H-benzo[d]imidazole (10d). (195.5 mg, 74%) Thick
liquid; 1H NMR (400 MHz, Chloroform-d): δ 7.79 – 7.70 (m, 1H), 7.65 (d, J = 1.3 Hz, 1H), 7.26
– 7.10 (m, 3H), 6.98 (d, J = 8.3 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.71 (dd, J = 8.5, 2.5 Hz, 1H),
5.84 (t, J = 6.6 Hz, 1H), 3.76 (s, 3H), 3.05 (dd, J = 9.1, 5.8 Hz, 1H), 2.95 (m, 1H), 2.76 – 2.57 (m,
1H), 2.36 – 2.16 (m, 1H). 13C NMR (101 MHz, Chloroform-d): δ 160.7, 145.6, 144.3, 141.9, 133.2,
131.5, 125.7, 122.6, 122.1, 120.4, 113.6, 110.4, 110.1, 60.2, 55.4, 33.7, 30.6. HRMS (ESI, QTOF)
calculated for C17H16N2O, [M+H]+ 265.1335; found: 265.1337.
1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-2-methyl-1H-benzo[d]imidazole (10e). (211.4 mg,
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76%); White solid, Mp. 125-127 C; H NMR (400 MHz, Chloroform-d) δ 7.62 (d, J = 8.0 Hz,
1H), 7.23 – 7.01 (m, 2H), 6.87 (d, m,, 2H), 6.78 (d, J = 8.4 Hz, 1H), 6.64 (dd, J = 8.5, 2.4 Hz, 1H),
5.91 (t, J = 8.3 Hz, 1H), 3.76 (s, 3H), 3.19 – 3.07 (m, 1H), 2.99 (m, 1H), 2.62 (d, J = 15.6 Hz, 4H),
13
2.33 (m, 1H). C NMR (101 MHz, Chloroform-d) δ 160.4, 151.6, 144.5, 131.7, 125.2, 121.74,
121.71, 118.9, 113.3, 110.1, 60.1, 55.4, 32.0, 30.6, 14.6. HRMS (ESI, QTOF) calculated for
C18H18N2O, [M+H]+ 279.1492; found: 279.1488.
1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-5,6-dimethyl-1H-benzo[d]imidazole (10f). (192.8 mg,
66%); Thick liquid; 1H NMR (400 MHz, Chloroform-d): δ 6.32 (d, J = 9.4 Hz, 2H), 5.79 (d, J =
8.4 Hz, 1H), 5.74 (s, 1H), 5.65 (s, 1H), 5.52 (dd, J = 8.5, 2.3 Hz, 1H), 4.59 (t, J = 6.7 Hz, 1H), 2.58
(s, 3H), 1.93 – 1.81 (m, 1H), 1.74 (m, 1H), 1.52 – 1.39 (m, 1H), 1.11 (s, 3H), 1.09 (s, 3H), 1.04
13
(m, 1H). C NMR (101 MHz, Chloroform-d): δ 160.6, 145.5, 142.9, 141.1, 131.84, 131.78,
131.69, 131.0, 125.7, 120.3, 113.5, 110.5, 110.1, 60.1, 55.4, 33.7, 30.6, 20.6, 20.2. HRMS (ESI,
QTOF) calculated for C19H20N2O, [M+H]+ 293.1653; found: 293.1648.
1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-2-phenyl-1H-benzo[d]imidazole (10g). (231.3 mg,
0
1
68%); White solid, Mp. 293-294 C H NMR (400 MHz, Chloroform-d) δ 7.87 – 7.71 (m, 3H),
7.52 (dd, J = 5.4, 1.9 Hz, 3H), 7.20 (t, J = 7.6 Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H), 6.87 (d, J = 9.0
Hz, 2H), 6.67 (dd, J = 18.4, 8.2 Hz, 2H), 6.14 (t, J = 8.4 Hz, 1H), 3.80 (s, 3H), 3.18 (m, 1H), 2.99
(m, 1H), 2.70 – 2.53 (m, 2H). 13C NMR (101 MHz, Chloroform-d) δ 160.2, 154.4, 144.2, 143.7,
133.33, 132.28, 130.8, 129.7, 129.5, 128.7, 124.8, 122.2, 122.0, 120.0, 113.2, 112.5, 110.1, 61.0,
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55.4, 32.0, 30.4. HRMS (ESI, QTOF) calculated for C23H20N2O, [M+H]+ 341.1648; found:
341.1644.
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1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-4,5-diphenyl-4,5-dihydro-1H-imidazole (10h). (278.0
mg, 76%); Thick liquid; H NMR (400 MHz, Chloroform-d); δ 7.40 (d, J = 6.6 Hz, 5H), 7.36 –
1
7.31 (m, 2H), 7.19 (s, 1H), 7.12 (dd, J = 8.3, 6.7 Hz, 2H), 7.04 (dd, J = 19.0, 7.8 Hz, 2H), 6.77 –
6.70 (m, 2H), 5.30 (t, J = 7.0 Hz, 1H), 3.75 (s, 3H), 2.97 (m, 1H), 2.76 (m, J = 16.0, 7.7 Hz, 1H),
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2.44 (m, 1H), 2.15 – 2.03 (m, 1H). C NMR (101 MHz, Chloroform-d) δ 160.5, 145.4, 137.9,
134.9, 134.6, 133.0, 131.12, 131.10, 129.1, 128.8, 128.7, 128.1, 126.5, 126.2, 125.4, 113.6, 109.9,
59.5, 55.5, 35.8, 30.4. HRMS (ESI, QTOF) calculated for C25H22N2O, [M+H]+ 367.1805; found:
367.1808.
1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-1H-imidazole-4,5-dicarbonitrile (10i). (117.0 mg,
0
66%); White solid, 138-140 C; 1H NMR (800 MHz, Chloroform-d) δ 7.37 (s, 1H), 7.13 (d, J =
8.5 Hz, 1H), 6.94 – 6.82 (m, 2H), 5.83 (dd, J = 7.8, 4.0 Hz, 1H), 3.84 (s, 3H), 3.16 (m, 1H), 3.05
(m, 1H), 2.94 – 2.77 (m, 1H), 2.27 (m, 1H); 13C NMR (201 MHz, Chloroform-d) δ 161.6, 146.3,
139.83, 139.81, 139.79, 128.8, 125.7, 123.5, 114.4, 111.6, 111.4, 110.2, 107.8, 63.4, 55.5, 34.7,
30.4. HRMS (ESI, QTOF) calculated for C15H12N4O, [M+Na]+ 287.0903; found: 287.0895.
1-(5-methoxy-2,3-dihydro-1H-inden-1-yl)-5-phenyl-1H-tetrazole (10j). (146.0 mg, 74%); White
solid, 75-77 0C; 1H NMR (800 MHz, Chloroform-d) δ 8.22 – 8.01 (m, 2H), 7.43 (m, 3H), 7.18 (d,
J = 8.4 Hz, 1H), 6.85 (d, J = 2.5 Hz, 1H), 6.74 (dd, J = 8.5, 2.4 Hz, 1H), 6.35 (t, J = 6.2 Hz, 1H),
3.77 (s, 3H), 3.43 – 3.35 (m, 1H), 3.07 – 2.99 (m, 1H), 2.78 (q, J = 7.3 Hz, 2H). 13C NMR (201
MHz, Chloroform-d) δ 165.0, 160.8, 145.9, 131.3, 130.0, 128.7, 127.5, 126.7, 125.6, 113.3, 109.8,
67.8, 55.3, 32.4, 30.9. HRMS (ESI, QTOF) calculated for C17H16N4O, [M+Na]+ 315.1216; found:
315.1208.
General Procedure for Benzylic Oxidation:
An oven dry 25 mL round bottom flask, equipped with a rubber septum and magnetic stir bar was
charged with 4-methoxyethylbenzene 3 (1.0 mmol), BrCCl3 2 (2.2 mmol), K2CO3 (2.2 mmol)
MeCN:H2O (20:1; 10 mL) and Ir(dF(CF3)ppy)2(dtbbpy)PF6 1 (1 mol%) under argon atmosphere.
The flask was degassed 3 times using freeze-pump-thaw method. The round bottom flask was
stirred at room temperature at a distance of approximately 2 cm from a blue light-emitting
diodes (LED, max = 445 ± 10 nm, 700 mA, 3.0 W) for 22-24 h. After reaction was completed
(progress of the reaction was monitored by TLC), the mixture was poured into a separatory funnel
containing 20 mL of EtOAc and 10 mL of H2O, layers were separated and the aqueous layer
extracted with ethyl acetate (2×10 mL).The combined organic phases were washed with brine (10
mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude reaction mixture
was purified by silica gel chromatography using pet-ether /ethyl acetate to afford pure product 8.
The identity of reported compounds were confirmed by matching 1H and 13C and GCMS data of
compound 8b,28a 8c,38 8d,28a 8e,22 8g,38 8i,38 8j,38 8k,31h 8l,22 8m,22 8n,22 8o28a authentic samples.
The 1H, 13C data of representative compounds 8a, 8f and 8h are given below.
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1-(4-methoxyphenyl)ethan-1-one (8a). (93.6 mg, 62 %); Color less liquid; H NMR (400 MHz,
Chloroform-d) δ 7.79 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 2.40 (s, 3H). 13C
NMR (101 MHz, Chloroform-d) δ 196.4, 163.2, 130.3, 130.0, 113.4, 55.1, 26.0.
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[1,1'-biphenyl]-4-yl(phenyl)methanone (8f). (165.7 mg, 75%); White solid, Mp. 100-102 C; H
NMR (800 MHz, Chloroform-d) δ 7.93 – 7.79 (m, 4H), 7.73 – 7.68 (m, 2H), 7.67 – 7.62 (m, 2H),
7.62 – 7.57 (m, 1H), 7.49 (dt, J = 15.7, 7.7 Hz, 4H), 7.40 (t, J = 7.3 Hz, 1H). 13C NMR (201 MHz,
Chloroform-d) δ 196.3, 145.2, 139.9, 137.7, 136.2, 132.3, 130.7, 130.0, 128.9, 128.3, 128.1, 127.3,
126.9.
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Isochroman-1-one (8h). (125.8 mg, 85%); Color less liquid; 1H NMR (400 MHz, Chloroform-d)
δ 7.97 (d, J = 7.8 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.28 (t, J = 7.7 Hz, 1H), 7.18 (d, J = 7.6 Hz,
1H), 4.42 (t, J = 6.0 Hz, 2H), 2.96 (t, J = 6.0 Hz, 2H). 13C NMR (101 MHz, Chloroform-d) δ 164.9,
139.4, 133.5, 130.03, 130.00, 129.98, 127.4, 127.1, 125.0, 76.7, 67.1, 27.5.
Acknowledgement:
G.P. thanks to DST, New Delhi for financial support (J.C. Bose Fellowship) and D.S. and R.L.
thanks CSIR, New Delhi for award of a research fellowship.
Supporting Information:
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Copies of H NMR and C NMR spectra of products. The Supporting Information is available
free of charge on the ACS Publications website at DOI:
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