Photoredox removal of p-methoxybenzyl ether protecting group with hydrogen peroxide as terminal oxidant

Article abstract of DOI:10.1002/adsc.201400936

We report a mild protocol for removal of the p-methoxybenzyl ether protecting group under acidic conditions with eosin Y combined with LEDs as a photoredox catalysis system and hydrogen peroxide as the terminal oxidant. This protocol is compatible with ethers derived from primary, secondary, and tertiary alcohols, as well as with various functional groups. The protocol showed unusual selectivity for a tertiary ether over a primary ether. The scale up to gram scale is also explored and identical reactivity is observed.

Full text of DOI:10.1002/adsc.201400936

Supporting Information
© Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2014

Photoredox Removal of p-Methoxybenzyl Ether
Protecting Group with Hydrogen Peroxide as
Terminal Oxidant
Zheng Liu, Yi Zhang, Zheren Cai, Hao Sun, and Xu Cheng*
Institute of Chemistry and Biomedical Sciences, School of Chemistry and Chemical Engineering,
Nanjing University, Xianlin Road 163, Nanjing, China, 210023
Fax: (86)-25-84687372; e-mail: chengxu@nju.edu.cn
Supporting Information
1
General: H NMR and 13C NMR spectra were recorded on Bruker Avance II 400
spectrometer and resolved with MestreNova software. IR spectra were recorded on
ThermoFisher Nicolet iS5. Column chromatography was performed on silica gel from
Qingdao Marine Chemical Industry. Fluorescence quenching experiments were
performed on HITACHI F-7000FL 5J1-0004. Solvents used for chromatography were
AR grade, as appropriate. Acetonitrile, ethyl acetate, 1,4-Dioxane, EtOH and DCE
were distilled from commercial available source.
Procedures for Preparation of Starting Materials
A flame dried round bottom flask equipped with a magnetic stir bar was charged with
o
compound 1b (680 mg, 5 mmol), dry THF (20 mL) and cooled to 0 C. The mixture
was then treated with 60% dispersion of NaH (240 mg, 6 mmol) in mineral oil and
stirred at room temperature for 30 minutes. PMBCl (936 mg, 6 mmol) and Bu4NBr
(166 mg, 0.5 mmol) were then added consequently. The mixture was stirred at room
temperature for 12 hours, and then water and ethyl acetate was added. The mixture
was extracted with ethyl acetate three times. The combined organic layer was dried
(Na2SO4) and concentrated. Then it was purified by silica gel chromatography with
PE/EA (v/v = 9:1) as eluent to give the product 1a as colorless oil (980 mg, 78%).
1H NMR (400 MHz, CDCl3) δ 7.29 (dd, J = 7.6, 5.6 Hz, 4H), 7.21 (dd, J = 7.2, 4.1 Hz,
3H), 6.91 (d, J = 8.4 Hz, 2H), 4.46 (s, 2H), 3.83 (s, 3H), 3.49 (t, J = 6.4 Hz, 2H), 2.78
– 2.67 (m, 2H), 1.97 – 1.90 (m, 2H).

DL-menthanol 2b (156 mg, 1 mmol), PMBCl (234 mg, 1.5 mmol), NaI (15 mg, 0.1
mmol) and DIPEA (208 mg, 1.6 mmol) were charged in a reaction vessel equipped
with a magnetic stir bar under nitrogen atmosphere. The mixture was refluxed at 150
oC for 2 hours. The resulting mixture was typically a biphasic mixture. Ethyl acetate
and 10% aqueous sodium bisulfate were added to the mixture and the aqueous layer
was extracted with ethyl acetate three times. The combined organic layer was dried
(Na2SO4) and concentrated. The residue was purified by silica gel chromatography
with PE/EA (v/v = 7:1) as eluent to give the product 2a as colorless oil (237 mg,
86%).
1H NMR (400 MHz, CDCl3) δ7.27 (d, J = 8.6 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 4.59
(d, J = 11.0 Hz, 1H), 4.33 (d, J = 11.0 Hz, 1H), 3.80 (s, 3H), 3.18 – 3.11 (m, 1H), 2.32
– 2.15 (m, 2H), 1.69 – 1.58 (m, 2H), 1.41 – 1.23 (m, 2H), 1.04 – 0.79 (m, 9H), 0.69 (d,
J = 6.9 Hz, 3H).
Alcohol 3b (198 mg, 1 mmol), PMBCl (234 mg, 1.5 mmol), NaI (15 mg, 0.1 mmol)
and DIPEA (208 mg, 1.6 mmol) were charged in reaction vessel equipped with
o
magnetic stir bar under nitrogen atmosphere. The mixture was refluxed at 150 C for
2 hours. Ethyl acetate and 10% aqueous sodium bisulfate were added to the mixture.
The aqueous layer was extracted with ethyl acetate three times. The combined organic
layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel
chromatography with PE/EA (v/v = 19:1) as eluent to give the product 3a as colorless
oil (216 mg, 68%).
1H NMR (400 MHz, CDCl3) δ 7.49 – 7.47 (m, 4H), 7.37 – 7.33 (m, 6H), 7.28 (d, J =
7.2 Hz, 2H), 6.93 (d, J = 8.6 Hz, 2H), 4.32 (s, 2H), 3.84 (s, 3H), 2.01 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 158.87, 146.76, 131.64, 128.72, 128.04, 126.87,
126.85, 113.73, 80.96, 64.50, 55.32, 26.06.
IR (thin film cm-1): 756, 823, 900, 1032, 1123, 1172, 1247, 1301, 1380, 1444, 1492,
1512, 1585, 1612, 2834, 2906, 2979, 3023, 3058.
EI (M+): calc. for 318, found: 318.
+
HRMS, ESI (M+Na+), calc. for (C22H22NaO2 ) 341.1512, found: 341.1517

Alcohol 4b (150 mg, 1 mmol), PMBCl (234 mg, 1.5 mmol), NaI (15 mg, 0.1 mmol)
and DIPEA (208 mg, 1.6 mmol,) were charged in a reaction vessel equipped with a
o
magnetic stir bar under nitrogen atmosphere. The mixture was refluxed at 150 C for
2 hours. Ethyl acetate and 10% aqueous sodium bisulfate were added to the mixture
and the mixture was extracted with ethyl acetate three times. The combined organic
layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel
chromatography with PE/EA (v/v = 9:1) as eluent to give the product 4a as colorless
oil (205 mg, 76%).
1H NMR (400 MHz, CDCl3) δ 7.32 – 7.20 (m, 7H), 6.88 (d, J = 8.7 Hz, 2H), 4.47 (s,
2H), 3.81 (s, 3H), 2.88 (s, 2H), 1.24 (s, 6H).
To a mixture of adamantan-1-ol (304 mg, 2 mmol) in DMF (5 mL) was added NaH
o
(100 mg, 60% in mineral oil, 100 mg, 2.5 mmol,) at 0 C. After 10 minutes, PMBCl
(374 mg, 2.4 mmol) was added dropwise. The reaction was stirred for 1 hour and then
quenched with Sat. NH4Cl (1 mL). The mixture was extracted with CH2Cl2 (5 mL x
3). The combined organic layer was dried over MgSO4, filtered and concentrated
under reduced pressure. The mixture was then purified by silica gel flash column
chromatography with PE/EA (v/v = 9:1) as eluent to give the compound 5a as white
solid (400 mg, 73%).
1H NMR (400 MHz, CDCl3) δ7.27 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 4.44
(s, 2H), 3.79 (s, 3H), 2.17 (s, 3H), 1.84 (d, J = 2.1 Hz, 6H), 1.72 – 1.58 (m, 6H).
A flask equipped with a magnetic stir bar was charged with compound 6b (643 mg,
2.7 mmol), Et3N (810 mg, 8 mmol), DMAP (33 mg, 0.27 mmol) and DCM (16 mL)
under nitrogen atmosphere. The TBDPSCl (890 mg, 3.22 mmol,) was added to the
mixture after 5 minutes. Then the mixture was stirred at room temperature for 12

hours. The mixture was added water and DCM. The aqueous layer was extracted with
DCM three times. The combined organic layer was dried (Na2SO4) and concentrated.
The residue was purified by silica gel chromatography with PE/EA (v/v = 19:1) as
eluent to give the product 6a as colorless oil (964 mg, 75%).
1H NMR (400 MHz, CDCl3) δ 7.72 – 7.69 (m, 4H), 7.47 – 7.38 (m, 6H), 7.29 (d, J =
8.6 Hz, 2H), 6.90 (d, J = 8.7 Hz, 2H), 4.46 (s, 2H), 3.82 (s, 3H), 3.69 (t, J = 6.5 Hz,
2H), 3.45 (t, J = 6.6 Hz, 2H), 1.66 – 1.57 (m, 4H), 1.41 – 1.36 (m, 4H), 1.09 (s, 9H).
13C NMR (101 MHz, CDCl3) δ 159.14, 135.60, 134.20, 130.84, 129.51, 129.23,
127.60, 113.79, 72.56, 70.17, 63.96, 55.28, 32.58, 29.80, 26.93, 26.01, 25.71, 19.26.
IR (thin film cm-1): 1037, 1112, 1172, 1247, 1301, 1360, 1427, 1452, 1461, 1512,
1612, 2857, 2934.
MS, ESI (M+Na+), calc. for 499, found: 499.
HRMS, ESI (M+Na+), calc. for (C30H40NaO3Si+) 499.2639, found: 499.2639.
Alcohol 7b (166 mg, 1 mmol), PMBCl (234 mg, 1.5 mmol), NaI (15 mg, 0.1 mmol)
and DIPEA (208 mg, 1.6 mmol) were charged in a reaction vessel equipped with a
o
magnetic stir bar under nitrogen atmosphere. The mixture was refluxed at 150 C for
2 hours. The resulting mixture typically showed 2 phases. Ethyl acetate and 10%
aqueous sodium bisulfate were added to the mixture and the aqueous layer was
extracted with ethyl acetate three times. The combined organic layer was dried
(Na2SO4) and concentrated. The residue was purified by silica gel chromatography
with PE/EA (v/v = 19:1) as eluent to give the product 7a as colorless oil (160 mg,
56%).
1H NMR (400 MHz, CDCl3) δ 8.09 – 8.03 (m, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.44 (t, J
= 7.7 Hz, 2H), 7.28 (d, J = 8.6 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 4.54 (s, 2H), 4.51 –
4.47 (m, 2H), 3.83 – 3.75 (m, 5H).
A flask equipped with a magnetic stir bar was charged with compound 8b (640 mg,
2.7 mmol), Et3N (810 mg, 8 mmol), DMAP (33mg, 0.27 mmol) and DCM (16 mL)
under nitrogen atmosphere. The t-BuCOCl (390 mg, 3.22 mmol,) was added to the
mixture after 5 minutes. Then the mixture was stirred at room temperature for 12
hours. The mixture was added water and DCM. The aqueous layer was extracted with

DCM three times. The combined organic layer was dried (Na2SO4) and concentrated.
The residue was purified by silica gel chromatography with PE/EA (v/v = 9:1) as
eluent to give the product 8a as colorless oil (608 mg, 70%).
1H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 7.2 Hz, 2H), 6.88 (d, J = 7.8 Hz, 2H), 4.43
(s, 2H), 4.04 (t, J = 6.5 Hz, 2H), 3.81 (s, 3H), 3.44 (t, J = 6.5 Hz, 2H), 1.65 – 1.57 (m,
4H), 1.43 – 1.31 (m, 4H), 1.19 (s, 9H).
A flask equipped with a magnetic stir bar was charged with compound 9b (250 mg, 1
mmol), 4-methoxybenzyl 2,2,2-trichloroacetimidateand(565 mg, 2 mmol) and DCM
(10 mL) under nitrogen atmosphere. Then TfOH (14 μL, 0.1 mmol) was added to the
mixture. The mixture was stirred at room temperature for 24 hours and concentrated.
The residue was suspended on hexanes and filtered through filter paper. The filtrate
was concentrated and purified by silica gel chromatography with PE/EA (v/v = 9:1) as
eluent to give the product 9a as colorless oil (112 mg, 30%).
1H NMR (400 MHz, CDCl3) δ 7.38 – 7.28 (m, 5H), 7.23 (d, J = 8.6 Hz, 2H), 6.86 (d,
J = 8.6 Hz, 2H), 4.54 – 4.43 (m, 4H), 4.19 – 4.06 (m, 3H), 3.79 (s, 3H), 3.62 – 3.56
(m, 2H), 2.58 (ddd, J = 20.5, 15.1, 6.3 Hz, 2H), 1.91 (q, J = 6.2 Hz, 2H), 1.26 (t, J =
7.1 Hz, 3H).
13C NMR (101 MHz, CDCl3) δ 171.59, 159.22, 138.47, 130.62, 129.44, 128.39,
127.69, 127.58, 113.77, 73.22, 72.98, 71.53, 66.55, 60.45, 55.26, 40.29, 34.82, 14.25.
IR (thin film cm-1): 1034, 1096, 1173, 1248, 1302, 1367, 1453, 1462, 1513, 1612,
1729, 1737, 2860, 2933.
MS, ESI (M+Na+), calc. for 395, found: 395.
+
HRMS, ESI (M+Na+), calc. for (C22H28NaO5 ) 395.1829, found: 395.1835.
A
flask equipped with
a
magnetic stir bar was charged with
3-(4-bromophenyl)propionic acid (1.2 g, 5.3 mmol) and dry THF (20 mL), and then
o
cooled to 0 C. The mixture was then added LAH (608 mg, 16 mmol) slowly. Then

the mixture was stirred at room temperature for 12 hours. After the completion of the
reaction, water was added to the mixture and the organic layer was separated. The
aqueous layer was extracted with ethyl acetate three times. The combined organic
layer was dried (Na2SO4) and concentrated. The residue was used for next step
without purification.
1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 8.2 Hz, 2H), 7.07 (d, J = 8.1 Hz, 2H), 3.66
(t, J = 6.4 Hz, 2H), 2.70 – 2.62 (m, 2H), 1.91 – 1.81 (m, 2H).
Alcohol 3-(4-Bromophenyl)propan-1-ol (639 mg, 3 mmol), PMBCl (702 mg, 4.5
mmol), NaI (45 mg, 0.3 mmol) and DIPEA (624 mg, 4.8 mmol) were charged into a
reaction vessel equipped with a magnetic stir bar under nitrogen atmosphere. The
o
mixture was refluxed at 150 C for 2 hours. Ethyl acetate and 10% aqueous sodium
bisulfate were added to the mixture and the aqueous layer was extracted by ethyl
acetate three times. The combined organic layer was dried (Na2SO4) and concentrated.
The residue was purified by silica gel chromatography with PE/EA (v/v = 19:1) as
eluent to give the product s-1a as colorless oil (872 mg, 87%).
1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 7.06
(d, J = 8.3 Hz, 2H), 6.92 (d, J = 8.6 Hz, 2H), 4.45 (s, 2H), 3.83 (s, 3H), 3.46 (t, J = 6.3
Hz, 2H), 2.70 – 2.66 (m, 2H), 1.95 – 1.88 (m, 2H).
13C NMR (101 MHz, CDCl3) δ 159.16, 142.04, 130.71, 129.29, 128.49, 128.30,
125.74, 113.79, 72.59, 69.23, 55.30, 32.42, 31.39.
IR (thin film cm-1): 1011, 1041, 1073, 1100, 1171, 1247, 1302, 1377, 1452, 1461,
1488, 1513, 2850.
EI (M+): calc. for 334, found: 334.
+
HRMS, ESI (M+Na+), calc. for (C17H19BrNaO2 ) 357.0461, found: 357.0462.
o
To a solution of s-1a (334 mg, 1 mmol) in anhydrous THF (5mL) at -78 C under
nitrogen atmosphere, n-BuLi (0.5 mL, 2 mol/L in n-hexane, 1 mmol) was added. The
o
solution was stirred for 15 minutes at -78 C. Then DMF (88 mg, 1.2 mmol) was
o
added dropwise. The reaction was stirred for another 2 hours at -78 C and then
warmed to room temperature. The reaction was quenched with NH4Cl aqueous
solution. The aqueous layer was extracted with ethyl acetate three times. The
combined organic layer was dried (Na2SO4) and concentrated. The residue was
purified by silica gel column chromatography with PE/EA (v/v = 19:1) to give the
product 10a as colorless oil (142 mg, 50%).
1H NMR (400 MHz, CDCl3) δ 9.93 (s, 1H), 7.76 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.0
Hz, 2H), 7.26 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 4.42 (s, 2H), 3.77 (s, 3H),
3.44 (t, J = 6.2 Hz, 2H), 2.79 – 2.75 (m, 2H), 1.96 – 1.89 (m, 2H).
13C NMR (101 MHz, CDCl3) δ 191.98, 159.22, 149.59, 134.51, 130.49, 129.92,
129.30, 129.17, 113.80, 72.65, 68.78, 55.29, 32.68, 30.97.
IR (thin film cm-1): 827, 1034, 1098, 1169, 1213, 1247, 1303, 1364, 1462, 1512, 1576,
1585, 1606, 1692, 1703, 2856, 2934.

EI (M+): calc. for 284, found: 284.
HRMS, ESI (M+Na+), calc. for (C18H20NaO3 ) 307.1305, found: 307.1308
+
Alcohol 11b (122 mg, 1 mmol), PMBCl (234 mg, 1.5 mmol), NaI (15 mg, 0.1 mmol)
and DIPEA (208 mg, 1.6 mmol) were charged into a reaction vessel equipped with a
o
magnetic stir bar under nitrogen atmosphere. The mixture was refluxed at 150 C for
2 hours. Ethyl acetate and 10% aqueous sodium bisulfate were added to the mixture
and the aqueous layer extracted by ethyl acetate three times. The combined organic
layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel
chromatography with PE/EA (v/v = 9:1) as eluent to give the product 11a as colorless
oil (193 mg, 80%).
1H NMR (400 MHz, CDCl3) δ 7.41 – 7.34 (m, 4H), 7.32 – 7.27 (m, 1H), 7.24 (d, J =
8.6 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 4.48 (q, J = 6.5 Hz, 1H), 4.38 (d, J = 11.4 Hz,
1H), 4.22 (d, J = 11.4 Hz, 1H), 3.80 (s, 3H), 1.46 (d, J = 6.5 Hz, 3H).
HPLC, AD-H, 220nm, IPA/n-hexane = 19:1(v/v), 0.5mL/min, tminor = 10.12 min, tmajor
= 11.22 min, ee = 99.5%.
Alcohol 12b (124 mg, 1 mmol), PMBCl (234 mg, 1.5 mmol), NaI (15 mg, 0.1 mmol)
and DIPEA (208 mg, 1.6 mmol) were charged into a reaction vessel equipped with a
o
magnetic stir bar under nitrogen atmosphere. The mixture was refluxed at 150 C for
2 hours. Ethyl acetate and 10% aqueous sodium bisulfate were added to the mixture
and the aqueous layer extracted with ethyl acetate three times. The combined organic
layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel
chromatography with PE/EA (v/v = 19:1) as eluent to give the product 12a as
colorless oil (195 mg, 80%).
1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.5 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 4.60
(s, 2H), 3.80 (s, 3H), 2.54 (s, 1H), 1.99 – 1.96 (m, 2H), 1.74 – 1.54 (m, 7H), 1.37 –
1.26 (m, 1H).
13C NMR (101 MHz, CDCl3) δ 159.00, 131.29, 129.28, 113.75, 85.54, 73.78, 65.18,
55.29, 37.25, 25.44, 22.71.
IR (thin film cm-1): 821, 1036, 1076, 1172, 1248, 1301, 1378, 1450, 1462, 1513, 1612,
2858, 2935, 3289.

EI (M+): calc. for 244, found: 244
HRMS, ESI (M+Na+), calc. for (C16H20NaO2 ) 267.1356, found: 267.1358
+
A 50 mL round bottom flask equipped with a magnetic stir bar was charged with
compound 13b (711 mg, 3.0 mmol), Na2CO3 (318 mg, 3.0 mmol), THF (12 mL) and
H2O (3 mL) and treated with FmocCl (775 mg, 3 mmol). The mixture was stirred at
room temperature for 12 hours. The mixture was poured into a separator funnel
containing 50 mL of ethyl acetate and 50 mL of H2O. The layers were separated and
the aqueous layer was extracted with ethyl acetate (50 mL x 2). The combined organic
layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel
chromatography with PE/EA (v/v = 4:1) as eluent to afford the product 13a as a white
solid (1.02 g, 74%).
1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.0 Hz, 2H), 7.59 (d, J = 7.0 Hz, 2H), 7.40
(t, J = 7.0 Hz, 2H), 7.31 (t, J = 7.0 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2 H), 6.87 (d, J = 8.5
Hz, 2H), 4.73 (s, 1H), 4.43(s, 3H), 4.40 (d, J = 6.8 Hz, 2H), 4.22 (t, J = 6.8 Hz, 1H),
3.80 (s, 3H), 3.43 (t, J = 6.5 Hz, 2H), 3.18 (q, J = 6.5 Hz, 2H), 1.63 – 1.57 (m, 2H),
1.53 – 1.46 (m, 2H), 1.41 – 1.30 (m, 4H).
A flame dried 50 mL round bottom flask equipped with a magnetic stir bar was
charged with compound 14b (218 mg, 2 mmol) and dry THF (10 mL) and cooled to 0
oC. To the mixture was added with NaH (60% in mineral oil, 120 mg, 3 mmol). After
the reaction was stirred for at room temperature for 30 minutes, PMBCl (312 mg, 2
mmol) was added. The reaction was stirred at room temperature for 12 hours,
followed by addition of water and ethyl acetate. The layers were separated and the
aqueous layer was extracted with ethyl acetate three times. The combined organic
layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel
chromatography with PE/EA (v/v = 3:1) as eluent to give the product 14a as colorless
oil (265 mg, 58%).
1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 8.54 (d, J = 3.9 Hz, 1H), 7.70 (d, J = 7.8
Hz, 1H), 7.29 – 7.26 (m, 3H), 6.89 (d, J = 8.6 Hz, 2H), 4.52 (d, J = 6.6 Hz, 4H), 3.80
(s, 3H).
13C NMR (101 MHz, CDCl3) δ 159.41, 149.09, 148.90, 135.65, 133.91, 129.81,
129.47, 123.46, 113.93, 72.23, 69.19, 55.30.

IR (thin film cm-1): 819, 1031, 1174, 1248, 1302, 1359, 1426, 1462, 1513, 1585, 1612,
2857, 2934.
EI (M+): calc. For 229, found: 229.
+
HRMS, ESI (M+H+), calc. for (C14H16NO2 ) 230.1176, found: 230.1178.
NaH
PMBCl
OH
OPMB
PMBO
PMBO
NaI
70 oC
15b
15a
A flame dried round bottom flask equipped with a magnetic stir bar was charged with
o
compound 15b (224 mg, 1 mmol) dry THF (10mL) and cooled to 0 C. The mixture
was then treated with NaH (60% in mineral oil, 60 mg, 1.5 mmol) and stirred at room
temperature for 30 minutes. PMBCl (234 mg, 1.5 mmol) and NaI (15 mg, 0.1 mmol)
o
were then added. The mixture was stirred at 70 C for 12 hours. The mixture was
cooled to room temperature, and then water and ethyl acetate were added. The
aqueous layer was extracted with ethyl acetate three times. The combined organic
layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel
chromatography with PE/EA (v/v = 9:1) as eluent to give the product 15a as colorless
oil (120 mg, 35%).
1H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.6 Hz, 2H), 7.20 (d, J = 8.6 Hz, 2H), 6.89
– 6.84 (m, 4H), 4.44 (s, 2H), 4.33 (s, 2H), 3.80 (d, J = 3.6 Hz, 6H), 3.61 (t, J = 7.3 Hz,
2H), 1.93 (t, J = 7.3 Hz, 2H), 1.27 (s, 6H).
13C NMR (101 MHz, CDCl3) δ 159.14, 158.86, 131.75, 130.67, 129.31, 128.85,
113.79, 113.75, 74.26, 72.69, 66.41, 63.37, 55.29, 55.28, 39.80, 26.19.
IR (thin film cm-1): 820, 1035, 1093, 1171, 1247, 1301, 1364, 1462, 1513, 1612, 2853,
2928.
MS, ESI (M+Na+), calc. for 367, found: 367.
HRMS, ESI (M+Na+), calc. for (C21H28NaO4 ) 367.1880, found: 367.1882
+

General Procedure A:
A flask equipped with a rubber septum and magnetic stir bar was charged with PMB
ether 1a (25.6 mg, 0.1 mmol), NaHSO4 (12 mg, 0.1 mmol), H2O2 (30 mg, 30%, 0.26
mmol,), MeCN/H2O (v/v = 1:1, 1 mL), and Eosin Y (3.2 mg, 0.005 mmol). The
mixture was then irradiated with green LED under ambient atmosphere. After 15
hours, more 30 mg H2O2 was added to the mixture. When the reaction was completed
after 10 hours (monitored by TLC analysis), the mixture was poured into a mixture of
Sat. NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate
three times. The combined organic layer was dried (Na2SO4) and concentrated. The
residue was purified by silica gel chromatography with PE/EA (v/v = 9:1) as eluent to
give the product 1b as colorless oil (11.5 mg, 85%).
1H NMR (400 MHz, CDCl3) δ7.31 – 7.18 (m, 5H), 3.69 (t, J = 6.4 Hz, 2H), 2.78 –
2.66 (m, 2H), 1.95 – 1.86 (m, 2H).
Compound 2b was prepared from 2a according to the general procedure A in the yield
of 83%.
1H NMR (400 MHz, CDCl3) δ3.44 – 3.38 (m, 1H), 2.22 – 2.13 (m, 1H), 1.96 (d, J =
11.6 Hz, 1H), 1.70 – 1.57 (m, 2H), 1.48 – 1.35 (m, 2H), 1.16 – 1.07 (m, 1H), 0.98 (dd,
J = 12.4, 3.4 Hz, 2H), 0.92 (d, J = 6.5 Hz, 6H), 0.81 (d, J = 7.0 Hz, 3H).

Compound 3b was prepared from 3a according to the general procedure A in the yield
of 68%.
1H NMR (400 MHz, CDCl3) δ 7.37 – 7.29 (m, 10H), 2.05 (s, 3H).
Compound 4b was prepared from 4a according to the general procedure A in the yield
of 72%.
1H NMR (400 MHz, CDCl3) δ 7.35 – 7.19 (m, 5H), 2.77 (s, 2H), 1.23 (s, 6H).
Compound 6b was prepared from 6a according to the general procedure A in the yield
of 65%.
1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.3 Hz, 4H), 7.45 – 7.34 (m, 6H), 3.70 –
3.58 (m, 4H), 1.68 – 1.55 (m, 4H), 1.44 – 1.35 (m, 4H). 1.05 (s, 9H).
Compound 7b was prepared from 7a according to the general procedure A in the yield
of 73%.
1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 7.3 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.45
(t, J = 7.7 Hz, 2H), 4.50 – 4.44 (m, 2H), 4.00 – 3.94 (m, 2H).

Compound 8b was prepared from 8a according to the general procedure A in the yield
of 78%.
1H NMR (400 MHz, CDCl3) δ 4.05 (t, J = 6.4 Hz, 2H), 3.64 (t, J = 6.4 Hz, 2H), 1.67
–1.61 (m, 3 H), 1.59 – 1.55 (m, 2 H), 1.41 – 1.37 (m, 4 H), 1.19 (s, 9 H).
Compound was 9b prepared from 9a according to the general procedure A in the yield
of 65%.
1H NMR (400 MHz, CDCl3) δ 7.38 – 7.27 (m, 5H), 4.52 (s, 2H), 4.29 – 4.20 (m, 1H),
4.16 (q, J = 7.1 Hz, 2H), 3.75 – 3.61 (m, 2H), 2.49 (d, J = 6.3 Hz, 2H), 1.81 (dd, J =
11.5, 6.1 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H).
Compound 10b was prepared from 10a according to the general procedure A in the
yield of 89% (80% purity).
1H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 7.81 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.0
Hz, 2H), 3.70 (t, J = 6.3 Hz, 2H), 2.87 – 2.72 (m, 2H), 1.98 – 1.88 (m, 2H).
Compound 11b was prepared from 11a according to the general procedure A in the
yield of 71% and 94% ee.

1H NMR (400 MHz, CDCl3) δ 7.40 – 7.27 (m, 5H), 4.91 (q, J = 6.5 Hz, 1H), 1.51 (d,
J = 6.5 Hz, 3H).
HPLC, CJ of Venusil, 220nm, IPA/hexane = 9:1(v/v), 0.5mL/min, tminor =17.7 min,
tmajor = 19.9 min, ee = 94%.
Compound 12b was prepared from 12a according to the general procedure A in the
yield of 56%.
1H NMR (400 MHz, CDCl3) δ 2.48 (s, 1H), 1.96 – 1.87 (m, 2H), 1.73 – 1.53 (m, 8H).
Compound 15b was prepared from 15a according to the general procedure A in the
yield of 67%.
1H NMR (400 MHz, CDCl3) δ 7.18 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 8.6 Hz, 2H), 4.38
(s, 2H), 3.73 (s, 3H), 3.61 (t, J = 5.9 Hz, 2H), 1.71 (t, J = 5.9 Hz, 2H), 1.15 (s, 6H).
General Procedure B:
A flask equipped with a rubber septum and a magnetic stir bar was charged with PMB
ether 5a (27.2 mg, 0.1 mmol), NaHSO4 (12 mg, 0.1 mmol), H2O2 (30 mg, 30%, 0.26
mmol), MeCN (1 mL), H2O (0.5 mL) and Eosin Y (3.2 mg, 0.005 mmol). The
mixture was then irradiated with green LED under ambient atmosphere. After 24
hours, H2O2 (30 mg, 30%, 0.26 mmol) was added to the mixture. Upon the completion
of reaction after another 24 hours, the mixture was poured into a mixture of Sat.
NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate three
times. The combined organic layer was dried (Na2SO4) and concentrated. The residue
was purified by silica gel chromatography with PE/EA (v/v = 9:1) as eluent to give
the product 5b as white solid (11mg, 72%).

1H NMR (400 MHz, CDCl3) δ 2.14 (s, 3H), 1.71 (d, J = 2.3 Hz, 6H), 1.66 – 1.57 (m,
6H).
Compound 13b was prepared from 13a according to the general procedure B in the
yield of 77%.
1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz, 2H), 7.59 (d, J = 7.4 Hz, 2H), 7.40
(t, J = 7.4 Hz, 2H), 7.31 (t, J = 7.4 Hz, 2H), 4.78 (s, 1H), 4.41 (d, J = 6.7 Hz, 2H),
4.22 (t, J = 6.6 Hz, 1H), 3.63 (t, J = 6.5 Hz, 2H), 3.19 (d, J = 4.7 Hz, 2H), 1.60 – 1.50
(m, 4H), 1.37 – 1.24 (m, 4H).
General Procedure C:
A flask equipped with a rubber septum and a magnetic stir bar was charged with PMB
ether 14a (23 mg, 0.1 mmol), NaHSO4 (12 mg, 0.1 mmol), H2O2 (30 mg, 30%, 0.26
mmol,), Eosin Y (3.2 mg, 0.005 mmol), MeCN (1 mL) and H2O (0.5 mL). The
mixture was then irradiated with green LED under ambient atmosphere. After 24
hours, H2O2 (30 mg, 30%, 0.26 mmol,) was added to the mixture. Upon the
completion after another 24 hours (monitored by TLC analysis), the reaction mixture
was poured into a mixture of Conc. HCl and ethyl acetate. The organic layer was
extracted with water three times. Then the combined aqueous layer was brought to pH
= 8 with sat. NaHCO3, and extracted with ethyl acetate three times. The combined
organic layer was dried (Na2SO4) and concentrated. The residue was purified by silica
gel chromatography with PE/EA (v/v = 1:3) as eluent to give the product 14b as
colorless oil (6.2 mg, 57%).
1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 8.40 – 8.32 (m, 1H), 7.68 (d, J = 7.8 Hz,
1H), 7.23 (dd, J = 7.6, 4.9 Hz, 1H), 4.65 (s, 2H).
Photoredox cleavage of PMB ether 1a at gram scale

A flask equipped with a rubber septum and magnetic stir bar was charged with PMB
ether 1a (1.53 g, 6 mmol), NaHSO4 (720 mg, 6 mmol), H2O2 (1.8 g, 30%, 15.6mmol),
MeCN/H2O (v/v, 1:1, 60 mL), and Eosin Y (192 mg, 0.3 mmol). The mixture was
then irradiated with 24W green LED under ambient atmosphere. After 24 hours, H2O2
(1.8 g, 30%, 15.6mmol) was added to the mixture. Upon the full conversion
monitored by TLC analysis after another 24 hours, the mixture was poured into a
mixture of Sat. NaHCO3 and ethyl acetate. The aqueous layer was extracted with
ethyl acetate three times. The combined organic layer was dried (Na2SO4) and
concentrated. The residue was purified by silica gel chromatography with PE/EA (v/v
= 9:1) as eluent to give the product 1b as colorless oil (700 mg, 81%).
Fluorescence quenching experiments:
All Eosin Y solutions were irradiated at 530 nm and the emission intensity at 555 nm
was observed. In a typical experiment, a 5 mM solution of Eosin Y in MeCN/H2O
was added to appropriate amount of quencher. Then the emission spectrum of the
sample was collected.
Eosin Y Emission Quenching by H2O2

Eosin Y Emission Quenching by PMB ether
TEMPO additive experiment:
A flask equipped with a rubber septum and magnetic stir bar was added PMB ether 1a
(25.6 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), NaHSO4 (12 mg, 0.1 mmol),
H2O2 (30 mg, 30%, 0.26 mmol), MeCN/H2O (v/v = 1:1, 1 mL), and Eosin Y (3.2 mg,
0.005 mmol). The mixture was then irradiated with green LED under ambient
atmosphere. After 15 hours, H2O2 (30 mg, 30%, 0.26 mmol) was added. Upon the full
conversion with additional 10 hours (monitored by TLC analysis), the mixture was
poured into a mixture of Sat. NaHCO3 and ethyl acetate. The aqueous layer was
extracted with ethyl acetate three times. The combined organic layer was dried
(Na2SO4) and concentrated. The residue was purified by silica gel chromatography
with PE/EA (v/v = 9:1) as eluent to give the product 1b as colorless oil (11 mg, 81%).