Nickel-catalyzed removal of alkene protecting group of phenols, alcohols via chain walking process

Article abstract of DOI:10.3390/molecules25030602

An efficient nickel-catalyzed removal of alkene protection group under mild condition with high functional group tolerance through chain walking process has been established. Not only phenolic ethers, but also alcoholic ethers can be tolerated with the retention of stereocenter adjacent to hydroxyl group. The new reaction brings the homoallyl group into a start of new type of protecting group.

Full text of DOI:10.3390/molecules25030602

Communication
Nickel-Catalyzed Removal of Alkene Protecting
Group of Phenols, Alcohols via Chain
Walking Process
Chenkai Meng, Haolin Niu, Juehan Ning, Wengang Wu and Jun Yi *
Jiangsu Laboratory of Advanced Functional Material, School of Materials Engineering, Changshu Institute of
Technology, Changshu 215500, China; mengchenkai@163.com (C.M.); niuhaolin1@126.com (H.N.);
juehanning@126.com (J.N.); 505609053@139.com (W.W.)
* Correspondence: yijun08@mail.ustc.edu.cn; Tel.: +86-512-5225-1842
Received: 11 December 2019; Accepted: 28 January 2020; Published: 30 January 2020
Abstract: An efficient nickel-catalyzed removal of alkene protection group under mild condition
with high functional group tolerance through chain walking process has been established. Not only
phenolic ethers, but also alcoholic ethers can be tolerated with the retention of stereocenter adjacent
to hydroxyl group. The new reaction brings the homoallyl group into a start of new type of
protecting group.
Keywords: deprotection; nickel; chain walking; phenol; alcohol
1. Introduction
Functional group protecting and deprotecting is a common strategy widely used in organic
chemistry especially in total synthesis [1]. The most conventional masking of phenols and alcohols
are allylethers derived from facile base-promoted substitution of allyl halides [2]. Meanwhile,
allylethers are easily removed under acidic, basic, reductive, or oxidative conditions with or without
the aid of transition metals (Scheme 1a) [3–11]. On the other hand, it means allylethers are not stable
in these conditions which diminished its usage in application. Long-chain alkene ethers such as
homoallylethers are significantly steadier than allylethers which have been serving as a protecting
group for decades [12–18], but lack of utility in practice due to the few deprotection methods.
Ozonolysis of homoallylic carboxylic esters was reported by Barrett [19]. Cossy [20] and Lipshutz [21]
reported removal of homoallyl group by Grubbs-Hoveyda catalyst through isomerization or
metathesis. These reports are encountered from harsh reaction conditions. Meanwhile, chain walking
strategy in bond construction has been emerging as a powerful tool utilizing alkene as feedstock in
synthetic chemistry [22–25]. Hu [26,27], Martin [28–30], Zhu [31–36], and Hartwig [37] recently
demonstrated that nickel was a prominent catalyst in chain walking chemistry. Streuff reported a
zirconium catalyzed deallylation through chain walking mechanism [38]. Inspired by these reports
and our interest in group transfer reactions [39] and nickel-catalyzed reactions [40], we envisaged
that the nickel-hydride complex I formed through en route nickel-boryl [41–43] water or methanol
addiction intermediate σ-bond metathesis would trigger the chain walking process (III, Scheme 1c).
Low valent Nickel(I) was reported to go through oxidative addition to allyl C-O bond [44–46], which
made the formation of intermediate V possible. The alkene (VI) was released after reductive
elimination and regenerated the catalyst. Free phenols or alcohols would be retrieved by simple acid
workup of VIII. Herein, we report the nickel-catalyzed removal of alkene protection group of phenols
and alcohols under mild condition with high functional group tolerance through chain walking
process.
Molecules 2020, 25, 602; doi:10.3390/molecules25030602
www.mdpi.com/journal/molecules

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a. Prior art:
b. This work:
RO
Cat. Ni
n
cat. Pd, Ru Fe, Ni, Cu
2
ROH ( )
1
( )
RO
ROH
n= 0, 1, 2, 3
R= Aryl, Alkyl
R= Aryl, Alkyl
c. Mechanistic rationale: chain walking process
hv
RO
N
NiI
H
X = H or Me
II
N
I
H
X
O
IX
N
N
H
NiI Bpin
N
N
NiI
VIII
ROBpin
III
OR
B pin + LiOtBu
SET
2
2
H
NiI
N
N
N
NiI OR
N
VII
IV
OR
H
N
N
NiIII
H
OR
VI
V
Scheme 1. Different removal of alkene protecting group and new mechanistic rationale.
2. Results
In order to testify our proposal, we began our study by optimizing the reaction conditions using
4-(but-3-enyloxy)biphenyl (1a) as the model substrate (Table 1). Investigation of a range of
parameters, we found that the combination of nickel(II) chloride ethylene glycol dimethyl ether
complex (NiCl2∙DME, 5 mol%), 6,6′-dimethyl-2,2′-bipyridine (L1) as ligand, Bis(pinacolato)diboron
(B2pin2, 1.5 equiv) as the reductant, Lithium tert-butoxide as the base, in N,N-dimethylacetamide
(DMA) (0.1M) with methanol and water as additives gave excellent isolated yield (92%) (entry 1,
Table 1). Other nickel sources such as zero valent Bis(1,5-cyclooctadiene)nickel (Ni(COD)2, entry 2,
Table 1) or less soluble NiCl2 (entry 3, Table 1) diminished the yield. Similar to the previous reports
[31–36], more bulky ligand was critical for the reaction and probably facilitate the chain walking
process (entry 4–5, Table 1). Other common phosphine ligands such as triphenylphosphine (entry 6,
Table 1) and tricyclohexylphosphine (entry 7, Table 1) were all low efficient. Nickel(I) was proposed
as the active spices in the chain walking reactions [31–36], so we tested some reductant to generate of
nickel(I) spices. B2pin2 in combination of base was reported as efficient reductant in nickel-catalyzed
reductive reactions [47], to our pleased moderated yield was observed (entry 8, Table 1). Other widely
used metal reductants in nickel-catalyzed cross reductive reaction such as Zn and Mn gave very few
product (entry 9–10, Table 1) [48–52]. Next, we surveyed some additives to accelerate the reaction.
We found that a certain amount of methanol greatly prompted the yield (entry 11, Table 1). Water
was added to further boost the efficiency of the reaction. Both water and methanol might serve as a
hydride donor in σ-bond metathesis. Considering both Lithium tert-butoxide and water were added,
in situ lithium hydroxide might be formed. Directly using lithium hydroxide as base did not have a
similar result (entry 13, Table 1). Switching reaction solvent from DMA to less polar solvent such as
tetrahydrofuran (THF) resulted in lower yields (entries 15, Table 1). Finally, control experiments
showed that both nickel and B2pin2 were indispensable for the reaction. In order to demonstrate its
possibility in large scale synthesis, a 20 mmol scale reaction was done (entry 18, Table 1). The yield

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was lower but still outstanding. The attempt to lower the loading of nickel catalyst and ligand greatly
diminished the yield with substantial starting material left (entry 19, Table 1).
Table 1. Optimization of removal homoallyl group.
a
entry
1
Deviation from standard conditions
None
Yield of 2 (%)
b
96(92)
2
Ni(COD)2
84
53
37
9
3
NiCl2 instead of NiCl2(DME)
L2 instead of L1
L3
4
5
6
L4
42
45
61
5<
5<
73
78
71
68
7
L5
8
B2pin2 w/o additives
Zn instead of B2pin2
Mn instead of B2pin2
No CH3OH
9
10
11
12
13
14
No H2O
LiOH instead of LiOtBu
KOH instead of LiOtBu

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15
16
17
18
THF instead of DMA
No Ni
56
0
No B2pin2
0
20 mmol scale
86
c
19
1% loading of nickel, 2% L1
52(42)
a
Conditions: 1a (0.2 mmol), Amine (1.5 equiv), Determined by dibromomethane as an internal
standard by 1H NMR. b Isolated yield. c 1a remained in reaction.
With the optimized condition in hand, the scope of substrate of the reaction was examined (Table
2). First, we tested the phenol scope. Ortho methyl group of phenol (1d) gave good yields, although
ortho position was more hindered. Electron effect of the substitution groups did not play great roll on
the yield. Strong electron-donating (benzyloxy, 1m) as well as strong electron-withdrawing
(trifluoromethyl, 1p) groups were all tolerated. More strikingly, fragile groups in basic conditions
such as aldehyde (1o), ester (1i), even free carboxylic acid (1l) were all tolerated in the reaction
conditions, although the yield of aldehyde (1o) was low Furthermore, different halides (1e–1h) even
iodide were untouched during the reactions which could be used in the further elaborating reactions,
for instance, Suzuki reactions. It is worth highlighting that heteroaromatics (1q, 1r), which are
prevalent structure motifs in medicinal molecular, did not corrupt the efficiency of the reaction.

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Table 2. Scope of phenol. Conditions: See Supplementary Materials for details.
Next, different alkene protecting groups of phenol were tested (Table 3). Interestingly, vinyl (3a–
3c) was removed at the comparable yield without nickel catalyst indicated another mechanism might
be involved. Except for the homoallyl group, the allyl group also could be easily removed under
existing conditions (3d–3i). Interestingly, not only the acyclic alkene protecting groups, but also the
cyclic alkene was smoothly detached in outstanding yield (3i). Longer alkene protecting group
(pentenyl) afforded products albeit in relatively lower yields (3j–3m). Control experiments showed
that nickel catalyst was indispensable for alkene protecting groups longer than vinyl.

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a
Table 3. Scope of alkene protecting groups. Conditions: Without Ni catalyst and ligand. See
Supplementary Materials for details.
We tried to expand the scope from phenols to aliphatic alcohols (Scheme 2). To our delight, allyl
protected alcohols were easily removed to give both aminoalcohol (5) and cholesterol (7) in moderate
yield. More importantly, the stereocenter adjacent to hydroxyl of 7 was preserved after the reaction.
For the homoallyl ether analogs the yield dropped to around 40% which was not practical in synthetic
view.

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Scheme 2. Removal of alcohol protecting groups. Conditions: See Supplementary Materials for
details.
Taking further advantage of our new reaction (Scheme 3, Method B), we compared it with the
classic palladium deprotection protocol (Scheme 3, Method A). These two methods were about the
same efficiency when the alkene protecting groups were closed to the oxygen atom (n < 1). In contrast,
Method A drastically lost its activity when the interval between the alkene and oxygen is prolonged
(n > 2), meanwhile, Method B still maintained medium yield even at n = 4. Through this comparison,
it is possible to remove allyl and homoallyl protecting groups sequentially by utilizing these methods.
Scheme 3. Comparison with previous method.
Although the clear panorama of the catalytic cycle was still under pursuing, the control
experiments were designed to unveil the reaction mechanism (Scheme 4). First, butoxybenzene (8)
was put into the optimized condition, no product was detected. It means the coordination of the
nickel catalyst of the substrate was necessary. Second, ((2,2-dimethylbut-3-en-1-yl)oxy)benzene (9)
was subjected to optimal condition, similarly no desire product was observed (3), which means the

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chain walking was intercepted with the quaternary carbon to stop the formation of key allyl ether.
When we analyzed the byproduct of the reaction 3j by GC-MS, the borylated alkene 10 was not
detected which means the reaction might not be initiated by Ni-Bpin. Due to the low boiling point of
pentene (30 °C), we did not see pentene signal on the GC-MS. Substrate (11) was synthesized to get
more information of the fate of deprotected group. Allylbenzene (12) was detected as equivalent to
the product instead of the corresponding borylation product (13) indicating the alkene was formed
after the deprotection. The combination of B2pin2 and water/methanol might serve as a hydride donor
to form the Ni-H species. A preliminary survey with silane to generate Ni-H in situ [11] was done
and a great amount of product was also found which supported the possibility of Ni-H as the true
catalyst in the reaction.
Scheme 4. Mechanistic studies. Conditions: See Supplementary Materials for details.
3. Discussion
To summarize, we reported the nickel-catalyzed removal of alkene protecting groups of phenols
and alcohols through chain walking process. The facile and mild reaction condition as well as high
functional tolerance highlight its utilization in the future. More importantly, the nonconventional
homoallyl may rival as protecting group with this report that is complementary to existing protocols.
Future efforts are directed toward expanding this type of new transformation in practice as well as
understanding the mechanism of the reaction.
4. Experimental Section
4.1. Representative General Procedure for Nickel-Catalyzed Deprotecting Reaction
In glovebox, B2pin2 (76.17 mg, 0.3 mmol, 1.5 equiv), NiCl2(DME) (2.20 mg, 0.01 mmol, 0.05 equiv),
6,6-dimethyl-2,2-dipyridyl (3.68 mg, 0.02 mmol, 0.10 equiv), LiOtBu (32 mg, 0.4 mmol, 2.0 equiv), and

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protected phenol (if solid) (0.2 mmol) were added to an oven-dried tube. The reaction tube was
equipped with a magnetic stir bar and sealed with Teflon-lined cap, refilled the system with argon
and performed two more evacuation-backfill cycles, protected phenol was added by syringe under
argon flow (if liquid). DMA (2.00 mL), H2O (50 µL), MeOH (25 µL) were added to the tube
sequentially. The reaction mixture turned dark and was stirred at 30 °C for 24 h. When the reaction
was finished, 10 mL aqueous HCl (0.1 M) was added to the mixture and extracted with CH2Cl2 (2 ×
10 mL), dried over anhydrous MgSO4, and concentrated in vacuo. The resulting residue was purified
by silica gel flash chromatography to give the product.
4.2. Characterization Data for Products 2a–2s, 5 and 7 (Table 2, 3 and Scheme 2)
−1
4-Phenylphenol (2a): White solid. IR (cm , KBr): 3434, 3367, 3130, 1662, 1611, 1522, 1477, 1459, 1401,
1
1257, 1139, 1069, 998, 954, 862, 833, 758, 686, 555, 517. H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.4 Hz,
2H), 7.51 (d, J = 8.1 Hz, 2H), 7.45 (t, J = 7.3 Hz, 2H), 7.35 (d, J = 7.1 Hz, 1H), 6.94 (d, J = 8.1 Hz, 2H), 4.95
13
(s, 1H). C NMR (101 MHz, CDCl3) δ 155.0, 140.7, 134.0, 128.7, 128.4, 126.7, 115.6. m.p.: 163–164 °C.
−1
1
Phenol (2b): White solid. IR (cm , KBr): 3440, 3134, 1659, 1624, 1401, 1075, 989, 951, 858, 538. H NMR
(400 MHz, CDCl3) δ 7.31 (t, J = 7.7 Hz, 2H), 7.02 (t, J = 7.3 Hz, 1H), 6.93 (d, J = 8.2 Hz, 2H), 6.04 (s, 1H).
13
C NMR (101 MHz, CDCl3) δ 155.2, 129.9, 121.2, 115.6. m.p.: 103–104 °C.
−1
3-Methoxyphenol (2c): Brown liquid. IR (cm , KBr): 3439, 3133, 1671, 1609, 1401, 1163, 1073, 991, 946,
1
856, 769, 689, 541. H NMR (400 MHz, CDCl3) δ 7.16 (t, J = 8.0 Hz, 1H), 6.54 (d, J = 7.8 Hz, 1H), 6.47 (d,
13
J = 7.9 Hz, 2H), 5.65 (s, 1H), 3.80 (s, 3H). C NMR (101 MHz, CDCl3) δ 160.8, 156.7, 130.3, 108.1, 106.6,
101.7, 55.3.
−1
1
o-Cresol (2d): Brown liquid. IR (cm , KBr): 3439, 3134, 1661, 1401, 1075, 993, 952, 858, 536. H NMR
(400 MHz, CDCl3) δ 7.28 (d, J = 7.2 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.02 (t, J = 7.4 Hz, 1H), 6.90 (d, J =
13
8.0 Hz, 1H), 5.70 (s, 1H), 2.40 (s, 3H). C NMR (101 MHz, CDCl3) δ 153.7, 131.3, 127.3, 124.4, 121.1,
115.3, 15.9.
−1
3-Fluorophenol (2e): Light yellow liquid. IR (cm , KBr): 3441, 3134, 1666, 1627, 1131, 1074, 993, 952,
1
857, 774, 531. H NMR (400 MHz, CDCl3) δ 7.22 (dd, J = 15.2, 7.9 Hz, 1H), 6.74–6.57 (m, 3H), 5.76 (s,
13
1H). C NMR (101 MHz, Chloroform-d) δ 163.7 (d, J = 245.6 Hz), 156.3 (d, J = 11.3 Hz), 130.7 (d, J =
10.0 Hz), 111.3 (d, J = 2.9 Hz), 108.2 (d, J = 21.3 Hz), 103.3 (d, J = 24.7 Hz).
−1
3-Chlorophenol (2f): Yellow liquid. IR (cm , KBr): 3439, 3134, 1664, 1623, 1401, 1250, 1138, 1074, 996,
1
952, 857, 771, 682, 530. H NMR (400 MHz, CDCl3) δ 7.19 (t, J = 8.1 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H),
13
6.89 (s, 1H), 6.75 (dd, J = 7.2, 0.9 Hz, 1H), 5.35 (s, 1H). C NMR (101 MHz, CDCl3) δ 155.9, 135.0, 130.6,
121.3, 116.0, 113.8.
−1
2-Iodophenol (2g): Brown solid. IR (cm , KBr): 3440, 3133, 1658, 1624, 1401, 1050, 1075, 991, 951, 858,
1
535. H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 7.9 Hz, 1H), 7.27 (t, J = 6.4 Hz, 1H), 7.03 (d, J = 8.1 Hz,
13
1H), 6.75–6.63 (m, 1H), 5.36 (s, 1H). C NMR (101 MHz, CDCl3) δ 154.8, 138.3, 130.2, 122.5, 115.2, 85.7.
m.p.: 41–42 °C.
−1
2-Bromophenol (2h): Brown liquid. IR (cm , KBr): 3439, 3132, 1663. 1619, 1401, 1160, 1077, 993, 946, 858,
1
744, 539. H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.0 Hz, 1H), 7.25 (t, J = 7.7 Hz, 1H), 7.06 (d, J = 8.1
13
Hz, 1H), 6.84 (t, J = 7.7 Hz, 1H), 5.59 (s, 1H). C NMR (101 MHz, CDCl3) δ 152.3, 132.1, 129.2, 121.8,
116.2, 110.3.
−1
Methyl 4-hydroxybenzoate (2i): White solid. IR (cm , KBr): 3305, 2963, 2846, 2806, 1919, 1684, 1372, 1114,
1
954, 851, 691. H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.6 Hz, 2H), 6.33 (s, 1H),
13
3.92 (s, 2H). C NMR (101 MHz, CDCl3) δ 167.3, 160.2, 131.9, 122.3, 115.2, 52.0. m.p.: 130–131 °C.
−1
Ethyl 3-hydroxybenzoate (2j): Colorless liquid. IR (cm , KBr): 3350, 2385, 2581, 1692, 1597, 1512, 1459,
1
1415, 1311, 1232, 1163, 1108, 1074, 926, 881, 760, 670, 565, 522. H NMR (400 MHz, DMSO) δ 9.83 (s,
1H), 7.43–7.35 (m, 2H), 7.31 (t, J = 7.8 Hz, 2H), 7.03 (d, J = 7.9 Hz, 1H), 4.28 (q, J = 7.0 Hz, 2H), 1.30 (t, J
13
= 7.0 Hz, 3H). C NMR (101 MHz, CDCl3) δ 167.6, 156.3, 131.3, 129.7, 121.6, 120.5, 116.4, 61.6, 14.1.

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−1
4-tert-Butylphenol (2k): White solid. IR (cm , KBr): 3144, 2962, 2868, 1608, 1513, 1447, 1399, 1269, 1175,
1
822, 543. H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.5 Hz, 2H), 5.53 (s, 1H), 1.36
13
(s, 9H). C NMR (101 MHz, CDCl3) δ 152.9, 143.7, 126.5, 115.0, 34.1, 31.6. m.p.: 97–99 °C.
−1
4-Hydroxybenzoic acid (2l): White solid. IR (cm , KBr): 3382, 3130, 3013, 1676, 1600, 1402, 1321, 1286,
1
1238, 1160, 1096, 1000, 929, 848, 611, 541. H NMR (400 MHz, DMSO) δ 12.41 (s, 1H), 10.21 (s, 1H),
13
7.79 (d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H). C NMR (101 MHz, DMSO) δ 167.6, 162.0, 132.0, 121.8,
115.5. m.p.: 213–215 °C.
−1
4-Benzyloxyphenol (2m): White solid. IR (cm , KBr): 3429, 3132, 1659, 1614, 1510, 1401, 1236, 1164, 1086,
1
1012, 818, 734, 520. H NMR (400 MHz, CDCl3) δ 7.48–7.39 (m, 4H), 7.38–7.33 (m, 1H), 6.89 (d, J = 8.8
13
Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 5.04 (s, 1H). C NMR (101 MHz, CDCl3) δ 153.0, 149.7, 137.2, 128.5,
127.9, 127.5, 116.1, 116.1, 70.8. m.p.: 122–124 °C.
−1
2-Naphthol (2n): White solid. IR (cm , KBr): 3501, 3190, 1628, 1590, 1510, 1459, 1401, 1277, 1215, 1168,
1
955, 845, 813, 741, 476. H NMR (400 MHz, CDCl3) δ 7.84–7.77 (m, 2H), 7.71 (d, J = 8.2 Hz, 1H), 7.48 (t,
13
J = 7.5 Hz, 1H), 7.39 (t, J = 7.4 Hz, 1H), 7.21–7.11 (m, 2H), 5.52 (s, 1H). C NMR (101 MHz, CDCl3) δ
153.3, 134.6, 129.9, 129.0, 127.8, 126.6, 126.4, 123.7, 117.8, 109.6. m.p.: 120–122 °C.
−1
p-Hydroxybenzaldehyde (2o): White solid. IR (cm , KBr): 3144, 2962, 1608, 1513, 1399, 1239, 1176, 821,
1
543. H NMR (400 MHz, DMSO) δ 10.59 (s, 1H), 9.79 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.4 Hz,
13
2H). C NMR (101 MHz, DMSO) δ 191.3, 163.7, 132.5, 128.9, 116.3. m.p.: 116–118 °C.
−1
3-Trifluoromethylphenol (2p): Yellow liquid. IR (cm , KBr): 3440, 3132, 1662, 1622, 1401, 1160, 1076, 946,
1
858, 538. H NMR (400 MHz, CDCl3) δ 7.38 (t, J = 7.9 Hz, 1H), 7.23 (d, J = 7.7 Hz, 1H), 7.12 (s, 1H), 7.04
13
(d, J = 8.1 Hz, 1H), 5.36 (s, 1H). C NMR (101 MHz, CDCl3) δ 155.3, 132.4 (q, J = 32.7 Hz), 130.3, 123.8
(q, J = 271.3 Hz), 117.9 (q, J = 4.1 Hz), 112.3 (q, J = 4.1 Hz).
−1
tert-Butyl 4-hydroxy-1H-indole-1-carboxylate (2q): Corlorless liquid. IR (cm , KBr): 3449, 3135, 1664,
1
1626, 1400, 1136, 1074, 962, 855. H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.1 Hz, 1H), 7.55 (d, J = 3.5
13
Hz, 1H), 7.18 (t, J = 8.1 Hz, 1H), 6.68 (dd, J = 10.2, 5.8 Hz, 2H), 5.40 (s, 1H), 1.70 (s, 9H). C NMR (101
MHz, CDCl3) δ 149.8, 148.7, 136.9, 125.1, 124.7, 119.6, 108.3, 107.7, 103.5, 83.8, 28.2.
−1
6-Hydroxyflavone (2r): White solid. IR (cm , KBr): 3437, 3128, 3013, 1621, 1569, 1402, 1255, 1077, 835.
1
H NMR (400 MHz, DMSO) δ 10.02 (s, 1H), 8.08 (d, J = 6.9 Hz, 2H), 7.66 (d, J = 9.0 Hz, 1H), 7.59 (d, J =
13
6.5 Hz, 3H), 7.34 (d, J = 2.2 Hz, 1H), 7.27 (dd, J = 9.1, 2.3 Hz, 1H), 6.95 (s, 1H). C NMR (101 MHz,
DMSO) δ 177.4, 162.6, 155.3, 149.8, 132.0, 131.8, 129.5, 126.7, 124.7, 123.5, 120.3, 107.9, 106.4. m.p.: 238–
240 °C.
−1
4-Cyanophenol (2s): White solid. IR (cm , KBr): 3283, 2229, 1603, 1505, 1441, 1391, 1283, 1221, 1159, 834,
1
13
696, 534. H NMR (400 MHz, DMSO) δ 10.63 (s, 1H), 7.61 (s, 2H), 7.13–6.68 (m, 2H). C NMR (101
MHz, CDCl3) δ 160.6, 134.3, 119.3, 116.5, 102.5. m.p.: 112–114 °C.
−1
2-(N,N-Dibenzylamino)-2-phenylethan-1-ol (2t): White solid. IR (cm , KBr): 3440, 3134, 1661, 1624, 1401,
1
1070. H NMR (400 MHz, CDCl3) δ 7.53–7.19 (m, 15H), 4.17 (t, J = 10.6 Hz, 1H), 4.00–3.91 (m, 3H), 3.64
13
(dd, J = 10.6, 5.1 Hz, 1H), 3.18 (d, J = 13.4 Hz, 2H), 3.04 (s, 1H). C NMR (101 MHz, CDCl3) δ 139.1,
135.1, 129.3, 129.0, 128.5, 128.4, 128.0, 127.2, 63.0, 60.4, 53.5. m.p.: decomposed.
−1
1
Cholesterol (7): White solid. IR (cm , KBr): 3435, 3132, 2943, 1666, 1624, 1459, 1399, 1057. H NMR (400
MHz, CDCl3) δ 5.37 (d, J = 4.3 Hz, 1H), 3.69–3.35 (m, 1H), 2.35–2.19 (m, 2H), 2.01 (t, J = 14.8 Hz, 2H),
13
1.86 (d, J = 9.9 Hz, 3H), 1.60–0.85 (m, 34H), 0.70 (s, 3H). C NMR (101 MHz, CDCl3) δ 140.7, 121.7,
71.7, 56.7, 56.1, 50.1, 42.3, 42.3, 39.8, 39.5, 37.2, 36.5, 36.2, 35.8, 31.9, 31.6, 28.2, 28.0, 24.3, 23.8, 22.8, 22.5,
21.1, 19.4, 18.7, 11.8. m.p.: 146–148 °C.
Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Figure S1: title, Table
S1: title, Video S1: title.

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Author Contributions: J.Y. conceived and designed the experiments; C.M., H.N., J.N., W.W. performed the
experiments; W.W., J.Y. checked and analyzed the data; J.Y. wrote and revised the paper; All authors have read
and agreed to the published version of the manuscript.
Funding: Financial Support from National Natural Science Foundation of China (Grant 21602017), Natural
Science Foundation of Jiangsu Province (Grant No. BK20160405) and Research Start-up Fund of Changshu
Institute of Technology (No. XZ1508).
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds 2a–2p are available from the authors.
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