Zinc-Mediated Efficient and Selective Reduction of Carbonyl Compounds

Article abstract of DOI:10.1002/ejoc.201700887

We herein describe for the first time that an optimized combination of Zn and NH₄Cl can be used for the selective reduction of aldehydes and ketones to the corresponding alcohols. The aldehyde and keto groups are selectively reduced in the presence of azide, cyano, epoxy, ester, and carbon–carbon double-bond functional groups. A broad functional-group compatibility, chemoselective reduction of aldehydes in the presence of ketones, and selective reduction of isatins at the C3 carbonyl group are the highlights of the present method.

Full text of DOI:10.1002/ejoc.201700887

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Title: Zinc-Mediated Efficient and Selective Reduction of Carbonyl
Compounds
Authors: Jyotirmayee Dash
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10.1002/ejoc.201700887
European Journal of Organic Chemistry
FULL PAPER
Zinc-Mediated Efficient and Selective Reduction of Carbonyl
Compounds
Tirtha Mandal[a], Snehashish Jana[a], Jyotirmayee Dash[a]*
Dedication ((optional))
Abstract: We herein describe for the first time that an optimized
combination of Zn and NH4Cl can be used for the selective reduction
of aldehydes and ketones to the corresponding alcohols. The
aldehyde and keto groups are selectively reduced in the presence of
azide, cyano, epoxy, ester and carbon-carbon double bond
HCl is used for the Clemmensen reduction of aldehydes and
ketones to provide the corresponding hydrocarbons. Zn is
known to reduce benzil and its derivatives to keto-hydroxy
compounds.[14] Zn in combination with NH4Cl has been used for
the reduction of nitro and azido groups to the corresponding
amines.[15] Zinc is cheap and non-toxic compared to sodium
borohydride, a commonly used reagent for the reduction of
aldehydes and ketones on a laboratory scale. We envisioned
that Zn could be used for the reduction of aldehydes and
ketones in the presence of a proton source to selectively obtain
the reduced products.
functional groups.
A
broad functional group compatibility,
chemoselective reduction of aldehydes in the presence of ketones
and selective reduction of isatins at C3 carbonyl are the highlights of
the present method.
Introduction
The reduction of aldehydes and ketones is one of the
fundamental transformations for the preparation of alcohols,
which are used as chemical intermediates for the synthesis of
natural products, pharmaceuticals, agrochemicals and functional
materials.[1] Therefore, numerous reduction methods such as
Results and Discussion
We
started
our
optimization
studies
using
4-
methylbenzaldehyde 1a1 as a model substrate to optimize the
reaction conditions using different metals, proton sources at
different temperatures using THF as the solvent (Table 1). The
reaction did not proceed by using catalytic amount of Zn (Table
1, entry 1). Using 1 equiv of Zn, low conversion was observed
along with the formation of both the desired alcohol 2a1 and the
pinacol product 3a1 (entries 2, 3). By increasing the amount of
Zn to 3 equiv as well as increasing the reaction temperature to
60 °C, the formation of 3a1 was decreased but a complete
conversion could not be achieved (entries 4, 5). To our delight,
the reaction proceeded smoothly by using 5 equiv of Zn leading
to the selective formation of 2a1 (entries 9-10, 13) even at room
temperature. Gratifyingly, 4-methylbenzyl alcohol 2a1 was
exclusively obtained in just 20 minutes by using 5 equiv of Zn in
the presence of 8 M aqueous NH4Cl (10 mL) (entry 13). When
less concentrated NH4Cl solution was used, the reaction was
slow providing both the alcohol 2a1 and diol 3a1 (entry 9, 10).
However, more concentrated NH4Cl solution did not interfere
with the outcome of the reaction. No reaction was observed by
using solid NH4Cl (entry 11). The use of aqueous NH4Cl solution
(freshly prepared) was necessary for the reaction as no reaction
took place using only H2O as the proton source (entry 12). A
closely related result was also obtained using HCl (6 N) as the
proton source (entry 17), but the reaction was less efficient than
aq. NH4Cl (entry 13). The reaction also proceeded in the
presence of AcOH (6N), but a trace amount of diol 3a1 was also
formed (entry 16). When the reaction was performed using 5
equiv. of collidine.HCl as a proton source,[6c] no product was
formed after 20 min at rt (entry 18). However, a complete
conversion of 1a1 was observed by giving longer reaction time (4
h, rt), providing alcohol 2a1 as the major product along with
pinacol 3a1 (entry 19). The reduction of 1a1 in deuteriated
solvents like THF-d8 and D2O suggest that aq NH4Cl is the
proton source (see supporting information, Table S1).
metal
hydrides,[2]
boron
based
reagents,[3]
catalytic
hydrogenation,[4] and biocatalytic reductions[5] have been
reported.[1-5] However, many of these methods often generate
stoichiometric amount of waste and involve long reaction times,
harsh conditions (under nitrogen; in acid or alkaline conditions)
and complicated operations and therefore, pose significant
environmental and economic problems especially in large-scale
industrial processes. Furthermore, only a few protocols are
known for the chemoselective reduction of aldehydes in the
presence of a keto group.[6] In this context, we planned to
develop a mild and a viable process for the reduction of a wide
range of aldehydes, ketones and isatins in aqueous media.
Aldehydes and ketones undergo pinacol coupling to form the
corresponding diols in the presence of excess low-valent metals
such as Zn−Cu couple,[7] Mg,[8] Mn,[9] Zn,[10] Sm,[11] Al,[12] V[13] and
other metals. In these cases, the reduced product is formed as a
minor by-product. Recently, it is reported that Mn in combination
with 2,4,6-collidinium hydrochloride can chemoselectively
reduce aldehydes to the alcohols, while ketones do not react
under these conditions.[6c]
Among these metals, Zn has been widely used as a
reducing reagent. Zinc in the presence of acetic acid is used as
a reducing agent for the reduction of a range of organic
functional groups. Zinc amalgam (Zn/Hg alloy) in concentrated
[a]
T. Mandal, S. Jana, Prof. Dr. J. Dash
Department of Organic Chemistry
Indian Association for the Cultivation of Science
Jadavpur, Kolkata-700032, India
E-mail: ocjd@iacs.res.in
Supporting information for this article is given via a link at the end
of the document.
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10.1002/ejoc.201700887
European Journal of Organic Chemistry
FULL PAPER
Table 1. Optimization for the reduction of aldehydes.[a]
of 2a1 (95%) was obtained when THF was used as the solvent
(Table S2, S.I.). The reaction also proceeded in dioxane, toluene
and CH3CN; but poor conversion was observed using DMSO,
DMF, CH2Cl2 and DCE (Table S2, S.I.). No reaction took place
using only water as the solvent (Table S2, S.I.). We determined
the optimal reaction conditions to selectively obtain the reduced
product 2a1 as follows: Zn (5 equiv), 8 M NH4Cl (10 mL) in THF
(2 mL), rt, 20 min.
M.
Conv.(%);
Entry
Proton source
T (° C)
Time
[b]
(equiv.)
2a1:3a1
1
NH4Cl (2 M)
NH4Cl (2 M)
NH4Cl (2 M)
NH4Cl (4 M)
NH4Cl (4 M)
AcOH (4 N)
HCl (4 N)
Zn (0.2)
Zn (1)
Zn (1)
Zn (3)
Zn (3)
Zn (3)
Zn (3)
Zn (3)
Zn (5)
Zn (5)
Zn (5)
Zn (5)
Zn (5)
Zn (5)
Zn (5)
Zn (5)
Zn (5)
Zn (5)
Zn (5)
Fe (5)
Fe (5)
Mg (5)
Mn (5)
In (5)
rt or 60 °C[c]
6 h
No reaction
20; 40:60
25; 50:50
80; 60:40
80; 70:30
90; 60:40
95; 70:30
95; 70:30
100; 90:10
100; 90:10
No reaction
No reaction
100; >99:1
100; 90:10
100; 90:10
100; 95:5
100; 95:5
No reaction
100; 80:20
No reaction
30; 50:50
70; 70:30
70; 60:40
No reaction
With the optimal reaction conditions in hand, the substrate
scope of Zn mediated reduction of aldehydes was explored
(Table 2). We found that a wide range of aldehydes regardless
of the substituent position and electronic property were smoothly
reduced to give the corresponding alcohols in good to excellent
yields. The reduction of p-anisaldehyde and 4-dimethylamino
benzaldehyde proceeded slowly at room temperature but they
were efficiently reduced upon heating at 60 °C for 3 h to provide
benzyl alcohols 2a4 (81%) and 2a5 (83%) respectively, in high
yields; some amount of the pinacols (15 % and 12 %,
respectively) were also obtained. Many functional groups such
as -OH, -Cl, -Br, -F, -CN, -CO2Me (2a3, 2a7-2a11) were tolerated.
Importantly, the aldehyde group was selectively reduced in the
presence of an azido (2a13) and epoxy group (2a35). The labile
methoxymethyl (MOM) and mesyl (Ms) groups were well
tolerated under the reaction conditions (2a14, 2a15).
2
rt
4 h
3
60 °C
4 h
4
rt
3 h
5
60 °C
3 h
6
rt or 60 °C[c]
3 h
7
rt or 60 °C[c]
3 h
8
H2SO4 (4 N)
NH4Cl (4 M)
NH4Cl (4 M)
NH4Cl [d]
rt or 60 °C[c]
3 h
9
rt
1 h
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
60 °C
45 min
6 h
rt
Table 2. Reduction of aldehydes.[a]
Zn (5 equiv)
H2O
rt
8 h
R-CHO
R-CH2OH
THF, aqs. NH4Cl (8 M)
rt, 20 min
1a1-1a38
2a1-2a39
NH4Cl (8 M)
AcOH (4 N)
HCl (4 N)
rt
20 min
45 min
1 h
rt or 60 °C[c]
rt or 60 °C[c]
rt or 60 °C[c]
rt or 60 °C[c]
rt
OH
OH
OH
R1
OH
R1
F
Cl
R1
R1 = Me; 2a1, 94 %
R1 = H; 2a2, 90 %
R1 = OH; 2a3, 93%
R1 = F; 2a9, 88%
2a
R1 = OH; 16, 92%
R1 = OMe; 2a17, 90%
R1 = Cl; 18, 83%
R1 = Br; 19, 87%
2a
R1 = OH; 20, 93%
2a
23, 87%
2a
R1 = CN; 10, 89%
2a
R1 = Cl; 21, 80%
2a
AcOH (6 N)
HCl (6 N)
30 min
30 min
20 min
4 h
R1 = CO2Me; 11, 95%
2a
2a
R1 = F; 2a22, 86%
[b]
2a
2a
R1 = OMe; 4, 81% R1 = CF3; 12, 95%
[b] R1 = N3; 2a13, 88%
2a
R1 = NMe2; 5, 83%
2a
R1 = OMOM; 14, 96%
2a
R1 = Ph; 6, 95%
2a
R1 = OMs; 15, 94%
2a
R1 = Cl; 7, 82%
OH
2a
R1 = Br; 8, 84%
Collidine.HCl [e]
Collidine.HCl [e]
NH4Cl (8 M)
NH4Cl (8 M)
NH4Cl (8 M)
NH4Cl (8 M)
NH4Cl (8 M)
OH
OH
OH
OH
rt
F
N
2a28, 88 %
F
2a24, 90 %
2a25, 86 %
2a26, 86 %
2a
27, 91%
rt
20 min
20 min
20 min
20 min
20 min
OH
H3C
OH
R2
OH
S
60 °C
OH
O
N
N
N
rt or 60 °C[c]
rt or 60 °C[c]
rt or 60 °C[c]
2a
29, 91%
2a
30, 90%
Bn
2a33,
91%
N
2a
31, R2 = CHO, 98%
2a32, R2 = CH2OH, 90%[c]
OH
OH
OH
OH
OH
n
O
[a] The reactions were performed on a 1.0 mmol scale in THF (2 mL) using a proton source
(10 mL); [b] The conversion and ratio of 2a1 and 3a1 were determined from crude NMR of
the reaction mixture; [c] The outcome of reaction remain similar at 60 °C; [d] Using 5 equiv.
solid NH4Cl; [e] Using 5 equiv. Collidine.HCl
2a
1
38, n = , 84%
2a
37, 78%
2a34, 98%
2a36, 78%
2a35, 92%
2a39, n = 5, 80%
[a] The reactions were performed on a 1.0 mmol scale using Zn (5 equiv), THF
[b]
(2 mL), 8 M aqs. NH4Cl solution (10 mL) at room temperature for 20 min;
60 °C for 3 h; 15% and 12% of pinacols were isolated; [c] Reaction was carried
out for 45 min at rt.
It is worth mentioning that Zn and aqueous NH4Cl solution
were added at the same time to make the reaction faster by
preventing the formation of pinacol product. The other metal
sources like Fe, Mn, Mg and In were found to be inefficient
(Table 1, entries 20-24). The reaction with Mg and Mn provided
both the reduced and the pinacol products (Table1, entries 22,
23). Then, various solvents including DMF, DMSO, MeCN, DCM,
H2O, toluene and dioxane were evaluated (entries 1−9, Table S2,
S.I.). The solvent screening results showed that the highest yield
The polycyclic aromatic aldehydes and heterocyclic
aldehydes also furnished the corresponding benzyl alcohols
(2a25-2a27, 2a28-2a33) in excellent yields. The carbazole
dialdehyde[16] gave the reduced mono-aldehyde derivative 2a31
in excellent yield at room temperature after 20 min. However,
both the formyl groups were reduced by conducting the reaction
for 45 min to provide the diol 2a32 in excellent yield. In case of
pyridine-4-aldehyde and 4-cyanobenzaldehyde, trace amounts
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10.1002/ejoc.201700887
European Journal of Organic Chemistry
FULL PAPER
of the corresponding pinacols were also formed but the reduced
products were easily separated by column chromatography (2a28
and 2a10). In all the other cases, no column purification was
needed as the corresponding alcohols were obtained in near
quantitative yields. Interestingly, the chiral indolyl aldehyde[17]
underwent facile reduction to give the corresponding alcohol
2a33 with retention in stereochemistry. The α,β-unsaturated
aldehyde gave the desired alcohol 2a34,[6g,i] in which the E-
stereochemistry was preserved. Aliphatic aldehydes provided
their corresponding alcohols in excellent yields at room
temperature but the reaction took slightly longer time with
formation of trace amount of the pinacol product (2a36-2a39).
Pivalaldehyde and cyclopropyl carboxaldehyde did not furnish
the desired products under the optimized reaction conditions.
Since excess Zn was used in the reduction, we have recovered
the used Zn after completion of the reaction and reused to carry
out further reactions. Zn showed diminished activity in
subsequent reaction cycles (Table S3, S.I.).
reduced efficiently to give the desired products 5i (syn:anti >
99:1) and 5j (dl/meso = 90:10) respectively, in excellent yields
and diastereoselectivities. Both the keto groups of benzil 4k
were reduced to provide the diol 5j (dl/meso = 90:10). The
heteroaryl 4n, cyclic 4p-q and acyclic 4r aliphatic ketones were
also reduced to give the corresponding reduced products by
giving a slightly longer reaction time (4 h). In few cases, the
pinacol products 6 were obtained as the minor products (0-27%),
which could be easily separated out by column chromatography
(Table 4).
Table 4. Reduction of ketones.[a]
We were delighted to find out that ketones although reacted
slowly under the optimized reaction conditions, gave the desired
alcohols 5 as the major products at 60 oC (Table 3). The
reduction of ketone 4a was inefficient using collidinium
hydrochloride (entries 6,7);[6c] a low (40%) conversion of 4a
occurred after 3 h at 60 °C and a mixture of alcohol 5a and diol
6a were obtained by giving a longer reaction time (8 h).
Table 3. Optimisation for the reduction of ketones.[a]
Zn
(equiv.)
Conversion
(%),[b]
6a
Entry
T (° C)
Time
(dl:meso)[c]
ratio of 5a:6a
1
2
3
4
5
6
7
3
3
5
5
5
5
5
Rt
6 h
6 h
4 h
3 h
14 h
3 h
8 h
10, 50:50
70, 60:40
40, 60:40
100, 75:25
80, 50:50
40, 60:40[d]
> 99, 50:50[d]
Nd
60 °C
Rt
50:50
Nd
60 °C
Rt
60:40
Nd
[a] The reactions were performed on a 1.0 mmol scale using Zn (5 equiv), THF
(2 mL), 8 M aqs. NH4Cl solution (10 mL) at 60 oC for 3 h; [b] The dl:meso or
syn:anti ratios were evaluated from the NMR spectra of isolated pinacol
products; [c] ND = pinacol product was not isolated; [d]NF = pinacol product was
not formed, [e] 4 h.
60 °C
60 °C
Nd
Nd
[a] The reactions were performed on a 1.0 mmol scale in solvent (2 mL);
[b]
The conversion and ratio (5a:6a) were determined from NMR spectra of the
crude reaction mixture; [c] The dl:meso ratio was determined from the NMR
[d]
spectra of isolated 6a;
The reactions were performed using 5 equiv. of
collidinium hydrochloride.
Aromatic ketones containing –OH, -OMe, -NH2 and -Br
groups were efficiently reduced to produce the corresponding
secondary alcohols (5c-5f). Importantly, the keto group was
reduced selectively in the presence of ester, double bond and
epoxy groups (5n, 5k, 5l). The 2,2,2-trifluoro acetophenone
derivative 4g was reduced to afford the corresponding
fluorinated secondary alcohol 5g in high yield. It is important to
note that benzophenone 4h gave exclusively the alcohol 5h in
excellent yield (92%), better than the reported metal mediated
reductions. The α-ketohydroxy derivatives 4i and 4j were
Scheme 1. Chemoselective reduction of an aldehyde in the presence of a
ketone.
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Next we have evaluated the chemoselectivity of the
reduction process by using 4-acetylbenzaldehyde 7 (Scheme 1)
as the substrate. At rt, the benzyl alcohol 8 was isolated as the
sole product in 90% yield, indicating the reduction of aldehydes
could be performed with excellent selectivity without concomitant
reduction of the keto group. Many reducing agents would have
reacted with both the functional groups providing a mixture of
products.[1-5] Although a few methods have been developed for
the chemoselective reduction of aldehydes in the presence of
ketones,[6] the development of a practical and bench scale
process is still desirable. We have established a mild protocol for
chemoselective reduction of aldehydes in the presence of
ketones that can be applied for large scale synthesis. By heating
the aldehyde 7 at 60 °C for 3 h, both aldehyde and keto groups
were reduced to provide the diol 9, which was also obtained
from the hydrogenation of 8.
radical coupling to form the pinacol or it can follow another
electron transfer to form the reduced alcohol. Since the pinacol
product is obtained as a minor product, the electron transfer and
subsequent protonation are faster than the radical coupling to
provide the reduced alcohol as the major product.
O
Zn
O
H3O
OH
R2
HO
R1
OH
R1
R2
R1
R1
Zn2+
R1
R2
1 e
R2
R2
B
A
Pinacol (minor)
1 e
OH
R1
OH
R2
H3O
R1
H
R2
major
Reduced product
Scheme 2. Proposed mechanism via SET pathway.
The method was also used to achieve the selective
reduction of C3 carbonyl group of isatins (Table 5). Only a few
methods are known for the reduction of isatins.[18] NaBH4 is the
commonly used reagent for the selective reduction of isatin
derivatives at the C3 position, however, 5-halo substituted
isatins gave the corresponding 3-hydroxy indolines in poor yields.
Recently, a combination of CeCl3 and NaBH4 has been
developed for the efficient reduction of 5-halo substituted
isatins.[19] In contrary, our reaction conditions (3 equiv. Zn,
aqueous 8 M NH4Cl in THF) constitute a mild and simple
alternative for the chemoselective reduction of isatins, affording
the 3-hydroxy indoline derivatives 11 in near quantitative yields.
The 5-halo substituted isatins were reduced efficiently under the
optimized reaction conditions, affording the corresponding 3-
hydroxy indolines in excellent yields without any column
purification. These reactions were completed within 10 min.
Moreover, these reductions could be easily performed on gram
scale; the reduction of 4-methylbenzaldehyde and N-methyl
isatin were carried out in 2 g scale to provide the corresponding
reduced products in 90% and 94 % yields respectively.
Conclusions
In summary, we have developed a general protocol for the
reduction of different kinds of aldehydes (aliphatic, aromatic,
polycyclic aromatic, heterocyclic and ,β-unsaturated) and
ketones to the corresponding alcohols using an optimized
amount of Zn and NH4Cl under mild reaction conditions. The
method can be used for the rapid reduction of isatins at the C3
position. The reactions proceed efficiently with excellent yields
and high chemoselectivity. In most cases, the products were
isolated directly without chromatographic purification. The
selective reduction of aldehyde group is achieved in the
presence of ketones, ester, cyano, azide, and epoxy and
carbon-carbon double bond thus providing a mild, economic and
attractive alternative to other reagents.
EXPERIMENTAL SECTION
Table 5. Reduction of isatin derivatives. [a]
General Information: All experiments were carried out
under open atmosphere in flame dried flasks. Solvents were
dried using standard procedures. All starting materials were
obtained from commercial suppliers and used as received.
Products were purified by flash chromatography on silica gel
(100-200 mesh, Merck). Unless otherwise stated, yields refer to
analytical pure samples. NMR spectra were recorded in CDCl3
and DMSO-d6. 1H NMR spectra were recorded at 500 MHz and
400 MHz instruments at 278 K. Data is reported as follows:
chemical shift, integration, multiplicity (s = singlet, d = doublet, t
= triplet, q = quartet, m = multiplet) and coupling constants (Hz).
13C NMR spectra were recorded on either a 100 MHz or a 125
MHz with complete proton decoupling. Chemical shifts (δ) are
reported in ppm. Infrared (FTIR) spectra were recorded on a
spectrophotometer with the KBr disk and KBr plate techniques
for solid and liquid samples, max cm-1.
[a] The reactions were performed on a 1.0 mmol scale using Zn (3 equiv), THF
(2 mL), aqs. NH4Cl (8 M, 10 mL) at room temperature for 10 min.
General procedure for the reduction of aldehydes (GP-I):
To a solution of aldehydes 1 (1.0 mmol, 1 equiv.) in THF (2 mL)
were added Zn dust (5 mmol, 325 mg, 5 equiv.) and aqueous
NH4Cl solution (8 M, 10 mL) simultaneously. The reaction
mixture was stirred at room temperature until complete
conversion of starting material (as monitored by TLC), typically
for 20 min. The reaction mixture was filtered through cotton into
a separatory funnel and extracted with EtOAC (3 X 5 mL). The
The reduction process proceeds through a typical single
electron transfer mechanism. The reduction of 1a1 was inhibited
in the presence of radical scavengers like TEMPO or galvinoxyl,
corroborating a radical pathway (Table S4, S.I.). The electron
transfer from Zn to the aldehyde and ketone functional groups
generates reactive alkoxy radical intermediate (A), which upon
protonation in the presence of aqueous NH4Cl forms the radical
intermediate B (Scheme 2). The intermediate B can undergo
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10.1002/ejoc.201700887
European Journal of Organic Chemistry
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combined organic extracts were washed with brine, dried over
anhydrous Na2SO4, filtered and the solvent was evaporated to
give the corresponding alcohols 2. In most cases, the product
was sufficiently pure and no further purification was needed.
1H NMR (500 MHz, DMSO-d6): 2.10 (3H, s), 4.30 (2H, s), 4.96
(1H, br s), 6.94 (2H, d, J = 8.2 Hz), 7.04 (2H, d, J = 8.2 Hz); 13
C
(125 MHz, DMSO-d6): 20.8, 62.9, 126.6, 128.7, 135.7, 139.6;
HRMS (ESI) calcd for C8H10O[M+H]+: 123.0732; Found:
123.0735.
General procedure for the reduction of ketones (GP-II):
To a solution of ketones 4 (1 mmol, 1 equiv.) in THF (2 mL) were
added Zn dust (5 mmol, 325 mg, 5 equiv.) and aqueous NH4Cl
solution (8 M, 10 mL) simultaneously. The reaction mixture was
stirred at 60 °C until complete conversion of starting material (as
monitored by TLC), typically for 3-4 h. The reaction mixture was
filtered through cotton into a separatory funnel and extracted
with EtOAC (3 X 5 mL). The combined organic extracts were
washed with brine, dried over anhydrous Na2SO4, filtered and
the solvent was evaporated. The residue was purified by column
chromatography on silica gel using hexanes/EtOAC as eluent
(80:20-60:40) to give the corresponding secondary alcohols 5. In
some cases, the pinacol product 6 was obtained as a minor
product, which was separated by using column chromatography.
Benzyl alcohol (2a2):[6f] Following GP-I, benzaldehyde 1a2
(106 mg, 1.0 mmol, 1.0 equiv.) afforded benzyl alcohol 2a2 (98
mg, 90%) as a colorless liquid. 1H NMR (500 MHz, CDCl3): 2.90
(1H, br s), 4.65 (2H, s), 7.23-7.35 (5H, m); 13C (125 MHz,
CDCl3): 65.1, 127.0, 127.5, 128.5, 140.9; HRMS (ESI) calcd for
C7H8O[M+H]+: 109.0575; Found: 109.0572.
4-Hydroxybenzyl alcohol (2a3):[20] Following GP-I, 4-
hydroxybenzaldehyde 1a3 (122 mg, 1.0 mmol, 1.0 equiv.)
afforded 4-hydroxybenzyl alcohol 2a3 (116 mg, 93%) as a
colorless liquid. 1H NMR (500 MHz, DMSO-d6): 4.37 (2H, s),
4.90 (1H, br s), 6.72 (2H, d, J = 8.4 Hz), 7.0 (2H, d, J = 8.4 Hz),
9.23 (1H, s); 13C (100 MHz, DMSO-d6): 62.9, 114.8, 128.1, 132.8,
156.2; HRMS (ESI) calcd for C7H8O2 [M+H]+: 125.0524; Found:
125.0522.
General procedure for reduction of isatins (GP-III): To a
solution of isatins 10 (1 mmol, 1 equiv.) in THF (2 mL) were
added Zn dust (3 mmol, 195 mg, 3 equiv.) and aqueous NH4Cl
solution (8 M, 10 mL) simultaneously. The reaction mixture was
stirred at room temperature until complete conversion of starting
material (as monitored by TLC), typically for 10 min. The
reaction mixture was filtered through cotton into a separatory
funnel and extracted with EtOAC (3 X 5 mL). The combined
organic extracts were washed with brine, dried over anhydrous
Na2SO4, filtered and the solvent was evaporated to give the
desired products 11. The product thus obtained was sufficiently
pure and no further purification was needed.
(4-Methoxyphenyl)methanol (2a4):[6f] Following GP-II, 4-
methoxybenzaldehyde 1a4 (136 mg, 1.0 mmol, 1.0 equiv.)
afforded (4-methoxyphenyl)methanol 2a4 (112 mg, 81%) as a
colorless liquid. 1H NMR (500 MHz, DMSO-d6): 3.61 (3H, s),
4.31 (2H, d, J = 6.7 Hz), 4.94 (1H, t, J = 6.7 Hz), 6.76 (2H, d, J =
11.0 Hz), 7.12 (2H, d, J = 11.0 Hz); 13C (125 MHz, DMSO-d6):
54.9, 62.6, 113.5, 127.9, 134.6, 158.2; HRMS (ESI) calcd for
C8H10O2 [M+H]+: 139.0681; Found: 139.0680.
(4-(Dimethylamino)phenyl)methanol (2a5):[6j] Following
GP-II, 4-dimethylaminobenzaldehyde 1a5 (148 mg, 1.0 mmol,
1.0 equiv.) afforded methyl (4-(dimethylamino)phenyl)methanol
Gram scale experiments:
1
2a5 (126 mg, 83%) as a straw yellow liquid. H NMR (500 MHz,
Preparation of 4-methylbenzyl alcohol (2a1): To a solution
of 4-methylbenzaldehyde 1a1 (2.0 g, 16.6 mmol, 1.0 equiv.) in
THF (20 mL) were added Zn dust (5.4 g, 83 mmol, 5.0 equiv.)
and aqueous NH4Cl solution (8 M, 40 mL) simultaneously. The
reaction mixture was stirred at room temperature until
completion of the reaction as monitored by TLC (30 min. to be
specific in this case). The reaction mixture was filtered through
cotton into a separatory funnel and extracted with EtOAC (3 X
20 mL). The combined organic extracts were washed with brine,
dried over anhydrous Na2SO4, filtered and the solvent was
evaporated to give the 4-methylbenzyl alcohol 2a1 (1.8 g, 92 %)
as a colorless liquid.
DMSO-d6): 2.88 (6H, s), 4.39 (2H, d, J = 5.7 Hz), 4.96 (1H, t, J =
5.65 Hz), 6.71 (2H, d, J = 8.8 Hz), 7.16 (2H, d, J = 8.8 Hz); 13C
(125 MHz, DMSO-d6): 40.4, 63.0, 112.3, 127.9, 130.2, 149.7;
HRMS (ESI) calcd for C9H13NO[M+H]+: 152.0997; Found:
152.0999.
[1,1'-Biphenyl]-4-ylmethanol (2a6):[6g] Following GP-I, [1,1'-
biphenyl]-4-carbaldehyde 1a6 (182 mg, 1.0 mmol, 1.0 equiv.)
afforded [1,1'-biphenyl]-4-ylmethanol 2a6 (87 mg, 95%) as a
1
colorless liquid. H NMR (500 MHz, DMSO-d6): 4.57 (2H, d, J =
5.7 Hz), 5.30 (1H, t. J = 5.7 Hz), 7.34 (1H, t, J = 7.6 Hz), 7.46-
7.41 (4H, m), 7.65-7.60 (4H, m); 13C (100 MHz, DMSO-d6): 62.7,
126.4, 126.6, 127.1, 127.3, 128.9, 138.7, 140.2, 141.8; HRMS
(ESI) calcd for C13H12O[M+H]+: 185.0888; Found: 185.0889.
Preparation of 3-hydroxy-1-methylindolin-2-one (11b): To
a solution of N-methyl isatin 10b (2.0 g, 12.4 mmol, 1.0 equiv.) in
THF (15 mL) were added Zn dust (2.5 g, 38.0 mmol, 3 equiv.)
and aqueous NH4Cl solution (8 M, 40 mL) simultaneously. The
reaction mixture was stirred at room temperature until
completion of the reaction as monitored by TLC (15 min to be
specific in this case). The reaction mixture was filtered through
cotton into a separatory funnel and extracted with EtOAC (3 X
20 mL). The combined organic extracts were washed with brine,
dried over anhydrous Na2SO4, filtered and the solvent was
evaporated to give 3-hydroxy-1-methylindolin-2-one 11b (1.94 g,
95%) as a pale yellow solid.
4-Chlorobenzyl alcohol (2a7):[6b] Following GP-I, 4-
chlorobenzaldehyde 1a7 (140 mg, 1.0 mmol, 1.0 equiv.) afforded
4-chlorobenzyl alcohol 2a7 (116 mg, 82%) as a straw yellow
1
liquid. H NMR (500 MHz, DMSO-d6): 4.35 (2H, d, J = 5.6 Hz),
5.17 (1H, t, J = 6.4 Hz), 7.15 (2H, d, J = 8.2 Hz), 7.48 (2H, d, J =
8.8 Hz); 13C (125 MHz, DMSO-d6): 62.1, 119.5, 128.5, 130.8,
141.8; HRMS (ESI) calcd for C7H7ClO[M+H]+: 143.0185; Found:
143.0183.
4-Bromobenzyl alcohol (2a8):[6h] Following GP-I, 4-
bromobenzaldehyde 1a8 (184 mg, 1.0 mmol, 1.0 equiv.) afforded
4-bromobenzyl alcohol 2a8 (158 mg, 84%) as a straw yellow
Analytic data of compounds:
1
liquid. H NMR (500 MHz, DMSO-d6): 4.45 (2H, d, J = 5.7 Hz),
4-Methylbenzyl alcohol (2a1):[6f] Following GP-I, 4-
methylbenzaldehyde 1a1 (120 mg, 1.0 mmol, 1.0 equiv.) afforded
4-methylbenzyl alcohol 2a1 (114 mg, 94%) as a colorless liquid.
5.27 (1H, t, J = 6.3 Hz), 7.25 (2H, d, J = 8.2 Hz), 7.48 (2H, d, J =
8.8 Hz); 13C (125 MHz, DMSO-d6): 62.2, 119.6, 128.6, 130.9,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700887
European Journal of Organic Chemistry
FULL PAPER
141.9; HRMS (ESI) calcd for C7H7BrO[M+H]+: 186.9680; Found:
186.9678.
3-Hydroxybenzyl alcohol (2a16):[20] Following GP-I, 3-
hydroxybenzaldehyde 1a16 (122 mg, 1.0 mmol, 1.0 equiv.)
afforded 3-hydroxybenzyl alcohol 2a16 (114 mg, 92%) as a
4-Fluorobenzyl alcohol (2a9):[6g] Following GP-I, 4-
flurobenzaldehyde 1a9 (124 mg, 1.0 mmol, 1.0 equiv.) afforded
4-flurobenzyl alcohol 2a9 (110 mg, 88%) as a colorless liquid. 1H
NMR (500 MHz, DMSO-d6): 4.37 (2H, d, J = 5.6 Hz), 5.13 (1H, t,
1
colorless liquid. H NMR (500 MHz, DMSO-d6): 4.42 (2H, d, J =
5.1 Hz), 5.10 (1H, t, J = 5.7 Hz), 6.62 (1H, dd, J = 1.9, 5.7 Hz),
6.72 (1H, d, J = 7.6 Hz), 6.76 (1H, s), 7.10 (1H, t, J = 8.0 Hz),
9.27 (1H, s); 13C (100 MHz, DMSO-d6): 63.0, 113.4, 113.6, 117.1,
129.1, 144.1, 157.3; HRMS (ESI) calcd for C7H8O2 [M+H]+:
125.0524; Found: 125.0524.
J = 5.6 Hz), 7.0-7.10 (2H, m), 7.24 (2H, dd, J = 6.3, 2.5 Hz); 13
(125 MHz, DMSO-d6): 62.2, 114.6, 114.8, 128.3, 128.4, 138.6,
138.7, 160.2, 162.1; HRMS (ESI) calcd for C7H7FO[M+H]+:
127.0481; Found: 127.0479.
C
(3-Methoxyphenyl)methanol (2a17):[6f] Following GP-I, 3-
methoxybenzaldehyde 1a17 (136 mg, 1.0 mmol, 1.0 equiv.)
afforded (3-methoxyphenyl)methanol 2a17 (124 mg, 90%) as a
colourless liquid. 1H NMR (400 MHz, DMSO-d6): 3.72 (3H, d, J =
2. Hz), 4.48 (2H, d, J = 5.5 Hz), 5.19 (1H, t, J = 6.1 Hz), 6.76 (1H,
d, J = 10.3 Hz), 6.90 (2H, s), 7.21 (1H, t, J = 7.3 Hz); 13C (100
MHz, DMSO-d6): 54.9, 62.8, 111.8, 112.1, 118.5, 129.1, 144.3,
159.3; HRMS (ESI) calcd for C8H10O2 [M+H]+: 139.0681; Found:
139.0680.
4-Cyanobenzyl alcohol (2a10):[6h] Following GP-I, 4-
cyanobenzaldehyde 1a10 (130 mg, 1.0 mmol, 1.0 equiv.)
afforded 4-cyanobenzyl alcohol 2a10 (118 mg, 89%) as a
1
colorless liquid. H NMR (500 MHz, DMSO-d6): 4.52 (2H, d, J =
5.0 Hz), 5.38 (1H, t, J = 5.9 Hz), 7.44 (2H, d, J = 7.5 Hz), 7.71
(2H, d, J = 7.5 Hz); 13C (125 MHz, DMSO-d6): 62.2, 109.3, 119.0,
126.9, 132.0, 148.5; HRMS (ESI) calcd for C8H7NO [M+H]+:
134.0528; Found: 134.0526.
3-Chlorobenzyl alcohol (2a18):[6b] Following GP-I, 3-
chlorobenzaldehyde 1a18 (140 mg, 1.0 mmol, 1.0 equiv.)
afforded 3-chloro benzyl alcohol 2a18 (118 mg, 83%) as a straw
yellow liquid. 1H NMR (500 MHz, DMSO-d6): 4.50 (2H, d, J = 1.9
Hz), 5.40-5.35 (1H, m), 7.24 (2H, d, J = 7.6 Hz), 7.33-7.30 (1H,
m), 7.35 (1H, s); 13C (100 MHz, DMSO-d6): 62.3, 125.0, 126.2,
126.6, 130.0, 133.0, 145.3; HRMS (ESI) calcd for
C7H7ClO[M+H]+: 143.0185; Found: 143.0183.
Methyl 4-(hydroxymethyl)benzoate (2a11):[6f] Following
GP-I, Methyl 4-formylbenzoate 1a11 (164 mg, 1.0 mmol, 1.0
equiv.) afforded methyl 4-(hydroxymethyl)benzoate 2a11 (158 mg,
1
95%) . H NMR (500 MHz, DMSO-d6): 3.80 (3H, s), 4.53 (2H, d,
J = 7.4 Hz), 5.30 (1H, t, J = 7.7 Hz), 7.42 (2H, d, J = 9.8 Hz),
7.88 (2H, d, J = 9.8 Hz); 13C (125 MHz, DMSO-d6): 51.9, 62.4,
126.2, 126.3, 129.0, 148.3, 166.2; HRMS (ESI) calcd for
C9H10O3 [M+H]+: 167.0630; Found: 167.06329.
3-Bromobenzyl alcohol (2a19):[6f] Following GP-I, 3-
bromobenzaldehyde 1a19 (184 mg, 1.0 mmol, 1.0 equiv.)
afforded 3-bromobenzyl alcohol 2a19 (162 mg, 87%) as a straw
yellow liquid. 1H NMR (500 MHz, DMSO-d6): 4.51 (2H, d, J = 5.7
Hz), 5.38 (1H, t, J = 5.7 Hz), 7.32-7.36 (2H, m), 7.41 (1H, d, J =
7.6 Hz), 7.52 (1H, s); 13C (100 MHz, DMSO-d6): 62.2, 121.6,
125.3, 129.1, 129.5, 130.3, 145.5; HRMS (ESI) calcd for
C7H7BrO[M+H]+: 186.9680; Found: 186.9678.
(4-(Trifluoromethyl)phenyl)methanol (2a12):[6h] Following
GP-I, 4-trifluoromethyl benzaldehyde 1a12 (174 mg, 1.0 mmol,
1.0 equiv.) afforded 4-(trifluoromethyl)phenyl)methanol 2a12 (168
1
mg, 95%). H NMR (500 MHz, DMSO-d6): 4.62 (2H, d, J = 5.0
Hz), 5.48 (1H, t, J = 5.7 Hz), 7.55 (2H, d, J = 8.2 Hz), 7.68 (2H, d,
J = 8.2 Hz); 13C (100 MHz, DMSO-d6): 62.3,123.1, 124.9, 125.9,
126.9, 127.3, 127.7, 147.5; HRMS (ESI) calcd for
C8H7F3O[M+H]+: 177.0449; Found: 177.0449.
2-Hydroxybenzyl alcohol (2a20):[6k] Following GP-I, 2-
hydroxybenzaldehyde 1a20 (122 mg, 1.0 mmol, 1.0 equiv.)
afforded 2-hydroxy benzyl alcohol 2a20 (116 mg, 93%) as a
colorless liquid. 1H NMR (500 MHz, DMSO-d6): 4.45 (2H, s),
4.93 (1H, br s), 6.79 (2H, t, J = 10.8 Hz), 7.02-7.05 (1H, m), 7.28
(1H, d, J = 6.7 Hz), 9.28 (1H, s); 13C (100 MHz, DMSO-d6): 58.3,
114.5, 118.6, 127.2, 127.3, 128.5, 154.1; HRMS (ESI) calcd for
C7H8O2 [M+H]+: 125.0524; Found: 125.0523.
(4-Azidophenyl)methanol (2a13):[21] Following GP-I, 4-
azidobenzaldehyde 1a13 (146 mg, 1.0 mmol, 1.0 equiv.) afforded
(4-azidophenyl)methanol 2a13 (134 mg, 90%) as a straw yellow
1
solid. H NMR (400 MHz, DMSO-d6): 4.47 (2H, d, J = 5.9 Hz),
5.22 (1H, t, J = 5.9 Hz), 7.06 (2H, d, J = 8.3 Hz), 7.25 (2H, d, J =
8.3 Hz); 13C (100 MHz, DMSO-d6): 62.3, 118.7, 128.1, 137.6,
139.6; HRMS (ESI) calcd for C7H7N3O[M+H]+: 150.0589; Found:
150.0588.
2-Chlorobenzyl alcohol (2a21):[6b] Following GP-I, 2-
chlorobenzaldehyde 1a21 (140 mg, 1.0 mmol, 1.0 equiv.)
afforded 2-chlorobenzyl alcohol 2a21(114 mg, 80%) as a straw
yellow liquid. 1H NMR (500 MHz, DMSO-d6): 4.50 (2H, d, J =
5.65 Hz), 5.35 (1H, t, J = 5.65Hz), 7.16-7.12 (1H, m), 7.26-7.21
(2H, m), 7.47 (1H, d, J = 7.55 Hz); 13C (100 MHz, DMSO-d6):
60.5, 127.1, 128.2, 128.3, 128.8, 131.2, 139.6HRMS (ESI) calcd
for C7H7ClO[M+H]+: 143.0185; Found: 143.0183.
(4-(methoxymethoxy)phenyl)methanol (2a14): Following
GP-I, 4-(methoxymethoxy)benzaldehyde1a14 (166 mg, 1.0 mmol,
1.0 equiv.) afforded (4-(methoxymethoxy)phenyl)methanol 2a14
(164 mg, 96%) as a colourless liquid. 1H NMR (400 MHz,
CDCl3): 3.46 (3H, s), 4.56 (2H, s), 5.15 (2H, s), 7.00 (2H, d, J =
8.8 Hz), 7.25 (2H, d, J = 8.3 Hz); 13C (100 MHz, CDCl3): 55.9,
64.6, 94.5, 116.7, 128.5, 134.7, 156.7; HRMS (ESI) calcd for
C9H12O3 [M+H]+: 169.0786; Found: 169.0784.
2-Fluorobenzyl alcohol (2a22):[6g] Following GP-I, 2-
flurobenzaldehyde 1a22 (124 mg, 1.0 mmol, 1.0 equiv.) afforded
2-fluorobenzyl alcohol 2a22 (108 mg, 86%) as a colorless liquid.
1H NMR (500 MHz, DMSO-d6): 4.55 (2H, d, J = 5.7 Hz), 5.32-
5.29 (1H, m), 7.13-7.09 (1H, m), 7.18-7.15 (1H, m), 7.30-7.26
(1H, m), 7.48-7.45 (1H, m); 13C (125 MHz, DMSO-d6): 56.7, 56.8,
114.7, 114.9, 124.2, 124.3, 128.7, 128.8, 129.1, 129.2, 129.2,
129.2, 158.5, 160.9; HRMS (ESI) calcd for C7H7FO[M+H]+:
127.0481; Found: 127.0479.
4-(hydroxymethyl)phenyl
methanesulfonate
(2a15):
Following GP-I, 4-formylphenyl methanesulfonate 1a15 (200 mg,
1.0 mmol, 1.0 equiv.) afforded 4-(hydroxymethyl)phenyl
methanesulfonate 2a15 (190 mg, 94%) as a pale yellow liquid. 1H
NMR (400 MHz, CDCl3): 3.12 (3H, s), 4.65 (2H, s), 7.27-7.23
(2H, m), 7.41-7.36 (2H, m); 13C (100 MHz, CDCl3): 37.4, 64.2,
122.1, 128.5, 140.4, 148.5; HRMS (ESI) calcd for C8H10O4S
[M+H]+: 203.0300; Found: 203.0301.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700887
European Journal of Organic Chemistry
FULL PAPER
2-Chloro-4-fluorobenzyl alcohol (2a23):[22] Following GP-I,
2-chloro-4-flurobenzaldehyde 1a23 (158 mg, 1.0 mmol, 1.0
equiv.) afforded 2-chloro-4-fluorobenzyl alcohol 2a23 (140 mg,
Furan-2-ylmethanol (2a30):[6b] Following GP-I, furan-2-
carbaldehyde 1a30 (96 mg, 1.0 mmol, 1.0 equiv.) afforded furan-
2-ylmethanol 2a30 (88 mg, 90%) as a colorless liquid. 1H NMR
(500 MHz, DMSO-d6): 4.64 (2H, d, J = 5.9 Hz), 5.9 (1H, t, J = 5.9
Hz), 7.55 (1H, d, J = 3.4 Hz), 8 (1H, d, J = 3.4 Hz); 13C (100 MHz,
DMSO-d6): 55.7, 106.9, 110.3, 142.1, 155.5; HRMS (ESI) calcd
for C5H6O2[M+H]+: 99.0368; Found: 99.0367.
1
87%) as a colorless liquid. H NMR (500 MHz, DMSO-d6): 4.53
(2H, d, J = 5.0 Hz), 5.39 (1H, t, J = 5.7 Hz), 7.32-7.25 (2H, m),
7.48 (1H, t, J = 8.2 Hz); 13C (125 MHz, DMSO-d6): 56.4, 56.4,
115.3, 115.6, 124.5, 128.4, 128.5, 130.2, 130.3, 132.1, 132.2,
158.3, 160.8; HRMS (ESI) calcd for C7H6FClO[M+H]+: 161.5733;
Found: 161.5734.
9-(3-(Dimethylamino)propyl)-6-(hydroxymethyl)-9H-
carbazole-3-carbaldehyde (2a31): Following GP-I, 9-(3-
3,4-Difluorobenzyl alcohol (2a24):[23] Following GP-I, 3,4-
diflurobenzaldehyde 1a24 (142 mg, 1.0 mmol, 1.0 equiv.)
afforded 3,4-difluorobenzyl alcohol 2a24 (128 mg, 90%) as a
(dimethylamino)propyl)-9H-carbazole-3,6-dicarbaldehyde
(308 mg, 1.0 mmol, 1.0 equiv.) afforded
(dimethylamino)propyl)-6-(hydroxymethyl)-9H-carbazole-3-
1a31
9-(3-
1
colorless liquid. H NMR (500 MHz, DMSO-d6): 4.46 (2H, d, J =
carbaldehyde 2a31 (304 mg, 98%) as a pale yellow liquid. 1H
NMR (400 MHz, DMSO-d6): 1.92 (2H, t, J = 6.8 Hz), 2.12 (6H, s),
2.19 (2H, t, J = 6.7 Hz), 4.80 (2H, t, J = 6.7 Hz), 4.68 (2H, s),
5.22 (1H, br s), 7.51 (1H, d, J = 8.4 Hz), 7.66 (2H, d, J = 8.4 Hz),
7.76 (1H, d, J = 8.4 Hz), 7.98 (1H,d, J = 10.1 Hz), 8.21 (1H, s),
8.74(1H, s), 10.06 (1H, s); 13C (100 MHz, DMSO-d6): 26.3, 40.5,
45.0, 55.8, 63.3, 109.7, 109.8, 118.1, 122.0, 122.2, 124.1, 126.0,
126.2, 128.2, 134.6, 140.0, 143.8, 191.8; HRMS (ESI) calcd for
C19H22N2O2[M+H]+: 311.1681; Found: 311.1682.
6.3 Hz), 5.39 (1H, t, J = 6.3 Hz), 7.13-7.11 (1H, m), 7.40-7.37
(2H, m); 13C (100 MHz, DMSO-d6): 61.8, 115.1, 115.3,
116.9,117.1, 122.8, 122.8, 122.8, 122.9, 140.4, 140.5, 140.6,
147.1, 147.2, 148.2, 148.3, 149.5, 149.6, 150.6, 150.7; HRMS
(ESI) calcd for C7H6F2O[M+H]+: 145.0387; Found: 145.0389.
1-Naphthalenemethanol (2a25):[6j] Following GP-I, α-
napthaldehyde 1a25 (156 mg, 1.0 mmol, 1.0 equiv.) afforded 1-
naphthalenemethanol 2a25 (136 mg, 86%) as a colorless liquid.
1H NMR (400 MHz, DMSO-d6): 4.94 (2H, d, J = 4.2 Hz), 5.30
(1H, br s), 7.39-7.54 (4H, m), 7.75 (1H, d, J = 7.9 Hz), 7.85 (1H,
d, J = 8.6 Hz), 8.04 (1H, d, J = 7.3 Hz); 13C (100 MHz, DMSO-
d6): 61.2, 123.7, 124.2, 125.4, 125.6, 125.9, 127.3, 128.3, 130.7,
133.2, 137.8; HRMS (ESI) calcd for C11H10O[M+H]+: 159.0732;
Found: 159.0730
(9-(3-(dimethylamino)propyl)-9H-carbazole-3,6-
diyl)dimethanol
(dimethylamino)propyl)-9H-carbazole-3,6-dicarbaldehyde
(308 mg, 1.0 mmol, 1.0 equiv.) afforded
(dimethylamino)propyl)-9H-carbazole-3,6-diyl)dimethanol
(2a32):
Following
GP-I,
9-(3-
1a31
(9-(3-
2a32
(294 mg, 90%) as a pale yellow liquid. 1H NMR (400 MHz,
DMSO-d6): 1.92 (2H, t, J = 6.8 Hz), 2.15 (6H, s), 2.19 (2H, t, J =
6.8 Hz), 4.42 (2H, t, J = 6.4 Hz), 4.75 (4H, d, J = 3.0 Hz), 5.27
(2H, br s), 7.48 (2H, d, J = 9.3 Hz), 7.57 (2H, d, J = 8.3 Hz), 8.15
(2H, s); 13C (100 MHz, DMSO-d6): 26.5, 39.3, 45.0, 56.0, 63.6,
108.7, 118.4, 121.9, 125.0, 126.2, 132.9, 139.6; HRMS (ESI)
calcd for C19H24N2O2[M+H]+: 313.1838; Found: 313.1838.
2-Naphthalenemethanol (2a26):[6d] Following GP-I, 2–
naphthaldehyde 1a26 (156 mg, 0.50 mmol, 1.0 equiv.) afforded 2-
naphthalenemethanol 2a26 (136 mg, 86%) as a colorless liquid.
1H NMR (500 MHz, DMSO-d6): 5.65 (2H, d, J = 5.7 Hz), 5.37
(1H, t, J = 5.7 Hz), 7.38-7.44 (3H, m), 7.78-7.82 (4H, m);13C (100
MHz, DMSO-d6): 63.2, 124.4, 125.4, 125.5, 126.1, 127.6, 127.7,
132.3, 133.1, 140.3; HRMS (ESI) calcd for C11H10O[M+H]+:
159.0732; Found: 159.0731.
(R)-3-(1-benzyl-1H-indol-3-yl)butan-1-ol (2a33): Following
GP-I, (R)-3-(1-benzyl-1H-indol-3-yl)butanal 1a32 (276 mg, 1.0
mmol, 1.0 equiv.) afforded (R)-3-(1-benzyl-1H-indol-3-yl)butan-
(4,8-Dihydropyren-1-yl)methanol (2a27):[24] Following GP-I,
pyrenecarbaldehyde 1a27 (232 mg, 1.0 mmol, 1.0 equiv.)
afforded (4,8-dihydropyren-1-yl)methanol 2a27 (212 mg, 91%) as
a colorless liquid. 1H NMR (500 MHz, DMSO-d6): 1.98 (1H, br s),
5.39 (2H, s), 7.99-8.05 (4H, m), 8.14 (2H, t, J = 7.6 Hz), 8.20 (2H,
t, J = 6.7 Hz), 8.36 (1H, d, J = 9.2 Hz); 13C (100 MHz, DMSO-d6):
63.9, 123.3, 124.9, 125.1, 125.2, 125.5, 126.2, 126.3, 127.7,
128.1, 129.1, 131.1, 131.5, 130.9, 131.6, 134.3; HRMS (ESI)
calcd for C17H14O[M+H]+: 235.1045; Found: 235.1048.
1
1-ol 2a33 (256 mg, 92%) as a brown liquid. H NMR (500 MHz,
CDCl3): 1.40 (3H, d, J = 6.7 Hz), 1.96-1.92 (1H, m), 2.08-2.03
(1H, m), 3.26-3.22 (1H, m), 3.70-3.66 (2H, m), 5.28 (2H, s), 6.92
(1H, s), 7.13-7.10 (3H, m), 7.17 (1H, t, J = 6.7 Hz), 7.31-7.25
(4H, m), 7.68 (1H, d, J = 8.4 Hz); 13C (125 MHz, CDCl3): 22.0,
27.9, 40.6, 50.0, 61.8, 109.9, 119.0, 119.7, 121.1, 121.9, 124.5,
126.8, 127.5, 127.7, 128.9, 137.1, 137.9; HRMS (ESI) calcd for
C19H21NO[M+H]+: 280.1623; Found: 280.1622.
Trans-cinnamyl alcohol (2a34):[6f] Following GP-I, trans-
cinnamaldehyde 1a33 (132 mg, 1.0 mmol, 1.0 equiv.) afforded
Pyridine-4-ylmethanol (2a28):[6k] Following GP-I, pyridine-4-
carbaldehyde 1a28 (106 mg, 1.0 mmol, 1.0 equiv.) afforded
1
trans-cinnamyl alcohol 2a34 (130 mg, 98%) as a white solid. H
1
pyridine-4-ylmethanol 2a28 (96 mg, 88%) as a colorless liquid. H
NMR (400 MHz, DMSO-d6): 4.06-4.09 (2H, m), 4.82 (1H, t, J =
5.5 Hz), 6.30-6.36 (1H, m), 6.51 (1H, d, J = 15.8 Hz), 7.18 (1H, t,
J = 7.32 Hz), 7.28 (2H, t, J = 7.3 Hz), 7.37 (2H, d, J = 7.3 Hz);
13C (100 MHz, DMSO-d6): 61.4, 126.0, 127.1, 128.4, 128.3,
130.7, 136.9; HRMS (ESI) calcd for C9H10O[M+H]+: 135.0732;
Found: 135.0736.
NMR (400 MHz, DMSO-d6): 4.48 (2H, d, J = 6.1 Hz), 5.38 (1H, t,
J = 6.1 Hz), 7.27 (2H, d, J = 4.9 Hz), 8.46 (2H, d, J = 4.9 Hz);
13C (100 MHz, DMSO-d6): 61.4, 121.1, 149.3, 151.5; HRMS
(ESI) calcd for C6H7NO[M+H]+: 110.0528; Found: 110.0526.
Thiazol-2-ylmethanol (2a29):[25] Following GP-I, thiazole-2-
carbaldehyde 1a29 (112 mg, 1.0 mmol, 1.0 equiv.) afforded
(3-phenyloxiran-2-yl)methanol (2a35):[6f] Following GP-I, 3-
phenyloxirane-2-carbaldehyde 1a34 (148 mg, 1.0 mmol, 1.0
equiv.) afforded (3-phenyloxiran-2-yl)methanol 2a35 (140 mg,
92%) as a colourless liquid. 1H NMR (400 MHz, CDCl3): 2.67
(1H, br s), 3.23-3.21 (1H, m), 3.76 (1H, d, J = 11.2 Hz), 3.91 (1H,
d, J = 2.0 Hz), 4.02 (1H, d, J = 12.7 Hz), 7.36-7.25 (5H, m); 13C
(100 MHz, CDCl3): 55.8, 61.4, 62.7, 125.8, 128.4, 128.6, 136.7;
1
thiazol-2-ylmethanol 2a29 (104 mg, 91%) as a colorless liquid. H
NMR (500 MHz, DMSO-d6): 4.64 (2H, d, J = 5.9 Hz), 5.9 (1H, t, J
= 5.9 Hz), 7.55 (1H, d, J = 3.4 Hz), 8 (1H, d, J = 3.4 Hz); 13C
(100 MHz, DMSO-d6): 60.9, 119.5, 142.3, 173.7; HRMS (ESI)
calcd for C4H5NOS[M+H]+: 116.0092; Found: 116.0090.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700887
European Journal of Organic Chemistry
FULL PAPER
HRMS (ESI) calcd for C9H10O2[M+H]+: 151.0681; Found:
151.0680.
6.1 Hz), 4.52-4.56 (1H, m), 4.85 (1H, d, J = 3.6 Hz), 6.63 (2H, dd,
J = 1.8, 6.7 Hz), 7.06 (2H, t, J = 7.9 Hz), 9.12 (1H, s); 13C (125
MHz, DMSO-d6): 25.9, 67.7, 114.6, 126.4, 137.6, 159.9; HRMS
(ESI) calcd for C8H10O2[M+H]+: 139.0681; Found: 139.0679.
Cyclohex-3-en-1-ylmethanol (2a36):[26] Following GP-I, 3-
cyclohexenecarbaxaldehyde 1a35 (110 mg, 1.0 mmol, 1.0 equiv.)
afforded cyclohex-3-en-1-ylmethanol 2a36 (88 mg, 78%) as a
1-(4-Methoxyphenyl)ethanol (5e):[6e] Following GP-II, 4-
methoxyacetophenone 4e (150 mg, 1.0 mmol, 1.0 equiv.)
1
colorless liquid. H NMR (500 MHz, CDCl3): 1.23-1.15 (1H, m),
1.70-1.62 (2H, m), 1.78-1.75 (1H, m), 2.06-1.98 (3H, m), 3.34-
afforded 1-(4-methoxyphenyl)ethanol 5e (112 mg, 74%) as a
1
3.29 (2H, m ), 4.52 (1H, t, J = 5.0 Hz), 5.66 (2H, s); 13C(100 MHz, colorless liquid. H NMR (500 MHz, DMSO-d6): 1.23 (3H, d, J =
CDCl3): 24.3, 25.1, 27.9, 36.1, 65.8, 126.3, 126.9; HRMS (ESI)
calcd for C7H12O[M+H]+: 113.1045; Found: 113.1044.
5.9 Hz), 3.65 (3H, d, J = 10.0 Hz), 4.60 (1H, d, J = 3.4 Hz), 4.94
(1H, d, J = 2.5 Hz), 6.78 (2H, t, J = 5.0 Hz), 7.17 (2H, t, J = 5.0
Hz); 13C (100 MHz, DMSO-d6): 25.9, 55.0, 67.7, 113.3, 126.4,
139.4, 158.0;HRMS (ESI) calcd for C9H12O2[M+H]+: 153.0837;
Found: 153.0834.
Cyclohexylmethanol
(2a37):[6f]
Following
GP-I,
cyclohexanecarbaxaldehyde 1a36 (112 mg, 1.0 mmol, 1.0 equiv.)
afforded cyclohexylmethanol 2a37 (88 mg, 78%) as a colorless
1
liquid. H NMR (500 MHz, CDCl3): 0.87-0.95 (2H, m), 1.11-1.28
1-(4-aminophenyl)ethanol (5f):[6e] Following GP-II, 4-
aminoacetophenone 4f (135 mg, 1.0 mmol, 1.0 equiv.) afforded
1-(4-aminophenyl)ethanol 5f (114 mg, 80%) as a deep brown
(3H, m), 1.43-1.50 (1H, m), 1.65-1.75 (5H, m), 2.0 (1H, t, J =
11.4 Hz), 3.40 (2H, d, J = 3.3 Hz); 13C(100 MHz, CDCl3): 26.1,
26.8, 29.8, 40.7, 68.9; HRMS (ESI) calcd for C7H14O[M+H]+:
115.1045; Found: 115.1042.
1
liquid. H NMR (500 MHz, DMSO-d6): 1.26 (3H, d, J = 5.9 Hz),
4.57-4.52 (1H, m), 4.79 (1H, d, J = 2.5 Hz), 4.87 (2H, br s), 6.50
(2H, d, J = 8.4 Hz), 6.98 (2H, d, J = 8.4 Hz); 13C (125 MHz,
DMSO-d6): 25.8, 67.9, 113.5, 126.0, 134.6, 147.2; HRMS (ESI)
calcd for C8H11NO [M+H]+: 138.0841; Found: 138.0843.
Ethanol (2a38): Following GP-I, acetaldehyde 1a37 (44 mg,
1.0 mmol, 1.0 equiv.) afforded ethanol 2a38 (38 mg, 84%) as a
1
colorless liquid. H NMR (500 MHz, CDCl3): 0.85 (3H, t, J = 6.9
Hz), 3.28-3.33 (2H, m), 4.60 (1H, t, J = 4.4 Hz); 13C (125 MHz,
CDCl3): 17.5, 57.1; HRMS (ESI) calcd for C2H6O[M+H]+:
47.0419; Found: 47.0416.
2,2,2-trifluoro-1-phenylethanol (5g):[6e] Following GP-II,
2,2,2-trifluoro acetophenone 4g (174 mg, 1.0 mmol, 1.0 equiv.)
afforded 2,2,2-trifluoro-1-phenylethanol 5g (152 mg, 84%) as a
1
colorless liquid. H NMR (400 MHz, DMSO-d6): 5.17 (1H, q, J =
Hexan-1-ol (2a39):[6b] Following GP-I, hexanal 1a38 (100 mg,
1.0 mmol, 1.0 equiv.) afforded hexanol 2a39 (82 mg, 80%) as a
7.3 Hz), 7.44-7.38 (3H, m), 7.54 (2H, d, J = 6.7 Hz); 13C (100
MHz, DMSO-d6): 70.4, 70.7, 71.0, 71.3, 123.8, 126.7, 127.7,
128.3, 128.9, 136.1; HRMS (ESI) calcd for C8H7F3O[M+H]+:
177.0449; Found: 177.0450.
1
colorless liquid. H NMR (500 MHz, DMSO-d6): 0.87-0.85 (3H,
m), 1.30-1.22 (6H, m), 1.43-1.37 (2H, m), 3.39-3.35 (2H, m),
4.31 (1H, t, J = 5.7 Hz); 13C (100 MHz, DMSO-d6): 13.8, 22.1,
25.2, 31.2, 32.5, 60.7; HRMS (ESI) calcd for C6H14O[M+H]+:
103.1045; Found: 103.1039.
Diphenylmethanol (5h):[6j] Following GP-II, benzophenone
4h (182 mg, 1.0 mmol, 1.0 equiv.) afforded diphenylmethanol 5f
1
(175 mg, 95%) as a white solid. H NMR (500 MHz, DMSO-d6):
1-Phenylethanol (5a):[6e] Following GP-II, acetophenone 4a
(120 mg, 1.0 mmol, 1.0 equiv.) afforded 1-phenylethanol 5a (92
5.64 (1H, d, J = 6.9 Hz), 5.81 (1H, d, J = 3.8 Hz), 7.15-7.12 (2H,
m), 7.25-7.22 (2H, m), 7.31 (4H, d, J = 6.9 Hz); 13C (100 MHz,
DMSO-d6): 74.2, 126.2, 126.6, 128.0, 145.7; HRMS (ESI) calcd
for C13H12O[M+H]+: 185.0888; Found: 185.0886.
1
mg, 75%) as a colorless liquid. H NMR (400 MHz, DMSO-d6):
1.29 (3H, d, J = 6.7 Hz), 4..70 (1H, t, J = 4.9 Hz), 5.12 (1H, d, J
= 3.6 Hz), 7.16 (1H, t, J = 6.7 Hz), 7.33-7.25 (4H, m); 13C (100
MHz, DMSO-d6): 25.9, 68.2, 125.3, 126.5, 127.9, 147.4; HRMS
(ESI) calcd for C8H10O[M+H]+: 123.0732; Found: 123.0730.
1,2-Diphenylpent-4-ene-1,2-diol (5i):[29] Following GP-II, 4i
(252 mg, 1.0 mmol, 1.0 equiv.) afforded 1,2-diphenylpent-4-ene-
1
1,2-diol 5g (204 mg, 80%) as a white solid. H NMR of syn
1-(p-Tolyl)ethanol
(5b):[27]
Following
GP-II,
4-
isomer (400 MHz, CDCl3): 2.53 (2H, br s), 2.76 (1H, dd, J = 4.9,
9.2 Hz), 2.94 (1H, dd, J = 5.5, 8.7 Hz), 4.79 (1H, s), 5.09 (1H, d,
J = 10.3 Hz), 5.17 (1H, d, J = 17.1 Hz), 5.63-5.52 (1H, m), 6.99
(2H, dd, J = 1.2, 6.1 Hz ), 7.21-7.12 (8H, m); 13C of syn isomer
(100 MHz, CDCl3): 42.7, 78.5, 80.6, 119.9, 126.7, 127.0, 127.6,
127.7, 127.9, 128.8, 133.5, 139.5, 141.7;HRMS (ESI) calcd for
C17H18O2 [M+H]+: 255.1307; Found: 255.1309.
methylacetophenone 4b (134 mg, 1.0 mmol, 1.0 equiv.) afforded
1
1-(p-tolyl)ethanol 5b (100 mg, 73%) as a pale yellow liquid. H
NMR (500 MHz, DMSO-d6): 1.20 (3H, t, J = 3.8 Hz), 2.15 (3H, s),
4.55-4.59 (1H, m), 4.95 (1H, d, J = 4.4 Hz), 6.97 (2H, d, J = 7.6
Hz), 7.10 (2H, d, J = 7.6 Hz); 13C (100 MHz, DMSO-d6): 20.6,
25.9, 67.9, 125.2, 128.5, 135.4, 143.4; HRMS (ESI) calcd for
C9H12O[M+H]+: 137.0888; Found: 137.0884.
1,2-Diphenylethane-1,2–diol (5j):[10c] Following GP-II, 2-
hydroxy-1,2-diphenylethanone 4j (212 mg, 1.0 mmol, 1.0 equiv.)
afforded 1,2-diphenylethane-1,2 –diol 5j (184 mg, 86%) as a
white solid.1H NMR of dl isomer (500 MHz, DMSO-d6): 4.57 (2H,
d, J = 1.3 Hz), 5.19 (2H, d, J = 1.2 Hz), 7.24-7.18 (10H, m); 13C
dl isomer (100 MHz, DMSO-d6): 76.9, 126.5, 127.2, 127.3,
143.2; HRMS (ESI) calcd for C14H14O2 [M+H]+: 215.0994; Found:
215.0991.
1-(4-Bromophenyl)ethanol (5c):[6d] Following GP-II, 4-
bromoacetophenone 4c (200 mg, 1.0 mmol, 1.0 equiv.) afforded
1-(4-bromophenyl)ethanol 5c (164 mg, 82%) as a straw yellow
1
liquid. H NMR (400 MHz, DMSO-d6): 1.22 (3H, d, J = 6.7 Hz),
4.62-4.65 (1H, m), 5.16 (1H, d, J = 4.3 Hz), 7.22 (2H, d, J = 8.5
Hz), 7.41 (2H, dd, J = 1.8, 6.9 Hz); 13C (100 MHz, DMSO-d6):
25.7, 67.4, 119.3, 127.5, 130.8, 146.7; HRMS (ESI) calcd for
C8H9BrO[M+H]+: 200.9837; Found: 200.9834.
1,2-Diphenylethane-1,2–diol (5j):[10c] Following GP-II, benzil
4k (210 mg, 1.0 mmol, 1.0 equiv.) afforded 1,2-diphenylethane-
1,2-diol 5j (176 mg, 82%) as a white solid.
4-(1-Hydroxyethyl)phenol (5d):[28] Following GP-II, 4-
hydroxyacetophenone 4d (136 mg, 1.0 mmol, 1.0 equiv.)
afforded 4-(1-hydroxyethyl)phenol 5d (106 mg, 77%) as a
1
colorless liquid. H NMR (400 MHz, DMSO-d6): 1.21 (3H, d, J =
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700887
European Journal of Organic Chemistry
FULL PAPER
(E)-1,3-diphenylprop-2-en-1-ol (5k): Following GP-II, (E)-
chalcone 4l (208 mg, 1.0 mmol, 1.0 equiv.) afforded (E)-1,3-
diphenylprop-2-en-1-ol 5k (194 mg, 86%) as a white solid.1H
NMR (400 MHz, DMSO-d6): 5.25 (1H, t, J = 5.5 Hz), 5.62 (1H, d,
J = 4.2 Hz), 6.39 (1H, dd, J = 6.1, 9.8 Hz), 6.63 (1H, d, J = 15.9
Hz), 7.24 (2H, dd, J = 7.9, 8.0 Hz), 7.36-7.29 (4H, m), 7.41 (4H, t,
J = 6.70 Hz); 13C (100 MHz, DMSO-d6): 73.1, 126.1, 126.2,
126.8, 126.7, 128.1, 128.5, 133.6, 136.6, 144.4; HRMS (ESI)
calcd for C15H14O [M+H]+: 211.1045; Found: 211.1044.
(dl/meso, 60:40 ratio) (100 MHz, CDCl3): 25.1, 25.2, 78.7, 78.9,
127.5, 127.4, 127.3, 127.2, 127.1, 127.0, 143.6, 143.9; HRMS
(ESI) calcd for C16H18O2[M+H]+: 243.1207; Found: 243.1205.
2,3-Di-p-tolylbutane-2,3-diol (6b):[9] Following GP-II, 4-
methylacetophenone 4b (134 mg, 1.0 mmol, 1.0 equiv.) afforded
2,3-di-p-tolylbutane-2,3-diol 6b (70 mg, 26%) as a white solid. 1H
NMR (dl/meso, 60:40 ratio) (500 MHz, CDCl3): 1.46 (6H, s), 1.53
(6H, s), 2.32 (12H, d, J = 6.7 Hz), 2.23 (2H, br s), 2.58 (2H, br s),
7.09-7.04 (14H, m), 7.14 (2H, d, J = 7.6 Hz); 13C (dl/meso, 60:40
Phenyl(3-phenyloxiran-2-yl)methanol (5l): Following GP-II, ratio) (100 MHz, CDCl3): 21.0, 21.1, 25.2, 25.4, 78.7, 78.9, 127.0,
phenyl(3-phenyloxiran-2-yl)methanone 4m (224 mg, 1.0 mmol,
1.0 equiv.) afforded phenyl(3-phenyloxiran-2-yl)methanol 5l (208
mg, 88%) as a colourless liquid. 1H NMR (500 MHz, DMSO-d6):
2.66 (1H, br s), 3.31-3.29 (1H, m), 4.01 (1H, d, J = 2.0 Hz), 4.72
(1H, s), 7.25 (2H, d, J = 7.3 Hz), 7.35-7.29 (4H, m), 7.38 (2H, t, J
= 6.9 Hz), 7.43 (2H, t, J = 7.4 Hz) ; 13C (100 MHz, DMSO-d6):
57.0, 65.8, 73.5, 125.9, 126.3, 126.7, 128.4, 128.5, 128.7, 128.9,
136.5, 140.3; HRMS (ESI) calcd for C15H14O2 [M+H]+: 227.0994;
Found: 227.0993.
127.4, 128.0, 128.1, 136.5, 136.7, 140.7, 141.1; HRMS (ESI)
calcd for C18H22O2 [M+H]+: 271.1620; Found: 271.1618.
1-(4-(Hydroxymethyl)phenyl)ethanone (8):[6h] Following
GP-I, 4-acetylbenzaldehyde 7 (148 mg, 1.0 mmol, 1.0 equiv.)
afforded 1-(4-(hydroxymethyl)phenyl)ethanone 8 (144 mg, 96%)
as a colorless liquid. 1H NMR (300 MHz, DMSO-d6): 2.52 (3H, s),
4.53 (2H, d, J = 5.9 Hz), 5.32 (1H, t, J = 5.9 Hz), 7.41 (2H, d, J =
8.1 Hz), 7.87 (2H, dd, J = 1.8, 4.4 Hz); 13C (125 MHz, DMSO-d6):
26.7, 62.5, 126.3, 128.2, 135.5, 148.2, 197.6; HRMS (ESI) calcd
for C9H10O2 [M+H]+: 151.0681; Found: 151.0684
1-(Pyridin-2-yl)ethanol (5m):[27] Following GP-II, 2-
acetylpyridine 4n (120 mg, 1.0 mmol, 1.0 equiv.) afforded 1-
(pyridin-2-yl)ethanol 5m (98 mg, 80%) as a pale yellow liquid. 1H
NMR (400 MHz, DMSO-d6): 1.44 (3H, d, J = 6.7 Hz), 4.85-4.79
(1H, m), 5.46 (1H, d, J = 4.3 Hz), 7.31-7.28 (1H, m), 7.60 (1H, d,
J = 7.9 Hz), 7.86-7.82 (1H, m), 8.55-8.54 (1H, m); 13C (100 MHz,
DMSO-d6): 24.2, 69.4, 119.3, 121.8, 136.6, 148.2, 165.6; HRMS
(ESI) calcd for C7H9NO[M+H]+: 124.0684; Found: 124.0680.
1-(4-(Hydroxymethyl)phenyl)ethanol (9):[31] Following GP-
II, 4-acetylbenzaldehyde 7 (148 mg, 1.0 mmol, 1.0 equiv.)
afforded 1-(4-(hydroxymethyl)phenyl)ethanol 9 (124 mg, 82%)
1
as a brown liquid. H NMR (400 MHz, DMSO-d6): 1.13 (3H, d, J
= 6.1 Hz), 4.29 (2H, d, J = 5.9 Hz), 4.49-4.51 (1H, m), 4.92-4.96
(2H, m), 7.08 (4H, dd, J = 8.0, 7.9 Hz); 13C (100 MHz, DMSO-
d6): 26.1, 63.0, 68.1, 125.1, 126.3, 140.8, 145.9; HRMS (ESI)
calcd for C9H12O2 [M+H]+: 153.0837; Found: 153.0835.
Ethyl 3-hydroxybutanoate (5n): Following GP-II, ethyl 3-
oxobutanoate 4o (130 mg, 1.0 mmol, 1.0 equiv.) afforded ethyl
1-(4-(Hydroxymethyl)phenyl)ethanol (9):[31] Following GP-
II, 1-(4-(hydroxymethyl)phenyl)ethanone 8 (150 mg, 1.0 mmol,
1.0 equiv.) afforded 1-(4-(hydroxymethyl)phenyl)ethanol 9 (130
mg, 86%) as a brown liquid.
1
3-hydroxybutanoate 5n (104 mg, 74%) as a colorless liquid. H
NMR (400 MHz, DMSO-d6): 1.00 (3H, d, J = 6.1 Hz), 1.09 (3H, t,
J = 6.7 Hz), 2.25 (2H, t, J = 7.9 Hz), 3.49 (1H, s), 3.98-3.90 (2H,
m), 4.63 (1H, d, J = 4.9 Hz); 13C (125 MHz, DMSO-d6): 14.1,
22.3, 43.9, 59.6, 63.4, 171.1; HRMS (ESI) calcd for
C6H12O3[M+H]+: 133.0786; Found: 133.0788.
3-Hydroxyindolin-2-one (11a):[18b] Following GP-III, isatin
10a (148 mg, 1.0 mmol, 1.0 equiv.) afforded 3-hydroxyindolin-2-
one 11a (140 mg, 94%) as a white solid. 1H NMR (500 MHz,
CDCl3): 3.18( 1H, br s), 5.08 (1H, s), 6.86 (1H, d, J = 7.6 Hz),
7.09 (1H, t, J = 7.5 Hz), 7.28 (1H, d, J = 7.6 Hz), 7.44 (1H, d, J =
6.9 Hz); 13C (100 MHz, CDCl3): 70.3, 110.4, 123.5, 125.8, 130.2,
138.8, 141.1, 178.4; HRMS (ESI) calcd for C8H7NO2 [M+H]+:
150.0477; Found: 150.0467.
Cyclohexanol (5o):[6e] Following GP-II, cyclohexanone 4p
(98 mg, 1.0 mmol, 1.0 equiv.) afforded cyclohexanol 5o (74 mg,
74%) as a colorless liquid.1H NMR (500 MHz, CDCl3): 0.97-1.11
(5H, m), 1.35 (1H, t, J = 4.2 Hz), 1.55 (2H, s), 1.70 (2H, s), 3.37
(1H, s), 3.74 (1H, br s); 13C (125 MHz, CDCl3): 24.0, 25.3, 35.1,
69.6; HRMS (ESI) calcd for C6H12O[M+H]+: 101.0888; Found:
101.0883.
3-Hydroxy-1-methylindolin-2-one (11b):[18b] Following GP-
III, N-methyl isatin 10b (160 mg, 1.0 mmol, 1.0 equiv.) afforded
3-hydroxy-1-methylindolin-2-one 11b (160 mg, 98%) as a pale
yellow solid. 1H NMR (500 MHz, DMSO-d6): 2.98 ( 3H, s), 4.80
(1H, d, J = 7.6 Hz ), 6.15 (1H, d, J = 7.1 Hz), 6.84 (1H, d, J = 7.6
Hz), 6.95 (1H, t, J = 6.7 Hz), 7.25-7.19 (2H, m); 13C (100 MHz,
DMSO-d6): 25.7, 68.7, 108.3, 122.1, 124.4, 128.5, 129.0, 143.7,
175.9; HRMS (ESI) calcd for C9H9NO2 [M+H]+: 164.0633; Found:
164.0631.
Cyclopentanol (5p):[30] Following GP-II, cyclopentanone 4q
(84 mg, 1.0 mmol, 1.0 equiv.) afforded cyclopentanol 5p (64 mg,
74%) as a colorless liquid. 1H NMR (500 MHz, CDCl3): 1.46-1.50
(4H, m), 1.66 (4H, t, J = 1.9 Hz), 2.89-3.04 (1H, m), 4.19 (1H, br
s); 13C (100 MHz, CDCl3): 23.2, 35.3, 73.6; HRMS (ESI) calcd
for C5H10O[M+H]+: 87.0732; Found: 87.0728.
Propan-2-ol (5q): Following GP-II, acetone 4r (60 mg, 0.50
mmol, 1.0 equiv.) afforded Propan-2-ol 5q (44 mg, 72%) as a
colorless liquid. 1H NMR (500 MHz, CDCl3): 1.0-1.05 (6H, m),
3.31-3.68 (1H, m), 3.83 (1H, br s); 13C (100 MHz, CDCl3): 25.0,
63.7; HRMS (ESI) calcd for C3H8O [M+H]+: 61.0575; Found:
61.0574.
1-Benzyl-5-chloro-3-hydroxyindolin-2-one
(11c):
Following GP-III, 5-chloro-N-benzyl isatin 10c (270 mg, 1.0
mmol, 1.0 equiv.) afforded 1-benzyl-5-chloro-3-hydroxyindolin-
2-one 11c (268 mg, 98%) as a white solid. 1H NMR (500 MHz,
DMSO-d6): 4.80 (2H, s), 5.05 ( 1H, d, J = 7.6 Hz), 6.48 (1H, d, J
= 7.6 Hz), 6.79 (1H, d, J = 7.5 Hz), 7.28-7.16 (6H, m), 7.33 (1H,
s); 13C (125 MHz, DMSO-d6): 42.6, 68.7, 110.5, 124.2, 126.6,
126.9, 127.2, 127.4, 128.7, 130.8, 135.9, 141.5, 175.8; HRMS
(ESI) calcd for C15H12ClNO2 [M+H]+: 274.0557; Found: 274.0564.
2,3-Diphenylbutane-2,3-diol (6a):[9] Following GP-II,
acetophenone 4a (120 mg, 1.0 mmol, 1.0 equiv.) afforded 2,3-
diphenylbutane-2,3-diol 6a (54 mg, 23%) as a white solid. 1H
NMR (dl/meso, 60:40 ratio) (500 MHz, CDCl3): 1.49 (6H, s), 1.57
(6H, s), 2.33 (2H, s), 2.64 (2H, s), 7.17-7.25 (20H, m); 13C
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10.1002/ejoc.201700887
European Journal of Organic Chemistry
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(11d):
Following GP-III, 5-fluoro-N-benzyl isatin 10d (254 mg, 1.0 mmol,
1.0 equiv.) afforded 1-benzyl-5-fluoro-3-hydroxyindolin-2-one
11d (254 mg, 99%) as a white solid. 1H NMR (400 MHz, CDCl3):
4.79 (2H, dd, J = 15.2, 15.3 Hz), 5.23 (1H, s), 5.59 (1H, br s),
6.56 (1H, dd, J = 4.9, 3.7 Hz), 6.83 (1H, t, J = 9.1 Hz), 7.27-7.15
(6H, m); 13C (125 MHz, CDCl3): 44.0, 69.9, 110.1, 110.2, 113.3,
113.5, 115.6, 115.8, 117.0, 117.2, 127.0, 127.3, 127.7, 127.9,
128.8, 128.9, 129.1, 129.2, 134.5, 135.0, 138.6, 139.4, 158.4,
160.8, 177.6; HRMS (ESI) calcd for C15H10FNO2 [M+H]+:
258.0696; Found: 258.0698.
1-benzyl-5-(trifluoromethoxy)-3-hydroxyindoline-2-one
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Acknowledgements ((optional))
We thank DST India for research funding. JD thanks DST for
a SwarnaJayanti fellowship. TM and SJ thank CSIR-India for
research fellowships.
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Keywords: Aldehyde · Chemoselective · Isatin · Ketone ·
Reduction · Zn
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
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Simple yet unknown! Aldehydes and
ketones can be easily reduced to the
corresponding alcohols using
Zn/NH4Cl, which is used for pinacol
coupling reactions. Chemoselective
reduction of aldehydes in the
presence of ketones is achieved.
Isatins can be efficiently reduced at
the C3 position.
Chemoselective reduction of
carbonyl compounds*
Tirtha Mandal, Snehasish Jana and
Jyotirmayee Dash*
Page No. – Page No.
Zinc-Mediated Efficient and Selective
Reduction of Carbonyl Compounds
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