Eco-friendly stereoselective reduction of α,β-unsaturated carbonyl compounds by Er(OTf)3/NaBH4 in 2-MeTHF

Article abstract of DOI:10.1016/j.tet.2014.12.005

An operationally simple and environmentally benign catalytic procedure has been developed to selectively reduce different α,β-unsaturated ketones. The corresponding allylic alcohols are obtained with high chemo- and diastereoselectivity using Er(OTf)₃ and NaBH₄ in 2-MeTHF. This protocol reduces the amount of catalyst and NaBH₄ needed, compared to classical procedures and the stages of extraction/purification are carried out in aqueous solutions avoiding the use of toxic solvents. Taking into account that Er(OTf)₃ can be considered even less toxic than table salt and the 'greenness' of 2-MeTHF as a solvent, the system Er(OTf)₃/2-MeTHF can be proposed as a cheap, efficient, and environmentally sustainable reduction system for the synthesis of allylic alcohols.

Full text of DOI:10.1016/j.tet.2014.12.005

Tetrahedron 71 (2015) 1132e1135
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Eco-friendly stereoselective reduction of
a,
b-unsaturated carbonyl
compounds by Er(OTf) /NaBH in 2-MeTHF
3
4
Monica Nardi a,*, Giovanni Sindona , Paola Costanzo , Manuela Oliverio ,
Antonio Procopio
a
a
b
b
b
Universit aꢀ della Calabria Ponte P. Bucci 12 C, 87037, CS, Italy
Universit aꢀ degli Studi della Magna Græcia Viale Europa, Germaneto, CZ, 88100, Italy
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 October 2014
Received in revised form 21 November 2014
Accepted 1 December 2014
Available online 24 December 2014
An operationally simple and environmentally benign catalytic procedure has been developed to selec-
tively reduce different
high chemo- and diastereoselectivity using Er(OTf)
amount of catalyst and NaBH needed, compared to classical procedures and the stages of extraction/
purification are carried out in aqueous solutions avoiding the use of toxic solvents. Taking into account
that Er(OTf) can be considered even less toxic than table salt and the ‘greenness’ of 2-MeTHF as a sol-
vent, the system Er(OTf) /2-MeTHF can be proposed as a cheap, efficient, and environmentally sus-
tainable reduction system for the synthesis of allylic alcohols.
a
,b
-unsaturated ketones. The corresponding allylic alcohols are obtained with
3
and NaBH in 2-MeTHF. This protocol reduces the
4
4
3
Keywords:
Luche reduction
3
a
,
b
-unsaturated carbonyl
Er (III) triflate
-MeTHF
Green chemistry
Ó 2014 Elsevier Ltd. All rights reserved.
2
1. Introduction
In recent years the use of non-toxic solvents, Lewis acid catalysts
active in aqueous media, ionic liquids and low energy conditions,
9
Allylic alcohols are important intermediates in agrochemistry,
pharmaceutical and fragrance chemistry, thus representing an
have been the subject of numerous publications.
Thus, according to our experience with the environmentally
benign Er (III) salts as catalyst in mild, non-dry reaction conditions,
1
important and highly versatile class of chiral building blocks for
organic synthesis.2
,3
both in homogeneous and in heterogeneous phase, we planned to
10
The chemoselective reduction of
a,
b-unsaturated carbonyl
explore the use of catalytic amounts of Er(OTf)
3
an eco-friendly
compounds with sodium borohydride in the presence of cerium
synthetic protocol for the reduction of
compounds (Scheme 1).
a,b-unsaturated carbonyl
11
(
III) chloride in methanol, known as the Luche reduction, is
4
,5
a common and simple method to synthesize allylic alcohols.
Many attempts were carried out to improve the performance of
the original Luche protocol, and very recently, calcium salts were
proposed as suitable catalysts in selective Luche reduction.6
However, all these procedures suffer two main drawbacks as the
original Luche protocol: the need of stoichiometric amounts of salts
and the use of harmful solvents such as methanol and
tetrahydrofuran.
O
OH
R'
OH
R'
R'
Er(OTf) /NaBH
3
4
+
R
R
R
2Me-THF
a
b
R=alkyl, aryl
R'=alkyl, aryl, H
major minor
Furthermore, some examples of heterogeneous catalysts suited
for the selective reduction of unsaturated aldehydes to allylic al-
cohols were reported,7 but unfortunately, they showed high se-
lectivity for the saturated ketone or alcohol when applied to
unsaturated ketones.8
Scheme 1. Possible products from reductions of
compounds.
a,b-unsaturated carbonyl
Moreover, taking into account Anastas and Warner’s 12 Princi-
12
13
ples of Green Chemistry, we looked at using 2-MeTHF instead of
THF based on three of the 12 principles: renewable feedstocks,
waste prevention and energy efficiency.
In fact, 2-MeTHF is derived from renewable resources such as
corncobs and bagasse, and it can replace tetrahydrofuran (THF) and
*
Corresponding author. Tel.: þ39 0984492850; fax: þ39 0984493307; e-mail
address: e-monica.nardi@unical.it (M. Nardi).
http://dx.doi.org/10.1016/j.tet.2014.12.005
0
040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

M. Nardi et al. / Tetrahedron 71 (2015) 1132e1135
1133
diethyl ether (DEE) as solvent reaction,14 giving often higher re-
action yields. 2-MeTHF allows easy product isolation because of its
water immiscibility, simple solvent recovery and drying, because it
forms a water-rich azeotrope at atmospheric pressure, and im-
proved extraction yields by reducing the number of extraction
The decrease of the amount of NaBH
and catalyst, respectively
4
to 1 and 0.1 M ratio (entries 9e12 in Table 1), shows excellent re-
sults at least in the case of CeCl $7H O (entry 9 in Table 1).
3
2
Surprisingly, when the same process was carried out in 2-
MeTHF, both cerium (III) and erbium (III) triflate gave quantita-
tive conversion of substrate 1 with very high yield of the allyl al-
cohol 1a (entries 14 and 16 in Table 1) especially in the case of
Er(OTf) , which showed high selectivity (94:6, 1a:1b) for the un-
3
saturated alcohol.
Decreasing or increasing the amount of the erbium (III) catalyst
did not improve yield and/or stereoselectivity of the process (en-
tries 17 and 18 in Table 1), whereas an excellent result was recorded
15
steps.
This solvent is increasingly being used in route development in
16
GSK and is considered negative for genotoxicity and mutagenic-
17
ity. Taken together these new data assist in broadening the usage
of 2-MeTHF in early phase development where the drug substance
is being prepared for short-term safety and clinical.
Thus, here we demonstrate that the Er(OTf)
3
in 2-MeTHF is
a very efficient system for the
a
,b
-unsaturated carbonyl compounds
4
using 0.75 M ratio of NaBH and only 5 mol % of Lewis acid, when
reduction to allylic alcohols.
a quantitative conversion of 1 with very high stereoselectivity for
unsaturated alcohol 1a was observed (entry 19 in Table 1). Finally, it
is worth noting that the same reaction performed in the absence of
catalyst, led to the quantitative formation of the saturated alcohol
1b (entry 20 in Table 1).
2
. Results and discussion
Our initial studies began with the optimization of the reaction
conditions using 2-cyclopentenone as lead substrate, Lewis acid
and NaBH as reducing system with different molar ratio substrate/
NaBH /Lewis acid.
2
Firstly, we compared the catalytic action of CeCl O, the
In light of these results the best reaction protocol was estab-
lished as follows: to a solution of the starting material and Er(OTf)
3
4
4
(5 mol %) in 2-MeTHF 1.0 equiv of sodium borohydride was added
under stirring at room temperature. Noteworthy, no purification
steps were necessary to isolate the organic products after work-up.
Anyhow, the work-up procedure itself involved the simple addic-
tion of water in order to quench the catalyst followed by the sep-
aration of organic phase and its evaporation under reduced
pressure.
Thus, to explore the generality of the described protocol, the
above reported experimental conditions were applied to the 1,2-
reduction of a broad range of a,b-unsaturated carbonyl compounds.
3
$7H
3 2
$6H O (Table 1) using
original Luche reaction promoter, and ErCl
the same conditions.
Table 1
Optimization of reduction reaction with 2-cyclopentenone as model substrate and
NaBH
4
as a reducing systema
Entry Lewis acid
Molar ratiob Solvent
CeCl $7H
Work-up Yield % Selectivityc
1
2
3
4
5
6
7
8
9
1
8
1
1
1
1
1
1
1
1
1
2
3
2
O
1/4/1
1/4/1
1/4/1
1/4/1
1/4/1
1/4/1
1/4/1
1/4/1
MeOH
MeOH
MeOH
MeOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
O/Et
O/Et
O/Et
O/Et
O/Et
O/Et
O/Et
O/Et
O/Et
O/Et
O/Et
O/Et
O/Et
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
100
100
42
100
100
100
44
100
100
100
100
40
100
100
100
49
97:3
95:5
92:8
90:10
96:4
91:9
93:7
91:9
95:5
Ce(OTf)
ErCl $6H
Er(OTf)
CeCl $7H
Ce(OTf)
ErCl $6H
Er(OTf)
CeCl $7H
Ce(OTf)
Er(OTf)
ErCl $6H
Er(OTf)
CeCl $7H
Ce(OTf)
ErCl $6H
3
We obtained almost complete selectivity for the majority of
substrates (Table). In particular, the selectivity was higher for six-
membered rings than for five- and seven-membered rings
(Table 2, entries 1 and 3) while for five-membered rings better
3
2
O
3
3
2
O
d
3
O
results were observed for
tries 2).
b-substituted compounds (Table 2, en-
3
2
3
3
2
O
1/1/0.1
1/1/0.1
1/4/1
Our results were comparable to the classical Luche reduction but
we realized a significant greening of the whole process compared
to several previous protocols that required the use of a stoichio-
metric amount of catalyst in harmful solvents.
0d
78:22
91:9
3
3
1
2
3
4
5
6
7
8
9
0
3
2
O
1/1/0.1
1/1/0.1
1/1/0.1
1/1/0.1
1/1/0.1
1/1/0.1
1/1/0.2
1/1/0.05
76:24
60:40
29:71
86:14
39:61
94:6
97:3
90:10
96:4
3
3
2
O
The protocol, tested on chiral substrates such as 3,5-
dimethylcyclohex-2-enone, (R)-carvone and (R)-pulegone, terpe-
3
O
O
O
O
O
O
O
3
2
O
15
noid important widespread in nature, displayed a significant
diastereoselectivity towards the cis-corresponding allyl alcohol
Er(OTf)
Er(OTf)
Er(OTf)
Er(OTf)
Er(OTf)
3
3
3
3
3
100
100
100
100
100
4
(Table 2, entries 8 and 9). This shows that NaBH prefers to ap-
proach the carbonyl group from the axial direction (Scheme 2)
forming the equatorial alcohol.
1/0.75/0.05 2-MeTHF
1/1/e 2-MeTHF
0:100
a
General reaction conditions: The 2-cyclopentenone and Lewis acid dissolved in
The yields obtained by our protocol were comparable with the
results reported in the literature, bringing at least three pivotal
advantages from an environmental point of view: escape the use of
alcoholic solvents, avoid the employment of stoichiometric
amounts of catalyst and reduce the use of organic solvent in the
solvent (2 mL) was added to sodium borohydride and left under stirring for 2 min
until complete conversion of starting material.
b
Substrate/NaBH
Ratio (1a:1b) and selectivity determined by GCeMS.
4
/Lewis acid.
c
d
6%, 20%, 6% and 3% of cyclopentanone for entries 6, 10, 13, and 15, respectively
determined by GCeMS.
3,4
subsequent products purification steps. Therefore our protocol
employing the Lewis acid catalyst in truly catalytic quantities and
2-MeTHF as solvent, is in perfect accord with the general principles
Considering the surprising advantages experienced recently
using triflate lanthanide salts as catalysts, we decided to explore
also the catalytic activity of Ce (III) and Er (III) tri-
fluoromethanesulfonates in the test reaction.
of green chemistry. Moreover, the method showed to be of wide
applicability being effective for both aldehydes and ketones.
3. Conclusions
As it is shown in Table 1, CeCl
tries 1 and 2 in Table 1) showed better catalytic properties than
ErCl $6H O and Er(OTf) (entries 3 and 4 in Table 1). Complete
3 2 3
$7H O and Ce(OTf) shown (en-
We have developed a new catalytic method for the regiose-
3
2
3
lective and diastereoselective reduction of
a-b-unsaturated car-
conversion of substrate 1 was again observed with cerium salts
when the reaction was performed in ethanol (entries 5 and 6 in
Table 1), while very poor stereoselectivity was observed in the case
of erbium salts (entries 7 and 8 in Table 1).
bonyl compounds by Er(OTf) in 2-MeTHF. The protocol allows
3
access to allylic alcohols in environmentally friendly conditions,
reducing the amount of catalyst required and simplifying extrac-
tion/purification steps thus avoiding the use of toxic solvents.

1134
M. Nardi et al. / Tetrahedron 71 (2015) 1132e1135
Table 2
Reduction of a variety of
a
,
b-unsaturated carbonyl compounds by Er(OTf)
3 4
/NaBH in
a
2-MeTHF
Entry
Substrate
Selectivity [%]b
90:10
Products
Time [min] Yield [%]c
O
O
OH
1
2
15
10
>99
>99
+
Scheme 2. The axial attack of nucleophile to carbonyl compound.
O
OH
100:0
using He as the carrier gas) and a DSQ 2010 mass detector. TLC
were performed using Kielsegel 60-F264 on aluminium plates,
commercially available from Merck. 1H NMR spectra were
recorded on a Bruker WM 300 in CDCl using tetramethylsilane
3
as internal standard. Chemical shifts are given in parts per mil-
lion (ppm) from tetramethylsilane as the internal standard
O
O
OH
OH
OH
OH
3
4
5
6
7
8
100:0
15
10
5
>99
>99
>99
>99
>99
>99
100:0
(
0.0 ppm). All products in this report are known and were
1
13
O
characterized by standard techniques ( H NMR, C NMR, GC/MS)
and the data were compared with those reported in the literature
for identification.
100:0 (cis 90%)
85:15
O
5
4.2. General procedure for the stereoselective reduction of
a,b-unsaturated carbonyl compounds
O
O
OH
OH
100:0
5
To -unsaturated carbonyl compound
(2.0 mmol) and Er(OTf) (0.1 mmol) in 2-MeTHF (3 mL) an equi-
4
molar quantity of NaBH (2.0 mmol) was added. The reaction
a
suspension of
a,
b
3
100:0 (cis 95%)
5
mixture was stirred at room temperature and monitored by GC/
MS until consumption of starting material. The crude reaction
O
OH
mixture was quenched with H
2
O (3 mL), the organic phase was
9
100:0 (cis 81%)
100:0
5
5
5
>99
>99
>99
dried on dry Na SO and the solvent was evaporated under re-
2
4
duced pressure. The desired product was obtained pure after
work-up.
O
OH
1
1
0
1
4
[
.2.1. Cyclopenten-2-ol (1a). Colourless liquid. MS: m/z (%)¼84 (32)
M]þ, 83 (100), 66 (32), 55 (90). (300 MHz, CDCl ) 1.48 (1H, br s,
OH), 1.60e1.70 (2H, m), 2.20e2.42 (2H, m), 4.83e4.90 (1H, m),
.81e5.86 (1H, m, H alkene), 5.97e6.10 (1H, m, H alkene);
O
OH
d
H
3
100:0
5
d
C
O
OH
6
3
(300 MHz, CDCl ) 28.9, 34.3, 81.7, 128.3, 135.2.
1
1
2
3
100:0
100:0
5
5
>99
>99
Ph
Ph
4
.2.2. Methylcyclopent-2-enol (2a). Colourless liquid. MS: m/z
(300 MHz,
) 1.60e1.75 (1H, m), 1.77 (3H, s, Me), 2.10e2.20 (1H, m),
.25e2.45 (1H, m), 2.45e2.55 (1H, m) 4.80 (1H, m), 5.44 (1H, m),
.50 (1H, m, alkene); (300 MHz, CDCl ) 22.4, 34.3, 38.1, 79.7,
O
OH
Ph
(%)¼97 (5), 83 (40), 80 (48), 79 (82), 40 (100).
d
H
Ph
Ph
Ph
CDCl
2
5
3
O
OH
H
1
1
4
5
6
100:0
100:0
100:0
5
5
5
>99
>99
>99
Ph
H
Ph
d
C
3
6
127.7, 140.2.
O
OH
H
H
4
.2.3. Cyclohexen-2-ol (3a). Colourless oil. MS: m/z (%)¼98 (30)
(300 MHz,
) 1.21e1.80 (4H, m), 1.80e2.10 (3H, m), 5.25 (1H, m), 5.75 (1H,
[Mþ], 97 (35), 83 (58), 79 (48), 70 (90), 40 (100).
d
H
1
O
OH
H
CDCl
3
H
a
m, alkene), 5.98 (1H, m, alkene);
33.3, 68.1, 122.7, 126.7.
d
C
(300 MHz, CDCl
3
)
d
18.8, 21.4,
General reaction conditions: The 2-cyclopentenone and Lewis acid dissolved in
6
solvent (2 mL) was added to sodium borohydride (molar ratio 1/0.75/0.05) and left
under stirring for 2 min until complete conversion of starting material.
b
Ratio (a:b) and selectivity determined by GCeMS.
Measurement by GC/MS.
4
1
(
(
.2.4. 3-Methylcyclohex-2-enol (4a). Colourless oil. MS: m/z (%)¼
12 (10) [Mþ], 111 (5), 97 (100), 94 (30), 84 (31), 83 (20), 79 (65), 77
26). (300 MHz, CDCl ) 1.46e1.50 (1H, m),1.52e1.55 (1H, m),1.63
3H, s, Me), 1.65 (1H, s, OH), 1.75e1.94 (1H, m), 1.98e2.20 (1H, m),
c
d
H
3
4
4
. Experimental section
.1. General
2.21e2.32 (1H, m), 3.72e3.80 (1H, m, CH(OH)), 5.49 (1H, m, al-
kene); (300 MHz, CDCl 19.0, 22.6, 30.5, 31.6, 66.2, 116.2,
134.6.
d
C
3
) d
6
The
a
,
b
-unsaturated ketones were purchased from Aldrich
4.2.5. 3,5-Dimethylcyclohex-2-enol
(5a). Colourless
oil.
d
H
and used without further purification. Reactions were monitored
using a GCeMS Shimadzu workstation, composed of a GC 2010
(300 MHz, CDCl ) 0.80e1.20 (3H, m), 1.52e1.54 (1H, m), 1.57 (1H, s,
OH), 1.59 (3H, s, Me), 1.65e1.85 (1H, m), 1.88e2.20 (1H, m),
1.98e2.20 (1H, m), 2.21e2.32 (2H, m), 3.62e3.80 (1H, m, CH(OH)),
3
(
30 m QUADREX 007-5MS, working on split mode, 1 mL/min

M. Nardi et al. / Tetrahedron 71 (2015) 1132e1135
1135
5
4
.40 (1H, m, alkene);
5.6, 66.2, 128.2, 137.6.
d
C
(300 MHz, CDCl
3
)
d
19.0, 22.6, 25.3, 42.5,
6.23e6.32 (1H, m, alkene), 6.55e6.68. (1H, m, alkene), 7.10e7.49
(5H, m, aromat.); (300 MHz, CDCl ) 65.3, 124.3, 126.7 (2C), 128.1,
28.6 (2C), 129.6, 135.2. Spectroscopic data compared to those of
the pure product.
5
d
d
C
3
1
4
CDCl
1
.2.6. (Z)-Cyclohept-2-enol (6a). Colourless oil.
) 1.10e1.40 (2H, m), 1.41e1.60 (1H, m), 1.41e1.60 (1H, m),
.61e1.80 (3H, m), 1.90e2.30 (3H, m), 3.95e4.15 (1H, m, CH(OH)),
H
d (300 MHz,
3
4.2.15. trans-2-Hexen-1-olo (15a). Colourless oil. MS: m/z (%)¼82
(4), 57 (25), 44 (15), 40 (100). (300 MHz, CDCl )0.93e1.00 (3H, m,
CH ), 1.22e1.49 (2H, m, CH ), 1.83e2.00 (2H, m, CH ), 4.15e4.25
2H, m, CH OH), 5.55e5.70. (2H, m, alkene), (300 MHz, CDCl
5
3
.70e5.78 (2H, m, H alkene);
d
C
(300 MHz, CDCl
3
) 24.3, 29.8, 31.6,
d
H
3
8.7, 68.5, 129.8, 130.1.6
3
2
2
(
2
d
C
3
)
4
.2.7. 3-Methyl-5,5-dimethylcyclohex-2-enol (7a). Colourless oil.
14.2, 22.3, 35.7, 66.1, 128.3, 129.4. Spectroscopic data compared to
those of the pure product.
MS: m/z (%)¼140 (20) [Mþ], 125 (100), 122 (18), 107 (64), 105 (11),
1 (29), 84 (60), 83 (30), 79 (19), 69 (40). (300 MHz, CDCl
.00e1.10 (6H, m), 1.41e1.53 (1H, m), 1.65e1.80 (2H, m), 1.95 (3H, s),
.96e2.10 (1H, m), 1.15e2.30 (1H, m), 3.65e3.75 (1H, m, CH(OH)),
9
1
1
5
d
H
3
)
4.2.16. cis-2-Hexen-1-olo (16a). Colourless oil.
CH ), 1.20e1.51 (2H, m, CH ), 1.80e2.00 (2H, m, CH
3
(2H, m, CH OH), 5.50e5.70. (2H, m, alkene), (300 MHz, CDCl )
d
H
0.90e1.00 (3H, m,
3
2
2
), 4.10e4.30
.20e5.30 (1H, m, H alkene);
d
C
(300 MHz, CDCl
3
) 22.3, 26.8, 47.9,
2
d
C
5
3.2, 62.5, 129.8, 134.1.
15.1, 22.8, 36.7, 66.8, 128.5, 129.8. Spectroscopic data compared to
those of the pure product.
4
.2.8. (2R,5R)-2-Methyl-5-(prop-1-en-2-yl)cyclohex-2-enol
(
(
1
8a). Colourless oil (d.r.¼95:5). MS: m/z (%)¼152 (z1) [Mþ], 134
51), 119 (50), 109 (83), 91 (73), 84 (100). (300 MHz, CDCl
.35e1.51 (1H, m), 1.74 (3H, s, Me), 1.76 (3H, s, Me), 1.90e1.99 (1H,
m), 2.00e2.10 (1H, m), 2.12e2.19 (1H, m), 2.20e2.30 (1H, m), 4.18
1H, m), 4.75 (2H, s, alkene), 5.52 (1H, s alkene); (300 MHz, CDCl
References and notes
d
H
3
)
1. (a) Sneed, R. A.; Grimes, S. D.; Schultze, A. E.; Brown, A. P.; Ganey, P. E. Toxicol.
Appl. Pharmacol. 1997, 144, 77e87; (b) Karas, M.; Chakrabarti, S. K. J. Environ.
Pathol., Toxicol. Oncol. 2001, 20, 141e154; (c) Campion, S. N.; Tatis-Rios, C.;
Augustine, L. M.; Goedken, M. J.; Rooijen, N.; Cherrington, N. J.; Manautou, J. E.
Toxicol. Appl. Pharmacol. 2009, 236, 49e58; (d) Shu, N.; Shen, H. Flavour Fra-
grance J. 2009, 24, 1e6.
(
1
d
C
3
)
6
9.0, 20.6, 31.0, 33.0, 36.4, 71.9, 108.1, 123.4, 123.5, 134.1, 150.0.
2
. (a) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 1307e1370; (b) Jo-
hansen, M.; Jørgensen, K. A. Chem. Rev. 1998, 98, 1689e1708.
4.2.9. (1R, 5R)-5-Methyl-2-(propan-2-ylidene)cyclohexanol (9a).
Colourless oil (d.r. 81:19). MS: m/z (%)¼154 (2) [Mþ], 139 (31), 136
50), 121 (59), 107 (48), 93 (69), 79 (100), 44 (100). (300 MHz,
CDCl ) 0.80e1.15 (3H, m, Me cis), 1.15e1.26 (3H, d, Me trans), 1.36
6H, d, Me), 1.50e1.85 (3H, m), 2.00e2.40 (3H, m), 3.65e3.75 (1H,
m, CH(OH)), 3.85e3.98 (1H, m, CH(OH)); (300 MHz, CDCl ) 19.0,
3. Jiang, H.; Holub, N.; Jørgensen, K. A. Proc. Natl. Acad. Sci. U.S.A. 2010, 107,
20630e20635.
(
d
H
4
. (a) Bergeret, G.; Gallezot, P. In Handbook of Heterogeneous Catalysis; Ertl, G.,
3
Kn o€ zinger, H., Weitkamp, J., Eds.; Wiley-VCH: Weinheim, Germany, 1997;
(
€
pp 439e464; (b) Krahling, L.; Krey, J.; Jakobson, G.; Grolig, J.; Miksche, L. Ull-
mann’s Encyclopedia of Industrial Chemistry; Wiley-VCH: Weinheim, Germany,
2002; (c) Ahlsten, N.; Bartoszewicz, A.; Martin-Matute, B. Dalton Trans. 2012, 41,
d
C
3
5
d
21.6, 23.0, 25.0, 39.8, 42.0, 68.0, 122.0, 130.0.
1660e1670.
5
6
. (a) Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226e2227; (b) Luche, J. L.; Ro-
driguez-Hahn, L.; Crab, M. P. Chem. Commun. 1978, 601e602; (c) Gemal, A. L.;
Luche, J. L. J. Org. Chem. 1979, 44, 4187e4189; (d) Luche, J. L.; Gemal, A. L. J. Am.
Chem. Soc. 1981, 103, 5454e5459.
4
.2.10. (E)-4-(2,6,6-Trimethylcyclohex-2-enyl)but-3-en-2-ol
(
1
10a). Colourless oil. MS: m/z (%)¼194 (<1) [Mþ], 176 (5), 161 (5),
38 (40), 120 (49), 105 (62), 95 (100). (300 MHz, CDCl ) 1.10 (6H,
d
H
3
. Forkel, N. V.; Henderson, D. A.; Fuchter, M. J. Green. Chem. 2012, 14, 2129e2132.
s, Me), 1.25e1.35 (1H, m), 1.36 (3H, d, J¼3.3 Hz, Me), 1.67e1.80 (1H,
7. (a) Blackmond, D. G.; Oukaci, R.; Blanc, B.; Gallezot, P. J. Catal. 1991, 131,
01e411; (b) Poltarzewski, Z.; Galvagno, S.; Pietropaolo, R.; Staiti, P. J. Catal.
986, 102, 190e196.
4
1
m), 1.83e2.00 (2H, m), 2.50e2.70 (1H, m), 4.00e4.10 (1H, m,
CH(OH)), 5.30e5.50 (2H, m, alkene), 5.50e5.70 (1H, m, alkene);
d
C
8. Torres, G. C.; Ledesma, S. D.; Jablonski, E. L.; De Miguel, S. R.; Scelza, O. A. Catal.
(
300 MHz, CDCl )19.2, 21.8, 23.5, 28.6 (2C), 31.6, 39.8, 68.5, 123.5,
3
Today 1999, 48, 65e72.
18
129.5, 132.6, 133.8.
9. (a) Bortolini, O.; De Nino, A.; Garofalo, A.; Maiuolo, L.; Russo, B.; Procopio, A.
Appl. Catal., A: General 2010, 372, 124e129; (b) Di Gioia, M. L.; Barattucci, A.;
Bonaccorsi, P.; Leggio, A.; Minuti, L.; Romio, E.; Temperini, A.; Siciliano, C. RSC
Adv. 2014, 4, 2678e2686.
4
.2.11. (E)-4-(2,6,6-Trimethylcyclohex-1-enyl)but-3-en-2-ol
(
1
(
1
(
5
(
11a). Colourless oil. MS: m/z (%)¼195 (6), 194 (33) [Mþ], 179 (19),
76 (36), 162 (17), 1 (100), 133 (25), 123 (26), 121 (55), 119 (45), 107
38), 105 (53), 91 (44), 43 (53). (300 MHz, CDCl )1.10 (3H, Me),
.48 (3H, d, J¼4.1 Hz, Me), 1.40e1.65 (4H, m), 1.72 (3H, s), 1.80e1.90
3H, m), 4.05e4.20 (1H, m, CH(OH)), 5.25e5.50 (1H, m, alkene),
.50e5.70 (1H, m, alkene); (300 MHz, CDCl ) 14.3, 16.8, 18.5, 28.3
2C), 34.3, 36.7, 38.5, 69.3, 129.7, 132.3, 134.8, 139.6.
10. (a) Bartoli, G.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.; Procopio, A.;
Tagarelli, A. Green. Chem. 2004, 6, 191e192; (b) Procopio, A.; Dalpozzo, R.; De
Nino, A.; Maiuolo, L.; Nardi, M.; Russo, B. Adv. Synth. Catal. 2005, 347,
d
H
3
1447e1450; (c) Procopio, A.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Oliverio, M.; Russo, B. Carbohydr. Res. 2007, 342, 2125e2131; (d) Procopio, A.;
Das, G.; Nardi, M.; Oliverio, M.; Pasqua, L. ChemSusChem 2008, 1, 916e919; (e)
Procopio, A.; Alcaro, S.; Nardi, M.; Oliverio, M.; Ortuso, F.; Sacchetta, P.; Pier-
agostino, D.; Sindona, G. J. Agric. Food Chem. 2009, 57, 11161e11167; (f) Dal-
pozzo, R.; Nardi, M.; Oliverio, M.; Paonessa, R.; Procopio, A. Synthesis 2009, 20,
d
C
3
1
9
3433e3438; (g) Procopio, A.; Cravotto, G.; Oliverio, M.; Costanzo, P.; Nardi, M.;
Paonessa, R. Green. Chem. 2011, 13, 436e443; (h) Nardi, M.; Cozza, A.; De Nino,
A.; Oliverio, M.; Procopio, A. Synthesis 2012, 44, 800e804.
11. (a) Procopio, A.; Costanzo, P.; Curini, M.; Nardi, M.; Oliverio, M.; Sindona, G. ACS
Sustainable Chem. Eng. 2013, 1, 541e544; (b) Oliverio, M.; Costanzo, P.; Paonessa,
R.; Nardi, M.; Procopio, A. RSC Adv. 2013, 3, 2548e2552.
4
.2.12. (E)-4-Phenylbut-3-en-2-ol
) 1.41 (3H, d, J¼6.0 Hz, Me), 4.35e4.55 (1H, m,
CH(OH)), 6.15e6.35 (1H, m, alkene), 6.50e6.60 (1H, m, alkene),
.12e7.50 (5H, m, aromat.); (300 MHz, CDCl ) 22.3, 68.8, 124.5,
(12a). Colourless
oil.
d
H
(
300 MHz, CDCl
3
7
d
C
3
1
2. Anastas, P.; Warmer, J. C. Green Chemistry Theory & Practice; Oxford University:
Oxford, UK, 1998.
3. (a) Pace, V.; Castoldi, L.; Alc aꢁ ntarab, A. R.; Holzera, W. Green. Chem. 2012, 14,
859e1863; (b) Aycock, D. F. Org. Process Res. Dev. 2007, 11, 156e159.
4. Comanita, B.; Aycock, D. Ind. Pharma Mag. 2005, 17, 54e56.
6
126.3 (2C), 127.4, 129.1 (2C), 129.3, 134.7.
1
1
4
.2.13. (E)-1,3-Diphenylprop-2-en-1-ol (13a). Colourless oil.
) 2.10 (1H, d, J¼3.3 Hz, OH), 5.35 (1H, m, CH(OH)),
.13e6.40 (1H, m, alkene), 6.55 (1H, d, J¼14.7 Hz, alkene), 6.90e7.49
(300 MHz, CDCl ) 75.3, 126.3, 126.5 (2C), 127.6
2C), 127.8, 128.4 (2C), 128.6 (2C), 130.5, 131.5, 134.5, 142.3.
d
H
1
(
300 MHz, CDCl
3
15. Henderson, R. K.; Jim eꢁ nez-Gonz ꢀa lez, C.; Constable, D. J. C.; Alston, S. R.; Inglis,
G. G. A.; Fisher, G.; Sherwood, J.; Blinks, S. P.; Curzons, A. D. Green. Chem. 2011,
6
1
3, 854e862.
6. Antonucci, V.; Coleman, J.; Ferry, J. B.; Johnson, N.; Mathe, M.; Scott, J. P.; Xu, J.
Org. Process Res. Dev. 2011, 15, 939e941.
7. Dams, I.; Bia1o nꢁ ska, A.; Ciunik, Z.; Wawrze nꢁ czyk, C. Eur. J. Org. Chem. 2004,
662e2668.
8. Dhulut, S.; Bourin, A.; Lannou, M.; Etienne, F.; Lensen, N.; Chelain, E.; Fahy, J.
(
(
10H, m, aromat.);
d
C
3
1
6
1
2
4
(
(
.2.14. (E)-3-Phenylprop-2-en-1-ol (14a). Colourless oil. MS: m/z
%)¼134 (52) [Mþ], 133 (16), 115 (51), 105 (49), 92 (100), 91 (78), 78
67), 77 (57). (300 MHz, CDCl ) 4.10e4.25 (2H, m, CH OH),
1
Eur. J. Org. Chem. 2007, 5235e5243.
19. Akai, S.; Hanada, R.; Fujiwara, N.; Kita, Y.; Egi, M. Org. Lett. 2010, 12, 4900e4903.
d
H
3
2