RuCl2(DMSO)4 catalyzes the β-alkylation of secondary alcohols with primary alcohols through a hydrogen autotransfer process

Article abstract of DOI:10.1016/j.tet.2006.07.012

The electrophilic β-alkylation of secondary alcohols with primary alcohols is accomplished by a hydrogen autotransfer process catalyzed by RuCl₂(DMSO)₄. The reaction can produce either simple alkylated secondary alcohols or α,β-unsaturated ketones with good to excellent results just by choosing the appropriate starting secondary alcohol (methyl or longer chain secondary alcohol, respectively), as well as quinolines (by using 2-aminobenzyl alcohol).

Full text of DOI:10.1016/j.tet.2006.07.012

Tetrahedron 62 (2006) 8982–8987
RuCl2(DMSO)4 catalyzes the b-alkylation of secondary alcohols
with primary alcohols through a hydrogen autotransfer process
*
Ricardo Martınez, Diego J. Ramon and Miguel Yus
*
´
ꢀ
´
Instituto de Sıntesis Organica (ISO) and Departamento de Quımica Organica, Facultad de Ciencias,
ꢀ
´
ꢀ
Universidad de Alicante, Apdo. 99, E-03080-Alicante, Spain
Received 2 June 2006; revised 5 July 2006; accepted 5 July 2006
Available online 1 August 2006
Abstract—The electrophilic b-alkylation of secondary alcohols with primary alcohols is accomplished by a hydrogen autotransfer process
catalyzed by RuCl2(DMSO)4. The reaction can produce either simple alkylated secondary alcohols or a,b-unsaturated ketones with good to
excellent results just by choosing the appropriate starting secondary alcohol (methyl or longer chain secondary alcohol, respectively), as well
as quinolines (by using 2-aminobenzyl alcohol).
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
metal derivative to give the corresponding carbonyl com-
pound.5 In the case of using methyl ketones as starting
materials, the presence and extra equivalent of primary
alcohol forced the process to yield the related secondary
alkylated alcohol6 after a final Meerwein–Ponndorf–Verley
reduction.7
Alcohols are one of the most important classes of organic
compounds owing to their wide variety of uses in industrial
and laboratory chemistry. Although a plethora of methods
for the synthesis of alcohols are known,1 their simple crea-
tion by carbon–carbon bond manipulation is very unusual.
In this approach, the usual protocol involves the oxidation
of alcohol to ketone, followed by alkylation, and final reduc-
tion of the carbonyl moiety to the alcohol. Therefore, any
new strategy for simple alkylation of alcohols would be
welcome, more if it is environmentally benign and supports
the sustainable chemical industry.2
C
R1 H + R2
P
R1 + R2
P H
C
H
Mw of Final Product
(Equiv. x Mw of all reagents)
Atom
= Yield (%) x
Efficiency (%)
Σ
i
i
The hydrogen autotransfer process, which can be considered
as a new type of domino reaction,3 involves an initial re-
moval of hydrogen from at least one of the initial reagents
(R1-H) by a catalyst (C), followed by reaction of the new re-
agents (R1 and R2) to form a new compound (P), which is in
turn the hydrogen acceptor of the previously formed hydro-
genated catalyst (C-H), renewing the catalyst (Scheme 1).
This strategy has been used in the alkylation of different car-
bonyl derivatives using primary alcohols as electrophiles.4
The reaction starts with the oxidation of the primary alcohol
to give the corresponding aldehyde and the hydride metal
derivative, followed by condensation with the carbonyl
derivative to render the corresponding a,b-unsaturated car-
bonyl derivative, which is finally reduced with the hydride
Scheme 1. General scheme for a hydrogen autotransfer process.
Despite the high atom efficiency obtained in the a-alkylation
of methyl ketone derivatives with alcohols through a hydro-
gen autotransfer process, the related process using 2-alkanol
derivatives, as masked ketones, has been scarcely reported.
In fact, there are only two examples of this process.8 The first
one uses the air sensitive RuCl2(PPh3)3 as catalyst, a double
amount of primary alcohol, and a large excess of 1-dodecene
as sacrificial additive.9 The second one uses the very expen-
sive catalyst [Cp*IrCl2]2, sodium tert-butoxide, and a slight
excess of the primary alcohol.10 The yields in both cases are
comparable, in the range of 70–80%.
Here we report an alternative protocol for the b-alkylation
of secondary alcohols with primary alcohols catalyzed by
RuCl2(DMSO)4.11
* Corresponding authors. Tel.: +34 965 90 35 48; fax: +34 965 90 35 49;
e-mail addresses: djramon@ua.es; yus@ua.es
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.012

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R. Martınez et al. / Tetrahedron 62 (2006) 8982–8987
8983
Table 2. b-Alkylation of 2-alkanol derivatives 1 with primary alcohols 2a
2. Results and discussion
OH
RuCl2(DMSO)4
(2 mol%)
OH
2.1. b-Alkylation of 2-alkanol derivatives using primary
alcohols as electrophiles
R1
R2
OH
+
R1
1,4-dioxane, 100 ºC
KOH (200 mol%), 7 d
R2
1
2
3
The alkylation of equimolecular amounts of 1-phenyl-
ethanol (1a) with benzylic alcohol to give the corresponding
alcohol 3a was chosen as the reaction model in order to
optimize all different parameters, with the solvent being
the first one (Table 1). The reaction in toluene gave the ex-
pected product with modest yield after seven days, while
the reaction failed using other more polar solvents, such as
water, MeCN or DMSO (entries 1–4).
Entry
R1
R2
Ph
Compd no.
Yield (%)b
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a
95
4-ClC6H4
3-ClC6H4
4-MeOC6H4
1-Naphthyl
2-Furyl
Pri
3b
3c
3d
3e
3f
3g
3h
3i
69
98c
98c
85
98c
42 (47)
80
4-F3CC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
But
Ph
Ph
Despite these disappointing results, we found that the reac-
tion using 1,4-dioxane gave the expected compound 3a
with an excellent yield (Table 1, entry 5). The reaction can
also be performed in solvent-free conditions12 giving
slightly lower results but in only three days (entry 6). After
finding dioxane as the best solvent, we studied the influence
of the amount of base (KOH), the decrease or increase
from 2 equiv being detrimental (Table 1, entries 5 and 7–9).
The increase of the temperature also renders lower results
(entries 10 and 11). Finally the nature of base was also tested
at different temperatures, giving in all cases worse results
(entries 12–14).
9
98c
76
10
11
12
13
4-ClC6H4
3,4-(MeO)2C6H3
Ph
3j
3k
3l
71
48 (58)
<5
n-C5H11
Ph
3m
a
All reactions were performed using 5 mmol (100 mol %) of each alcohol.
Isolated yield after column chromatography (silica gel: hexane/ethyl ace-
tate); in parenthesis: yields obtained under solvent-free conditions after
three days.
b
c
Compound obtained pure after work-up.
efficiency (see Scheme 1: in our case 57% and in the litera-
ture 129 and 43%10) than the reported procedures.
On the basis of the above results, we next examined the re-
actions of various 2-alkanols with primary alcohols under
optimized conditions (Table 2). The standard reaction to
give compound 3a permitted us to compare our results
with those of literature. Thus, the reaction using the catalyst
RuCl2(PPh3)3 gave 82% yield,9 while using [Cp*IrCl2]2
gave 75% yield,10 both yields being lower than those in
our case (Table 2, entry 1). Our protocol gave not only better
chemical yield for compound 3a but also better atom
The reaction gave homogeneous results for primary aro-
matic alcohols, independent of the nature of the substituent
on the aromatic ring, even using heteroaromatic derivatives
(Table 2, entries 1–6). However, the reaction with aliphatic
primary alcohols gave lower chemical yield, also under
solvent-free conditions (entry 7). The reaction gave good re-
sults when different aromatic secondary ethanol derivatives
1 were tested (entries 8–11), with the yield being lower for
substituted aliphatic alcohols or null for non-substituted
reagents (entries 12 and 13, respectively).
Table 1. Optimization of b-alkylation of alcoholsa
OH
RuCl2(DMSO)4
OH
Concerning a possible mechanism, and considering the pre-
viously proposed catalytic cycle for the related a-alkylation
of ketones4n (deduced by detecting different by-products
such as aldehydes and a,b-unsaturated ketones, as well as
by isotopic labelling experiments), we propose the catalytic
cycle shown in Scheme 2 which contains an extra oxidation–
reduction step.
(2 mol%)
Ph
+
Ph
OH
Ph
1a
Base, solvent
Ph
3a
2a
Entry Solvent
Base (%)
T (ꢀC) t (day) Yield (%)b
1
2
3
4
5
6
7
8
PhMe
H2O
MeCN
DMSO
Dioxane
KOH (200)
KOH (200)
KOH (200)
KOH (200)
KOH (200)
KOH (200)
KOH (100)
KOH (300)
KOH (600)
100
100
100
100
100
100
100
100
100
120
120
100
120
7
3
3
3
7
3
7
7
7
3
3
3
2
3
56c
0d
0d
Probably, in the reaction medium the initial ruthenium com-
plex evolves to form the real catalyst, which could be a poly-
metallic species, even bearing hydroxy groups,13 although
the permanence of chlorine ligands cannot be ruled out. In
turn, this intermediate reacts with alkoxide derivatives to
form the corresponding mono- or dihydride ruthenium cata-
lytic active species.14 The necessary use of stoichiometric
amounts of base can indicate that its role is not only in the
deprotonation of the in situ formed ketone 8 but also in the
deprotonation of the alcohols 1 and 2. The corresponding
oxidized carbonyl compounds 8 and 9 suffer a classical basic
aldol condensation to render the a,b-unsaturated ketone 5.
The last steps are the reduction of carbon–carbon double
bond through a Michael-type addition to form the a-alky-
lated ketone 12 and final reduction of the carbonyl group
to the alcohol 3,15 renewing the catalyst.
0d
98
91
38
87
56
92
73
85
73
76
e
—
Dioxane
Dioxane
Dioxane
9
10
11
12
13
14
Dioxanef KOH (200)
THFf
Dioxane
KOH (200)
KOBut (200)
Dioxanef KOBut (200)
Dioxane
NaNH2 (200) 100
a
All reactions were performed using 5 mmol (100 mol %) of each alcohol.
Yields determined by 1H NMR using N,N-diphenyl formamide as internal
standard.
b
c
d
e
f
Forty-three percent of corresponding ketone was detected.
Initial reagents were recovered unchanged.
The reaction was performed under solvent-free conditions.
The reaction was performed in a pressure tube.

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R. Martınez et al. / Tetrahedron 62 (2006) 8982–8987
8984
Table 3. Reaction of secondary bicyclic alcohols 4 with benzylic alcohols 2a
OH
R2
OH
R
R1
R
2
OH
1
RuCl2(DMSO)4
(2 mol%)
R
R
O
KOH
R
+
1,4-dioxane, 100 ºC
KOH (200 mol%), 7 d
R
OK
OH
H2O
X
R2
OK
R1
X
7
6
4
2
5
Entry
R
Alcohol 4
X
Compd no.
Yield (%)b
1
2
3
4
5
6
H
H
Me
Me
Me
Me
Mixturec
Mixturec
endo
endo
endo
H
5a
5b
5c
5d
5e
5e
85
96
71
47 (34)
62
73
[Ru-X]
O
MeO
H
Me
MeO
MeO
R1
8
[Ru-X]
OK
exo
R1
a
10
All reactions were performed using 5 mmol (100 mol %) of each alcohol.
Isolated yield after column chromatography (silica gel: hexane/ethyl
acetate); in parenthesis: yields obtained under solvent-free conditions
after three days.
O
b
R2
H
9
KOH
c
[Ru-H]
Mixture of isomer endo:exo¼83:17.
O
was unambiguously determined by the X-ray of compound
5e and by NOESY experiments of compounds 5a and e.4n
R1
R2
5
H2O
2.3. Synthesis of quinolines
[Ru-H]
Finally, it should be pointed out that the above reaction with
2-aminobenzyl alcohol 13 gave the corresponding quino-
lines 14 (Table 4).18 The tentative mechanism pathway
would involve the oxidation of both alcohols to the corre-
sponding carbonyl compounds of type 8 and 9, followed
by either the ketone-imine formation and final aldol conden-
sation process, or by an aldol reaction to give the corre-
sponding a,b-unsaturated ketone of type 5 and final ring
closing imine formation. Benzophenone was used as hydride
scavenger, in order to reoxidize the ruthenium hydride inter-
mediate and renewing the starting ruthenium catalyst. The
reaction worked nicely for aromatic and heteroaromatic
substituted ethanol derivatives, giving pure quinoline deri-
vative 14 in practically quantitative yield after acidic/basic
O[Ru]
R1
R2
11
O
R1
R2
12
OH
R1
R2
3
Scheme 2. Proposed catalytic cycle for the b-alkylation of 2-alkanols with
primary alcohols.
Table 4. Synthesis of quinolinesa
2.2. Reaction of secondary bicyclic alcohols with
primary alcohols
OH
RuCl2(DMSO)4
R2
R1
OH
(2 mol%)
NH2
+
R1
1,4-dioxane, 100 ºC
Ph2CO (250 mol%)
KOH (200 mol%), 3 d
When the same above protocol was followed using bicyclic
alcohols 4 as secondary alcohol partners, ketone derivatives
5 were isolated instead of the expected alcohol of type 3
(Table 3). The reason for this fact is not yet very clear but
it would be related with the higher stability of trisubstituted
carbon–carbon double bond, as well as the higher instability
of ruthenium bicyclic enolate of type 11, which would make
more difficult the corresponding Michael-type addition
of the ruthenium hydride intermediate, the reoxidation of
this hydride complex being accomplished either by the
molecular oxygen16 or by direct generation of hydrogen.17
N
R2
1 or 4
13
14
Entry
Compd no.
R1
R2
Yield (%)b
1
2
3
4
5
14a
14b
14c
14d
14e
Ph
H
H
H
Me
98c (98)c
98c
4-MeC6H4
2-Furyl
Et
98c
98c,d
–(CH2)4–
71d (89)
6
14f
41d,e
The reaction worked nicely for different substituted benzylic
alcohols 2, giving similar results for the protocol using
dioxane as solvent as well as for solvent-free conditions
(entry 4). The use of borneol or isoborneol did not have any
important difference, obtaining similar results (Table 3,
entries 5 and 6). The Z-configuration of the double bond
a
All reactions were performed using 5 mmol (100 mol %) of each alcohol.
Isolated yield after acidic/basic aqueous extraction; in parenthesis: yields
obtained under solvent-free conditions after three days.
Compound obtained pure after work-up.
Yield after seven days’ reaction time.
Purified by column chromatography (silica gel: hexane/ethyl acetate).
b
c
d
e

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R. Martınez et al. / Tetrahedron 62 (2006) 8982–8987
8985
aqueous extraction (entries 1–3). Surprisingly, the reaction
gave excellent results also for non-substituted secondary
alcohols, which could indicate that prior to the aldol reac-
tion, the formation of imine derivative takes place. Finally,
it should be pointed out that the reaction performed under
solvent-free conditions gave in some cases better chemical
yields in shorter reaction times.
products. Physical and spectroscopic data as well as litera-
ture references follow.
4.2.1. 3-(4-Chlorophenyl)-1-phenyl-1-propanol (3b).10 Rf
0.29 (hexane/ethyl acetate: 4/1); tR 16.5; n (film) 3408
(O–H), 3026, 1648 (C]CH), 1063 cmꢂ1 (C–O); dH 1.84
(1H, s, OH), 1.90–2.15 (2H, m, CH2CO), 2.55–2.75 (2H,
m, CH2CH2CO), 4.65–4.70 (1H, m, CHO), 7.11, 7.23, and
7.25–7.40 (2H, 2H, and 5H, respectively, d, d, and m, respec-
tively, J¼8.5 and 8.5 Hz, respectively, ArH); dC 31.35,
40.30, 73.70, 125.85 (2C), 127.75, 128.45 (2C), 128.55
(2C), 129.75 (2C), 1312.55, 140.20, 144.40; m/z 248
(M++2, 1%), 246 (3), 230 (21), 229 (11), 228 (61), 193
(33), 125 (12), 107 (10), 103 (15), 79 (48), 77 (33).
3. Conclusion
In summary, we have described here the use of
RuCl2(DMSO)4 for a simple and direct b-alkylation of
secondary alcohols with not only high yields but also atom
efficiency, using secondary alcohols as the source of nucleo-
philes and primary alcohols as the electrophilic partners. The
final product depends strongly on the alcohol nature, obtain-
ing either the simple alkylation for 2-alkanol derivatives or
a,b-unsaturated ketones when methylenic bicyclic alcohols
were used as starting materials. In this way, wide variety
of quinolines could be prepared with excellent yields just
by using 2-aminobenzyl alcohol derivative as alkylating
agent. It is worthy to note that this procedure constitutes
a good example of very high atom efficiency reaction. More-
over, the waste material of the reactions is water, making
them a very interesting process from an environmental and
industrial point of view. The catalyst used is very cheap,
stable, easy to handle and prepare.19 All these facts make
the RuCl2(DMSO)4-catalyzed alkylation process very inter-
esting comparing to other protocols using expensive and
difficult-to-handle catalysts.
4.2.2. 3-(3-Chlorophenyl)-1-phenyl-1-propanol (3c). Rf
0.15 (hexane/ethyl acetate: 4/1); tR 16.4; n (film) 3381
(O–H), 3069, 1589, 1566 (C]CH), 1078 cmꢂ1 (C–O); dH
1.97 (1H, s, OH), 1.90–2.15 (2H, m, CH2CO), 2.55–2.80
(2H, m, CH2CH2CO), 4.65 (1H, dd, J¼5.5, 7.6 Hz, CHO),
7.05–7.40 (9H, m, ArH); dC 31.65, 40.10, 73.65, 125.85,
126.00, 126.60, 127.75 (2C), 128.40, 128.55 (2C), 129.60,
134.05, 143.80, 144.30; m/z 248 (M++2, 8%), 246 (M+,
23), 228 (14), 126 (10), 107 (100), 103 (11), 91 (11), 79
(41), 77 (29). HRMS: M+ found 246.0808. C15H15OCl
requires 246.0811.
4.2.3. 3-(4-Methoxyphenyl)-1-phenyl-1-propanol (3d).10
tR 16.9; Rf 0.7 (hexane/ethyl acetate: 4/1); n (film) 3419
(O–H), 3028, 1622, 1513 (C]CH), 1039 cmꢂ1 (C–O);
dH 1.95 (1H, s, OH), 2.00–2.15 (2H, m, CH2CO), 2.55–
2.75 (2H, m, CH2CH2CO), 3.76 (3H, s, CH3), 4.65–4.70
(1H, m, CHO), 6.80–6.85, 7.10–7.15, and 7.25–7.35
(2H, 2H, and 5H, respectively, 3m, ArH); dC 31.15,
40.70, 55.30, 73.85, 113.80 (2C), 125.95 (2C), 127.65,
128.55 (2C), 129.35 (2C), 133.80, 144.65, 157.80; m/z
242 (M+, 28%), 225 (17), 224 (100), 223 (20), 209
(15), 193 (19), 135 (16), 133 (11), 122 (22), 121 (51),
108 (14), 107 (32), 105 (12), 91 (13), 79 (29), 78 (11),
77 (26).
4. Experimental
4.1. Chemicals and instrumentation
Full general statements were described elsewhere.20 All re-
agents were commercially available (Acros, Aldrich, Strem)
and were used as received.
4.2. General procedure for reaction of secondary
alcohols with primary alcohols
4.2.4. 3-(2-Naphthyl)-1-phenyl-1-propanol (3e).9 tR 19.4;
Rf 0.68 (hexane/ethyl acetate: 4/1); n (film) 3375 (O–H),
3057, 1596, 1518 (C]CH), 1066 cmꢂ1 (C–O); dH 1.95
(1H, s, OH), 2.10–2.30 (2H, m, CH2CO), 3.05–3.15 and
3.20–3.30 (2H, m, CH2CH2CO), 4.75–4.80 (1H, m, CHO),
7.25–7.50, 7.70, 7.80–7.85, and 7.95–8.00 (9H, 1H, 1H,
and 1H, respectively, m, d, m, and m, respectively,
J¼8 Hz, ArH); dC 29.10, 39.80, 74.15, 123.75, 125.45,
125.55, 125.80, 125.95 (2C), 126.65, 127.70, 128.55 (2C),
128.75, 131.80, 133.90, 137.95, 144.50; m/z 262 (M+,
32%), 244 (24), 155 (17), 154 (11), 153 (38), 152 (14),
143 (12), 142 (100), 141 (40), 133 (11), 128 (13), 115
(22), 107 (20), 79 (22), 77 (18).
To a solution of RuCl2(DMSO)4 (0.048 g, 0.1 mmol) and
KOH (0.660 g, 10 mmol) in 1,4-dioxane (5 mL) was added
the corresponding secondary alcohol 1 or 4 (5 mmol), fol-
lowed by the addition of the corresponding primary alcohol
2 or 13 (5 mmol). In the case of using amino alcohols 13,
benzophenone (2.7 g, 15 mmol) was also added. The mix-
ture was stirred and heated at 80 ꢀC for a period of seven
days. Then, the mixture was quenched by addition of a satu-
rated NH4Cl solution (20 mL) and extracted with ethyl ace-
tate (3ꢁ15 mL). The combined organic layers were dried
over anhydrous Na2SO4, filtrated, and removed under re-
duced pressure. The resulting residue was purified by flash
chromatography on silica gel using suitable mixtures of
hexane/ethyl acetate to afford the corresponding product 3,
5 or 14. Yields are included in Tables 1–4. Compounds 3a,
3g, 3h, 3l, 5a, 5b, 5d, 5e, 14a–f, which have been previously
fully described by us,4n were characterized by comparison of
their spectroscopic (IR, 1H, and 13C NMR, and mass spectra)
and chromatographic data with those of the reported
4.2.5. 1-Phenyl-3-(2-furyl)-1-propanol (3f).21 Rf 0.23
(hexane/ethyl acetate: 4/1); tR 13.4; n (film) 3394 (O–H),
3021, 1597, 1514 (C]CH), 1065 cmꢂ1 (C–O); dH 1.95
(1H, s, OH), 2.00–2.15 (2H, m, CH2CO), 2.65–2.80 (2H,
m, CH2CH2CO), 4.70–4.75 (1H, m, CHO), 5.95–6.00,
6.25–6.30, and 7.25–7.35 (1H, 1H, and 6H, respectively,
3m, ArH); dC 24.35, 37.10, 73.65, 105.00, 110.10, 125.85
(2C), 127.65, 128.50 (2C), 140.95, 144.30, 155.50; m/z

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R. Martınez et al. / Tetrahedron 62 (2006) 8982–8987
8986
202 (M+, 6%), 185 (14), 184 (100), 183 (13), 155 (27), 141
(12), 120 (12), 107 (30), 105 (17), 104 (10), 91 (12), 81 (22),
79 (40), 77 (31).
and CTIDB/2002/318), and University of Alicante (UA).
We thank MEDALCHEMY company for the generous gift
of RuCl2(DMSO)4. R.M. thanks Generalitat Valenciana for
a predoctoral grant.
4.2.6. 1-(4-Methylphenyl)-3-phenyl-1-propanol (3i).9 Rf
0.39 (hexane/ethyl acetate: 4/1); tR 15.7; n (film) 3377
(O–H), 3023, 1607, 1520 (C]CH), 1066 cmꢂ1 (C–O);
dH 1.86 (1H, s, OH), 1.95–2.20 (2H, m, CH2CO), 2.34
(3H, s, CH3), 2.60–2.80 (2H, m, CH2CH2CO), 4.60–4.65
(1H, m, CHO), 7.15–7.30 (9H, m, ArH); dC 21.10,
32.05, 40.30, 73.70, 125.75, 125.85 (2C), 128.35 (2C),
128.40 (2C), 129.15 (2C), 137.70, 141.55, 141.80; m/z
226 (M+, 16%), 208 (21), 121 (100), 93 (27), 91 (30),
77 (17).
References and notes
1. (a) Wilkinson, S. G. Comprehensive Organic Chemistry;
Barton, D., Ollis, W. D., Eds.; Pergamon: Oxford, 1979;
Vol. 1, pp 579–706; (b) Mitsunobu, O. Comprehensive
Organic Synthesis; Winterfeldt, E., Ed.; Pergamon: Oxford,
1991; Vol. 6, pp 1–31; (c) Sweeny, J. B. Comprehensive
Organic Functional Group Transformations; Ley, S. V., Ed.;
Pergamon: Oxford, 1995; Vol. 2, pp 37–88; (d) Larock, R. C.
Comprehensive Organic Transformations, 2nd ed.; Wiley-
VCH: New York, NY, 1999; pp 959–1195.
2. (a) Metzger, J. O.; Eissen, M. C.R. Chimie 2004, 7, 569–581;
(b) Jenck, J. F.; Agterberg, F.; Droescher, M. J. Green Chem.
2004, 6, 544–556; (c) Thomas, J. M.; Raja, R. Annu. Rev.
Mater. Res. 2005, 35, 315–350; (d) Parthasarathy, G.; Hart,
R.; Jamro, E.; Miner, L. Clean Technol. Environ. Policy 2005,
7, 219–229.
4.2.7. 3-(4-Chlorophenyl)-1-(4-methylphenyl)-1-propa-
nol (3j). Rf 0.46 (hexane/ethyl acetate: 8/2); tR 17.6;
n (film) 3377 (O–H), 3115, 3028, 1500 (C]CH), 1095
(C–O); dH 1.82 (1H, s, OH), 1.85–2.15 (2H, m, CH2CO),
2.55–2.75 (2H, m, CH2CH2CO), 2.35 (3H, s, CH3), 4.62
(1H, t, J¼5.7 Hz, CHO), 7.05–7.3 (8H, m, ArH); dC 21.00,
31.40, 40.20, 73.50, 125.80, 128.40, 129.2, 129.75, 131.2,
137.2, 140.3, 141.4; m/z 260 (M+, 6%), 242 (23), 121
(100), 93 (25), 91 (19), 77 (16). HRMS: M+ found
260.0966. C16H17OCl requires 260.0968.
3. (a) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl.
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4.2.8. 3-(3,4-Dimethoxyphenyl)-1-(4-methylphenyl)-1-
propanol (3k). Rf 0.18 (hexane/ethyl acetate: 8/2); tR
19.5; n (film) 3437 (O–H), 3004, 1595 (C]CH), 2839
(MeO), 1033 cmꢂ1 (C–O); dH 1.90 (1H, s, OH), 1.90–
2.15 (2H, m, CH2CO), 2.35 (3H, s, CH3), 2.60–2.70 (2H,
m, CH2CH2CO), 3.85 (6H, s, 2ꢁMeO), 4.65 (1H, t, J¼
5.1 Hz, CHO), 6.70–6.80, 7.16, and 7.24 (3H, 2H, and
2H, respectively, m, d, and d, respectively, J¼7.9 and
8.3 Hz, respectively, ArH); dC 21.00, 31.65, 40.50, 55.75,
55.85, 73.70, 111.15, 111.65, 120.15, 125.85, 129.15,
134.40, 137.30, 141.55, 147.10, 148.75; m/z 287 (M++1,
13%), 286 (M+, 66), 268 (21), 237 (21), 153 (10), 152
(100), 151 (29), 137 (18), 121 (48), 93 (16), 91 (21), 77
(16). HRMS: M+ found 286.1563. C18H22O3 requires
286.1569.
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15.7; n (KBr) 3054, 1656 (C]CH), 1728 cmꢂ1 (C]O);
dH 0.80, 0.99, and 1.03 [3H each, 3s, (CH3)2CCCH3],
1.45–1.60, 1.75–1.80, and 2.15–2.20 (2H, 1H, and 1H,
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127.40, 128.55 (2C), 128.60, 129.65 (2C), 135.55, 142.00,
208.10; m/z 240 (M+, 100%), 225 (31), 212 (14), 198 (12),
197 (46), 184 (12), 171 (10), 169 (21), 158 (42), 157 (51),
156 (31), 155 (26), 149 (16), 141 (30), 134 (13), 130 (12),
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