The efficiency of the metal catalysts in the nucleophilic substitution of alcohols is dependent on the nucleophile and not on the electrophile

Article abstract of DOI:10.1002/asia.201201178

In this study, we investigate the effect of the electrophiles and the nucleophiles for eight catalysts in the catalytic S_N1 type substitution of alcohols with different degree of activation by sulfur-, carbon-, oxygen-, and nitrogen-centered nucleophiles. The catalysts do not show any general variance in efficiency or selectivity with respect to the alcohols and follow the trend of alcohol reactivity. However, when it comes to the nucleophile, the eight catalysts show general and specific variances in the efficiency and selectivity to perform the desired substitution. Interestingly, the selectivity of the alcohols to produce the desired substitution products was found to be independent of the electrophilicity of the generated carbocations but highly dependent on the ease of formation of the cation. Catalysts based on iron(III), bismuth(III), and gold(III) show higher conversions for S-, C-, and N-centered nucleophiles, and Bi^III was the most efficient catalyst in all combinations. Catalysts based on rhenium(I) or rhenium(VII), palladium(II), and lanthanum(III) were the most efficient in performing the nucleophilic substitution on the various alcohols with the O-centered nucleophiles. These catalysts generate the symmetrical ether as a by-product from the reactions of S-, C-, and N-centered nucleophiles as well, resulting in lower chemoselectivity. Who's the boss? In a comprehensive study of catalytic S _N1 type direct substitution of alcohols, the catalysts do not show any general variance in efficiency or selectivity with respect to the alcohols but are highly variable with respect to the nucleophiles. The reactivity of the alcohols is independent of the electrophilicity of the generated carbocations but highly dependent on the ease of formation of the cation.

Full text of DOI:10.1002/asia.201201178

FULL PAPER
DOI: 10.1002/asia.201201178
The Efficiency of the Metal Catalysts in the Nucleophilic Substitution of
Alcohols is Dependent on the Nucleophile and Not on the Electrophile
Srijit Biswas and Joseph S. M. Samec*[a]
Abstract: In this study, we investigate
the effect of the electrophiles and the
nucleophiles for eight catalysts in the
catalytic SN1 type substitution of alco-
hols with different degree of activation
by sulfur-, carbon-, oxygen-, and nitro-
gen-centered nucleophiles. The cata-
lysts do not show any general variance
in efficiency or selectivity with respect
to the alcohols and follow the trend of
alcohol reactivity. However, when it
comes to the nucleophile, the eight cat-
alysts show general and specific varian-
ces in the efficiency and selectivity to
perform the desired substitution. Inter-
estingly, the selectivity of the alcohols
to produce the desired substitution
products was found to be independent
of the electrophilicity of the generated
carbocations but highly dependent on
the ease of formation of the cation.
sions for S-, C-, and N-centered nucleo-
philes, and BiIII was the most efficient
catalyst in all combinations. Catalysts
based on rhenium(I) or rhenium
ACHTUNGTRENNUNG(VII),
palladium(II), and lanthanum(III) were
AHCTUNGTRENNUNG
the most efficient in performing the nu-
cleophilic substitution on the various
alcohols with the O-centered nucleo-
philes. These catalysts generate the
symmetrical ether as a by-product from
the reactions of S-, C-, and N-centered
nucleophiles as well, resulting in lower
chemoselectivity.
Catalysts based on iron
ACHTUNGTREN(NGNU III), bismuth-
A
ACHTUNGTRENNUNG
Keywords: alcohols
·
atom
economy · homogeneous catalysis ·
nucleophilic substitution
Introduction
tion.[2] However, this reaction requires stoichiometric carnci-
nogenic and explosive DEAD[3] and also generates stoichio-
metric amounts of waste, which gives rise to tedious purifi-
cation problems. From perspectives of safety, environment,
and economy, these stoichiometric and waste-generating
methodologies are not desirable.[4] This fact was recently ac-
knowledged when the nucleophilic substitution of alcohols
was selected as the second most desired reaction that phar-
maceutical companies wanted greener alternatives for.[5]
Catalytic nucleophilic substitution of alcohols is an attrac-
tive and useful synthetic tool, which owes its efficiency to
the atoms and heeds environmental constraints, since water
is the only by-product of this single-step reaction
(Scheme 2).[6] Various metal complexes have been reported
Activation of the hydroxy group is fundamental to organic
chemistry when alcohols are used as substrates in nucleo-
philic substitutions. Traditionally, the hydroxy group is con-
verted into a better leaving group in a separate step
(Scheme 1). The conversion of the hydroxy group into, for
Scheme 1. Traditional substitution of the hydroxy group requires an addi-
tional step, uses a stoichiometric amount of reagents, and generates
waste.
example, a tosyl group or a halide, requires the addition of
stoichiometric amounts of reagent and base and also makes
the synthetic procedure one step longer.[1] The intermediates
that form are often carcinogenic due to their strong alkylat-
ing properties. Furthermore, stoichiometric amounts waste is
generated in the subsequent nucleophilic substitution step.
An alternative route, used for stereospecific substitutions of
enantioenriched alcohols, is the one-step Mitsunobu reac-
Scheme 2. Catalytic nucleophilic substitution of alcohols. [M]=metal-
based catalyst.
to be active for the catalytic nucleophilic substitution of al-
cohols. Lewis acids based on metal salts, such as iron
bismuth
(III),[8] boron(III),[9] cerium(III),[10] indium(III),[11]
gold rhenium and
(III),[12] rhenium(V),[13] (VII),[14]
lanthanum
(III),[15] have been reported to catalyze nucleo-
ACHTUNGTRENNUNG
(III),[7]
A
E
N
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
[a] Dr. S. Biswas, Dr. J. S. M. Samec
Department of Chemistry, BMC
Uppsala University
AHCTUNGTRENNUNG
philic substitution of different alcohols. Also, certain transi-
tion metals prone to cycle between different oxidation
Box 576, 751 23 Uppsala (Sweden)
Fax : (+46)018-471 3818
E-mail: Joseph.Samec@kemi.uu.se
states, such as ruthenium
(I,III),[18] and palladium(0,II),[19] have been reported to be
active for this transformation.
(I,II),[16] rhenium(I,III),[17] iridium-
ACHUTGTNRENNUG CAHTUNGTRENNUGN
A
ACHTUNGTRENNUNG
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201201178.
Chem. Asian J. 2013, 8, 974 – 981
974
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Srijit Biswas and Joseph S. M. Samec
The research field of catalytic nucleophilic substitution of
Choice of Electrophiles
alcohols is difficult to overview. To our knowledge, there is
only one review that covers the research topic.[20] The great-
est challenge to the understanding of the reactivity is that
different research groups use different reaction conditions.
Table 1 gives an example of an etherification reaction be-
We have chosen five different alcohols, all of which have
different degrees of activation (Scheme 3). The aim was to
map the reactivity of 1) alcohols with different degrees of
activation and 2) different activating groups (benzyl, allyl,
propargyl, alkyl). Another aim was to use substrates that
may react at different positions and thereby map regiose-
lectivity in, for example, allyl and propargyl alcohols.
Table 1. Representative reports on the catalyzed etherification reaction in
the literature.
Entry[ref] Catalyst
Catalyst
loading
T
[8C]
Solvent ROH
t
Conv.
[%]
ACHTUNGTRENNUNG
AHCTUNGTRENGN[UN mol%]
1[12a]
2[17]
3[14]
4[7a]
5[19a]
NaAuCl4
[ReBr(CO)]5
ReMeO3
FeCl3
2
3
2
20
4
70
160
rt C6H6
40
–
–
5
5
10
150
1
1
12
48
58
87
91
0
G
–
n.r.[b]
A
N
50 MeNO2
24
99
Scheme 3. Alcohols used in the current study. PMP=para-methoxyphen-
yl.
[a] diop=4R,5R-(+)-O-Isopropylidene-2,3-di-hydroxy-1,4-bis(diphenylphos-
phanyl)butane. [b] Not reported.
In a precise and well-defined study, an electrophilicity pa-
rameter and two nucleophilicity parameters have been in-
troduced by Mayr et al.[21] in describing the rate of reaction
between a carbocationic electrophile and a nucleophile.[21a]
The most important outcome of their study is to consider all
the parameters, such as electrophilicity of the generated car-
bocation, nucleophilic properties of the nucleophile, as well
as the solvent and the generated by-product while defining
an empirical scale of reactivity applicable for SN1 type reac-
tions.[21b] Moreover, they have established a rule explaining
the feasibility of the reaction between a given electrophile–
nucleophile pair.[21c]
tween a primary aliphatic alcohol (nucleophile) and a pri-
mary benzylic alcohol (electrophile). The following issues
make a comparison between the catalysts impossible: 1) cat-
alyst loadings vary between 2 and 20 mol%, 2) reaction tem-
peratures vary between room temperature and 1608C,
3) some reports use solvent where others do not, 4) the nu-
cleophile is used in either an equimolar amount or in excess,
5) reaction time varies from 1 to 48 h. To our knowledge,
there are no attempts to evaluate the performance of the
different catalysts with respect to electrophile or nucleo-
phile.
Herein, we study the scope and limitations of nucleophilic
substitution of alcohols with respect to the catalyst and the
electrophile as well as the nucleophile. We investigate
whether certain metal catalysts have 1) higher rates of con-
version for certain electrophiles, 2) higher regioselectivity in
allylic and propargylic alcohols, 3) higher rates of conversion
for certain nucleophiles, 4) higher chemoselectivity for cer-
tain nucleophiles. To our knowledge, this is the first compre-
hensive study on the catalytic nucleophilic substitution of al-
cohols that covers a broad range of both electrophiles and
nucleophiles.
Interestingly, in the present study, the efficiency order of
the electrophilic alcohols in terms of selectivity to form the
desired substitution products was found to be governed by
the ease of generating the corresponding carbocation rather
than the electrophilicity of the generated cation.
4-Methoxybenzyl alcohol (1a) was the most efficient alco-
hol to generate the desired products in this study. The
second next reactive alcohol, 4-phenyl-3-butene-2-ol (1b)
was chosen in order to discriminate the allylic reactivity.[7i] It
was chosen over the far more commonly used 1,3-diphenyl-
2-propen-1-ol,[11a,16g] which does not discriminate between
benzylic and allylic reactivity. 1-Phenylethanol (1c) is a fre-
quently used substrate in catalytic nucleophilic substitution
studies and was chosen to represent a secondary benzylic al-
cohol with medium reactivity.[7c,11a] tert-Butyl alcohol (1d)
was chosen to represent a tertiary alkyl alcohol.[12a] tert-
Butyl alcohol was found to be susceptible to water elimina-
tion, producing volatile isobutylene in appreciable amount
in case of most of the catalyst where no or low amount of
product formation was observed (see the Supporting Infor-
mation for details).[8b] 4-Phenyl-3-butyn-2-ol (1e) was
chosen over the more frequently used 1,3-diphenyl[7n,8d] ana-
logue for the same reason as for the allylic substrate (see
above). For both substrates 1b and 1e, the attack on the nu-
Results and Discussion
In order to perform a comprehensive study of the catalytic
nucleophilic substitution of alcohols, the choices of electro-
philes, nucleophiles, and metal catalysts are pivotal. In this
section, a discussion regarding the choices made for this
study will be presented.
Chem. Asian J. 2013, 8, 974 – 981
975
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Srijit Biswas and Joseph S. M. Samec
cleophile could occur at either the benzylic or alcoholic po-
sitions and therefore, these substrates may discriminate re-
gioselectivity.
Lewis Acidic Metals
To study how the hardness or softness and the group identi-
ty (main group, transition metal, lanthanide) of the metal in-
fluence the efficiency to perform the reaction with respect
to both the electrophile and the nucleophile, different Lewis
Choice of Nucleophiles
We have chosen four different nucleophiles, with different
atom centers (S, C, O, N) to distinguish between the com-
patibility of the nucleophile and that of the catalyst
(Scheme 4). Another aim was to determine the efficiency of
the metal catalysts with hard–soft (O-, S-centered) nucleo-
philes as compared to their efficiency with weak–strong
(amide, thiol) nucleophiles.
acids (iron
tetrachloroaurate
flate) were selected. FeIII has been reported to be active in
G
ACHTUNGTRENNUNG
R
ACHTUNGTRENNUG
[7a,b,f]
[7k,m,n]
[7c]
À
À
À
C O,
C N,
and C C bond-forming reactions
with benzyl alcohols. BiIII has been reported to be active in
[8a,b,c]
[8d]
[8f]
À
À
C O,
À
various reactions, including C C,
C S, and
[8e]
C N bond-forming reactions. AuIII has been reported to
be active in etherification[12a] and amidation[12b,c] of benzylic
and tertiary alkyl alcohols. Lanthanoid salts have been re-
À
À
À
À
ported to be active in C C, C O, and C N bond-forming
[15]
À
reactions but not in C S bond-forming reactions.
Redox Metals
We wanted to compare how the oxidation state of the transi-
tion metal affected the compatibility with the nucleophile as
well as the electrophile. Also, we wanted to study how dif-
ferent transition metals that have been reported to be active
for different activating groups (i.e. Pd to allyls and Re to al-
kynes) perform on the selected substrates. Bis(acetonitrile)-
palladium(II)chloride, bromorhenium(I)pentacarbonyl and
Scheme 4. Nucleophiles used in the current study.
The commonly used thiophenol (2a) was chosen to repre-
sent a soft and strong nucleophile in this study. Acetyl ace-
tone (2b) was chosen to represent a strong and soft nucleo-
phile in which the enolate formation may be promoted by
Lewis acids.[7c,o] We chose 3-phenyl propanol (2c)[12a] as an
O-centered nucleophile because this substrate is not volatile
and can easily be monitored by TLC. Attempts to employ
phenol as an O-centered nucleophile were unsuccessful in
a pre-screening, probably because of the strong complex for-
mation between the phenolic OH group and the metal,
methylrhenium
ACHTUNGTREN(NUNG VII)trioxide represent the redox metal cata-
lysts in this study. PdII has been reported to be active in C
À
À
À
O, C N, and C S bond-forming reactions and is prone to
form p–allyl complexes with allylic alcohols.[19a,b] The ReI
À
carbonyl compound has been reported to be active in C O
bond-forming reactions and is reported to form p–propargyl
complexes with propargylic alcohols.[14] ReVII does not have
the possibility to perform oxidative addition and has been
which would deactivate the catalyst. Benzamide ACTHNUTRGNEUG(N 2d), the
weakest nucleophile, was chosen because aniline was ob-
served to generate a complex with certain metals and para-
toluenesulfonamide was not reactive with some of the alco-
hols in an initial screening.
À
À
reported to be active in C O and C N bond-forming reac-
tions. It should be pointed out in this respect that AuIII can
also act as a redox-metal catalyst (AuIII/AuI).
Mineral Acids
Choice of Catalysts
We chose HCl as our mineral acid, because the Lewis acids
in our study may act as a precursor to generate the corre-
sponding mineral acid that could be the true catalyst.[8e] To
achieve adequate comparison, 20 mol% instead of 5 mol%
has been used with respect to the corresponding electrophil-
ic alcohol.
In a preliminary study, we included 20 catalysts that were
found in the literature of related studies.[7–19] However, the
study became too extensive to provide an accessible over-
view, and some of the catalysts showed similar reactivity.
For example, the anion effect was studied for BiBr3, BiCl3,
and BiI3, and only a negligible difference in efficiency was
observed. Therefore, after an initial screening, eight cata-
lysts were selected (Scheme 5). These catalysts have all been
reported in one or more of the different combinations of
electrophiles and nucleophiles. We have divided the cata-
lysts into three different categories: Lewis acidic metals,
redox metals, and mineral acids.
Catalytic Procedure
Reference compounds of all products were prepared using
catalytic methods in which the alcohol and nucleophile re-
acted in the presence of an appropriate catalyst. In many re-
actions, side reactions, such as homo-etherification to gener-
ate the symmetrical ether were observed. All by-products
were isolated and characterized separately. Temperatures
and reaction times of all reactions were pre-screened. It is
important to note that these reaction parameters were set in
order to differentiate between the reactivity of the combina-
tions in transformations. That is, the reaction parameters
Scheme 5. Catalysts used in the current study.
Chem. Asian J. 2013, 8, 974 – 981
976
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Srijit Biswas and Joseph S. M. Samec
were not optimized to generate the corresponding products
in high yields, but to disclose differences in reactivity among
the electrophiles, nucleophiles and catalysts.
of substrate 1b. If the reaction proceeded through a p-allyl
intermediate, such regioisomers would be expected.
For the less reactive alcohols (1d,e) in terms of selectivity
towards formation of the desired substitution product, the
Lewis acids promoted the thioetherification better, while
the redox metals showed low or no conversion to the de-
sired product. BiIII showed the highest degree of efficiency
and generated the desired products in a 50–79% yield. ReI
catalysts, which are known to generate p-propargylic metal
complexes, were unreactive in this transformation.[22] In
analogy to substrates 1a–c, etherification of 1e to generate
the symmetrical ether was observed. Using BiIII or FeIII cata-
lysts, symmetrical ethers were obtained in a 23–26% yield.
In the case of AuIII, an attack of the triple bond of 1e was
observed.[23] Moreover, the reactions involving tert-butyl al-
cohol 1d produced isobutylene as the major side product for
all the catalyst except bismuth, which generated 3d in 79%
yield (see the Supporting Information for details). The cata-
lysts that gave low conversion in direct substitution reactions
leading to thioetherification generally ended up with more
disulfide formation by oxidation of the unreacted thiophe-
nol.
Choice of Solvent
Pre-screening revealed nitromethane to be the best solvent
for all nucleophile–electrophile combinations. Dichloro-
ethane showed similar reactivity for reactions that were effi-
cient at low temperature. However, certain combinations of
electrophile and nucleophile required higher reaction tem-
perature. Running the reactions in toluene gave poor re-
sults.
Catalytic Nucleophilic Substitution by S-Centered
Nucleophile 2a
The results from the thioetherification reactions are given in
Table 2. The reactions were run under three different reac-
tion conditions, depending on the electrophile. Reactions
employing substrates 1a–1c were run at room temperature
for 10 h, 1e was run at 608C for 60 h, and 1d was run at
808C for 48 h. It is worth noting that, of the metals screened
in this study, only LaIII, BiIII, and PdII have been reported to
be active in the thioetherification reaction before.[15,19a]
Catalytic Nucleophilic
Substitution by C-Centered
Table 2. Conversion in the catalytic nucleophilic substitution of alcohols (1) by thiophenol (2a).[a,b]
Nucleophile 2b
À
The results from the C C
bond-forming reactions are
given in Table 3. The reactions
were run under three different
reaction conditions depending
on the electrophile. Reactions
employing substrates 1a and 1b
were run at room temperature
for 10 h, 1c was run at 608C for
10 h, and 1d and 1e were run
at 808C for 10 h. To our knowl-
edge, only FeIII[7c,o] and Pd0[19k]
have been reported to be active
in the nucleophilic substitution
of 2b.
Products
Catalysts
FeCl3
BiBr3
NaAuCl4·2H2O
69%
92%
81%
59%
86%
88%
99%
47% (70%)[c,d]
50% (85%)[c]
16%[d]
trace (82%)[e]
79%
66% (78%)[c]
74%
41% (61%)[c]
10% (23%)[c]
38% (57%)[c]
0%[d]
12% (45%)[e]
30% (89%)[c,e]
0% (21%)[e]
13% (57%)[e]
6% (51%)[e]
0% (23%)[e]
La
[PdCl
[ReBr(CO)5]
T
66% (79%)[c]
62% (73%)[c]
0%
10% (30%)[c]
0%[d]
A
U
61%
N
50%[d]
0%[d]
MeReO3
HCl[f]
80%
79%
61% (71%)[c,d]
53%[c]
48% (78%)[c,d]
32% (54%)[c]
19%[d]
8%[d]
[a] The reactions were run using alcohol 1 (1 mmol), 2a (1 mmol) in nitromethane (2.5 mL), and metal catalyst
(5 mol%). Reactions to form 3a–c were run at room temperature for 10 h. The reaction to form 3e was run at
608C for 60 h. The reaction to form 3d was run at 808C for 48 h. [b] Conversion was determined by 1H NMR
spectroscopy using toluene as an internal standard. Bold entries indicate reactions with higher efficiencies.
[c] In parenthesis: overall conversion of the electrophile where more than 10% formation of symmetrical
ether were observed. [d] The reactions were repeated at least twice to confirm the reproducibility of the ob-
served yield. [e] In parenthesis: overall conversion of tert-butyl alcohol to product and isobutylene determined
by 1H NMR spectroscopy. [f] 20 mol% with respect to the electrophile was used.
For the carbon nucleophile
2b, the allylic substrate 1b
showed the highest selectivity
for forming the desired product.
Except for ReI and ReVII, most
For thiophenol 2a, the benzylic and allylic substrates 1a–
c were the most selective electrophiles in the catalytic thioe-
therification reaction. Lewis acids generally performed well
in the thioetherification reaction, and BiIII showed the high-
est reactivity and also generated the desired products 3a–
c in 86–99% conversions. Other catalysts showed moderate
to good reactivity for these three electrophiles using the
same reaction conditions. For substrates 1a–c, homoetherifi-
cation was observed for PdII, AuIII, LaIII, ReVII and HCl,
which generated the symmetrical ether product in up to
30% yield. No regioisomers were observed in the reaction
catalysts generated the desired product 4b in 49–88% con-
version in less than 10 h. Generally, the Lewis acids gave
higher yields than the redox metals, where BiIII and FeIII
gave 88% and 87% product yield, respectively. AuIII, which
À
has never been reported to catalyze C C bond-forming re-
actions using 2b, generated the desired product in 80%
yield. Interestingly, PdII produced the product in 74% yield.
À
The mineral acid also catalyzed the C C bond-forming reac-
tion, though it generated the product in a lower yield.
The primary benzylic alcohol 1a was the second most se-
À
lective alcohol in the C C bond-forming reaction with 2b as
Chem. Asian J. 2013, 8, 974 – 981
977
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Srijit Biswas and Joseph S. M. Samec
Table 3. Conversion in the catalytic nucleophilic substitution of alcohols (1) by acetylacetone (2b).[a,b]
Scheme 6. Stabilization of 2b
by Lewis acidic catalysts.
Products
Catalysts
Catalytic Nucleophilic
Substitution by O-Centered
Nucleophile 2c
FeCl3
BiBr3
NaAuCl4·2H2O
87%
88%[c]
80%
69%
74%
0%[c]
12%[c]
49%
30%
65%
67%
99%[c]
38%[c]
0% (81%)[d]
0%
92%[c]
38%[c]
63% (75%)[c,e]
23% (33%)[c,e]
98%[c]
11%[c]
0% (42%)[d]
0% (80%)[d]
0% (22%)[d]
0% (73%)[d]
0% (57%)[d]
0% (24%)[d]
La
[PdCl
[ReBr(CO)5]
T
47% (70%)[e]
63%
23% (34%)[c,e]
0%[c]
The results from the etherifica-
tion by 3-phenylpropanol 2c
are given in Table 4. The reac-
tions were run under three dif-
ferent reaction conditions de-
pending on the electrophile.
Reactions employing substrates
1a and 1b were run at room
temperature for 10 h, 1c was
run at 608C for 6 h, and 1d and
1e were run at 908C for 10 h.
All catalysts in this study have
been reported to be active in
A
CHTUNGTRENNUNG
T
0% (19%)[e]
0% (30%)[e]
29%
15%[c]
17% (28%)[c,e]
0% (10%)[c,e]
0%[c]
MeReO3
0% (25%)[c,e]
12%[c]
HCl[f]
[a] The reactions were run using alcohol 1 (1 mmol), 2b (1 mmol) in nitromethane (2.5 mL), and metal catalyst
(5 mol%). Reactions to form 4a,b were run at room temperature for 10 h. The reaction to form 4c was run at
608C for 10 h. Reactions to form4d,e were run at 808C for 10 h. [b] Conversion was determined by 1H NMR
spectroscopy using toluene as an internal standard. Bold entries indicate reactions with higher efficiencies.
[c] The reactions were repeated at least twice to confirm the reproducibility of the observed yield. [d] In pa-
renthesis: overall conversion of tert-butyl alcohol to product and isobutylene determined by H NMR spectros-
copy. [e] In parenthesis: overall conversion of the electrophile where more than 10% formation of symmetrical
ether was observed. [f] 20 mol% with respect to the electrophile was used.
1
nucleophile and showed similar but lower efficiency than
the allylic substrate to generate 4a in 30–67% yield. LaIII,
ReVII, and ReI generated a substantial amount (23%, 30%,
and 19%) of the symmetrical ether of 1a.
etherification reactions.
Generally, the redox metals and LaIII were more efficient
in term of selectivity in generating the desired ethers than
the other Lewis acids. For both 1a and 1b, the Re-based cat-
alysts and also the La catalyst were the most efficient in the
etherification reaction to generate products 5a,b. In the re-
action of 1a, the symmetrical ether was generated in 20–
30% as a side product in the case of both catalysts. The al-
lylic substrate was more reactive than the primary benzylic
substrate, and both rhenium-based catalysts generated 5b in
62–66% conversions and 5a in 46–57% conversion. The Pd-
based catalyst was efficient in the transformation of the al-
lylic electrophile, but not for transformation of the primary
benzylic electrophile. Generally, the mineral acid and the
Lewis acids were not efficient in the transformation of allyl-
ic and primary benzylic substrates using these reaction con-
ditions.
The secondary benzylic alcohol 1c required heating at
608C and gave excellent yields of 4c with FeIII, BiIII and
PdII. Also, moderate reactivity of the AuIII catalyst was ob-
served in generating the product. The other catalysts
showed low or no activity in this reaction. The etherification
to generate the symmetrical ether was a major side reaction
in almost all cases where lower yield of product 4c was ob-
served. The symmetrical ether may be an intermediate for
many catalysts in this transformation. It should be noted
that ReVII was not active in this transformation; instead, the
symmetrical ether was generated in 25% yield.
Propargylic alcohol 1e was a poor substrate in this trans-
formation and required heating to 808C for 10 h. Using
either Fe- or Bi-based catalysts generated the desired prod-
uct 4e in a 38% yield, and the symmetrical ether was ob-
served as a by-product, especially with the Re- and La-
based catalysts.
Substrate 1d was even more challenging. After heating
the reaction mixture to 808C overnight, no conversion to 4d
was observed with any of the catalysts in this study, whereas
water elimination from tert-butyl alcohol was found to be
operating for all catalysts except bismuth, giving rise to the
formation of volatile isobutylene in 22–81% conversion. A
possible explanation for the higher reactivity of the Lewis
acids and PdII is that both the electrophile and the nucleo-
phile are activated by the catalyst. The catalyst stabilizes the
activated enolate ion and may form a chelated complex 2b’
(Scheme 6).
The secondary benzylic alcohol 1c required heating to
608C for 6 h in the etherification to generate 5c. Substrate
1c gave relatively good conversions, and ReI and AuIII
showed highest reactivity. Up to 20% symmetrical ether was
observed when LaIII, ReI,VII, and HCl were employed as cat-
alysts.
The least selective electrophiles to form the desired sub-
stitution products were the propargylic and tertiary aliphatic
alcohols. These substrates required higher reaction tempera-
tures and longer reaction times than the other substrates. In
general, the propargylic alcohol was slightly more reactive
than the tertiary alcohol. LaIII, ReI, ReVII and BiIII gave high
rates of conversion to 5e (60–76%). Remarkably, the PdII
catalyst was not efficient in this transformation. We found
that when the acetonitrile ligands were exchanged for stron-
ger donor ligands (phenanthroline or triphenylphosphine)
Chem. Asian J. 2013, 8, 974 – 981
978
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Srijit Biswas and Joseph S. M. Samec
Table 4. Conversion in the catalytic nucleophilic substitution of alcohols (1) by 3-phenyl propanol (2c).[a,b]
For benzamide 2d, the allylic
alcohol 1b was the most effi-
cient electrophile and was ami-
dated at room temperature by
BiIII catalysis. After 10 h, 59%
of 6b was obtained. All other
catalysts gave no or low rates of
conversion to product at this
Products
Catalysts
temperature.
However,
at
FeCl3
BiBr3
NaAuCl4·2H2O
0%
0%
0%
0%
0%
trace
54%[c]
23% (87%)[d]
41%
higher reaction temperatures,
most other catalyst showed
moderate to good reactivity.
The generation of the allylic
cation was previously reported
by Jana et al.,[7i] who employed
two diastereomeric allylic alco-
68%
64%[c]
31%
19%
Trace
46%[c]
57%
0%
76%[c]
45%[c]
34% (59%)[d]
30% (83%)[d]
51% (60%)[d]
52% (79%)[d]
48% (70%)[d]
21% (38%)[d]
La
[PdCl
[ReBr(CO)5]
T
67%[c]
58%[c]
66%[c]
62%[c]
0%
42% (62%)[c,e]
59%
76%[c]
N
U
0%,[c] 30%[f]
71%[c]
U
78%[c]
MeReO3
64%
60%[c]
HCl[g]
37% (47%)[e]
52%[c]
[a] The reactions were run using alcohol 1 (1 mmol), 2b (1 mmol) in nitromethane (2.5 mL), and metal catalyst
(5 mol%). Reactions to form 5a,b were run at room temperature for 10 h. The reaction to form 5c was run at
608C for 6 h. Reactions to form 5d,e was run at 908C for 10 h. [b] Conversion was determined by 1H NMR
hols, one having
a hydroxy
group to the more hindered
spectroscopy using toluene as an internal standard. Bold entries indicate reactions with higher efficiencies. side near the Ph group and an-
[c] The reactions were repeated at-least twice to confirm the reproducibility of the observed yield. [d] Overall
conversion in parenthesis of tert-butyl alcohol to product and isobutylene determined by H NMR spectrosco-
py. [e] Overall conversion in parenthesis of the electrophile where more than 10% formations of symmetrical
ether were observed. [f] Phenantroline and OTf was used as ligands. [g] 20 mol% with respect to the electro-
other having a hydroxy group
at the less hindered side. They
1
observed the formation of same
product catalyzed by FeIII salt
phile was used.
in nitromethane solvent, which
supports the formation of the
and the chlorides were exchanged for the less coordinating
triflates, 5e was generated in 30% yield after 10 h
(Scheme 7). Still, only one regioisomer was formed.
The tertiary alcohol 1d was the least efficient substrate in
the etherification reaction to form the desired substitution
product. ReI,VII and PdII performed the reaction the best,
and ether 5d was generated in 48–52% conversions. A pos-
sible hypothesis for the higher efficiency of the redox metals
in the etherification reaction is that a hydrogen-borrowing
mechanism is operating. We concluded by experiment that
this was not the case (see the Supporting Information). In
addition to formation of the desired product, an appreciable
amount of isobutylene was observed by water elimination of
tert-butyl alcohol (see the Supporting Information for de-
tails).
allylic cation during the course of the reaction.
The second most selective electrophile in the amidation
reaction was the tertiary alcohol 1d. Interestingly, this sub-
strate showed less efficiency towards product formation for
the other nucleophiles in this study. The tertiary alcohol was
amidated by 2d at 808C by both FeIII and BiIII catalysis.
After 10 h, the product 6d was formed in 31% and
52%yield, respectively. No other catalyst was efficient for
amidation of 1d under these reaction conditions. In analogy
to the other transformations using 1d, isobutylene formation
was a major side reaction for all the catalyst except bismuth
(see the Supporting Information for details).
The secondary benzylic alcohol 1c was amidated at 1008C
and the reactions were run for 12 h. FeIII and BiIII were the
most efficient and gave 6c in 47% and 48% of conversions,
respectively. ReI, AuIII, and PdII were also reactive and gave
Catalytic Nucleophilic Substitution by N-Centered
Nucleophile 2d
6c in 29–36% conversion. In the case of ReI, the desired
I
À
product was generated in 35% yield. This Re -catalyzed C
The results from the amidation reactions are given in
Table 5. The reactions were run under three different reac-
tion conditions depending on the electrophiles; 1b was run
at room temperature for 10 h, 1a and 1d were run at 808C
N bond-forming reaction has not been reported before.
LaIII, ReVII, and HCl showed low reactivity in the amidation
reaction of 1c. LaIII, ReI, and HCl produced the symmetrical
ether in 31–45% conversion. Primary benzylic alcohol 1a
was amidated at 808C with all catalysts except FeIII to gener-
ate 6a in low yields. BiIII showed the highest catalytic activi-
ty and generated the product in 43% yield after 12 h. The
other catalysts generated the
for 12 h, and 1c and 1e were run at 1008C for 12 h. All cata-
I
À
lysts except Re have been reported to be active in C N
bond-forming reactions.
product in 17–31% of conver-
sions.
The propargylic alcohol 1e
was the least reactive alcohol in
the amidation reactions. Only
Scheme 7. Donating dative ligands and less-coordinating triflate ligand on palladium are necessary for reactivi-
ty in etherification of 1e.
FeIII and BiIII showed any reac-
Chem. Asian J. 2013, 8, 974 – 981
979
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Srijit Biswas and Joseph S. M. Samec
Table 5. Conversion in the catalytic nucleophilic substitution of alcohols (1) by benzamide (2d).[a,b]
cleophile, PdII and ReVII gave
moderate rates of conversion
whereas ReI performed poorly.
In the case of the C-centered
nucleophile, only PdII was
active. For the O-centered nu-
cleophile, all redox metals per-
formed with high efficiency. For
the N-centered nucleophile, ReI
performed better than both PdII
and ReVII. Formation of volatile
isobutylene was observed as
major side product for most of
the reactions employing tert-
butyl alcohol (1d) as electro-
phile, except in the case of bis-
muth (see the Supporting Infor-
mation for details). This could
be an explanation why bismuth
was efficient to produce rela-
tively high conversion of the
desired products with most of
the nucleophiles involving 1d
as electrophile compared to
Products
Catalysts
FeCl3
BiBr3
NaAuCl4·2H2O
43%[c]
59%[c]
25%[c]
0%
28%
0%
31% (84%)[d]
52%
0%
47%
48%
36%
20%
13%
0%
trace
0%
0%
0%
0%
43%
31%
21%
27%[c]
31%
28%
17%
0% (41%)[d]
0% (81%)[d]
0% (18%)[d]
10% (76%)[d]
trace (50%)[d]
0% (22%)[d]
La
[PdCl
[ReBr(CO)5]
T
trace (45%)[e]
29%
N
G
R
35%[c]
MeReO3
HCl[f]
0%
0%
0% (37%)[c,e]
11% (31%)[e]
[a] The reactions were run using alcohol 1 (1 mmol), 2d (1 mmol) in nitromethane (2.5 mL) using metal cata-
lyst (5 mol%). The reactions to form 6b was run at room temperature for 10 h. Reactions to form 6a,d were
run at 808C for 12 h. Reactions to form 6c,e were run at 1008C for 12 h. [b] Conversion was determined by
1H NMR spectroscopy using toluene as an internal standard. Bold entries indicate reactions with higher effi-
ciencies. [c] The reactions were repeated at least twice to confirm the reproducibility of the observed yield.
[d] In parenthesis: overall conversion of tert-butyl alcohol to product and isobutylene determined by 1H NMR
spectroscopy. [e] In parenthesis: overall conversion of the electrophile where more than 10% formation of
symmetrical ether were observed. [f] 20 mol% with respect to the electrophile was used.
tivity towards desired product formation, where the former
other Lewis acids.
catalyst generated 6e in 20% conversion.
Interestingly, in this study, the efficiency of the reactions
to generate the products was found to be highly dependent
on the reactivity of the nucleophiles. Currently we are inves-
tigating the detailed mechanism, supported by theoretical
calculations.
Synopsis
The aim of this study was to determine the efficiency of dif-
ferent metals in performing catalytic nucleophilic substitu-
tion of alcohols with respect to the electrophile as well as
the nucleophile. In the following section, we conclude and
discuss the reactivity of the metals with respect to electro-
philes and nucleophiles.
No major deviations among the catalysts with regards to
the electrophiles were observed in this study. The trend in
Scheme 3 was consistent for all metals, regardless of the nu-
cleophile. Furthermore, there was no observed difference in
regioselectivity of any of the substrates. Even in the case of
substrates with allylic or propargylic functionality, only sub-
Conclusions
This study provides an objective overview over the factors
that govern the reactivity in the catalytic nucleophilic substi-
tution of alcohols. Surprisingly, there is no observed devia-
tion in reactivity or regioselectivity between the catalysts
and the electrophiles; that is, the ease to generate the carbo-
cation from the alcohol substrate is what governs the con-
version to the desired product, and not the catalyst.
However, there are several differences in reactivity and
chemoselectivity with respect to the nucleophile in these re-
actions. We found that: 1) ReI,VII, PdII, and LaIII generally
favor O-centered nucleophiles and 2) FeIII, BiIII, and AuIII
give better results with the S-, C-, and N-centered nucleo-
philes.
À
stitution at the C O position was observed. For the nucleo-
philes, general and specific differences between the metals
were observed. Overall, FeIII, BiIII, and AuIII showed greater
efficiency than the redox metals for S-, C-, and N-centered
nucleophiles, and PdII, ReI, ReVII, and LaIII showed higher
efficiency for the O-centered nucleophile. Within the group
of Lewis acids, BiIII gave the best results, regardless of the
nucleophile (except O-centered). Across the range of nucle-
ophiles, FeIII and BiIII showed similar reactivity. Generally,
AuIII was observed to perform with slightly lower efficiency
than FeIII and BiIII. Interestingly, the use of LaIII produced
lower rates of conversion than the other Lewis acids for all
nucleophiles except for the O-centered 2c.
Experimental Section
Representative experimental procedure for the synthesis of 1-(3-((E)-4-
Phenylbut-3-en-2-yloxy)propyl)benzene (5b):
Allylic alcohol 1b (148 mg, 1 mmol), 3-phenyl propanol 2c (136 mL,
1 mmol), and LaACHTNUGTRENUNG(OTf)3 (29 mg, 0.05 mmol) were stirred at room temper-
ature in nitromethane (2.5 mL) under nitrogen for 10 h (see general
screening procedure in the Supporting Information for details). Nitrome-
thane was evaporated under reduced pressure and the crude reaction
Within the group of redox metals, the reactivity was also
highly dependent on the nucleophile. For the S-centered nu-
Chem. Asian J. 2013, 8, 974 – 981
980
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Srijit Biswas and Joseph S. M. Samec
mixture was purified by silica-gel column chromatography to afford 5b
[11] a) M. Yasuda, T. Somyo, A. Baba, Angew. Chem. 2006, 118, 807;
Angew. Chem. Int. Ed. 2006, 45, 793; b) M. Yasuda, S. Yamasaki, Y.
Onishi, A. Baba, J. Am. Chem. Soc. 2004, 126, 7186; c) M. Yasuda,
T. Saito, M. Ueba, A. Baba, Angew. Chem. 2004, 116, 1438; Angew.
Chem. Int. Ed. 2004, 43, 1414.
[12] a) A. B. Cuenca, G. Mancha, G. Asensio, M. Medio-Simꢃn, Chem.
Eur. J. 2008, 14, 1518; b) V. Terrasson, S. Marque, M. Georgy, J.-M.
Campagne, D. Prim, Adv. Synth. Catal. 2006, 348, 2063; c) M.
Georgy, V. Boucard, J.-M. Campagne, J. Am. Chem. Soc. 2005, 127,
14180; d) W. Rao, P. W. H. Chan, Chem. Eur. J. 2008, 14, 10486.
[13] M. R. Luzung, D. F. Toste, J. Am. Chem. Soc. 2003, 125, 15760.
[14] Y. Liu, R. Hua, H.-B. Sun, X. Qiu, Organometallics 2005, 24, 2819.
[15] M. Noji, T. Ohno, K. Fuji, N. Futaba, H. Tajima, K. Ishii, J. Org.
Chem. 2003, 68, 9340.
[16] a) J. He, J. W. Kim, K. Yamaguchi, N. Mizuno, Angew. Chem. 2009,
121, 10072; Angew. Chem. Int. Ed. 2009, 48, 9888; b) Y. Inada, Y.
Nishibayashi, M. Hidai, S. Uemura, J. Am. Chem. Soc. 2002, 124,
15172; c) Y. Nishibayashi, Y. Inada, M. Hidai, S. Uemura, J. Am.
Chem. Soc. 2003, 125, 6060; d) Y. Nishibayashi, Y. Inada, M. Yoshi-
kawa, M. Hidai, S. Uemura, Angew. Chem. 2003, 115, 1533; Angew.
Chem. Int. Ed. 2003, 42, 1495; e) Y. Yamauchi, G. Onodera, K.
Sakata, M. Yuki, Y. Miyake, S. Uemura, Y. Nishibayashi, J. Am.
Chem. Soc. 2007, 129, 5175; f) Y. Nishibayashi, A. Shinoda, Y.
Miyake, H. Matsuzawa, M. Sato, Angew. Chem. 2006, 118, 4953;
Angew. Chem. Int. Ed. 2006, 45, 4835; g) A. B. Zaitsev, S. Gruber,
P. A. Plꢄss, P. S. Pregosin, L. F. Veiros, M. Wçrle, J. Am. Chem. Soc.
2008, 130, 11604.
(162 mg, 0.61 mmol, 61% yield of isolated product) as a colorless oil. IR
(Neat): n˜ =2930, 1722, 1453, 1097, 747, 696 cmÀ1 1H NMR (300 MHz,
.
CDCl3): d=1.35 (d, 6.3 Hz, 3H, H-methyl), 1.87–1.96 (m, 2H,
PhCH2CH2), 2.71 (dt, 2H, J=1.8 Hz, 7.2 Hz, 2H, PhCH2), 3.34–3.41 (m,
1H, OCH2), 3.50–3.57 (m, 1H, OCH2), 3.96–4.01 (m, 1H, OCH), 6.13
(dd, J=7.5 Hz, 16.2 Hz, 1H, H-olefin), 6.51 (d, J=15.9 Hz, 1H, H-
olefin), 7.07–7.41 ppm (m, 10H, H-arom). 13C NMR (100 MHz, CDCl3):
d=21.6, 31.5, 32.5, 67.5, 76.4, 125.7, 126.4, 127.5, 128.2, 128.4, 128.5,
128.5, 128.9, 130.7, 132.2 ppm. HRMS: calcd. for C19H22NaO 289.1568;
found: 289.1552. Elemental anal. (%) calcd. for C19H22O (266.38):
C 85.67, H 8.32; found C 85.70, H 8.36.
The reaction yield was determined by NMR spectroscopy to be 67%
before purification by taking out 100 mL of the reaction mixture and
using toluene as internal standard (see the Supporting Information).
Acknowledgements
We thank Vetenskapsrꢁdet, Stiftelsen Olle Engqvist Byggmꢂstare, Kun-
gliga Vetenskapsakademin, and Carl Tryggers Stiftelse for financial sup-
port. Dr. Biswas is a Wenner–Gren scholar.
[1] A. R. Katritzky, B. E. Brycki, Chem. Soc. Rev. 1990, 19, 83.
[2] O. Mitsunobu, Synthesis 1981, 1.
[3] DEAD is diethyl azodicarboxylate.
[4] a) R. A. Sheldon, Pure Appl. Chem. 2000, 72, 1233; b) B. M. Trost,
Science 1991, 254, 1471.
[5] D. J. C. Constable, P. J. Dunn, J. D. Hayler, G. R. Humphrey, Jr.,
J. L. Leazer, R. J. Linderman, K. Lorenz, J. Manley, B. A. Pearlman,
A. Wells, A. Zaks, T. Y. Zhang, Green Chem. 2007, 9, 411.
[6] Other methods include hydrogen borrowing, see, G. Guillena, D. J.
Ramon, M. Yus, Chem. Rev. 2010, 110, 1611.
[17] Z. Zhu, J. H. Espenson, J. Org. Chem. 1996, 61, 324.
[18] a) B. Blank, R. Kempe, J. Am. Chem. Soc. 2010, 132, 924; b) A.
Prades, R. Corberan, M. Poyatos, E. Peris, Chem. Eur. J. 2008, 14,
11474.
[19] a) K. J. Miller, M. M. Abu-Omar, Eur. J. Org. Chem. 2003, 1294;
b) Y. Bikard, R. Mezaache, J.-M. Weibel, A. Benkouider, C. Sirlin,
P. Pale, Tetrahedron 2008, 64, 10224; c) Y. Tamaru, Eur. J. Org.
Chem. 2005, 2647; d) J. Muzart, Tetrahedron 2005, 61, 4179; e) J.
Muzart, Eur. J. Org. Chem. 2007, 3077; f) T. Yamamoto, M. Akimo-
to, O. Saito, A. Yamamoto, Organometallics 1986, 5, 1559; g) S. Sa-
wadjoon, J. S. M. Samec, Org. Biomol. Chem. 2011, 9, 2548; h) S. Sa-
wadjoon, J. S. M. Samec, unpublished results; i) A. Lundstedt,
J. S. M. Samec, patent application WO2012121659 (A1); j) S. Sawad-
joon, A. Lundstedt, J. S. M. Samec, ACS Catal. 2013, in press, DOI:
10.1021/cs300785r; k) Y. Kayaki, T. Koda, T. Ikariya, J. Org. Chem.
2004, 69, 2595.
[7] a) P. Salehi, N. Iranpoor, F. K. Behbahani, Tetrahedron 1998, 54,
943; b) V. V. Namboodiri, R. S. Varma, Tetrahedron Lett. 2002, 43,
4593; c) U. Jana, S. Biswas, S. Maiti, Tetrahedron Lett. 2007, 48,
4065; d) Y. Nishimoto, Y. Onishi, M. Yasuda, A. Baba, Angew.
Chem. 2009, 121, 9295; Angew. Chem. Int. Ed. 2009, 48, 9131; e) S.-
K. Xiang, L.-H. Zhang, N. Jiao, Chem. Commun. 2009, 6487; f) A.
Mirzaei, S. Biswas, J. S. M. Samec, Synthesis 2012, 44, 1213; g) I.
Iovel, K. Mertins, J. Kischel, A. Zapf, M. Beller, Angew. Chem.
2005, 117, 3981; Angew. Chem. Int. Ed. 2005, 44, 3913; h) Z.-P.
Zhan, J.-l. Yu, H.-J. Liu, Y.-Y. Cui, R.-F. Yang, W.-Z. Yang, J.-P. Li,
J. Org. Chem. 2006, 71, 8298; i) U. Jana, S. Maiti, S. Biswas, Tetrahe-
dron Lett. 2008, 49, 858; j) U. Jana, S. Maiti, S. Biswas, Tetrahedron
Lett. 2007, 48, 7160; k) U. Jana, S. Biswas, S. Maiti, Eur. J. Org.
Chem. 2008, 5798; l) Y. Zhao, S. W. Foo, S. Saito, Angew. Chem.
2011, 123, 3062; Angew. Chem. Int. Ed. 2011, 50, 3006; m) J. Mi-
chaux, V. Terrasson, S. Marque, J. Wehbe, D. Prim, J.-M. Cham-
pagne, Eur. J. Org. Chem. 2007, 2601; n) W. Yan, Q. Wang, Y. Chen,
J. L. Petersen, X. Shi, Org. Lett. 2010, 12, 3308; o) S. Maiti, S.
Biswas, U. Jana, Synth. Commun. 2010, 41, 243; p) S. Biswas, S.
Maiti, U. Jana, Eur. J. Org. Chem. 2009, 2354.
[8] a) S. Kobayashi, T. Ogino, H. Shimuzu, S. Ishikawa, T. Hamada, K.
Manabe, Org. Lett. 2005, 7, 4729; b) F. Howard, S. Sawadjoon,
J. S. M. Samec, Tetrahedron Lett. 2010, 51, 4208; c) Y. Nishimoto, M.
Kajioka, T. Saito, M. Yasuda, A. Baba, Chem. Commun. 2008, 6396;
d) H. Qin, N. Yamagiwa, S. Matsunaga, M. Shibasaki, Angew. Chem.
2007, 119, 413; Angew. Chem. Int. Ed. 2007, 46, 409; e) P. A. Evans,
J. Cui, S. J. Gharpure, R. J. Hinkle, J. Am. Chem. Soc. 2003, 125,
11456; f) Z.-P. Zhan, W.-Z. Yang, R.-F. Yang, J.-L. Yu, J.-P. Li, H.-J.
Liu, Chem. Commun. 2006, 3352; g) S. Biswas, S. Maiti, U. Jana,
Eur. J. Org. Chem. 2010, 2861.
[20] E. Emer, R. Sinisi, M. G. Capdevila, D. Petruzziello, F. De Vincen-
tiis, P. G. Cozzi, Eur. J. Org. Chem. 2011, 647.
[21] a) H. Mayr, B. Kempf, A. R. Ofial, Acc. Chem. Res. 2003, 36, 66;
b) H. Mayr, M. Patz, Angew. Chem. 1994, 106, 990; Angew. Chem.
Int. Ed. Engl. 1994, 33, 938; c) C. Schindele, K. N. Houk, H. Mayr, J.
Am. Chem. Soc. 2002, 124, 11208; d) H. Mayr, O. Kuhn, M. F.
Gotta, M. Patz, J. Phys. Org. Chem. 1998, 11, 642; e) H. Mayr, T.
Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker, B. Kempf, R.
Loos, A. R. Ofial, G. Remennikov, H. Schimmel, J. Am. Chem. Soc.
2001, 123, 9500; f) S. Minegishi, S. Kobayashi, H. Mayr, J. Am.
Chem. Soc. 2004, 126, 5174; g) H. Mayr, A. R. Ofial in Carbocation
Chemistry (Eds.: G. A. Olah, G. K. S. Prakash), Wiley, Hoboken, NJ,
2004, chap. 13, p. 331; h) S. T. A. Berger, F. H. Seeliger, F. Hofbauer,
H. Mayr, Org. Biomol. Chem. 2007, 5, 3020; i) M. Baidya, G. Y. Re-
mennikov, P. Mayer, H. Mayr, Chem. Eur. J. 2010, 16, 1365.
[22] a) C. P. Casey, C. S. Yi, J. Am. Chem. Soc. 1992, 114, 6597; b) C. P.
Casey, A. D. Selmeczy, J. R. Nash, C. S. Yi, D. R. Powell, R. K. Hay-
ashi, J. Am. Chem. Soc. 1996, 118, 6698; c) C. P. Casey, T. M. Boller,
J. S. M. Samec, J. R. Reinert-Nash, Organometallics 2009, 28, 123.
[23] S. Biswas, J. S. M. Samec, Chem. Commun. 2012, 48, 6586.
Received: December 12, 2012
Revised: January 25, 2013
Published online: March 7, 2013
[9] V. Gevorgyan, M. Rubin, S. Benson, J.-X. Liu, Y. Yamamoto, J. Org.
Chem. 2000, 65, 6179.
[10] S.-Y. Wang, S.-J. Ji, Synlett 2007, 2222.
Chem. Asian J. 2013, 8, 974 – 981
981
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim