Metal-free regioselective β-alkylation of pyrroles with carbonyl compounds and hydrosilanes: Use of a Bronsted acid as a catalyst

Article abstract of DOI:10.1002/adsc.201400497

A Bronsted acid, trifluoromethanesulfonimide [HN(SO₂CF₃)₂], was found to catalyze reductive β-alkylation of pyrroles with carbonyl compounds and hydrosilanes. This metal-free process features lower catalyst loadings compared to the original indium variant and exclusive generation of β-alkylpyrroles.

Full text of DOI:10.1002/adsc.201400497

UPDATES
DOI: 10.1002/adsc.201400497
Metal-Free Regioselective b-Alkylation of Pyrroles with Carbonyl
Compounds and Hydrosilanes: Use of a Brønsted Acid as a
Catalyst
Shota Nomiyamaa and Teruhisa Tsuchimotoa,*
a
Department of Applied Chemistry, School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku,
Kawasaki 214-8571, Japan
Fax : (+81)-44-934-7228; e-mail: tsuchimo@meiji.ac.jp
Received: May 19, 2014; Revised: August 18, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400497.
Abstract: A Brønsted acid, trifluoromethanesulfoni-
mide [HN(SO2CF3)2], was found to catalyze reduc-
tive b-alkylation of pyrroles with carbonyl com-
pounds and hydrosilanes. This metal-free process
features lower catalyst loadings compared to the
original indium variant and exclusive generation of
b-alkylpyrroles.
sized,[10,11] would further enhance the practicality and
utility of the strategy. In terms of the social require-
ments of sustainable development, we aimed at ach-
ieving the b-alkylation as a metal-free process. We
now report details of more sophisticated b-alkylation
of pyrroles, where a Brønsted acid as a commercial
source shows outstanding catalytic performance.
We first examined the effect of Brønsted acid cata-
lysts in the reaction of N-methylpyrrole (2a) with 2-
decanone (5a) and Et3SiH (3a) under the conditions
in 1,4-dioxane at 858C for 5 h (Table 1). Despite that
HNTf2 (25 mol%, Tf=SO2CF3) was totally inactive
in the preceding study with the corresponding alkyne
(1-decyne),[7] 3 mol% of HNTf2 successfully catalyzed
Keywords: alkylation; Brønsted acids; heterocycles;
hydrides; regioselectivity
b-Alkylpyrroles are key structural motifs in natural the reaction of 5a, giving 3-(decan-2-yl)-1-methylpyr-
products and biologically active compounds[1] as well role (4a) as a single isomer in 91% yield (entry 1).
as functional materials.[2] Due to sufficient aromaticity The non-formation of its a-isomer and complete con-
and p-excessive nature of pyrroles, a straightforward sumption of dipyrrolylalkanes 6a as plausible inter-
approach to b-alkylpyrroles seems to be SEAr-based mediates are noteworthy. Although using other sulfo-
direct introduction of an alkyl group onto the pyrrole nimides as well as oxygen and carbon analogues of
ring.[3] However, preferential a-nucleophilicity of pyr- HNTf2 resulted in a complete conversion of 5a, a sig-
roles actually makes the b-alkylation considerably dif- nificant amount of 6a remained unconsumed (en-
ficult.[4,5,6] Despite such characteristics of pyrroles, we tries 2–6). In addition to CF3COOH, inorganic
have recently achieved SEAr-based regioselective b-
alkylation of pyrroles by simply mixing alkynes 1, pyr-
roles 2 and Et3SiH (3a) under indium catalysis
(Scheme 1).[7] This was the first example of the SEAr-
based b-alkylation of pyrroles performed in one-step
and catalytically. However, the alkyl unit installable
onto 2 was restricted to the secondary alkyl group
with a methyl substituent since 1 has been limited
mainly to terminal alkynes. We therefore improved
the issue by replacing 1 with carbonyl compounds 5,
which serve as a source of a broad range of alkyl
groups including primary, secondary and tertiary as
well as cyclic structures.[8] In addition to the improve-
ment, we envisaged that exploiting a new catalyst in
lieu of the indium salt, which includes a rather expen-
sive indium metal[9] and is required to be pre-synthe- Scheme 1. Catalytic reductive b-alkylation of pyrroles.
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
ÞÞ
These are not the final page numbers!

UPDATES
Shota Nomiyama and Teruhisa Tsuchimoto
Table 1. Brønsted acid-catalyzed reductive b-2-decylation of
2a.[a]
Entry Catalyst
Solvent
Conv. Yield
(%)[b] (%)[c]
Scheme 2. Reductive b-2-decylation of 2a: HNTf2 versus
In(NTf2)3. Yields of isolated 4a based on 5a are shown here.
5a
4a
6a
1
2
HNTf2 [d]
HNNf2
1,4-dioxane
1,4-dioxane
>99
>99
91
79
<1
8
As shown in Scheme 2, the performance of 3 mol%
of HNTf2 is comparable enough to that of 10 mol%
of In(NTf2)3. HNTf2 as a catalyst has several advan-
tages over In(NTf2)3: 1) no indium as a rather rare
metal is required, 2) no metallic waste remains after
the reaction, 3) pre-synthesis of In(NTf2)3 from In2O3
and HNTf2 is unnecessary, 4) HNTf2 is commercially
available and reasonable in price,[12] 5) the weight
used of the catalyst can be reduced to less than one-
tenth, that is, from 57.3 mg of In(NTf2)3 to 5.1 mg of
HNTf2 in the 0.6 mmol-scale reaction.
With the suitable reaction conditions in hand, we
next explored the scope of the HNTf2-catalyzed reac-
tion (Table 2). Besides the 2-decyl group, the different
length of the secondary alkyl chains and the cyclic
structures were installed onto the b-position of 2a ex-
clusively (4b–4 f). In the use of 2-adamantanone, its
direct reduction occurred, giving 2-adamantanol (6%
NMR yield). The undesired reduction was suppressed
entirely by switching the procedure (method A) to
method B, where 3a is added after consumption of
carbonyl compounds 5 (4e).[13] The compatibility of
the functional groups, sulfide, alkenyl, alkynyl, ester,
chloro, and boryl [B(pin)=B(pinacolate)], is notewor-
thy (4 f–4k, 4q and 4t). The tolerance of the alkynyl
part is especially remarkable and is thus an additional
advantage of this method over the corresponding
indium reaction because an indium catalyst is capable
of activating the CꢀC bond (4h).[14,15] In fact, use of
3
1,4-dioxane
>99
62
21
4
5
6
7
8
9
10
11
12
13
14
15
16
17[f]
18[g]
19[h]
HOTf
1,4-dioxane
1,4-dioxane
HCTf2(C6F5) 1,4-dioxane
>99
>99
>99
<1
74
21
<1
93
96
>99
83
>99
<1
>99
98
15
12
66
<1
5
<1
<1
19
46
69
61
88
<1
87
84
76
50
51
25
<1
49
HONf[d]
CF3COOH
HBF4 aq.
H2SO4
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
Bu2O
PhMe
PhCl
MeNO2
5
HNO3
<1
<1
<1
10
<1
<1
<1
<1
<1
<1
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
HNTf2
EtCN
DMF[e]
1,4-dioxane
1,4-dioxane
1,4-dioxane
>99
[a]
Reagents: 5a (0.60 mmol), 2a (1.8 mmol), 3a
(0.90 mmol), catalyst (18 mmol), solvent (0.60 mL).
Determined by GC.
[b]
[c]
[d]
[e]
[f]
1
Determined by H NMR.
Nf=SO2C4F9.
DMF=N,N-dimethylformamide.
Performed with 2a (1.2 mmol).
Performed with 2a (0.60 mmol).
Performed with 2a (0.60 mmol) and 3a (0.60 mmol).
[g]
[h]
Brønsted acids such as HBF4, H2SO4 and HNO3 were In(NTf2)3 instead of HNTf2 as a catalyst provided no
much less effective (entries 7–10). With HNTf2 as 4h due to the formation of a complex mixture of
a promising catalyst, the continuous survey of the sol- products. Pyrroles with a benzyl (Bn), iPr, 1-phenyl-
vent effect showed that 1,4-dioxane is the solvent of ethyl, tBu, Ph, and cumyl group on the nitrogen atom
choice for the reaction (entries 1 and 11–16). The also participated in this protocol (4l–4p and 4s–4x).
effect of the amounts of 2a and 3a was also exam- Of these, the reactions of N-iPr- and N-tBu-pyrrole
ined. Reducing the amount of 2a from 3 to 2 and with 5a allowed us to further reduce the loading of
1 molar equivalents to 5a lowered the yield of 4a but HNTf2 to 1 mol% (4m and 4o). Despite that 1,2-di-
not significantly (entries 17 and 18). Accordingly, in methylpyrrole has the two unsymmetrical b-sites, only
the case that pyrrole substrates are expensive and the C4-position was alkylated (4q). In contrast to the
elaborate, the use of less than 3 molar equivalents of pyrroles that have been used so far, no b-alkylation
the pyrrole should be a possible choice of the reaction proceeded in the reaction using an electron-deficient
conditions. On the other hand, reducing the quantity pyrrole such as N-Boc-pyrrole (Boc=tert-butoxycar-
of both 2a and 3a resulted in further decrease of the bonyl); reagents and conditions used are given in the
yield (entry 19).
reference section.[16] The reaction of pyrrole with no
2
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

UPDATES
Metal-Free Regioselective b-Alkylation of Pyrroles
Table 2. HNTf2-catalyzed reductive b-alkylation of pyrroles.[a]
[a]
Reagents: 5 (0.60 mmol), 2 (1.8 or 2.4 mmol), 3a (0.90 or 1.8 mmol), HNTf2 (6.0–42 mmol), 1,4-dioxane (0.60 mL). Yields
of isolated 4 based on 5 are shown here. The methods used are shown in parentheses. See experimental section for fur-
ther details.
[b]
The yield when performed on 7.5 mmol scale is shown in parentheses.
Ac=acetyl.
The product was obtained as a 78:22 mixture of diastereomers.
Performed on 7.0 mmol scale.
[c]
[d]
[e]
[f]
3a (4.2 mmol) was used.
substituent on the nitrogen atom also led to a poor 3 molar equivalents of N-(1-phenylethyl)pyrrole to
result; a reaction scheme is provided in the reference acetone were used in the reaction giving 4n. The pyr-
section.[17] These results suggest that electron-rich pyr- role that remained unreacted was thus recovered with
roles with alkyl and aryl groups on the nitrogen atom efficiency of 95%, which was calculated based on the
should be essential for the progress of the reductive excess amount of the pyrrole: 2 molar equivalents in
b-alkylation of pyrroles. When using aryl and hetero- this case (see the Experimental Section for further de-
aryl ketones, method B is valid to exclude a small tails). This result indicates that pyrrole substrates
extent of a-alkylation that was concurrent with the b- used as an excess amount are recoverable and reusa-
alkylation in the use of method A (4r–4u). Upon in- ble.
troducing a primary alkyl group, the yield of the prod-
As a practical application, gram-scale synthesis can
uct was found to tend to increase with increasing the be performed. For example, 4b and 4n were prepared
size of the alkyl unit (4v–4x). As Table 2 shows, 3–4 on 7.5 and 7.0 mmol scales, respectively, to provide
molar equivalents of 2 to 5 are used, but the excess 1.15 g of 4b (92% yield) and 1.40 g of 4n (92%
amount of 2 can be recovered if desired. For example, yield).
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3
ÞÞ
These are not the final page numbers!

UPDATES
Shota Nomiyama and Teruhisa Tsuchimoto
Scheme 3. HNTf2-catalyzed b-alkylation of pyrroles with car-
bonyl compounds and carbon nucleophiles (3b: Me3SiCN,
3c: 2-methylfuran, 3d: 4-vinylanisole).
Scheme 5. A plausible reaction mechanism.
tuted and nitrogen-unsubstituted b-alkylpyrroles with
primary, secondary and tertiary alkyl groups.
Some pieces of experimental observations are avail-
able for the mechanistic studies (Scheme 4). Thus, the
reaction of 5a with 2a and HNTf2 (3 mol%), but
without Et3SiH (3a), gave an isomeric mixture of di-
pyrrolylalkanes 6a, as observed in the reaction per-
formed by method B. The isolated mixture (6a) then
reacted with 3a in the presence of HNTf2 (3 mol%)
and H2O,[18] giving 4a exclusively in 94% yield. These
results indicate that dipyrrolylalkanes 6 are intermedi-
ates in the three-component reaction. On the basis of
these results and our previous ones,[7,8] a plausible
mechanism is shown in Scheme 5, in which one pyr-
role ring of 6 is fixed as the b-pyrrolyl ring, due ac-
tually to the non-formation of an a-alkylpyrrole de-
Scheme 4. HNTf2-catalyzed reaction for mechanistic studies.
Besides hydride nucleophile 3a, carbon nucleo- rived inevitably from a,a’-6. The HNTf2 (H+) first as-
philes [Nu(C)] 3 such as Me3SiCN (3b), 2-methylfur- sembles 5 and 2 into 6, one pyrrole ring of which un-
an (3c) and 4-vinylanisole (3d) can be used for ex- dergoes protonation and then eliminates to give cat-
tending a carbon–carbon bond (Scheme 3).[8] The use ionic species b-8 via the C(sp3)–C(pyrrolyl) bond
of such nucleophiles enables us to create the quater- cleavage, as previously reported.[19] The trapping of b-
nary carbon center with the b-pyrrolyl group. Here 8 by nucleophile (Nu) 3 leads to product 4 or 7. As
again, the b-selectivities were perfectly controlled in previously noted, the origin of the observed b-selec-
all the cases. In the use of 3d, the bicyclic ring was tivity would be ascribed to the dominant generation
formed at once via a regioselective three carbon– of b-8 being much more stable than possible alterna-
carbon bond-forming cascade, where a benzylic cation tive cationic species a-8 that has 1,3-allylic-type strain
generated after nucleophilic attack of the C=C bond between R1 and R3.[20]
of 3d is likely to accept the a-carbon of the pyrrolyl
group.
In conclusion, we have disclosed that HNTf2 works
as a powerful catalyst for the regioselective b-alkyla-
As thus far described, nitrogen-substituted b-alkyl- tion of pyrroles with carbonyl compounds and nucleo-
pyrroles with primary, secondary and tertiary alkyl philes. The use of the Brønsted acid catalyst has sev-
groups can be prepared by utilizing the present eral distinct advantages in comparison to the corre-
method. Importantly, we have previously demonstrat- sponding indium-catalyzed reaction. This method also
ed that the benzyl and cumyl groups on the nitrogen features a wide range of substrate coverage with the
atom are easily removable.[8] Therefore, combining high functional group tolerance, and thus would be
this method and the deprotection reaction enables useful and reliable tool for the synthesis of b-alkylpyr-
preparation of all six types including nitrogen-substi- roles.
4
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

UPDATES
Metal-Free Regioselective b-Alkylation of Pyrroles
thylamine (6.06 g, 50.0 mmol), 2,5-dimethoxytetrahydrofur-
an (6.61 g, 50.0 mmol) and acetic acid (22.5 mL), and isolat-
Experimental Section
ed in 60% yield (5.15 g) by vacuum distillation (828C/
133 Pa). A colorless oil. H NMR (500 MHz, CDCl3) d 1.83
General Remarks
1
All manipulations were conducted with a standard Schlenk
technique under an argon atmosphere. Nuclear magnetic
resonance (NMR) spectra were taken on a JEOL JMN-
ECA 400 (1H, 400 MHz; 13C, 100 MHz) or JEOL JMN-ECA
500 (1H, 500 MHz; 13C, 125 MHz) spectrometer using tetra-
methylsilane (1H and 13C) as an internal standard. Analytical
gas chromatography (GC) was performed on a Shimadzu
(d, J=6.9 Hz, 3H), 5.28 (q, J=7.1 Hz, 1H), 6.19 (dd, J=2.3,
1.7 Hz, 2H), 6.76 (dd, J=2.3, 1.7 Hz, 2H), 7.09 (d, J=
7.5 Hz, 2H), 7.22–7.27 (m, 1H), 7.31 (t, J=7.4 Hz, 2H).
13C NMR (100 MHz, CDCl3) d 22.1, 58.1, 108.0, 119.5, 125.8,
127.4, 128.6, 143.5. HRMS (FI) Calcd for C12H13N: M,
171.1048. Found: m/z 171.1020.
model GC-2014 instrument equipped with
a capillary
Synthesis of N-tert-Butylpyrrole
column of InertCap 5 (5% phenyl polysilphenylene-silox-
ane, 30 m ꢁ 0.25 mm ꢁ 0.25 mm) using nitrogen as carrier
gas. Gas chromatography–mass spectrometry (GC–MS)
analyses were performed with a Shimadzu model GCMS-
QP2010 instrument equipped with a capillary column of ID-
N-tert-Butylpyrrole was synthesized according to the follow-
ing modified literature procedure.[22] Under an argon atmos-
phere, a 300 mL two-necked round-bottomed flask was
charged with tert-butylamine (29.3 g, 400 mmol), acetic acid
(90.0 mL) and 2,5-dimethoxytetrahydrofurran (26.4 g,
200 mmol). After stirring at 808C for 50 h, the reaction mix-
ture was diluted with Et2O (200 mL). The resulting solution
was washed with a 2m NaOH aqueous solution (100 mL
x 3), H2O (100 mL) and brine (100 mL), and then dried over
anhydrous sodium sulfate. Filtration and evaporation of the
solvent followed by vacuum distillation (788C/80 hPa) pro-
vided N-tert-butylpyrrole (16.6 g, 67% yield) as a colorless
BPX5 (5% phenyl polysilphenylene-siloxane, 30 m
ꢁ
0.25 mm ꢁ 0.25 mm) by electron ionization at 70 eV using
helium as carrier gas. Preparative recycling high-per-
formance liquid chromatography (HPLC) was performed
with JAI LC-9104 equipped with JAIGEL-GS320 column
using a mixture of hexane–ethyl acetate (EtOAc) as eluent.
Preparative recycling gel permeation chromatography
(GPC) was performed with JAI LC-9105 equipped with
JAIGEL-1H and JAIGEL-2H columns using chloroform as
eluent. High-resolution mass spectra (HRMS) were ob-
tained with a JEOL JMS-T100GCV spectrometer. All melt-
ing points were measured with a Yanaco Micro Melting
Point apparatus and uncorrected. Kugelrohr bulb-to-bulb
distillation was carried out with a Sibata glass tube oven
GTO-250RS apparatus. Dibutyl ether and 1,4-dioxane were
distilled under argon from sodium just prior to use. Toluene
(PhMe) and chlorobenzene (PhCl) were distilled under
argon from calcium chloride just prior to use. Propionitrile
(EtCN) was distilled under argon from P2O5 just prior to
use. Nitromethane was stored over molecular sieves 4 A
(MS 4 A) under argon. Anhydrous N,N-dimethylformamide
(DMF) was purchased from Wako pure chemical industries
and used as received. N-(2-Phenylpropan-2-yl)pyrrole,[8] 6-
heptyn-2-one,[21] and 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxabor-
olan-2-yl)phenyl]ethanone[8] were prepared according to the
respective literature procedures. Unless otherwise noted,
other substrates and reagents were commercially available
and used as received.
1
oil. H NMR (400 MHz, CDCl3) d 1.54 (s, 9H), 6.16 (t, J=
2.2 Hz, 2H), 6.84 (t, J=2.3 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 30.8, 54.6, 107.4, 117.5. HRMS (FI) Calcd for
C8H13N: M, 123.1048. Found: m/z 123.1017.
HNTf2-Catalyzed Reductive b-Alkylation of Pyrroles
with Carbonyl Compounds and Et3SiH. A General
Procedure of Method A for Table 2
A flame-dried 20 mL Schlenk tube was filled with argon and
then charged with HNTf2 [(1.69 mg, 6.00 mmol), (5.06 mg,
18.0 mmol), (8.43 mg, 30.0 mmol) or (11.8 mg, 42.0 mmol)]
and 1,4-dioxane (0.60 mL). The solution was stirred at room
temperature for 3 min. To this were added carbonyl com-
pound
5 (0.600 mmol), pyrrole derivative 2 (1.80 or
2.40 mmol) and Et3SiH (3a) (0.900, 1.80 or 4.20 mmol), and
the resulting mixture was stirred at 50, 85 or 1008C. After
the time specified in Table 2 (see t1), a saturated NaHCO3
aqueous solution (0.3 mL) was added, and the aqueous
phase was extracted with EtOAc (5 mL x 3). The combined
organic layer was washed with brine (1 mL) and then dried
over anhydrous sodium sulfate. Filtration and evaporation
of the solvent followed by column chromatography on silica
gel using hexane–EtOAc or hexane–CHCl3 as eluent gave
the corresponding product (4). The results are summarized
in Table 2. Unless otherwise noted, products 4 synthesized
Synthesis of N-Isopropylpyrrole
Based on the literature procedure,[22] N-isopropylpyrrole
was synthesized with the following reagents: isopropylamine
(5.91 g, 100 mmol), 2,5-dimethoxytetrahydrofuran (13.2 g,
100 mmol) and acetic acid (50.0 mL), and isolated in 29%
yield (3.17 g) by vacuum distillation (858C/160 hPa). A col-
1
here were fully characterized by H and 13C NMR spectros-
copy and HRMS.
1
orless oil. H NMR (400 MHz, CDCl3) d 1.45 (d, J=5.4 Hz,
6H), 4.25 (sept, J=5.4 Hz, 1H), 6.15 (t, J=1.7 Hz, 2H),
6.73 (t, J=1.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 24.0,
50.7, 107.7, 118.1. HRMS (FI) Calcd for C7H11N: M,
109.0892. Found: m/z 109.0868.
HNTf2-Catalyzed Reductive b-Alkylation of Pyrroles
with Carbonyl Compounds and Et3SiH. A General
Procedure of Method B for Table 2
A flame-dried 20 mL Schlenk tube was filled with argon and
then charged with HNTf2 [(5.06 mg, 18.0 mmol) or (11.8 mg,
42.0 mmol)] and 1,4-dioxane (0.60 mL). The solution was
stirred at room temperature for 3 min. To this were added
carbonyl compound 5 (0.600 mmol) and pyrrole derivative 2
Synthesis of N-(1-Phenylethyl)pyrrole
Based on the literature procedure,[22] N-(1-phenylethyl)pyr-
role was synthesized with the following reagents: 1-phenyle-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
5
ÞÞ
These are not the final page numbers!

UPDATES
Shota Nomiyama and Teruhisa Tsuchimoto
(1.80 or 2.40 mmol), and the resulting mixture was stirred at
85 or 1008C for 3, 4 or 24 h. Et3SiH (3a) (0.900 or
1.80 mmol) was then added, and the resulting solution was
stirred further at 85 or 1008C. After the time specified in
Table 2 (see t3), the work-up process was carried out similar-
ly as above. The results are summarized in Table 2. Unless
otherwise noted, products 4 prepared here were fully char-
2.57–2.71 (m, 1H), 3.59 (s, 3H), 5.99 (dd, J=2.3, 2.1 Hz,
1H), 6.37 (t, J=1.9 Hz, 1H), 6.49 (dd, J=2.5, 2.3 Hz, 1H).
3-(Adamant-2-yl)-1-methyl-1H-pyrrole (4e): The title
compound was synthesized with the following reagents
based on method A: 2-adamantanone (0.600 mmol), 2a
(1.80 mmol), 3a (0.900 mmol), HNTf2 (18.0 mmol) and 1,4-
dioxane (0.60 mL) or with the following reagents based on
method B: 2-adamantanone (0.600 mmol), 2a (2.40 mmol),
3a (0.900 mmol), HNTf2 (18.0 mmol) and 1,4-dioxane
(0.60 mL), and isolated by column chromatography on silica
gel (hexane/EtOAc=30:1). Compound 4e has already ap-
peared in the literature, and its spectral and analytical data
are in good agreement with those reported in ref. 8. There-
fore, only 1H NMR data are provided here. 1H NMR
(500 MHz, CDCl3) d 1.51 (d, J=13.2 Hz, 2H), 1.75 (s, 3H),
1.84–1.96 (m, 5H), 1.99 (d, J=12.6 Hz, 2H), 2.15 (dd, J=
4.9, 3.2 Hz, 2H), 2.92 (s, 1H), 3.63 (s, 3H), 6.02 (t, J=
2.0 Hz, 1H), 6.42 (dd, J=3.2, 2.0 Hz, 1H), 6.54 (t, J=
2.3 Hz, 1H).
1
acterized by H and 13C NMR spectroscopy and HRMS.
3-(Decan-2-yl)-1-methyl-1H-pyrrole (4a): The title com-
pound was synthesized with the following reagents based on
method A: 5a (0.600 mmol), 2a (1.80 mmol), 3a
(0.900 mmol), HNTf2 (18.0 mmol) and 1,4-dioxane
(0.60 mL), and isolated by column chromatography on silica
gel (hexane/EtOAc=80:1). Compound 4a has already ap-
peared in the literature, and its spectral and analytical data
are in good agreement with those reported in ref. 8. There-
fore, only 1H NMR data are provided here. 1H NMR
(400 MHz, CDCl3) d 0.87 (t, J=7.0 Hz, 3H), 1.17 (d, J=
6.9 Hz, 3H), 1.20–1.35 (m, 12H), 1.36–1.47 (m, 1H), 1.48–
1.58 (m, 1H), 2.60 (sext, J=7.0 Hz, 1H), 3.60 (s, 3H), 5.98
(t, J=2.1 Hz, 1H), 6.37 (dd, J=2.0, 1.8 Hz, 1H), 6.51 (t, J=
2.5 Hz, 1H).
1-Methyl-3-(tetrahydro-2H-thiopyran-4-yl)-1H-pyrrole
(4 f): The title compound was synthesized with the following
reagents based on method A: tetrahydro-2H-thiopyran-4-
one (0.600 mmol), 2a (1.80 mmol), 3a (0.900 mmol), HNTf2
(30.0 mmol) and 1,4-dioxane (0.60 mL), and isolated by
column chromatography on silica gel (hexane/EtOAc=
20:1). Compound 4 f has already appeared in the literature,
and its spectral and analytical data are in good agreement
3-(Hexan-2-yl)-1-methyl-1H-pyrrole (4b): The title com-
pound was synthesized with the following reagents based on
method A: for the reaction performed on 0.600 mmol scale:
2-hexanone (0.600 mmol), 2a (1.80 mmol), 3a (0.900 mmol),
HNTf2 (18.0 mmol) and 1,4-dioxane (0.60 mL), and isolated
by column chromatography on silica gel (hexane/EtOAc=
80:1); for the reaction performed on 7.50 mmol scale: 2-hex-
anone (7.50 mmol), 2a (22.5 mmol), 3a (11.3 mmol), HNTf2
(225 mmol) and 1,4-dioxane (7.5 mL), and isolated by
column chromatography on silica gel (hexane/EtOAc=
1
with those reported in ref. 8. Therefore, only H NMR data
1
are provided here. H NMR (400 MHz, CDCl3) d 1.73 (dtd,
J=13.3, 12.0, 3.4 Hz, 2H), 2.21 (dq, J=13.8, 3.4 Hz, 2H),
2.47 (tt, J=11.8, 3.3 Hz, 1H), 2.62–2.70 (m, 2H), 2.79 (td,
J=12.9, 2.5 Hz, 2H), 3.61 (s, 3H), 5.99 (t, J=2.2 Hz, 1H),
6.38 (t, J=1.8 Hz, 1H), 6.51 (t, J=2.4 Hz, 1H).
1
80:1). A colorless oil. H NMR (500 MHz, CDCl3) d 0.88 (t,
J=7.0 Hz, 3H), 1.17 (d, J=6.9 Hz, 3H), 1.22–1.34 (m, 4H),
1.37–1.48 (m, 1H), 1.49–1.59 (m, 1H), 2.60 (sext, J=6.9 Hz,
1H), 3.60 (s, 3H), 5.99 (t, J=2.2 Hz, 1H), 6.37 (t, J=2.0 Hz,
1H), 6.50 (dd, J=2.6, 2.3 Hz, 1H); 13C NMR (125 MHz,
CDCl3) d 14.1, 22.2, 22.9, 29.9, 31.8, 36.0, 38.5, 106.7, 118.0,
121.2, 131.1. HRMS (FI) Calcd for C11H19N: M, 165.1518.
Found: m/z 165.1504.
1-Methyl-3-(6-methyl-5-hepten-2-yl)-1H-pyrrole (4g): The
title compound was synthesized with the following reagents
based on method A: 6-methyl-5-hepten-2-one (0.600 mmol),
2a (1.80 mmol), 3a (0.900 mmol), HNTf2 (42.0 mmol) and
1,4-dioxane (0.60 mL), and isolated by recycling GPC after
column chromatography on silica gel (hexane/CHCl3 =5:1).
Compound 4g has already appeared in the literature, and its
spectral and analytical data are in good agreement with
1-Methyl-3-(pentan-3-yl)-1H-pyrrole (4c): The title com-
pound was synthesized with the following reagents based on
method A: 3-pentanone (0.600 mmol), 2a (1.80 mmol), 3a
(0.900 mmol), HNTf2 (30.0 mmol) and 1,4-dioxane
(0.60 mL), and isolated by column chromatography on silica
1
those reported in ref. 8. Therefore, only H NMR data are
provided here. 1H NMR (400 MHz, CDCl3) d 1.19 (d, J=
6.9 Hz, 3H), 1.41–1.52 (m, 1H), 1.55–1.63 (m, 1H), 1.58 (s,
3H), 1.68 (d, J=0.9 Hz, 3H), 1.97 (q, J=7.6 Hz, 2H), 2.62
(sext, J=7.0 Hz, 1H), 3.60 (s, 3H), 5.08–5.16 (m, 1H), 5.99
(t, J=2.2 Hz, 1H), 6.37 (dd, J=2.1, 1.8 Hz, 1H), 6.51 (t, J=
2.4 Hz, 1H).
gel (hexane/EtOAc=100:1).
A
colorless oil. 1H NMR
(400 MHz, CDCl3) d 0.84 (t, J=7.5 Hz, 6H), 1.40–1.51 (m,
2H), 1.51–1.65 (m, 2H), 2.25 (tt, J=8.1, 5.6 Hz, 1H), 3.60 (s,
3H), 5.93 (t, J=2.2 Hz, 1H), 6.35 (t, J=1.9 Hz, 1H), 6.51 (t,
J=2.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 12.1, 29.0,
36.0, 41.2, 106.9, 119.0, 121.1, 128.6. HRMS (FI) Calcd for
C10H17N: M, 151.1361. Found: m/z 151.1334.
3-Cycloheptyl-1-methyl-1H-pyrrole (4d): The title com-
pound was synthesized with the following reagents based on
method A: cycloheptanone (0.600 mmol), 2a (1.80 mmol),
3a (0.900 mmol), HNTf2 (18.0 mmol) and 1,4-dioxane
(0.60 mL), and isolated by column chromatography on silica
gel (hexane/EtOAc=40:1). Compound 4d has already ap-
peared in the literature, and its spectral and analytical data
are in good agreement with those reported in ref. 8. There-
fore, only 1H NMR data are provided here. 1H NMR
(400 MHz, CDCl3) d 1.45–1.78 (m, 10H), 1.91–2.03 (m, 2H),
3-(6-Heptyn-2-yl)-1-methyl-1H-pyrrole (4h): The title
compound was synthesized with the following reagents
based on method A: 6-heptyn-2-one (0.600 mmol), 2a
(1.80 mmol), 3a (1.80 mmol), HNTf2 (42.0 mmol) and 1,4-di-
oxane (0.60 mL), and isolated by column chromatography
on silica gel (hexane/EtOAc=20:1).
A colorless oil.
1H NMR (500 MHz, CDCl3) d 1.20 (d, J=6.9 Hz, 3H), 1.49–
1.66 (m, 4H), 1.93 (t, J=2.6 Hz, 1H), 2.17 (td, J=6.7,
2.8 Hz, 2H), 2.63 (sext, J=6.8 Hz, 1H), 3.60 (s, 3H), 5.98
(dd, J=2.2, 1.9 Hz, 1H), 6.38 (t, J=1.9 Hz, 1H), 6.51 (t, J=
2.4 Hz, 1H); 13C NMR (125 MHz, CDCl3) d 18.6, 22.3, 26.6,
31.5, 36.0, 37.7, 68.0, 84.9, 106.6, 118.1, 121.4, 130.3. HRMS
(FI) Calcd for C12H17N: M, 175.1361. Found: m/z 175.1350.
6
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

UPDATES
Metal-Free Regioselective b-Alkylation of Pyrroles
4-(1-Methyl-1H-pyrrol-3-yl)pentyl acetate (4i): The title
compound was synthesized with the following reagents
based on method A: 5-acetoxypentan-2-one (0.600 mmol),
2a (1.80 mmol), 3a (0.900 mmol), HNTf2 (18.0 mmol) and
1,4-dioxane (0.60 mL), and isolated by column chromatogra-
phy on silica gel (hexane/EtOAc=8:1). Compound 4i has
already appeared in the literature, and its spectral and ana-
lytical data are in good agreement with those reported in
ref. 8. Therefore, only 1H NMR data are provided here.
1H NMR (400 MHz, CDCl3) d 1.20 (d, J=7.1 Hz, 3H), 1.46–
1.68 (m, 4H), 2.03 (s, 3H), 2.64 (sext, J=6.9 Hz, 1H), 3.60
(s, 3H), 4.04 (t, J=6.6 Hz, 2H), 5.98 (dd, J=2.3, 2.1 Hz,
1H), 6.38 (dd, J=2.1, 1.8 Hz, 1H), 6.51 (dd, J=2.5, 2.3 Hz,
1H).
(500 MHz, CDCl3) d 0.87 (t, J=7.0 Hz, 3H), 1.17 (d, J=
6.9 Hz, 3H), 1.21–1.34 (m, 12H), 1.37–1.48 (m, 1H), 1.49–
1.57 (m, 1H), 2.61 (sext, J=6.9 Hz, 1H), 5.00 (s, 2H), 6.03
(dd, J=2.6, 1.7 Hz, 1H), 6.44 (dd, J=2.0, 1.7 Hz, 1H), 6.59
(t, J=2.5 Hz, 1H), 7.07–7.12 (m, 2H), 7.24–7.28 (m, 1H),
7.31 (tt, J=7.3, 1.6 Hz, 2H).
3-(Decan-2-yl)-1-isopropyl-1H-pyrrole (4m): The title
compound was synthesized with the following reagents
based on method A: 5a (0.600 mmol), N-isopropylpyrrole
(1.80 mmol), 3a (0.900 mmol), HNTf2 (6.00 mmol) and 1,4-
dioxane (0.60 mL), and isolated by column chromatography
on silica gel (hexane/EtOAc=50:1).
A colorless oil.
1H NMR (500 MHz, CDCl3) d 0.87 (t, J=6.9 Hz, 3H), 1.18
(d, J=6.9 Hz, 3H), 1.20–1.35 (m, 12H), 1.37–1.47 (m, 1H),
1.43 (d, J=6.6 Hz, 6H), 1.50–1.60 (m, 1H), 2.60 (sext, J=
6.9 Hz, 1H), 4.16 (sept, J=6.7 Hz, 1H), 5.99 (t, J=2.3 Hz,
1H), 6.48 (t, J=2.0 Hz, 1H), 6.63 (dd, J=2.6, 2.3 Hz, 1H);
13C NMR (125 MHz, CDCl3) d 14.1, 21.9, 22.7, 23.9, 27.7,
29.4, 29.7, 29.9, 31.91, 31.94, 38.8, 50.4, 105.9, 114.5, 117.5,
130.3. HRMS (FI) Calcd for C17H31N: M, 249.2457. Found:
m/z 249.2460.
Dihydro-3-[1-(1-methyl-1H-pyrrol-3-yl)ethyl]-2(3H)-fura-
none (4j): The title compound was synthesized with the fol-
lowing reagents based on method A: 3-acetyldihydro-
2(3H)-furanone
(0.600 mmol),
2a
(1.80 mmol),
3
(1.80 mmol), HNTf2 (42.0 mmol) and 1,4-dioxane (0.60 mL),
and isolated by column chromatography on silica gel
(hexane/EtOAc=3:1) as a 78/22 mixture of diastereomers.
The mixture was then separated by recycling HPLC
(hexane/EtOAc=3:1). For the major isomer: A colorless
3-Isopropyl-1-(1-phenylethyl)-1H-pyrrole (4n): The title
compound was synthesized with the following reagents
based on method A: acetone (7.00 mmol), N-(1-phenyle-
1
oil. H NMR (500 MHz, CDCl3) d 1.27 (d, J=7.2 Hz, 3H),
2.10–2.23 (m, 2H), 2.88 (td, J=9.5, 3.8 Hz, 1H), 3.34 (qd,
J=7.1, 3.8 Hz, 1H), 3.61 (s, 3H), 4.10–4.20 (m, 2H), 6.01 (t,
J=2.3 Hz, 1H), 6.44 (t, J=1.7 Hz, 1H), 6.53 (t, J=2.4 Hz,
1H); 13C NMR (125 MHz, CDCl3) d 16.5, 24.3, 31.7, 36.1,
45.8, 66.7, 107.1, 118.8, 121.8, 126.5, 178.8. HRMS (FI)
Calcd for C11H15NO2: M, 193.1103. Found: m/z 193.1085.
thyl)pyrrole
(21.0 mmol),
3a
(10.5 mmol),
HNTf2
(0.350 mmol), and 1,4-dioxane (7.0 mL), and isolated by
column chromatography on silica gel (hexane/CHCl3 =3:1).
In the process of purifying 4n, N-(1-phenylethyl)pyrrole was
also collected with
(13.3 mmol), which was calculated based on 14.0 mmol of
a
recovery efficiency of 95%
1
For the minor isomer: A colorless oil. H MNR (500 MHz,
N-(1-phenylethyl)pyrrole used as an excess amount. A col-
1
CDCl3) d 1.34 (d, J=7.2 Hz, 3H), 2.05 (dq, J=12.7, 8.5 Hz,
1H), 2.12–2.20 (m, 1H), 2.68 (td, J=9.0, 4.5 Hz, 1H), 3.42
(qd, J=7.2, 4.3 Hz, 1H), 3.59 (s, 3H), 3.93 (td, J=8.7,
4.4 Hz, 1H), 4.09 (dt, J=8.6, 8.0 Hz, 1H), 6.00 (t, J=2.3 Hz,
1H), 6.43 (dd, J=2.0, 1.7 Hz, 1H), 6.50 (t, J=2.5 Hz, 1H);
13C NMR (125 MHz, CDCl3) d 19.7, 23.8, 31.7, 36.1, 46.5,
66.8, 107.5, 119.8, 121.5, 124.1, 179.4. HRMS (FI) Calcd for
C11H15NO2: M, 193.1103. Found: m/z 193.1097.
orless oil. H NMR (400 MHz, CDCl3) d 1.19 (d, J=6.6 Hz,
3H), 1.20 (d, J=6.9 Hz, 3H), 1.80 (d, J=7.1 Hz, 3H), 2.81
(sept, J=6.9 Hz, 1H), 5.20 (q, J=7.1 Hz, 1H), 6.07 (t, J=
2.2 Hz, 1H), 6.49–6.54 (m, 1H), 6.66 (t, J=2.5 Hz, 1H),
7.04–7.11 (m, 2H), 7.21–7.25 (m, 1H), 7.27–7.33 (m, 2H);
13C NMR (100 MHz, CDCl3) d 22.1, 24.05, 24.07, 26.5, 58.0,
106.5, 115.4, 119.0, 125.9, 127.3, 128.6, 131.7, 143.9. HRMS
(FI) Calcd for C15H19N: M, 213.1518. Found: m/z 213.1530.
1-tert-Butyl-3-(decan-2-yl)-1H-pyrrole (4o): The title
compound was synthesized with the following reagents
based on method A: 5a (0.600 mmol), N-tert-butylpyrrole
(1.80 mmol), 3a (0.900 mmol), HNTf2 (6.00 mmol) and 1,4-
dioxane (0.60 mL), and isolated by column chromatography
on silica gel (hexane/EtOAc=40:1). Compound 4o has al-
ready appeared in the literature, and its spectral and analyti-
cal data are in good agreement with those reported in ref. 8.
3-(6-Chlorohexan-2-yl)-1-methyl-1H-pyrrole (4k): The
title compound was synthesized with the following reagents
based on method A: 6-chlorohexan-2-one (0.600 mmol), 2a
(1.80 mmol), 3a (0.900 mmol), HNTf2 (18.0 mmol) and 1,4-
dioxane (0.60 mL), and isolated by column chromatography
on silica gel (hexane/EtOAc=20:1). Compound 4k has al-
ready appeared in the literature, and its spectral and analyti-
cal data are in good agreement with those reported in ref. 7.
1
1
1
1
Therefore, only H NMR data are provided here. H NMR
(400 MHz, CDCl3) d 1.19 (d, J=6.9 Hz, 3H), 1.36–1.61 (m,
4H), 1.76 (quint, J=7.1 Hz, 2H), 2.62 (sext, J=6.8 Hz, 1H),
3.51 (t, J=6.9 Hz, 2H), 3.60 (s, 3H), 5.98 (dd, J=2.3,
2.1 Hz, 1H), 6.37 (dd, J=2.1, 1.8 Hz, 1H), 6.51 (dd, J=2.5,
2.3 Hz, 1H).
Therefore, only H NMR data are provided here. H NMR
(500 MHz, CDCl3) d 0.87 (t, J=6.9 Hz, 3H), 1.18 (d, J=
7.2 Hz, 3H), 1.21–1.35 (m, 12H), 1.36–1.61 (m, 2H), 1.50 (s,
9H), 2.61 (sext, J=6.9 Hz, 1H), 6.00 (dd, J=2.6, 2.0 Hz,
1H), 6.58 (dd, J=2.3, 1.7 Hz, 1H), 6.73 (t, J=2.3 Hz, 1H).
3-(Decan-2-yl)-1-phenyl-1H-pyrrole (4p): The title com-
pound was synthesized with the following reagents based on
method B: 5a (0.600 mmol), N-phenylpyrrole (2.40 mmol),
3a (0.900 mmol), HNTf2 (18.0 mmol) and 1,4-dioxane
(0.60 mL), and isolated by column chromatography on silica
gel (hexane/CHCl3 =5:1). Compound 4p has already ap-
peared in the literature, and its spectral and analytical data
are in good agreement with those reported in ref. 8. There-
fore, only 1H NMR data are provided here. 1H NMR
(500 MHz, CDCl3) d 0.87 (t, J=6.9 Hz, 3H), 1.19–1.39 (m,
1-Benzyl-3-(decan-2-yl)-1H-pyrrole (4l): The title com-
pound was synthesized with the following reagents based on
method
A:
5a
(0.600 mmol),
1-benzyl-1H-pyrrole
(1.80 mmol), 3a (0.900 mmol), HNTf2 (18.0 mmol) and 1,4-
dioxane (0.60 mL), and isolated by column chromatography
on silica gel (hexane/CHCl3 =8:1). Compound 4l has al-
ready appeared in the literature, and its spectral and analyti-
cal data are in good agreement with those reported in ref. 7.
1
1
Therefore, only H NMR data are provided here. H NMR
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
7
ÞÞ
These are not the final page numbers!

UPDATES
Shota Nomiyama and Teruhisa Tsuchimoto
12H), 1.23 (d, J=6.9 Hz, 3H), 1.42–1.64 (m, 2H), 2.68 (sext,
J=6.9 Hz, 1H), 6.21 (dd, J=2.9, 1.7 Hz, 1H), 6.86–6.89 (m,
1H), 7.02 (dd, J=2.7, 2.4 Hz, 1H), 7.19 (tt, J=6.9, 1.7 Hz,
1H), 7.35–7.42 (m, 4H).
132.3, 133.9, 147.3 (A signal of the boron-bound carbon
atom was not detected due to quadrupolar relaxation of
boron). HRMS (FD) Calcd for C21H30BNO2: M, 339.2370.
Found: m/z 339.2396.
1,2-Dimethyl-4-(tetrahydro-2H-thiopyran-4-yl)-1H-pyr-
role (4q): The title compound was synthesized with the fol-
lowing reagents based on method A: tetrahydro-2H-thiopyr-
an-4-one (0.600 mmol), 1,2-dimethylpyrrole (1.80 mmol), 3a
(1.80 mmol), HNTf2 (42.0 mmol) and 1,4-dioxane (0.60 mL),
and isolated by column chromatography on silica gel
1-Isopropyl-3-[1-(3-thienyl)ethyl]-1H-pyrrole (4u): The
title compound was prepared with the following reagents
based on method B: 3-acetylthiophene (0.600 mmol), N-iso-
propylpyrrole (2.40 mmol), 3a (0.900 mmol), HNTf2 (42.0
mmol) and 1,4-dioxane (0.60 mL), and isolated by column
chromatography on silica gel (hexane/EtOAc=20:1). A col-
1
(hexane/EtOAc=20:1).
A
white solid, mp=60–618C.
orless oil. H NMR (500 MHz, CDCl3) d 1.411 (d, J=6.6 Hz,
1H NMR (500 MHz, CDCl3) d 1.71 (dtd, J=13.2, 12.1,
3.4 Hz, 2H), 2.16–2.22 (m, 2H), 2.18 (d, J=1.4 Hz, 3H),
2.42 (tt, J=11.6, 3.3 Hz, 1H), 2.62–2.68 (m, 2H), 2.78 (ddd,
13.7, 12.2, 2.4 Hz, 2H), 3.46 (s, 3H), 5.75 (d, J=0.9 Hz, 1H),
6.31 (d, J=2.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) d 11.9,
29.1, 33.4, 35.6, 36.0, 105.0, 116.7, 128.5, 128.7. HRMS (FI)
Calcd for C11H17NS: M, 195.1082. Found: m/z 195.1082.
1-Methyl-3-(1-phenylethyl)-1H-pyrrole (4r): The title
compound was synthesized with the following reagents
based on method B: acetophenone (0.600 mmol), 2a
(1.80 mmol), 3a (1.80 mmol), HNTf2 (42.0 mmol) and 1,4-di-
oxane (0.60 mL), and isolated by bulb-to-bulb distillation
(1008C/100 Pa) after column chromatography on silica gel
(hexane/EtOAc=20:1). Compound 4r has already appeared
in the literature, and its spectral and analytical data are in
good agreement with those reported in ref. 8. Therefore,
3H), 1.413 (d, J=6.6 Hz, 3H), 1.56 (d, J=7.0 Hz, 3H), 4.09
(q, J=7.1 Hz, 1H), 4.15 (sept, J=6.7 Hz, 1H), 5.98 (t, J=
2.2 Hz, 1H), 6.42–6.44 (m, 1H), 6.63 (t, J=2.5 Hz, 1H),
6.94–6.97 (m, 1H), 7.00 (dd, J=4.9, 1.3 Hz, 1H), 7.21 (dd,
J=5.0, 3.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) d 22.8,
23.88, 23.90, 33.6, 50.5, 106.7, 115.3, 117.8, 119.3, 124.8,
127.8, 128.5, 148.9. HRMS (FI) Calcd for C13H17NS: M,
219.1082. Found: m/z 219.1088.
3-(Decan-1-yl)-1-(2-phenylpropan-2-yl)-1H-pyrrole (4v):
The title compound was synthesized with the following re-
agents based on method A: 1-decanal (0.600 mmol), N-(2-
phenylpropan-2-yl)pyrrole (2.40 mmol), 3a (4.20 mmol),
HNTf2 (42.0 mmol) and 1,4-dioxane (0.60 mL), and isolated
by column chromatography on silica gel (hexane/EtOAc=
5:1). Compound 4v has already appeared in the literature,
and its spectral and analytical data are in good agreement
1
1
1
only H NMR data are provided here. H NMR (400 MHz,
CDCl3) d 1.56 (d, J=7.3 Hz, 3H), 3.58 (s, 3H), 4.00 (q, J=
7.2 Hz, 1H), 5.96 (t, J=2.1 Hz, 1H), 6.29–6.33 (m, 1H), 6.51
(dd, J=2.5, 2.3 Hz, 1H), 7.14–7.20 (m, 1H), 7.24–7.31 (m,
4H).
with those reported in ref. 8. Therefore, only H NMR data
1
are provided here. H NMR (500 MHz, CDCl3) d 0.88 (t, J=
7.0 Hz, 3H), 1.21–1.38 (m, 14H), 1.56 (quint, J=7.5 Hz,
2H), 1.86 (s, 6H), 2.45 (t, J=7.8 Hz, 2H), 6.04 (dd, J=2.0,
1.6 Hz, 1H), 6.52–6.55 (m, 1H), 6.70 (t, J=2.6 Hz, 1H),
6.95–6.99 (m, 2H), 7.21 (tt, J=7.3, 1.6 Hz, 1H), 7.24–7.30
(m, 2H).
3-(1-Cyclohexylmethyl)-1-(2-phenylpropan-2-yl)-1H-pyr-
role (4w): The title compound was synthesized with the fol-
lowing reagents based on method A: cyclohexanecarboxal-
1-Isopropyl-3-(1-phenylethyl)-1H-pyrrole (4s): The title
compound was synthesized with the following reagents
based on method B: acetophenone (0.600 mmol), N-isopro-
pylpyrrole (2.40 mmol), 3a (0.900 mmol), HNTf2 (18.0
mmol) and 1,4-dioxane (0.60 mL), and isolated by column
chromatography on silica gel (hexane/CHCl3 =10:3). A col-
dehyde
(0.600 mmol),
N-(2-phenylpropan-2-yl)pyrrole
1
orless oil. H NMR (500 MHz, CDCl3) d 1.41 (d, J=6.6 Hz,
(2.40 mmol), 3a (1.80 mmol), HNTf2 (42.0 mmol) and 1,4-di-
3H), 1.42 (d, J=6.6 Hz, 3H), 1.56 (d, J=7.2 Hz, 3H), 4.01
(q, J=7.2 Hz, 1H), 4.15 (sept, J=6.7 Hz, 1H), 5.95 (t, J=
2.3 Hz, 1H), 6.41–6.45 (m, 1H), 6.63 (t, J=2.6 Hz, 1H),
7.14–7.19 (m, 1H), 7.24–7.30 (m, 4H); 13C NMR (125 MHz,
CDCl3) d 22.8, 23.86, 23.91, 38.2, 50.5, 106.9, 115.5, 117.9,
125.6, 127.4, 128.1, 128.7, 148.1. HRMS (FI) Calcd for
C15H19N: M, 213.1518. Found: m/z 213.1509.
1-Isopropyl-3-{1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)phenyl]ethyl}-1H-pyrrole (4t): The title compound
was synthesized with the following reagents based on
method B: 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
oxane (0.60 mL), and isolated by column chromatography
on silica gel (hexane/CHCl3 =4:1). A colorless oil. H NMR
1
(500 MHz, CDCl3) d 0.89 (qd, J=12.0, 2.9 Hz, 2H), 1.08–
1.28 (m, 3H), 1.41 (ttt, J=11.2, 7.3, 3.7 Hz, 1H), 1.59–1.78
(m, 5H), 1.85 (s, 6H), 2.32 (d, J=7.2 Hz, 2H), 6.00 (dd, J=
2.8, 1.9 Hz, 1H), 6.50 (dd, J=2.5, 1.9 Hz, 1H), 6.70 (t, J=
2.6 Hz, 1H), 6.93–6.97 (m, 2H), 7.20 (tt, J=7.3, 1.6 Hz, 1H),
7.24–7.29 (m, 2H); 13C NMR (125 MHz, CDCl3) d 26.5, 26.7,
30.5, 33.4, 35.3, 39.5, 59.9, 108.4, 117.5, 118.7, 122.6, 124.9,
126.8, 128.3, 148.6. HRMS (FI) Calcd for C20H27N: M,
281.2144. Found: m/z 281.2158.
yl)phenyl]ethanone
(0.600 mmol),
N-isopropylpyrrole
1-tert-Butyl-3-neopentyl-1H-pyrrole (4x): The title com-
pound was synthesized with the following reagents based on
method A: pivalaldehyde (0.600 mmol), N-tert-butylpyrrole
(2.40 mmol), 3a (0.900 mmol), HNTf2 (18.0 mmol) and 1,4-
dioxane (0.60 mL), and isolated by column chromatography
on silica gel (hexane/EtOAc=100:1). Compound 4x has al-
ready appeared in the literature, and its spectral and analyti-
cal data are in good agreement with those reported in ref. 8.
Therefore, only H NMR data are provided here. H NMR
(500 MHz, CDCl3) d 0.88 (s, 9H), 1.50 (s, 9H), 2.31 (s, 2H),
5.93 (dd, J=2.6, 2.0 Hz, 1H), 6.55 (dd, J=2.3, 2.0 Hz, 1H),
6.70 (t, J=2.6 Hz, 1H).
(2.40 mmol), 3a (0.900 mmol), HNTf2 (18.0 mmol) and 1,4-
dioxane (0.60 mL), and isolated by column chromatography
on silica gel (hexane/EtOAc/NEt3 =92:5:3). A viscous color-
1
less oil. H NMR (500 MHz, CDCl3) d 1.34 (s, 12H), 1.40 (d,
J=6.6 Hz, 3H), 1.41 (d, J=6.6 Hz, 3H), 1.56 (d, J=7.2 Hz,
3H), 4.03 (q, J=7.2 Hz, 1H), 4.14 (sept, J=6.7 Hz, 1H),
5.95 (dd, J=2.3, 2.0 Hz, 1H), 6.39–6.46 (m, 1H), 6.62 (t, J=
2.6 Hz, 1H), 7.28 (t, J=7.6 Hz, 1H), 7.34 (ddd, J=7.7, 1.8,
1.4, Hz, 1H), 7.63 (ddd, J=7.2, 1.5, 1.2 Hz, 1H), 7.72–7.75
(m, 1H); 13C NMR (125 MHz, CDCl3) d 22.8, 23.86, 23.90,
24.9, 38.2, 50.5, 83.6, 107.0, 115.6, 117.8, 127.7, 128.8, 130.4,
1
1
8
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

UPDATES
Metal-Free Regioselective b-Alkylation of Pyrroles
1H NMR (500 MHz, CDCl3) d 1.56–1.72 (m, 6H), 1.76 (s,
2H), 1.78–1.85 (m, 2H), 1.95 (quint, J=2.9 Hz, 1H), 2.02
(ddd, J=12.7, 5.4, 3.3 Hz, 1H), 2.11 (dd, J=13.2, 6.6 Hz,
1H), 2.33 (ddd, J=12.6, 6.3, 3.5 Hz, 1H), 2.46 (ddd, J=13.3,
6.0, 3.5 Hz, 1H), 3.03 (dd, J=13.2, 8.3 Hz, 1H), 3.16 (s, 3H),
3.79 (s, 3H), 4.17 (dd, J=8.0, 6.9 Hz, 1H), 6.21 (d, J=
2.9 Hz, 1H), 6.50 (d, J=2.6 Hz, 1H), 6.83 (dt, J=8.9,
2.6 Hz, 2H), 7.07 (dt, J=8.6, 2.4 Hz, 2H); 13C NMR
(125 MHz, CDCl3) d 27.4, 27.6, 33.9, 34.3, 34.4, 34.8, 35.1,
37.4, 38.9, 39.8, 42.2, 49.8, 54.3, 55.2, 106.0, 113.9, 123.2,
128.4, 134.8, 137.7, 137.9, 158.0. HRMS (FD) Calcd for
C24H29NO: M, 347.2249. Found: m/z 347.2469.
HNTf2-Catalyzed b-Alkylation of Pyrroles with
Carbonyl Compounds and Carbon Nucleophiles. A
General Procedure for Scheme 3
A flame-dried 20 mL Schlenk tube was filled with argon and
then charged with HNTf2 [(4.22 mg, 15.0 mmol) or (5.90 mg,
21.0 mmol)] and 1,4-dioxane (0.30 or 2.4 mL). The solution
was stirred at room temperature for 3 min. To this were
added carbonyl compound 5 (0.300 mmol) and pyrrole de-
rivative 2 (1.20 mmol), and the resulting mixture was stirred
at 85 or 1008C for 8 or 20 h. Carbon nucleophile 3 (0.450,
0.750 or 0.900 mmol) was then added, and the resulting solu-
tion was stirred further at 70, 85 or 1008C. After the time
specified in Scheme 3 (see t2), a saturated NaHCO3 aqueous
solution (0.3 mL) was added, and the aqueous phase was ex-
tracted with EtOAc (5 mL x 3). The combined organic layer
was washed with brine (1 mL) and then dried over anhy-
drous sodium sulfate. Filtration and evaporation of the sol-
vent followed by column chromatography on silica gel using
hexane–EtOAc or hexane–CHCl3 as eluent gave the corre-
sponding product (7). The results are summarized in
Scheme 3. Unless otherwise noted, products 7 synthesized
HNTf2-Catalyzed Synthesis of Dipyrrolyldecanes 6a
by Treatment of 2-Decanone (5a) and N-
Methylpyrrole (2a) (Scheme 4)
A flame-dried 50 mL Schlenk tube was filled with argon and
then charged with HNTf2 (59.0 mg, 210 mmol) and 1,4-diox-
ane (7.0 mL). The solution was stirred at room temperature
for 3 min. To this were added 5a (1.09 g, 7.00 mmol) and 2a
(2.27 g, 28.0 mmol) successively, and the resulting mixture
was stirred at 858C for 5 h. A saturated NaHCO3 aqueous
solution (2 mL) was added, and the aqueous phase was ex-
tracted with EtOAc (50 mL x 3). The combined organic
layer was washed with brine (20 mL) and then dried over
anhydrous sodium sulfate. Filtration and evaporation of the
solvent followed by column chromatography on silica gel
(hexane/EtOAc=20:1) gave dipyrrolyldecanes 6a (1.92 g,
92% yield) as a mixture of three isomers including a,a’-6a,
a,b’-6a and b,b’-6a. The result is summarized in Scheme 4.
1H NMR spectra showed that b,b’-6a is a major isomer,
along with a,b’-6a and a small amount of a,a’-6a. The ratio
of a,a’-6a:a,b’-6a:b,b’-6a was determined to be 2:13:85 by
GC analysis. The two major isomers, a,b’-6a and b,b’-6a,
have already appeared in the literature, and their spectral
and analytical data are in good agreement with those report-
ed in ref. 7. Due to the small amount of a,a’-6a produced
here, other reaction for synthesizing a,a’-6a was carried out
under the reaction conditions shown in the next section, and
a,a’-6a was obtained as a pure form.
1
here were fully characterized by H and 13C NMR spectros-
copy and HRMS.
2-(1-Methyl-1H-pyrrol-3-yl)-2-adamantanecarbonitrile
(7a): The title compound was synthesized with the following
reagents
based
on
method
B:
2-adamantanone
(0.300 mmol), 2a (1.20 mmol), 3b (0.450 mmol), HNTf2
(21.0 mmol) and 1,4-dioxane (0.30 mL), and isolated by
column chromatography on silica gel (hexane/EtOAc=3:1).
1
A white solid, mp=106–1078C. H NMR (500 MHz, CDCl3)
d 1.61 (ddd, J=13.1, 3.6, 2.7 Hz, 2H), 1.70–1.77 (m, 3H),
1.92 (ddd, J=13.3, 3.6, 2.7 Hz, 2H), 1.97–2.05 (m, 3H), 2.41
(dd, J=13.2, 2.3 Hz, 2H), 2.46 (t, J=2.9 Hz, 2H), 3.64 (s,
3H), 6.10 (dd, J=2.9, 1.7 Hz, 1H), 6.55 (dd, J=2.3, 1.7 Hz,
1H), 6.57 (dd, J=2.9, 2.3 Hz, 1H); 13C NMR (125 MHz,
CDCl3) d 26.9, 31.5, 34.1, 34.9, 36.4, 37.63, 37.64, 42.9, 106.5,
119.6, 122.1, 123.0, 124.9. HRMS (FD) Calcd for C16H20N2:
M, 240.1627. Found: m/z 240.1624.
2-(1-Benzyl-1H-pyrrol-3-yl)-2-(5-methylfuran-2-yl)octane
(7b): The title compound was synthesized with the following
reagents based on method B: 2-octanone (0.300 mmol), 1-
benzyl-1H-pyrrole (1.20 mmol), 3c (0.750 mmol), HNTf2
(15.0 mmol) and 1,4-dioxane (2.4 mL), and isolated by
column chromatography on silica gel (hexane/CHCl3 =4:1).
Compound 7b has already appeared in the literature, and its
spectral and analytical data are in good agreement with
HNTf2-Catalyzed Synthesis of 2,2-Bis(1-methyl-1H-
pyrrol-2-yl)decane (a,a’-6a) by Treatment of 2-
Decanone (5a) and N-Methylpyrrole (2a)
A flame-dried 20 mL Schlenk tube was filled with argon and
then charged with HNTf2 (5.06 mg, 18.0 mmol) and 1,4-diox-
ane (0.60 mL). The solution was stirred at room temperature
for 3 min. To this were added 5a (93.8 mg, 0.600 mmol) and
2a (195 mg, 2.40 mmol) successively, and the resulting mix-
ture was stirred at room temperature for 3 h. A saturated
NaHCO3 aqueous solution (0.3 mL) was added, and the
aqueous phase was extracted with EtOAc (5 mL x 3). The
combined organic layer was washed with brine (1 mL) and
then dried over anhydrous sodium sulfate. Filtration and
evaporation of the solvent followed by column chromatogra-
phy on silica gel (hexane/CHCl3 =6:1) gave a,a’-6a
(29.0 mg, 16% yield) as a viscous colorless oil. 1H NMR
(500 MHz, CDCl3) d 0.87 (t, J=7.0 Hz, 3H), 1.04–1.34 (m,
12H), 1.59 (s, 3H), 2.01–2.09 (m, 2H), 3.02 (s, 6H), 6.02
(dd, J=3.6, 2.7 Hz, 2H), 6.07 (dd, J=3.8, 2.0 Hz, 2H), 6.45
1
those reported in the literature.[23] Therefore, only H NMR
1
data are provided here. H NMR (400 MHz, CDCl3) d 0.85
(t, J=6.9 Hz, 3H), 1.07–1.31 (m, 8H), 1.51 (s, 3H), 1.75–
1.86 (m, 1H), 1.88–2.00 (m, 1H), 2.24 (d, J=0.9 Hz, 3H),
5.00 (s, 2H), 5.80–5.83 (m, 1H), 5.85 (d, J=3.2 Hz, 1H),
6.06 (dd, J=2.7, 1.8 Hz, 1H), 6.45 (dd, J=2.3, 1.8 Hz, 1H),
6.56 (dd, J=2.7, 2.3 Hz, 1H), 7.04–7.10 (m, 2H), 7.22–7.34
(m, 3H).
5’,6’-Dihydro-6’-(4-methoxyphenyl)-1’-methyl-spiro[ada-
mantane-2,4’(1’H)-cyclopenta[b]pyrrole] (7c): The title
compound was synthesized with the following reagents
based on method B: 2-adamantanone (0.300 mmol), 2a
(1.20 mmol), 3d (0.900 mmol), HNTf2 (21.0 mmol) and 1,4-
dioxane (0.30 mL), and isolated by column chromatography
on silica gel (hexane/CHCl3 =2:1). A viscous colorless oil.
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!

UPDATES
Shota Nomiyama and Teruhisa Tsuchimoto
(t, J=2.3 Hz, 2H); 13C NMR (125 MHz, CDCl3) d 14.1, 22.7,
24.0, 26.7, 29.4, 29.6, 30.2, 31.9, 34.3, 38.7, 39.7, 105.8, 106.7,
122.8, 137.7. HRMS (FI) Calcd for C20H32N2: M, 300.2566.
Found: m/z 300.2568.
[3] Heterocyclic Chemistry, 5th ed. (Eds.: J. A. Joule, K.
Mills) Wiley, New York, 2010, pp. 9–10.
[4] For a selected review on the Friedel–Crafts alkylation
of pyrroles, see: B. A. Trofimov, N. A. Nedolya In
Comprehensive Heterocyclic Chemistry III, Vol.
3
(Eds.: A. R. Katritzky, C. A. Ramsden, E. F. V. Scriven,
R. J. K. Taylor, G. Jones), Elsevier, Oxford, 2008,
pp. 110–134.
HNTf2-Catalyzed Synthesis of 3-(Decan-2-yl)-1-
methyl-1H-pyrrole (4a) by Treatment of
Dipyrrolyldecanes 6a, Et3SiH (3a) and H2O
(Scheme 4)
[5] For reviews on b-alkylation of pyrroles, see: a) H. J.
Anderson, C. E. Loader, Synthesis 1985, 353; b) W. D.
Harman, Chem. Rev. 1997, 97, 1953; c) B. C. Brooks,
T. B. Gunnoe, W. D. Harman, Coord. Chem. Rev. 2000,
206–207, 3; d) T. Tsuchimoto, Chem. Eur. J. 2011, 17,
4064. For selected recent reports on b-alkylation of pyr-
roles, see: e) D. Prajapati, M. Gohain, B. J. Gogoi, Tet-
rahedron Lett. 2006, 47, 3535; f) O. I. Shmatova, N. E.
Shevchenko, E. S. Balenkova, G.-V. Rçschenthaler,
V. G. Nenajdenko, Eur. J. Org. Chem. 2013, 3049.; see
also refs. 6–8.
[6] Among the strategies for the SEAr-based b-alkylation
of pyrroles, a bulky triisopropylsilyl group on the nitro-
gen atom has been known to direct incoming electro-
philes to the b-position due to its effective steric shield-
ing of the a-position. For selected recent reports on the
b-alkylation of N-(iPr)3Si-pyrrole, see: a) C. Berini, F.
Minassian, N. Pelloux-Lꢃon, J.-N. Denis, Y. Vallꢃe, C.
Philouze, Org. Biomol. Chem. 2008, 6, 2574; b) J. Bar-
luenga, A. Fernꢄndez, F. Rodrꢅguez, F. J. FaÇanꢄs,
Chem. Eur. J. 2009, 15, 8121; c) C. Berini, N. Pelloux-
Lꢃon, F. Minassian, J.-N. Denis, Org. Biomol. Chem.
2009, 7, 4512; d) F. Martinelli, A. Palmieri, M. Petrini,
Chem. Eur. J. 2011, 17, 7183; e) L. Boiaryna, M. K.
El Mkaddem, C. Taillier, V. Dalla, M. Othman, Chem.
Eur. J. 2012, 18, 14192; f) F. de Nanteuil, J. Loup, J.
Waser, Org. Lett. 2013, 15, 3738; g) S. Lancianesi, A.
Palmieri, M. Petrini, Adv. Synth. Catal. 2013, 355, 3285.
[7] T. Tsuchimoto, T. Wagatsuma, K. Aoki, J. Shimotori,
Org. Lett. 2009, 11, 2129.
A flame-dried 20 mL Schlenk tube was filled with argon and
then charged with HNTf2 (2.53 mg, 9.00 mmol) and 1,4-diox-
ane (0.30 mL). The solution was stirred at room temperature
for 3 min. To this were added 6a (90.1 mg, 0.300 mmol), 3a
(52.3 mg, 0.450 mmol) and H2O (5.40 mg, 0.300 mmol) suc-
cessively, and the resulting mixture was stirred at 858C for
5 h. A saturated NaHCO3 aqueous solution (0.3 mL) was
added, and the aqueous phase was extracted with EtOAc
(5 mL x 3). The combined organic layer was washed with
brine (1 mL) and then dried over anhydrous sodium sulfate.
Filtration and evaporation of the solvent followed by
column chromatography on silica gel (hexane/EtOAc=40:1)
gave 4a (62.6 mg, 94% yield). The result is summarized in
1
Scheme 4. The full data on H NMR, 13C NMR spectroscopy
and HRMS analysis of 4a have been already collected in
ref. 8.
Acknowledgements
Partial financial support from Nissan Chemical Industries,
L.T.D. is gratefully acknowledged.
References
[1] For selected recent reviews, see: a) N. K. Garg, B. M.
Stoltz, Chem. Commun. 2006, 3769; b) N. R. William-
son, P. C. Fineran, F. J. Leeper, G. P. C. Salmond, Nat.
Rev. Microbiol. 2006, 4, 887; c) C.-C. Chang, W.-C.
Chen, T.-F. Ho, H.-S. Wu, Y.-H. Wei, J. Biosci. Bioeng.
2011, 111, 501. For selected recent reports, see: d) U.
Robben, I. Lindner, W. Gꢂrtner, J. Am. Chem. Soc.
2008, 130, 11303; e) C. P. Soldermann, R. Vallinayagam,
M. Tzouros, R. Neier, J. Org. Chem. 2008, 73, 764;
f) J. H. Frederich, P. G. Harran, J. Am. Chem. Soc.
2013, 135, 3788; g) C. Vergeiner, S. Banala, B. Krꢂutler,
Chem. Eur. J. 2013, 19, 12294.
[8] T. Tsuchimoto, M. Igarashi, K. Aoki, Chem. Eur. J.
2010, 16, 8975. Due to a request from one reviewer, re-
sults of some experiments performed to confirm wheth-
er HNTf2 is a true catalyst or not in the preceding
study are collected in the Supporting Information.
[9] For a report on increases in consumption and price of
indium during the last few decades, see: T. G. Goonan,
“Materials Flow of Indium in the United States in 2008
and 2009” that can be found at http://pubs.usgs.gov/
circ/1377.
[10] For synthesis of In(NTf2)3 (Tf=SO2CF3), see: a) C. G.
Frost, J. P. Hartley, D. Griffin, Tetrahedron Lett. 2002,
43, 4789; b) M. Nakamura, K. Endo, E. Nakamura,
Adv. Synth. Catal. 2005, 347, 1681. For synthesis of
In(ONf)3 (Nf=SO2C4F9), see: c) T. Tsuchimoto, H.
Matsubayashi, M. Kaneko, E. Shirakawa, Y. Kawaka-
mi, Angew. Chem. 2005, 117, 1360; Angew. Chem. Int.
Ed. 2005, 44, 1336.
[11] In(NTf2)3 is currently commercially available from
Sigma–Aldrich, but is expensive; 20,700 yen/1 g.
[12] HNTf2 is commercially available at 20,000 yen/250 g
(=80 yen/1 g) from Kanto Chemical Co., Inc.
[2] For selected recent examples, see: a) L. Jiao, E. Hao,
M. G. H. Vicente, K. M. Smith, J. Org. Chem. 2007, 72,
8119; b) G. Zotti, B. Vercelli, A. Berlin, Chem. Mater.
2008, 20, 397; c) X. Lv, L.-J. Hong, Y. Li, M.-J. Yang, J.
Appl. Polym. Sci. 2009, 112, 1287; d) M. Krayer, M.
Ptaszek, H.-J. Kim, K. R. Meneely, D. Fan, K. Secor,
J. S. Lindsey, J. Org. Chem. 2010, 75, 1016; e) J. T. Lee,
D.-H. Chae, Z. Ou, K. M. Kadish, Z. Yao, J. L. Sessler,
J. Am. Chem. Soc. 2011, 133, 19547; f) T.-T. Bui, A.
Iordache, Z. Chen, V. V. Roznyatovskiy, E. Saint-
Aman, J. M. Lim, B. S. Lee, S. Ghosh, J.-C. Moutet,
J. L. Sessler, D. Kim, C. Bucher, Chem. Eur. J. 2012, 18,
5853.
10
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

UPDATES
Metal-Free Regioselective b-Alkylation of Pyrroles
[13] Disappearance of carbonyl compounds 5 followed by
formation of dipyrrolylalkanes 6 can be confirmed by
GC and GC–MS analysis.
[18] The process of the HNTf2-catalyzed reaction of 5a with
2a produces one molar equivalent of H2O along with
the formation of 6a. Accordingly, the reaction was per-
formed in the presence of H2O (1 equiv.).
[19] a) D. M. Wallace, S. H. Leung, M. O. Senge, K. M.
Smith, J. Org. Chem. 1993, 58, 7245; b) G. R. Geier III,
B. J. Littler, J. S. Lindsey, J. Chem. Soc. Perkin Trans. 2
2001, 701; c) A. Auger, A. J. Muller, J. C. Swarts,
Dalton Trans. 2007, 3623.
[20] a) W. Adam, J. Glꢂser, K. Peters, M. Prein, J. Am.
Chem. Soc. 1995, 117, 9190; b) Y. Yokoyama, Chem.
Eur. J. 2004, 10, 4388.
[21] For synthesis of 6-heptyn-2-one, see: a) P. E. Peterson,
R. J. Kamat, J. Am. Chem. Soc. 1969, 91, 4521; for spec-
tral and analytical data of 6-heptyn-2-one, see: b) C. Le
Drian, A. E. Greene, J. Am. Chem. Soc. 1982, 104,
5473; c) B. M. Trost, M. J. Bartlett, Org. Lett. 2012, 14,
1322.
[14] For our representative reports on indium-catalyzed
transformation via activation of CꢀC bonds, see: a) T.
Tsuchimoto, T. Maeda, E. Shirakawa, Y. Kawakami,
Chem. Commun. 2000, 1573; b) T. Tsuchimoto, K. Ha-
tanaka, E. Shirakawa, Y. Kawakami, Chem. Commun.
2003, 2454; c) T. Tsuchimoto, H. Matsubayashi, M.
Kaneko, Y. Nagase, T. Miyamura, E. Shirakawa, J. Am.
Chem. Soc. 2008, 130, 15823; d) T. Tsuchimoto, M.
Kanbara, Org. Lett. 2011, 13, 912; e) Y. Nagase, H.
Shirai, M. Kaneko, E. Shirakawa, T. Tsuchimoto, Org.
Biomol. Chem. 2013, 11, 1456. See also refs. 7, 10c.
[15] Other research groups have also reported indium-cata-
lyzed transformation by way of activation of CꢀC
bonds. See an important review: Z.-L. Shen, S.-Y.
Wang, Y.-K. Chok, T.-P. Loh, Chem. Rev. 2013, 113,
271.
[22] A. D. Josey, Org. Synth. 1967, 47, 81.
[23] T. Tsuchimoto, T. Ainoya, K. Aoki, T. Wagatsuma, E.
[16] 5a (0.60 mmol), N-Boc-pyrrole (1.8 mmol), 3a
(0.90 mmol), HNTf2 (18 mmol), 1,4-dioxane (0.60 mL),
858C, 5 h.
Shirakawa, Eur. J. Org. Chem. 2009, 2437.
[17]
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
11
ÞÞ
These are not the final page numbers!

UPDATES
12 Metal-Free Regioselective b-Alkylation of Pyrroles with
Carbonyl Compounds and Hydrosilanes: Use of a Brønsted
Acid as a Catalyst
Adv. Synth. Catal. 2014, 356, 1 – 12
Shota Nomiyama, Teruhisa Tsuchimoto*
12
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!