Indium-catalyzed reductive alkylation of pyrroles with alkynes and hydrosilanes: Selective synthesis of β-alkylpyrroles

Article abstract of DOI:10.1021/ol900651u

Mixing readily available alkynes, pyrroles, and triethylsilane along with an indium catalyst was found to be an efficient procedure to introduce alkyl groups onto a β-position of pyrroles in a complete regioselective manner. This is the first demonstratio

Full text of DOI:10.1021/ol900651u

ORGANIC
LETTERS
2009
Vol. 11, No. 10
2129-2132
Indium-Catalyzed Reductive Alkylation of
Pyrroles with Alkynes and Hydrosilanes:
Selective Synthesis of ꢀ-Alkylpyrroles
Teruhisa Tsuchimoto,* Tatsuya Wagatsuma, Kazuki Aoki, and Jun Shimotori
Department of Applied Chemistry, School of Science and Technology, Meiji UniVersity,
Higashimita, Tama-ku, Kawasaki 214-8571, Japan
tsuchimo@isc.meiji.ac.jp
Received March 30, 2009
ABSTRACT
Mixing readily available alkynes, pyrroles, and triethylsilane along with an indium catalyst was found to be an efficient procedure to introduce
alkyl groups onto a ꢀ-position of pyrroles in a complete regioselective manner. This is the first demonstration of catalytic ꢀ-alkylation of
pyrroles in a single step.
Pyrroles having alkyl chains at the ꢀ-positions are key units
found in many natural products1 and functional organic
materials.2 Due to the sufficient aromaticity and π-excessive
nature of pyrroles,3 direct introduction of alkyl groups onto
pyrroles by electrophilic aromatic substitution appears to be
a straightforward route to access ꢀ-alkylpyrroles.4 However,
preferential R-nucleophilicity of pyrroles actually makes the
ꢀ-alkylation considerably difficult.5 Despite such character-
istics of pyrroles, two strategies are available to alter the
(3) Jones, G. B.; Chapman, B. J. In ComprehensiVe Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Bird, C. W.,
Eds.; Pergamon: Oxford, 1996; Vol. 2, pp 1-38.
(4) Intra- and Intermolecular ring closing reactions are alternative direct
or indirect ways to access ꢀ-alkylpyrroles, see: (a) Sundberg, R. J. In
ComprehensiVe Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Bird, C. W., Eds.; Pergamon: Oxford, 1996; Vol. 2, pp
119-206.
(5) For recent reports on selective R-alkylation of pyrroles with the
following alkylating agents by electrophilic aromatic substitution. For
alkenes: (a) Yadav, J. S.; Reddy, B. V. S.; Reddy, P. S. R.; Reddy, K. S.;
Reddy, P. N. Synlett 2003, 417–419. (b) Zhan, Z.-P.; Yang, W.-Z.; Yang,
R.-F. Synlett 2005, 2425–2428. (c) Zhang, C.-X.; Wang, Y.-Q.; Duan, Y.-
S.; Ge, Z.-M.; Cheng, T.-M.; Li, R.-T. Catal. Commun. 2006, 7, 534–537.
(d) An, L.-T.; Zou, J.-P.; Zhang, L.-L.; Zhang, Y. Tetrahedron Lett. 2007,
48, 4297–4300. (e) Unaleroglu, C.; Yazici, A. Tetrahedron 2007, 63, 5608–
5613. (f) Hashmi, A. S. K.; Salathe´, R.; Frey, W. Eur. J. Org. Chem. 2007,
1648–1652. (g) Trost, B. M.; Mu¨ller, C. J. Am. Chem. Soc. 2008, 130,
2438–2439. For allylic acetates: (h) Yadav, J. S.; Reddy, B. V. S.; Rao,
K. V.; Rao, P. P.; Raj, K. S.; Prasad, A. R.; Prabhakar, A.; Jagadeesh, B.
Synlett 2006, 3447–3450. For alcohols: (i) Liu, J.; Muth, E.; Flo¨rke, U.;
Henkel, G.; Merz, K.; Sauvageau, J.; Schwake, E.; Dyker, G. AdV. Synth.
Catal. 2006, 348, 456–462. For epoxides and aziridines: (j) Yadav, J. S.;
Reddy, B. V. S.; Parimala, G. Synlett 2003, 1143–1145. For diazo
compounds: (k) Yadav, J. S.; Reddy, B. V. S.; Satheesh, G. Tetrahedron
Lett. 2003, 44, 8331–8334. See also a review: (l) Schmuck, C.; Rupprecht,
D. Synlett 2007, 3095–3110.
(1) For selected examples, see: (a) de Leon, C. Y.; Ganem, B.
Tetrahedron 1997, 53, 7731–7752. (b) Adamczyk, M.; Johnson, D. D.;
Reddy, R. E. J. Org. Chem. 2001, 66, 11–19. (c) Grag, N. K.; Caspi, D. D.;
Stoltz, B. M. J. Am. Chem. Soc. 2004, 126, 9552–9553. (d) Murtagh, J. E.;
McCooey, S. H.; Connon, S. J. Chem. Commun. 2005, 227–229. (e) Fu¨rstner,
A.; Radkowski, K.; Peters, H.; Seidel, G.; Wirtz, C.; Mynott, R.; Lehmann,
C. W. Chem. Eur. J. 2007, 13, 1929–1945. (f) O’Neal, W. G.; Jacobi, P. A.
J. Am. Chem. Soc. 2008, 130, 1102–1108. (g) Oberhuber, M.; Berghold,
J.; Kra¨utler, B. Angew. Chem., Int. Ed. 2008, 47, 3057–3061. (h) Kawasaki,
T.; Sakurai, F.; Hayakawa, Y. J. Nat. Prod. 2008, 71, 1265–1267. See also
recent reviews: (i) Fu¨rstner, A. Angew. Chem., Int. Ed. 2003, 42, 3582–
3603. (j) Banwell, M. G.; Goodwin, T. E.; Ng, S.; Smith, J. A.; Wong,
D. J. Eur. J. Org. Chem. 2006, 3043–3060.
(2) For selected recent examples, see: (a) Meltola, N. J.; Wahlroos, R.;
Soini, A. E. J. Fluoresc. 2004, 14, 635–647. (b) Zotti, G.; Zecchin, S.;
Schiavon, G.; Vercelli, B.; Berlin, A.; Grimoldi, S. Macromol. Chem. Phys.
2004, 205, 2026–2031. (c) Xu, H.; Yu, G.; Xu, W.; Xu, Y.; Cui, G.; Zhang,
D.; Liu, Y.; Zhu, D. Langmuir 2005, 21, 5391–5395. (d) Foitzik, R. C.;
Kaynak, A.; Beckmann, J.; Pfeffer, F. M. Synth. Met. 2005, 155, 185–190.
(e) Zhao, W.; Carreira, E. M. Chem. Eur. J. 2006, 12, 7254–7263. (f) Foitzik,
R. C.; Kaynak, A.; Pfeffer, F. M. Synth. Met. 2006, 156, 637–642. (g)
Foitzik, R. C.; Kaynak, A.; Pfeffer, F. M.; Beckmann, J. Synth. Met. 2006,
156, 1333–1340. (h) Jiao, L.; Hao, E.; Vicente, G. H.; Smith, K. M. J.
Org. Chem. 2007, 72, 8119–8122. (i) King, R. C. Y.; Boussoualem, M.;
Roussel, F. Polymer 2007, 48, 4047–4054. (j) Zotti, G.; Vercelli, B.; Berlin,
A. Chem. Mater. 2008, 20, 397–412.
10.1021/ol900651u CCC: $40.75
Published on Web 04/21/2009
 2009 American Chemical Society

R-orientation to ꢀ-orientation:6 (1) use of pyrrole-metal
complexes7 and (2) use of pyrroles bearing an electron-
withdrawing group at the R-position.8 Some of these have
achieved high ꢀ-selectivities, but catalytic ꢀ-alkylation of
pyrroles proceeding in one-step has no precedent. At present,
a three-step process, introduced by Ru¨he and colleagues,
seems to have been the most reliable strategy to synthesize
ꢀ-alkylpyrroles.9,10
Scheme 1. Working Hypothesis for ꢀ-Alkylation of Pyrroles
We have reported that indium triflate [In(OTf)3, Tf )
SO2CF3] catalyzes double addition of N-substituted pyr-
roles 2 to alkynes 1, giving isomeric mixtures of gem-
dipyrrolylalkanes 3 and 4 (Scheme 1, In(OTf)3 ) In).11,12
The noticeable aspect is that ꢀ,ꢀ′-adducts 4 are produced
selectively due to their thermodynamic stability. During the
course of the mechanistic studies on the isomerization
between 3 and 4, we proposed the formation of cationic
species A11,13 and envisaged that in situ trapping of A with
hydride would offer a conceptually new synthetic route to
ꢀ-alkylpyrroles 5. Herein we disclose the first catalytic
(6) For a review, see: Anderson, H. J.; Loader, C. E. Synthesis 1985,
353–364.
(7) For pyrrolyl-N-MgCl: (a) Castro, A. J.; Duncan, W. G.; Leong,
A. K. J. Am. Chem. Soc. 1969, 91, 4304. For pyrrolyl-N-ZnBr: (b) Yadav,
J. S.; Reddy, B. V. S.; Reddy, P. M.; Srinivas, C. Tetrahedron Lett. 2002,
43, 5185–5187. For pyrrolyl-N-[Re]: (c) DuBois, M. R.; Vasquez, L. D.;
Peslherbe, L.; Noll, B. C. Organometallics 1999, 18, 2230–2240. For
pyrrole-η2-[Os]: (d) Myers, W. H.; Koontz, J. I.; Harman, W. D. J. Am.
Chem. Soc. 1992, 114, 5684–5692. (e) Hodges, L. M.; Gonzalez, J.; Koontz,
J. I.; Myers, W. H.; Harman, W. D. J. Org. Chem. 1995, 60, 2125–2146.
(f) Valahovic, M. T.; Myers, W. H.; Harman, W. D. Organometallics 2002,
21, 4581–4589. See also the following reviews on pyrrole-η2-[Os]: (g)
Harman, W. D. Chem. ReV. 1997, 97, 1953–1978. (h) Brooks, B. C.;
Gunnoe, T. B.; Harman, W. D. Coord. Chem. ReV. 2000, 206-207, 3–61.
(8) (a) Anderson, H. J.; Hopkins, L. C. Can. J. Chem. 1966, 44, 1831–
1839. (b) Groves, J. K.; Anderson, H. J.; Nagy, H. Can. J. Chem. 1971,
49, 2427–2432.
regioselective ꢀ-alkylation of pyrroles in a single step, by a
simple assembly of alkynes, pyrroles and hydrosilanes.
Because of the potent activity of In(OTf)3 in the double
addition of pyrroles to alkynes,11 we first tested its catalytic
activity in the reaction of 1-decyne (1a) and N-methylpyrrole
(2a) with HSiEt3 as a hydride donor (Scheme 2). Thus, the
(9) The strategy consists of the following three steps: ꢀ-acylation of
N-(arylsulfonyl)pyrroles followed by de-arylsulfonylation and reduction of
the carbonyl moiety: (a) Ru¨he, J.; Ezquerra, T.; Wegner, G. Makromol.
Chem., Rapid Commun. 1989, 10, 103–108. (b) Ru¨he, J.; Ezquerra, T. A.;
Scheme 2. Indium-Catalyzed Reductive ꢀ-2-Decylation of 2a
Wegner, G. Synth. Met. 1989, 28, C177-C181
.
(10) For examples making use of the Ru¨he strategy, see: (a) Sigmund,
W. M.; Bailey, T. S.; Hara, M.; Sasabe, H.; Knoll, W.; Duran, R. S.
Langmuir 1995, 11, 3153–3160. (b) Barr, G. E.; Sayre, C. N.; Connor,
D. M.; Collard, D. M. Langmuir 1996, 12, 1395–1398. (c) Ashraf, S. A.;
Chen, F.; Too, C. O.; Wallace, G. G. Polymer 1996, 37, 2811–2819. (d)
Ng, S.-C.; Chan, H. S. O.; Xia, J.-F.; Yu, W. J. Mater. Chem. 1998, 8,
2347–2352. (e) Zelikin, A.; Shastri, V. R.; Langer, R. J. Org. Chem. 1999,
64, 3379–3380. (f) de Lacy Costello, B. P. J.; Evans, P.; Guernion, N.;
Ratcliffe, N. M.; Sivanand, P. S.; Teare, G. C. Synth. Met. 2000, 114, 181–
188. (g) Freitas, J. M.; Abrantes, L. M.; Darbre, T. HelV. Chim. Acta 2005,
88, 2470–2478. See also references 2d, 2f and 2g
(11) Tsuchimoto, T.; Hatanaka, K.; Shirakawa, E.; Kawakami, Y. Chem.
Commun. 2003, 2454–2455
.
.
(12) For representative recent reviews on indium-catalyzed reactions,
see: (a) Ghosh, R.; Maiti, S. J. Mol. Catal. A: Chem. 2007, 264, 1–8. (b)
Auge´, J.; Lubin-Germain, N.; Uziel, J. Synthesis 2007, 1739–1764. (c) Chua,
G.-L.; Loh, T.-P. In Acid Catalysis in Modern Organic Synthesis; Yama-
moto, H., Ishihara, K., Eds.; Wiley-VCH: Weinheim, 2008; Vol. 1, chapter
8, pp 377-467.
(13) Cleavage of carbonspyrrolyl bonds of bis(pyrrol-2-yl)alkanes has
been suggested to occur as an undesired process during acid-catalyzed
synthesis of porphyrins: (a) Geier, G. R., III.; Littler, B. J.; Lindsey, J. S.
J. Chem. Soc., Perkin Trans. 2 2001, 701–711. (b) Auger, A.; Muller, A. J.;
reaction with 25 mol % of In(OTf)3 in 1,4-dioxane at 85 °C
for 3 h proceeded with 79% conversion of 1a to give 3-(2-
decyl)-N-methylpyrrole (5a) in 70% yield, along with 3%
yield of the isomeric double addition products 3a and 4a.
Noteworthy is that no R-isomer 6a was formed. The use of
the nonaflate salt [In(ONf)3, Nf ) SO2C4F9] enhanced the
conversion of 1a, while a considerable amount of 3a and 4a
remained unconsumed. The addition of H2O (0.1 equiv)
Swarts, J. C. Dalton Trans. 2007, 3623–3633, and references cited therein
.
(14) With 20 mol % of In(NTf2)3, 5a was obtained in a comparable
yield (91%). However, further lower loading of In(NTf2)3 (15 mol %)
resulted in 59% conversion of 1a, giving 5a in 50% yield.
(15) Although some hydrosilanes other than HSiEt3 were tested in the
reaction using In(NTf2)3 as a catalyst, their use considerably lowered the
yield of 5a as follows: H2SiEt2 (2% yield), H2SiMePh (1% yield),
H3Si(CH2)7CH3 (<1% yield).
2130
Org. Lett., Vol. 11, No. 10, 2009

affected their complete consumption, showing that H2O could
act as an activator enhancing nucleophilicity of a hydride
reagent by its coordination. In(NTf2)3 recorded the highest
yield of 5a without the aid of H2O,14,15 but InCl3 and a
Brφnsted acid, HNTf2, were totally inactive. As a result,
In(NTf2)3 and In(ONf)3 in combination with using H2O
turned out to be promising for the present reaction.
c-HexCt CH, which has the branched structure adjacent to
the Ct C bond, resulted in a poor yield and ꢀ-selectivity
(entry 7). After re-examination of the reaction conditions and
procedure, both the yield and selectivity were markedly
improved by the alteration of method A to method B and of
In(NTf2)3 to In(ONf)3. Thus, pretreatment of c-HexCt CH,
2a and In(ONf)3 at 85 °C for 1 h, followed by the addition
of HSiEt3 and H2O, and further stirring for 2 h gave 5g as
the sole product in 76% yield (entry 8). Here again, the
In(ONf)3-catalyzed reaction in the absence of H2O resulted
in a lower yield, as the case shown in Scheme 2 (entry 9).
Method B is valid also for the reactions of aryl- and
heteroarylalkynes having similar branched structures as
c-HexCt CH (entries 10 and 11). Pyrroles with sBn (Bn )
benzyl), st-Bu or sPh on the nitrogen atom (entries 12-17)
as well as 1,2-dimethylpyrrole (2b) (eq 1) accepted a certain
range of alkynes 1, together with HSiEt3, in a complete
ꢀ-selective manner, by the proper choices of methods and
indium catalysts. The reaction of internal alkyne 1b with 2a
also gave only 5q, while higher loadings of 2a and In(ONf)3
at higher temperature without solvent 1,4-dioxane were
required (eq 2). Utility of the strategy can be demonstrated
by performance of preparative scale synthesis. For example,
5a and 5f were prepared in 5.0 and 5.4 mmol scale,
respectively, and thus 1.02 g (85% yield) of 5a and 1.33 g
(89% yield) of 5f were obtained (eq 3).
We next surveyed the substrate scope of the reductive
ꢀ-alkylation (Table 1). Besides 1a, 4-phenyl-1-butyne, which
Table 1. Indium-Catalyzed Reductive ꢀ-Alkylation of Pyrrolesa
X in method yield (%),b ratio of
entry
R1
R2 InX3
(t)
product(s)
5:6c
1
2
3
Oct
Ph(CH2)2
Cl(CH2)4
AcO(CH2)3 Me NTf2 A (12)
HO(CH2)4 Me NTf2 A (4)
PI(CH2)3
c-Hex
c-Hex
c-Hex
Ph
3-thienyl
Oct
c-PenCH2
PI(CH2)3
Ph
Me NTf2 A (3)
Me NTf2 A (8)
Me NTf2 A (20)
91, 5a
79, 5b
53, 5c
78, 5d
71, 5ee
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
81:19
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
4
5d
6
f
Me NTf2 A (2.5) 92, 5f
Me NTf2 A (24)
7
9, 5g, 6g
76, 5g
51, 5g
76, 5h
75, 5i
81, 5j
85, 5k
76, 5l
8g
9
Me ONf
Me ONf
Me NTf2
Me NTf2
Bn ONf
Bn ONf
Bn ONf
Bn ONf
tBu NTf2
Phi ONf
B
B
B
B
A (2)
A (15)
A (5)
B
B
B
10
11
12g
13g
14g
15g
16
17g
h
f
84, 5m
89, 5n
87, 5o
Oct
Oct
a Reagents (unless otherwise specified): 1 (0.500 mmol), 2 (1.50 mmol
for method A or 2.00 mmol for method B), HSiEt3 (0.750 mmol), In(NTf2)3
or In(ONf)3 (0.125-0.150 mmol), 1,4-dioxane (1.0 mL). See Supporting
Information for further details. b Isolated yield based on 1. c Determined
by GC. d At 70 °C. e Product 5e′ having -OSiEt3 instead of -OH also
was formed in 2% yield. f PI ) phthalimidoyl. g Performed in the presence
of H2O (0.1 equiv). For method B, H2O was added successively after the
addition of HSiEt3. h c-Pen ) cyclopentyl. i N-Phenylpyrrole (3.0 equiv)
was used.
Unfortunately, the strategy cannot be applied well to
pyrrole (2, R2 ) H),17 but instead we secured a reliable two-
step synthetic route for ꢀ-alkylpyrrole 5 (R2 ) H). Thus,
is capable of cyclizing independently,16 reacted with 2a and
HSiEt3 to provide 5b exclusively, by the procedure shown
as method A (entries 1 and 2). The functional groups, sCl,
sOAc (Ac ) acetyl) and sOH are compatible with the
strategy (entries 3-5). The Ct C bond of N-(4-penty-
nyl)phthalimide also accepted the ꢀ-position of 2a exclu-
sively (entry 6). In contrast to these results, the reaction of
(17) On treatment of 1a, pyrrole, HSiEt3 (1:3:1.5) and 25 mol % of
In(NTf2)3 at 85 °C for 24 h using method A, a 54:46 mixture of ꢀ- and
R-(2-decyl)pyrroles was obtained in 17% yield.
(18) Talukdar, S.; Nayak, S. K.; Banerji, A. J. Org. Chem. 1998, 63,
4925–4929.
(19) Baba, Shibata and co-workers as well as Miura, Hosomi and co-
workers have proposed that treatment of indium salts (InX3; X ) Cl, Br,
OAc) with hydrosilanes brings about in situ generation of indium hydrides
(InsH). Therefore, an InsH might be formed also in the present reaction:
(a) Shibata, I.; Kato, H.; Ishida, T.; Yasuda, M.; Baba, A. Angew. Chem.,
Int. Ed. 2004, 43, 711–714. (b) Hayashi, N.; Shibata, I.; Baba, A. Org.
Lett. 2004, 6, 4981–4983. (c) Hayashi, N.; Shibata, I.; Baba, A. Org. Lett.
2005, 7, 3093–3096. (d) Miura, K.; Tomita, M.; Ichikawa, J.; Hosomi, A.
Org. Lett. 2008, 10, 133–136.
(16) For reviews, see: (a) Nevado, C.; Echavarren, A. M. Synthesis 2005,
167–182. (b) Bandini, M.; Emer, E.; Tommasi, S.; Umani-Ronchi, A. Eur.
J. Org. Chem. 2006, 3527–3544.
Org. Lett., Vol. 11, No. 10, 2009
2131

debenzylation of 5j or 5m, each of which has been prepared
in entry 12 or 15 of Table 1, upon treatment with a low-
valent titanium reagent gave 5r or 5s, respectively (eq 4).18
Importantly, the benzyl group, -CH(CH3)Ph, on the ꢀ-car-
bon atom of the pyrrole ring of 5m remained untouched.
Scheme 4. Possible Routes from 3a and 4a to Products
Some pieces of experimental observations are available
for the mechanistic studies. First, R,ꢀ′-dipyrrolyldecane 3a
and its ꢀ,ꢀ′-isomer (4a) were prepared simultaneously by
indium-catalyzed double addition of N-methylpyrrole (2a)
to 1-decyne (1a).11 On treatment of 3a or 4a with HSiEt3
and 10 mol % of In(NTf2)3, both reactions gave only ꢀ-(2-
decyl)pyrrole 5a in high yields, in which the reaction of 3a
proceeded faster (Scheme 3). The results suggest that the
active species remain unclear at present,19 the working
hypothesis shown in Scheme 1 surely indicates the outline
of the present process.20
Scheme 3. Indium-Catalyzed Reaction of 3a or 4a with HSiEt3
In conclusion, we have demonstrated the first example of
the catalytic regioselective ꢀ-alkylation of pyrroles in one-
step, by the assembly of readily available alkynes, pyrroles
and HSiEt3 with the aid of an indium catalyst. The highlight
of the strategy is the achievement of the exclusive synthesis
of ꢀ-alkylpyrroles 5. Studies on catalyst active species as
well as lowering the catalyst loading, including further
investigation of other catalysts, are currently underway.
reductive ꢀ-alkylation using 1a, 2a and HSiEt3 proceeds
through the formation of 3a and 4a. Scheme 4 illustrates
possible routes from 3a and 4a to the products. In the case
of 3a, both r-A and ꢀ-A, which result in 6a and 5a,
respectively, are possible intermediates. In practice, 5a was
formed exclusively, suggesting that ꢀ-A is much more stable
than r-A, which has serious steric repulsion between the
two hydrogen atoms. The reaction of 4a, whose intermediate
is limited to ꢀ-A, also gives only 5a. Considering that
the difference between 3a and 4a is the leaving group, the
result on the faster reaction of 3a compared with that of 4a
indicates that the R-pyrrolyl group has a superior leaving
ability to the ꢀ-pyrrolyl group. Therefore, the perfect
ꢀ-selectivities observed in this study are most likely the
results of the selective generation of ꢀ-A over r-A and
the higher leaving ability of the R-pyrrolyl groups over the
ꢀ-pyrrolyl groups. Consequently, though details of catalyst
Acknowledgment. We greatly thank Shin-Etsu Chemical
for supplying us with various hydrosilanes as generous gifts.
We are also grateful to Mitsubishi Materials for supplying
us with HNTf2 as a kind gift.
Supporting Information Available: Detailed experimen-
1
tal procedures, and characterization data and H and 13C
NMR spectra for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL900651U
(20) In the absence of HSiEt3, In(NTf2)3-catalyzed reaction of 1-decyne
(1a) and N-methylpyrrole (2a) in 1,4-dioxane at 85 °C for 2 h gives a 85:
14:1 mixture of 4a, 3a and R,R′-isomer almost quantitatively. No R-alkyl-
pyrrole 6a is formed in the corresponding reductive ꢀ-alkylation reaction
despite that the R,R′-isomer is an inevitable precursor of 6a (Scheme 2),
implying that the contribution of the R,R′-isomer to the reductive ꢀ-alkyl-
ation reaction is negligible.
2132
Org. Lett., Vol. 11, No. 10, 2009