Palladium(0)-catalyzed carbonylation-coupling-cyclization of allenic sulfonamides with aryl iodides and carbon monoxide

Article abstract of DOI:10.1021/ol006796o

(Matrix presented) α-Allenic sulfonamides undergo carbonylation-coupling-endo-cyclization with aryl iodides in the presence of Pd(PPh₃)₄ (5 mol %), K₂CO₃, and CO (20 atm) to form 3-aroyl-2- or 3-pyrrolines. Alte

Full text of DOI:10.1021/ol006796o

ORGANIC
LETTERS
2001
Vol. 3, No. 4
511-514
Palladium(0)-Catalyzed
Carbonylation−Coupling−Cyclization of
Allenic Sulfonamides with Aryl Iodides
and Carbon Monoxide
Suk-Ku Kang* and Kwang-Jin Kim
Department of Chemistry and BK-21 School of Molecular Science,
Sungkyunkwan UniVersity, Suwon 440-746, Korea
skkang@chem.skku.ac.kr
Received October 30, 2000
ABSTRACT
r-Allenic sulfonamides undergo carbonylation−coupling−endo-cyclization with aryl iodides in the presence of Pd(PPh3)4 (5 mol %), K2CO ,
3
and CO (20 atm) to form 3-aroyl-2- or 3-pyrrolines. Alternatively the carbonylation−coupling−exo-cyclization of γ- and δ-substituted sulfonamides
under the same conditions afforded pyrrolidine- or piperidine-substituted enones.
The palladium-catalyzed reaction of allene-substituted amine
derivatives to form highly regio- and stereoselective five-
and six-membered azacycles has received much attention in
recent years.1 Palladium has been reported to be an effective
catalyst for the cyclization of allenes bearing a protected
amino group separated from the carbon atom of the allene
moiety by one to four carbon atoms.2 Although the pal-
ladium-catalyzed cyclization of various allenic sulfonamides
to yield azacycles has been well-documented, the palladium-
catalyzed carbonylative cyclization of allenic sulfonamides
to form heterocycles is rare. Only the palladium(II)-catalyzed
cyclization of allenic amine derivatives by carbomethox-
ylation in the presence of carbon monoxide and methanol
to form pyrrolidine or piperidine carboxylic esters is known.3
Alternatively the acylation-cyclization of γ-allenic p-
toluenesulfonamide by treatment of a stoichiometric amount
of acyltetracarbonyl cobalt complexes from alkyl halides,
carbon monoxide, and NaCo(CO)4 to form the pyrrolidine-
substituted enones is known.4 Herein we wish to report the
palladium(0)-catalyzed three-component carbonylation-
(1) Review: Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A.
Chem. ReV. 2000, 100, 3257-3282.
(2) (a) Meguro, M.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 5421-
5424. (b) Davis, I. W.; Scopes, D. I. C.; Gallagher, T. Synlett 1993, 85-
87. (c) Karstens, W. F. J.; Rutjes, F. P. J. T.; Hiemstra, H. Tetrahedron
Lett. 1997, 38, 6275-6278. (d) Karstens, W. F. J.; Stol, M.; Rutjes, F. P.
J. T.; Hiemstra, H. Synlett 1998, 1126-1128. (e) Prasad, J. S.; Liebeskind,
L. S. Tetrahedron Lett. 1988, 29, 425 7-4260. (f) Ohno, H.; Toda, A.;
Miwa, Y.; Taga, T.; Osawa, E.; Yamaoka, Y.; Fujii, N.; Ibuka, T. J. Org.
Chem. 1999, 64, 2992-2993. (g) Rutjes, F. P. J. T.; Tjen, K. C. M. F.;
Wolf, L. B.; Karstens, W. F. J.; Schoemaker, H. E.; Hiemstra, H. Org.
Lett. 1999, 1, 717-720. (h) Anzai, M.; Toda, A.; Ohno, H.; Takemoto, Y.;
Fujii, N.; Ibuka, T. Tetrahedron Lett. 1999, 40, 7393-7397. (I) Kang, S.-
K.; Baik, T.-G.; Kulak, A. N. Synlett 1999, 324-326.
(3) The palladium-catalyzed methoxycarbonylation of allene-substituted
amines to form pyrrolidine or piperidine carboxylic esters was known by
Gallagher et al. See: (a) Gallagher, T.; Davies, I. W.; Jones, S. W.; Lathbury,
D.; Mahon, M. F.; Molloy, K. C.; Shaw, R. W.; Vernon, P. J. Chem. Soc.,
Perkin Trans. 1 1992, 433-440. (b) Fox, D. N. A.; Gallagher, T.
Tetrahedron 1990, 46, 4697-4710. (c) Fox, D. N. A.; Lathbury, D.; Mahon,
M. F.; Molloy, K. C.; Gallagher, T. J. Am. Chem. Soc. 1991, 113, 2652-
2656. (e) Lathbury, D.; Vernon, P.; Gallagher, T. Tetrahedron Lett. 1986,
27, 6009-6012.
(4) Bates, R. W.; Rama-Devi, T.; Ko, H.-H. Tetrahedron 1995, 51,
12939-12954.
10.1021/ol006796o CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/25/2001

Scheme 1
coupling-cyclization reaction of R-, γ-, and δ-allene sub-
sure) at 90 °C in CH3CN to obtain the carbonylative
cyclization product without success. After a series of
experiments we found that the reaction of R-allenic p-
toluenesulfonamide 1a with iodobenzene at 90 °C under CO
(20 atm) in CH3CN for 6 h afforded two easily separable
compounds, 3-benzoyl-3-pyrroline 3a (24%) and 3-benzoyl-
stituted p-toluenesulfonamide with aryl iodides and carbon
monoxide to form pyrrolines, pyrrolidine, and/or piperidine
heterocycles (Scheme 1).5
Our initial work began with R-allenic p-toluenesulfon-
amide 1a6 with iodobenzene under CO (atmospheric pres-
Table 1. Pd(0)-Catalyzed Carbonylative Cyclization of R-Allenic Sulfonamide Derivatives
a The abbreviation Mts represents 2,4,6-trimethylbenzenesulfonyl.
512
Org. Lett., Vol. 3, No. 4, 2001

Table 2. Pd(0)-Catalyzed Carbonylative Cyclization of γ- and δ-Allenic Sulfonamide Derivatives
2-pyrroline 4a (57%) in 81% combined yield (entry 1 in
Table 1).7-8 Presumably under the conditions with palladium
the compound 3a was isomerized to the thermodynamically
more stable compound 4a. For the formation of 3a the
plausible mechanism is shown in Scheme 2.
the same conditions with p-iodoanisole the coupling and
cyclization gave the two pyrrolines 3b and 4b in 72%
combined yield (entry 2). When alkyl-substituted R-allenic
mesitylsulfonyl amide 1b was reacted with iodobenzene,
3-pyrroline derivative 3c and 2-pyrroline derivative 4c were
afforded in 71% and 11% (total 82%) yields, respectively
(6) The R-allenic p-toluenesulfonamide 1a was prepared from deca-1,2-
diene-4-ol by Mitsunobu reaction followed by deprotection and tosylation
in 52% yield.
Scheme 2
(7) The same reactions and conditions under CO (10 atm) at 90 °C in
CH3CN for 18 h gave 3a and 4a in 42% yield. As the solvent, DMF can be
used to ovtain the similar products and yields.
(8) Typical Procedure. A stainless autoclave was charged with R-allenic
p-toluenesulfonamide 1a (100 mg, 0.33 mmol), CH3CN (3 mL), iodobenzene
(99.4 mg, 0.49 mmol), K2CO3 (179 mg, 1.30 mmol), and Pd(PPh3)4 (18.7
mg, 5 mol %) and flushed with 20 atm of CO three times. It was then
pressurized to 20 atm, and the reaction mixture was stirred at 90 °C for 6
h. The mixture was cooled and then quenched with saturated NH4Cl solution.
The reaction mixture was extracted with ether (20 mL × 3), and the organic
layer was dried over anhydrous MgSO4 and evaporated in vacuo. The crude
product was separated by SiO2 column chromatography (hexanes/EtOAc,
6:1) to give 3-pyrroline 3a (32 mg, 24%) and 2-pyrroline 4a (76 mg, 57%).
Walkup et al. suggested two possible mechanisms for cyclization-coupling
between aryl halides and γ-hydroxyallenes (ref 4).
It is presumed that oxidative addition of Pd(0) to ArI is
followed by carbonylation to give PhCOPdI, which adds to
the central carbon of allene moiety to provide π-allylpalla-
dium complex. Cyclization of this intermediate by the endo-
mode would give the pyrroline enone 3a (Scheme 2).9 Under
(9) The mechanistic path via an η3-allylpalladium(II) complex is
considered to be operative for intermolecular coupling nucleophilic reaction
with amines. See: (a) Shimizu, I.; Tsuji, J. Chem. Lett. 1984, 233-236.
(b) Cazes, B. Pure Appl. Chem. 1990, 62, 1867-1878. (c) Larock, R. C.;
Berrios-Pena, N. G.; Fried, C. A. J. Org. Chem. 1991, 56, 2615-2617.
Alper et al. suggested that the initial addition of aroylpalladium to allene is
followed by nucleophilic attack of the hydroxy group in the carbonylation
of o-iodophenol with allenes. See: Okuro, K.; Alper, H. J. Org. Chem.
1997, 62, 1566-1567.
(5) The palladium(0)-catalyzed cyclization-carbonylation-coupling of
aryl halides and γ-hydroxyallenes to form aryl(tetrafuran-2-yl)vinyl ketones
is known. See: Walkup, R. D.; Guan, L.; Kim, Y. S.; Kim, S. W.
Tetrahedron Lett. 1995, 36, 3805-3808.
Org. Lett., Vol. 3, No. 4, 2001
513

(entry 3). In the case of cyclohexyl-substituted R-allenic
sulfonamide 1c, the same coupling and cyclization with
iodobenzene under CO (20 atm) at 90 °C in CH3CN for 6 h
provided 3-benzoyl-2-pyrroline 3d in 72% as the sole product
(entry 4). However, with p-iodoanisole as an electrophile
two products, 3d and 4d, were obtained in 43% and 17%
yields, respectively (entry 5). The results of carbonylation-
coupling-cyclization of R-allenic sulfonamide derivatives
are summarized in Table 1.
iodobenzene, the piperidine-substituted enone 5c was af-
forded (entry 3). Finally, for the p-iodoanisole, carbonylation
gave the p-anisole-substituted enone 5d (entry 4). A plausible
mechanism for the formation of 5a is that this reaction may
occur by addition of an aroylpalladium intermediate to the
allene unit of the allenic p-toluenesulfonamide 1e to produce
a η3-allylpalladium species, which undergoes nucleophilic
attack via the exo-mode by p-toluenesulfonamide group to
produce the cyclized product 5a (Scheme 3).
Our carbonylation-coupling-cyclization method was
extended to γ- and δ-allenic p-toluenesulfonamides 1d and
1e, and the results are summarized in Table 2. When
γ-allenyl p-toluenesulfonamide 1d was treated with iodo-
benzene under CO, the pyrrolidine-substituted enone 5a was
provided in 83% yield (entry 1). The structure of 5a was
unambiguously confirmed by X-ray crystallography (Figure
1). When p-iodoanisole was utilized under the same condi-
Scheme 3
In conclusion, the palladium(0)-catalyzed carbonylation-
coupling-cyclization of allenic p-toluenesulfonamides with
aryl iodides under CO (20 atm) to give substituted pyrrolines
and pyrrolidine or piperidine enones was accomplished.
Acknowledgment. Generous financial support from
KOSEF-CMDS (Center for Molecular Design and Synthesis)
is gratefully acknowledged.
Supporting Information Available: Typical experimen-
tal procedures and characterization for 3a-4e and 5a-d.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 1. ORTEP drawing of 5a.
tions, the pyrrolidine 5b was obtained (entry 2). Alternatively,
when δ-allenyl p-toluenesulfonamide 1e was reacted with
OL006796O
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Org. Lett., Vol. 3, No. 4, 2001