Ru-catalyzed cyclocarbonylation of α-and β-allenic sulfonamides: Synthesis of γ- and δ-unsaturated lactams

Article abstract of DOI:10.1021/ol016281c

(equation presented) The Ru-catalyzed cyclocarbonylation of α-or β-allenic sulfonamides in the presence of Ru₃(CO)₁₂ (1 mol %) and Et₃N (1.5 equiv) under CO atmosphere (20 atm) in dioxane at 100°C for 9 h gave heterocyclic

Full text of DOI:10.1021/ol016281c

ORGANIC
LETTERS
2001
Vol. 3, No. 18
2851-2853
Ru-Catalyzed Cyclocarbonylation of r-
and â-Allenic Sulfonamides: Synthesis
of γ- and δ-Unsaturated Lactams
,†
Suk-Ku Kang,* Kwang-Jin Kim,† Chan-Mo Yu,† Jeong-Wook Hwang,‡ and
Young-Kyu Do‡
Department of Chemistry and BK-21 School of Molecular Science,
Sungkyunkwan UniVersity, Suwon 440-746, Korea, and Department of Chemistry, and
BK-21 School of Molecular Science, Korea AdVanced Institute of Science and
Technology, Taejon 305-701, Korea
skkang@chem.skku.ac.kr.
Received June 15, 2001
ABSTRACT
The Ru-catalyzed cyclocarbonylation of r- or â-allenic sulfonamides in the presence of Ru3(CO)12 (1 mol %) and Et3N (1.5 equiv) under CO
atmosphere (20 atm) in dioxane at 100 °C for 9 h gave heterocyclic γ- and δ-unsaturated lactams in good yields.
The palladium-catalyzed coupling reaction of allene-
substituted alcohols and amine has received much attention
in recent years.1 The palladium-catalyzed carbonylative
cyclization of various allenic alcohols and sulfonamides has
been known2,3 to be an efficient entry to heterocyclic ring
systems. Recently Takahashi et al.4 used a ruthenium catalyst
in carbonylative coupling and reported that a successful
cyclocarbonylation of allenic alcohols to form γ- and
δ-lactones was accomplished. Alternatively Murai et al.5
reported the Ru-catalyzed carbonylative [4 + 1] cycloaddi-
tion of R,â-unsaturated imines with carbon monoxide to form
R,â-unsaturated γ-lactams. As an extension of our research
efforts to utilize allenic sulfonamides in carbonylative
cyclization,6 we attempted to investigate the Ru(CO)3-
catalyzed cyclocarbonylation of R- and â-allenic sulfona-
mides to form γ- and δ-unsaturated lactams.
To find an optimum condition for the cyclization, a series
of experiments were performed; the results are shown in
Table 1. For the cyclization reaction of 1a, the catalysts tested
were Ru3(CO)12, [RuCl2(CO)3]2, RuCl(PPh3)3, and Ru(CO)-
H2(PPh3)3. Both Ru3(CO)12 and [RuCl2(CO)3]2 were equally
effective for the cyclization reaction of 1a. The use of Ru3-
† Sungkyunkwan University.
‡ Korea Advanced Institute of Science and Technology.
(1) Review: Zimmer, R..; Dinesh, C. U.; Nandanan, E.; Khan, F. A.
Chem. ReV. 2000, 100, 3257-3282.
(2) (a) Okuro, K.; Alper, H. J. Org. Chem. 1997, 62, 1566-1567. (b)
Walkup, R. D.; Guan, L.; Kim, Y. S.; Kim, S. W. Tetrahedron Lett. 1995,
36, 3805-3806.
(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. (d) Lathbury, D.; Vernon, P.; Gallagher, T. Tetrahedron Lett. 1986,
27, 6009-6012. (e) Walkup, R. D.; Guan, L.; Park, G. Tetrahedron Lett.
1987, 28, 1023-1026. (f) Kimura, M.; Saeki, N.; Uchida, S.; Harayama,
A.; Tanaka, S.; Fugani, K.; Tamaru, U. Tetrahedron Lett. 1993, 34, 7611-
7614.
(4) Yoneda, E.; Kaneko, T.; Zhang, S.-W.; Onitsuka, K.; Takahashi, S.
Org. Lett. 2000, 2, 441-443.
(5) Morimoto, T.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 1999, 121,
1758-1759.
(6) Kang, S.-K.; Kim, K.-J. Org. Lett. 2001, 3, 511-514.
10.1021/ol016281c CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/07/2001

Table 1. Ru-Catalyzed Cyclocarbonylation of r-Allenic Sulfonamide 1a
entry
catalysts (mol %)
base (equiv)
solvent
CO pressure (atm)
isolated yield (%)
1
2
3
4
5
6
7
8
9
Ru3(CO)12 (1)
Ru3(CO)12 (3)
Ru3(CO)12 (5)
Ru3(CO)12 (5)
Ru3(CO)12 (5)
Ru3(CO)12 (5)
Ru3(CO)12 (5)
Ru3(CO)12 (1)
[RuCl2(CO)3]2 (1)
RuCl2(PPh3)3 (1)
Ru(CO)H2(PPh3)3 (1)
Et3N (1.5)
Et3N (3.0)
Et3N (3.0)
Et3N (3.0)
Et3N (1.5)
K2CO3 (3.0)
Et3N (3.0)
Et3N (1.5)
Et3N (1.5)
Et3N (1.5)
Et3N (1.5)
dioxane
dioxane
dioxane
THF
CH3CN
DMF
10
10
15
20
20
20
20
20
20
20
20
42
58
82
45
53
0
43
85
85
61
0
DMF
dioxane
dioxane
dioxane
dioxane
10
11
(CO)12 or [RuCl2(CO)3]2, Et3N as a base, and dioxane as
solvent under 20 atm pressure of carbon monoxide afforded
γ-unsaturated lactam 2a in 85% yield. (entries 8 and 9 in
Table 1).7 Nevertheless, we chose Ru3(CO)12 as the catalyst
for further studies.
The results of Ru-catalyzed cyclocarbonylation of R-allenic
sulfonamide derivatives 1 are summarized in Table 2. The
R-allenic sulfonamide 1a reacted in the presence of Ru3-
(CO)12 (1 mol %) in dioxane at 100 °C under CO (20 atm)
for 9 h to produce the cyclized unsaturated γ-lactam 2a in
85% yield (entry 1 in Table 2). Under the same conditions
the R-allenic 2,4,6-trimethylbenzenesulfonamide 1c was
smoothly cyclized to 2c in 68% yield (entry 3). For the
R-allenic benzylamine 1d the reaction proceeded to provide
2d in 54% yield (entry 4). Treatment of cyclohexyl-
substituted R-allenic sulfonamide 1e under the same condi-
tions gave the lactam 2e in 70% yield (entry 5). With phenyl-,
2-furyl-, and 2-thienyl-substituted sulfonamides 1f, 1g, and
1h as substrates, the γ-lactams 2f, 2g, and 2h were obtained
in 80%, 95%, and 76% yields, respectively (entries 6-8).
For the compound 2f, the structure was unambiguously
confirmed by X-ray crystallography (Figure 1). This protocol
was extended to â-allenic sulfonamide 1i. The reaction of
1i with Ru3(CO)12 catalyst in the same reaction conditions
Table 2. Ru3(CO)12-Catalyzed Cyclocarbonylation of Allenic
Sulfonamide Derivatives
Figure 1. ORTEP drawing of 2f.
Org. Lett., Vol. 3, No. 18, 2001
2852

afforded the unsaturated δ-lactam 2i in 81% yield (entry 9).
Alternatively, for R-methyl-substituted â-allenic sulfon-
amides 1j the cyclocarbonylation under Ru-catalysis afforded
R-methyl-substituted δ-lactam 2j in 80% yield (entry 10).
To confirm the proposed mechanism we have conducted
studies on the carbocyclization of the deuterium-substituted
Scheme 2
1
R-allenic sulfonamide 3 by means of 500 MHz H NMR
spectrometry and high resolution mass spectrometry. It was
found that the deuterium was totally transferred to the product
lactam 48 (Scheme 1).
Scheme 1
For the formation of lactams 2 by the Ru-catalyzed
cyclocarbonylation, the plausible mechanism is shown in
Scheme 2. It is presumed that oxidative insertion of Ru-
(CO)4 to the N-H bond of the NHTs group in compound 1
followed by syn-addition of the Ru-H bond to the terminal
allene produces the intermediate A. Carbonyl insertion to
the N-Ru bond gives the intermediate B, which reacts with
CO to provide the product lactam with liberation of Ru(CO)4
(Scheme 2).
(7) Typical Procedure. A stainless autoclave was charged with allenic
sulfonamide 1a (70 mg, 0.25 mmol), 1.4-dioxane (3 mL), triethylamine
(38 mg, 0.38 mmol), and Ru3(CO)12 (1.6 mg, 1 mol %), and the system
was flushed with 20 atm of CO three times. It was then pressurized to 20
atm, and the reaction mixture was stirred at 100 °C for 9 h. The mixture
was cooled and then evaporated in vacuo. The crude product was separated
by SiO2 column chromatography (hexanes/EtOAc, 1:5) to give the product
2a (63 mg, 85%). 2a: colorless oil; IR (neat) 3056, 2987, 1724, 1424,
In conclusion, the Ru-catalyzed cyclocarbonylation of
allenic sulfonamides under CO (20 atm) to form γ- or
δ-lactams was accomplished successfully.
1
1359, 1266, 1171 cm-1; H NMR (500 MHz, CDCl3) δ 0.85 (t, 3H, J )
7.63 Hz), 1.09 (m, 2H), 1.28 (m. 2H), 1.81 (t, 3H, J ) 1.76 Hz), 1.83 (m,
1H), 2.14 (m, 1H ), 2.43 (s, 3H), 4.73 (m, 1H), 6.82 (t, 1H, J ) 1.76 Hz),
7.32 (d, 2H, J ) 8.21 Hz), 7.97 (d, 2H, J ) 8.21 Hz); 13C NMR (125
MHz, CDCl3) δ 170.6, 145.5, 145.5, 136.8, 134.3, 130.2, 128.7, 63.0, 32.7,
26.6, 23.2, 22.4, 14.6, 11.4; ΗRMS calcd for C16H21NO3S 307.1242, found
307.1236.
Acknowledgment. This work is supported by a National
Research Laboratory Grant by the Korea Ministry of Science
and Technology and KOSEF-CMDS (Center for Molecular
Design and Synthesis).
(8) Spectral and physical data of 3 and 4. 3: 1H NMR (500 MHz, CDCl3)
δ 0.85 (t, 3H, J ) 7.63 Hz), 1.20 (m, 8H), 1.50 (m, 2H), 2.42 (s, 3H), 3.80
(m, 1H), 4.63 (m, 1H), 4.72 (m, 1H), 4.96 (m, 1H), 7.30 (d, 2H, J ) 8.21
Hz), 7.75 (d, 2H, J ) 8.21 Hz); ΗRMS calcd for C17H24DNO2S 308.1668,
Supporting Information Available: Typical experimen-
tal procedures and characterization for 2a-i and 2j. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
found 308.1646. 4: H NMR (500 MHz, CDCl3) δ 0.87 (t, 3H, J ) 7.63
Hz), 1.06 (m, 1H), 1.12 (m, 1H), 1.22 (m, 6H), 1.81 (t, 2H, J ) 1.76 Hz),
1.82 (m, 1H), 2.13 (m, 1H ), 2.43 (s, 3H), 4.73 (m, 1H), 6.81 (t, 1H, J )
1.76 Hz), 7.32 (d, 2H, J ) 8.21 Hz), 7.97 (d, 2H, J ) 8.21 Hz); ΗRMS
calcd for C18H24DNO3S 336.1617, found 336.1616.
OL016281C
Org. Lett., Vol. 3, No. 18, 2001
2853