Palladium(0)-catalyzed coupling cyclization of functionalized allenes with hypervalent iodonium salts

Article abstract of DOI:10.1055/s-1999-2613

The palladium(0)-catalyzed coupling reaction of allenic alcohols, amines, acids with hypervalent iodonium salts afforded the cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions.

Full text of DOI:10.1055/s-1999-2613

324
LETTER
Palladium(0)-Catalyzed Coupling Cyclization of Functionalized Allenes with
Hypervalent Iodonium Salts
Suk-Ku Kang,* Tae-Gon Baik, Alexander N. Kulak
Department of Chemistry, Sungkyunkwan University, Natural Science Campus, Suwon 440-746, Korea
Received 26 October 1998
alyst. The catalyst Pd(OAc)2/Ph3P or Pd2(dba)3/Ph3P gave
Abstract: The palladium(0)-catalyzed coupling reaction of allenic
the coupled product 3a in lower yields. Of the solvent test-
alcohols, amines, acids with hypervalent iodonium salts afforded
ed, DMF ad preferably CH3CN were effective even if
the cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrro-
THF and NMP were not satisfactory. As base K2CO3 and
Cs2CO3 were more suitable than Et3N and NaOMe. The
yields were improved when the reaction was run at 60 °C
for 3 h rather than run at 80 °C for 1.5 h or at room tem-
perature for 18 h. The allenic alcohol 1a reacted with
diphenyliodonium tetrafluoroborate (2a) in the presence
of Pd(PPh3)4 (5 mol %) at 60 °C in CH3CN for 3 h to af-
ford the alkenyl-substituted tetrahydrofuran 3a6 in 76%
yield (entry 1 in Table 1).7 Under the same conditions
treatment of 1a with p-methoxyphenyl(phenyl)iodonium
tetrafluoroborate (2b) gave a mixture of two easily sepa-
rable tetrahydrofurans 3b (44%) and 3a (35%) in 79%
yield (entry 2). When aꢀmethyl-substituted allenic alco-
hols 1b were coupled with 2a, a mixture of cis- and trans-
tetrahydrofurans 3c6 was afforded in the ratio of 2 : 3 in
72% yield (entry 3). This method can be applied to 5,6-oc-
tadienol 1c to get tetrahydropyran derivatives. When the
allenol 1c was treated with the iodonium salt 2a under the
same conditions, the substituted tetrahydropyran 3d6 was
afforded in 74% yield (entry 4). Similarly, the reaction of
1c with p-methoxyphenyl(phenyl)iodonium salt 2b gave a
separable mixture of 3d and 3e in 73% yield (entry 5). Al-
ternatively, when 3,4-dienylamine 1d was subjected to
cyclize with 2a under the same conditions, a mixture of
the four-membered ring 3f6 and the six membered ring 3g6
were obtained (entry 6).
lidines, piperidines, or lactones under mild conditions.
Key words: allenes, coupling reaction, hypervalent elements,
palladium compounds
The palladium-catalyzed cyclization reaction received
much attention as an efficient method for the preparation
of oxygen- and nitrogen-containing heterocycles. Recent
reports by Walkup et al.1 have demonstrated that gꢀꢁhy-
droxyallenes or 4,5-hexadienoic acid reacted with arylpal-
ladium(II) halides generated in situ from palladium(0) and
aryl halides to form cyclized tetrahydrofurans or butyro-
lactones via sequential cyclization-coupling reaction. It is
also known by Gallagher et al.2 that g- allenic amines un-
dergo heteroatom cyclization with aryl halides in the pres-
ence of Pd(0) to give the substituted pyrrolidinone.3, 4
However, these methods are limited to the formation of
five-membered heterocycles and the drawbacks of the cy-
clization reactions are the use of excess (5 equiv) aryl ha-
lides and longer times at high temperature. In our effort to
broaden the synthetic utility of this type of cyclization re-
actions, we focused our attention on hypervalent iodoni-
um salts as the substitutes for aryl halides.5 Here we wish
to report the coupling and cyclization of allenic alcohols,
allenic acids, and allenic amines leading to 4, 5, and 6-
membered heterocycles with hypervalent iodonium salts
(1.2 equiv) in the presence of a palladium catalyst, which
is shown in Scheme 1.
In considering the plausible mechanism for the formation
of the four membered ring 3f and the six membered ring
3g simultaneously, it is presumed that the phenylpalladi-
-
um(II) tetrafluoroborate (PhPd+ BF4 ) formed from 2a and
Pd(0) species adds to allene to form p-allylpalladium
complex A, which undergoes intramolecular nucleophile
addition to give 3f and 3g (path a in Scheme 2).8 The four
memebered ring 3f can be converted to 3g by oxidative
addition with Pd(0) species to form -allylpalladium com-
plex under the reaction conditions, which eventually is
converted into six membered compound 3g. However, the
alternative mechanism1, 2 (path b) which involves the for-
mation of the phenylpalladium tetrafluoroborate B via ac-
Scheme 1
The results of Pd(0)-catalyzed coupling cyclization of
functionalized allenes with hypervalent iodonium salts
are summarized in Table 1.
-
tivating the allene by Ph Pd+BF4 for nucleopalladation
followed by reductive elimination cannot be ruled out,
which is shown in Scheme 2.
To determine optimum conditions, initially allenic alco-
hol 1a was reacted with diphenyliodonium tetrafluorobo-
rate (2a) to get the cyclized product 3a. After a series of
experiments, we found that Pd(PPh3)4 was suitable as cat-
For allenic amine derivatives 1e, the substituted pyrroli-
dine 3h6 was obtained in 95% yield (entry 7). Using 2b as
the iodonium source, a separable mixture of two pyrro-
Synlett 1999, No. 3, 324–326 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Palladium(0)-Catalyzed Coupling Cyclization of Functionalized Allenes
325
Scheme 1
lidines 3i and 3h was provided in 95% combined yield
(entry 8). When a-methyl allenic amine 1f was utilized as
starting material, pyrrolidine 3j (cis : trans = 2 : 3.2) was
formed (entry 9). The substituted piperidines 3l and 3k
were readily obtained from 5,6-octadienyl amine N-tosyl-
ate 1g (entries 10 and 11). These results are in contrast
with the results that the cyclization of 1g with iodoben-
zene could not provide piperidine derivatives.2 The allenic
acid 1i was also utilized to form the substituted furanone
3m in 61% yield (entry 12). To broaden the synthetic util-
ity of this coupling-cyclization, 5,6-heptadienoic acid 1j
was cyclized to give the six membered heterocyclic lac-
tones 3o6 and 3p (entries 14 and 15).
Acknowledgement
Generous financial support by Korea Research Foundation (BSRI-
98-3420) and KOSEF (97-0501-02-053) is gratefully acknowled-
ged.
Reference and Notes
(1) (a) Walkup, R. D.; Guan, L.; Mosher, M. D.; Kim, S. W.; Kim,
Y. S. Synlett 1993, 88-90. (b) Walkup, R. D.; Guan, L.; Kim,
Y. S.; Kim, S. W. 1 Tetrahedron Lett. 1995, 36, 3805-3808.
(2) Davies, I. W.; Scopes, D. I. C.; Gallagher, T. Synlett 1993, 85-
87.
(3) Yamamoto et al. reported the palladium-catalyzed intramole-
cular hydroamination of allenyl amine to form vinylpyrrol-
idines and vinylpiperidines. See Meguro, M.; Yamamoto, Y.
Tetrahedron Lett. 1998, 39, 5421-5424.
(4) (a) Karstens, W. F. J.; Rutjes, F. J. T.; Hiemstra, H. Tetrahe-
dron Lett. 1997, 38, 6275-6278. (b) Hiemstra, H. The 12th In-
tenational Conference on Organic Synthesis (ICOS-12), June
28-July 2, Italy, 1998, SL-34.
(5) Recently we have reported the palladium-catalyzed arylation
of a-allenic alcohols with hypervalent iodonium salts. See,
Kang, S-K.; Yamaguchi, T.; Pyun, S-J.; Lee, Y-T.; Baik, T-G.
Tetrahedron Lett. 1998, 39, 2127-2130.
(6) Satisfactory physical and spectral data were obtained in ac-
cord with the structure. Selected physical and spectral data are
as follows. 3a: TLC, SiO2, EtOAc/hexanes 1 : 3, Rf = 0.70. 1H
NMR (CDCl3, 400 MHz) d 1.67-2.10 (m,4H), 3.90 (m, 1H),
4.03 (m, 1H), 4.86 (t, 1H, J = 6.9 Hz), 5.30 (dd, 1H, J = 0.9,
1.6 Hz), 5.37 (dd, 1H, J = 1.6, 1.6 Hz), 7.21-7.40 (m, 5H). IR
(neat) 2959, 2927, 1654, 1560, 377 cm-1. MS (m/e) 174(M+),
173, 131, 103, 77, 71 (base peak).
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S.-K. Kang et al.
LETTER
3k: TLC, SiO2, EtOAc/hexanes 1 : 3, Rf = 0.58. 1H NMR
(CDCl3, 400 MHz) dꢁ1.26-1.37 (m, 3H), 1.38-1.41 (m, 2H),
1.72 (m, 1H), 2.40 (s, 3H), 3.18 (ddd, 1H, J = 3.6, 11.4, 14.6
Hz), 3.68 (ddd, 1H, J = 3.5, 3.6, 14.6 Hz), 5.20 (d, 1H, J = 1.36
Hz), 5.27 (s, 2H), 7.23-7.32 (m, 7H), 7.66 (m, 2H). IR (neat)
2950, 2932, 1608, 1511, 1300, 1120 cm-1. MS (m/e) 341(M+),
238(base peak), 154, 91.
3c: TLC, SiO2, EtOAc/hexanes 1 : 3, Rf = 0.66, 1H NMR
(CDCl3, 400 MHz) cis: dꢁꢂ.33 (d, 3H, J = 6.0 Hz), 1.53-1.56
(m, 2H), 2.15-2.18 (m, 2H), 4.11 (m, 1H), 4.84 (m, 1H), 5.27
(dd, 1H, J = 0.9, 1.6Hz), 5.39 (dd, 1H, J = 1.6, 1.6Hz), 7.27-
7.34 (m, 5H). trans: d 1.30 (d, 3H, J = 6.0 Hz), 1.64-1.69 (m,
2H), 2.06-2.11 (m, 2H), 4.27 (m, 1H), 5.00 (m, 1H), 5.32(dd,
1H, J = 0.9, 1.6 Hz), 5.39 (d, 1H, J = 1.6, 1.6 Hz), 7.27-7.32
(m, 5H). IR (neat) 2959, 2925, 1653, 1558, 1377, 1100 cm-1
3o: TLC, SiO2, EtOAc/hexanes 1 : 3, Rf = 0.48. 1H NMR
(CDCl3, 400 MHz) dꢁ1.62 (m, 1H), 1.82-1.90 (m, 2H), 1.97
(m, 1H), 2.55 (m, 1H), 2.66 (m, 1H), 5.30 (dd, 1H, J = 3.2, 9.3
Hz), 5.39 (s, 1H), 5.43 (s, 1H), 7.32-7.37 (m, 5H). IR (neat)
2950, 2932, 1736, 1511, 1461, 1243, 1035 cm-1 . MS (m/e)
202(M+), 174, 146, 134, 104, 103(base peak), 99, 83.
(7) The typical procedure is as follows. To a stirred solution of
.
MS (m/e) 188 (M+), 131, 118, 113, 71(base peak), 51.
3d: TLC, SiO2, EtOAc/hexanes 1 : 3, Rf = 0.68. 1H NMR
(CDCl3, 400MHz) dꢁ1.42 (m, 1H), 1.51-1.70 (m, 3H), 1.72 (m,
1H), 1.85 (m, 1H), 3.60 (ddd, 1H, J = 2.3, 11.5, 11.6 Hz), 4.13
(ddd, 1H, J = 2.2, 2.3, 11.6 Hz), 4.25 (dd, 1H, J = 2.8, 10.9
Hz), 5.31 (dd, 1H, J = 0.9, 1.6 Hz), 5.38 (dd, 1H, J = 1.6, 1.6
Hz), 7.26-7.46 (m, 5H). IR (neat) 2986, 2943, 1448, 1206,
1047 cm-1. MS (m/e) 188(M+), 144, 104, 85(base peak), 77.
3f: TLC, SiO2, EtOAc/hexanes 1 : 3, Rf = 0.66. 1H NMR
(CDCl3, 300 MHz) dꢁ2.04 (m, 1H), 2.34 (m, 1H), 2.46 (s, 3H),
3.72-3.80 (m, 2H), 4.80 (t, 1H, J = 8.7 Hz), 5.49 (dd, 1H, J =
0.9, 1.6 Hz), 5.68 (dd, 1H, J = 1.6, 1.6 Hz), 7.29-7.38 (m, 7H),
-
Ph2I+ BF4 (2a) (302 mg, 0.82 mmol) and K2CO3 (237 mg,
1.71 mmol) in CH3CN (1 mL) was added Pd(PPh3)4 (47 mg, 5
mol %) followed by allenic alcohol 1a (67 mg, 0.68 mmol) in
CH3CN (1 mL). The reaction mixture was stirred at 60 °C for
3 h, cooled to room temperature, and quenched with saturated
NH4Cl solution. The mixture was extracted with ether and the
organic layer was dried over anhydrous MgSO4 and evapora-
ted in vacuo. The crude product was separated by SiO2 column
chromatography (EtOAc/hexanes 1 : 3, Rf = 0.70) to afford the
cyclized ether 3a (90 mg, 76%).
7.75 (m, 2H). IR (neat) 2950, 2927,1500, 1309, 1105 cm-1 MS
.
(m/e) 313(M+ ), 209, 155, 130(base peak),128, 91.
3g: TLC, SiO2, EtOAc/hexanes 1 : 3, Rf = 0.58. 1H NMR
(CDCl3, 300 MHz) dꢁ2.43 (s, 3H), 2.45 (m, 2H), 2.86 (m, 1H),
3.24 (m, 1H), 3.67 (m, 1H), 3.94 (m, 1H), 7.13(m, 1H), 7.26-
7.38 (m, 7H), 7.73 (m, 2H). IR (neat) 2950, 2932, 1510, 1280,
1090 cm-1 MS (m/e) 313 (M+), 312, 239, 158, 130(base peak),
128, 91.
(8) (a) Shimizu, I.; Tsuji, J. Chem. Lett. 1984, 233-236. (b) Cazes,
B. Pure Appl. Chem. 1990, 62, 1867-1878. (b) Cazes, B. Pure
Appl. Chem. 1990, 62, 1867-1878. (c) Gamez, P.; Ariente, C.;
Gore, J.; Cazes, B. Tetrahedron 1998, 54, 14835-14844.
Synlett 1999, No. 3, 324–326 ISSN 0936-5214 © Thieme Stuttgart · New York