Palladium-catalyzed cyclization reactions of 2,3-allenyl amines with propargylic carbonates

Article abstract of DOI:10.1021/ol3007293

A highly efficient and atom-economic route to synthesize 5-(1,3,4-alkatrien-2-yl)oxazolidin-2-ones via palladium-catalyzed cyclization reactions of 2,3-allenyl amines with propargylic carbonates was reported. The CO₂ generated in situ from prop

Full text of DOI:10.1021/ol3007293

ORGANIC
LETTERS
2012
Vol. 14, No. 9
2312–2315
Palladium-Catalyzed Cyclization
Reactions of 2,3-Allenyl Amines with
Propargylic Carbonates
Juntao Ye,† Suhua Li,† and Shengming Ma*,†,‡
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032,
P. R. China, and Shanghai Key Laboratory of Green Chemistry and Chemical Process,
Department of Chemistry, East China Normal University, 3663 North Zhongshan Lu,
Shanghai 200062, P. R. China
masm@sioc.ac.cn
Received March 21, 2012
ABSTRACT
A highly efficient and atom-economic route to synthesize 5-(1,3,4-alkatrien-2-yl)oxazolidin-2-ones via palladium-catalyzed cyclization reactions of
2,3-allenyl amines with propargylic carbonates was reported. The CO2 generated in situ from propargylic carbonates is incorporated into the
oxazolidin-2-one unit with high efficiency, affording the products in 70ꢀ92% yields.
Oxazolidin-2-ones are an important class of compounds
of broad interest as both synthetic intermediates1 and
biologically active molecules.2 Given the versatile utilities
of oxazolidin-2-ones, considerable effort has been made in
the synthesis of the oxazolidin-2-one skeleton and numer-
ous methodologies have been reported.1a,f,3 Among the
reported methods, the oxazolidin-2-one nucleus is gener-
ally prepared from amino alcohols by carbonylation using
phosgene or its functional equivalent or by oxidative
carbonylation utilizing CO and Pd catalysts, which require
the use of either highly hazardous chemicals or harsh
reaction conditions. Methods for the preparation of ox-
azolidin-2-ones containing amendable functionalities for
further elaborations have yet to be well established.
Since Tsuji’s first report in 1985,4 palladium-catalyzed
transformations of propargylic carbonates have become a
powerful tool for constructing carbonꢀcarbon and carbonꢀ
heteroatom bonds.5 Recently, we have developed the
Pd-catalyzed cyclization of allenes bearing a nucleophilic
† Chinese Academy of Sciences.
‡ East China Normal University.
(1) For reviews, see: (a) Dyen, M. A.; Swern, D. Chem. Rev. 1967, 67,
197. (b) Evans, D. A.; Takacs, J. M.; McGee, L. R.; Ennis, M. D.;
Mathre, D. J.; Bartroli, J. Pure Appl. Chem. 1981, 53, 1109. (c) Evans,
D. A. Aldrichimica Acta 1982, 15, 23. (d) Ager, D. J.; Prakash, I.; Schaad,
D. R. Chem. Rev. 1996, 96, 835. (e) Ager, D. J.; Prakash, I.; Schaad,
D. R. Aldrichimica Acta 1997, 30, 3. (f) Zappia, G.; Gacs-Baitz, E.;
Monache, G. D.; Misiti, D.; Nevola, L.; Botta, B. Curr. Org. Chem.
2007, 4, 81. (g) Zappia, G.; Cancelliere, G.; Gacs-Baitz, E.; Monache,
G. D.; Misiti, D.; Nevola, L.; Botta, B. Curr. Org. Chem. 2007, 4, 283.
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(b) Barbachyn, M. R.; Ford, C. W. Angew. Chem., Int. Ed. 2003, 42,
2010. (c) Renslo, A. R.; Luehr, G. W.; Gordeev, M. F. Bioorg. Med.
Chem. 2006, 14, 4227. (d) Shaw, K. J.; Barbachyn, M. R. Ann. N.Y.
Acad. Sci. 2011, 1241, 48.
(3) For some of the most recent examples on the synthesis of
ꢀ
oxazolidin-2-ones, see: (a) Paz, J.; Perez-Balado, C.; Iglesias, B.;
~
Munoz, L. J. Org. Chem. 2010, 75, 3037. (b) Schindler, C. S.; Forster,
P. M.; Carreira, E. M. Org. Lett. 2010, 12, 4102. (c) Phung, C.; Pinhas,
A. R. Tetrahedron Lett. 2010, 51, 4552. (d) Fontana, F.; Chen, C. C.;
Aggarwal, V. K. Org. Lett. 2011, 13, 3454. (e) Kim, C.; Ko, S. Y. Bull.
Korean Chem. Soc. 2011, 32, 4450. (f) Kojima, R.; Sawamoto, S.;
Okamura, A.; Takahashi, H.; Tsunoi, S.; Shibata, I. Eur. J. Org. Chem.
2011, 7255. (g) Watile, R. A.; Bagal, D. B.; Patil, Y. P.; Bhanage, B. M.
Tetrahedron Lett. 2011, 52, 6383. (h) Grigg, R. D.; Rigoli, J. W.; Pearce,
S. D.; Schomaker, J. M. Org. Lett. 2012, 14, 280.
(4) Tsuji, J.; Watanabe, H.; Minami, I.; Shimizu, I. J. Am. Chem. Soc.
1985, 107, 2196.
(5) For reviews on Pd-catalyzed transformations of propargylic
carbonates, see: (a) Tsuji, J.; Mandai, T. Angew. Chem., Int. Ed. Engl.
1995, 34, 2589. (b) Tsuji, J. Palladium Reagents and Catalysts; JohnWiley
& Sons Ltd.: U.K., 2004; pp 543ꢀ564. (c) Guo, L.; Duan, X.; Liang, Y.
Acc. Chem. Res. 2011, 44, 111 and references cited therein.
r
10.1021/ol3007293
Published on Web 04/26/2012
2012 American Chemical Society

moiety in the presence of propargylic carbonates affording
allenyl cyclic products, in which the CO2 was eliminated
and released.6 Based on these previous works and retro-
synthetic analysis, we envisioned that allenic oxazolidin-2-
ones 3 may be efficiently constructed by using 2,3-allenyl
amines7 1 and propargylic carbonate 2 in an atom-
economic manner provided that the to-be-released CO2 can
be recycled8 intermolecularly with high efficiency (3 and 6 vs
4 and 5, Scheme 1) and the issue of regioselectivity can be
addressed (3 vs 6, Scheme 1). Herein, we report an efficient
synthesis of 5-(1,3,4-alkatrien-2-yl)oxazolidin-2-one 3 via
palladium-catalyzed cyclization reactions of 2,3-allenyl
amines in the presence of propargylic carbonates with
the in situ generated CO2 recycled under mild conditions.
obtained in 94% NMR yield and 88% isolated yield by
using 5 mol % Pd(PPh3)4, 1.5 equiv of 2a, and 2 equiv of
K2CO3 in DMSO at 70 °C for 4 h (entry 1, Table 1). Also,
we were pleasedtofind that the formation of 4- and 5-types
of non-CO2-incorporated cyclization products9,10 or the
6-type CO2-incorportaed regioisomer was not observed.
Encouraged by these results, further optimization of the
reaction conditions was carried out subsequently. Chang-
ing the palladium catalyst (entries 2 and 3, Table 1) or the
solvent (entries 4ꢀ7, Table 1) led to a decrease in the yield
of 3aa. Other bases such as Cs2CO3 or NEt3 were less
effective (entries 8 and 9, Table 1). Notably, 66% and 75%
NMR yields of 3aa were observed even in the absence of
K2CO3, indicating that the CO2 trapped in the oxazolidin-
2-one indeed comes from propargylic carbonates (entries 9
and 10, Table 1). Lowering or elevating the temperature
proved to be deleterious (entries 11 and 12, Table 1)
whereas lowering the amount of 2a to 1.2 equiv improved
the yield of 3aa to 99% by NMR (entry 13, Table 1). In
contrast, increasing the amount of 2a to 2 equiv resulted in
a lower yield of 3aa (entry 14, Table 1). Thus, 5 mol %
Pd(PPh3)4, 1.2 equiv of 2a, and 2 equiv of K2CO3 in
DMSO at 70 °C for 4 h were established as the standard
conditions for further study.
Scheme 1. Concepts and Selectivity Issue for the Synthesis of
Allenic Oxazolidin-2-ones 3
Table 1. Optimization of Reaction Conditions for the
Pd-Catalyzed Cyclization of 1a with 2aa
Initially, terminal 2,3-allenyl amine 1a and propargylic
carbonate 2a were chosen to test the feasibility of our
hypothesis. Gratifyingly, the expected product 3aa was
(6) (a) Ma, S.; Gu, Z.; Deng, Y. Chem. Commun. 2006, 94. (b) Shu,
W.; Jia, G.; Ma, S. Org. Lett. 2009, 11, 117. (c) Shu, W.; Ma, S.
Tetrahedron 2010, 66, 2869. (d) Chen, G.; Zhang, Y.; Fu, C.; Ma, S.
Tetrahedron 2011, 67, 2332.
yield of
3aa (%)b
entry
[Pd]
solvent
base
(7) For a report on the synthesis of oxazolidin-2-ones by Pd-cata-
lyzed cyclization of 2,3-allenyl amines with pressurized CO2 in 2ꢀ65%
NMR yields, see: Kayaki, Y.; Mori, N.; Ikariya, T. Tetrahedron Lett.
2009, 50, 6491.
(8) For reviews on synthesis of cyclic carbonates via intramolecular
“CO2 recycling” from allylic or propargylic carbonates, see: (a) Yoshida,
M.; Ihara, M. Chem.;Eur. J. 2004, 10, 2886. (b) Yoshida, M. J. Synth.
Org. Chem. Jpn. 2010, 68, 160and references cited therein. For reports
on the synthesis of oxazolidin-2-ones, see: (c) Yoshida, M.; Ohsawa, Y.;
Sugimoto, K.; Tokuyama, H.; Ihara, M. Tetrahedron Lett. 2007, 48,
8678. (d) Yoshida, M.; Komatsuzaki, Y.; Ihara, M. Org. Lett. 2008, 10,
2083.
(9) For reviews on Pd-catalyzed cyclization of allenes with a nucleo-
philic moiety, see: (a) Bates, R. W.; Satcharoen, V. Chem. Soc. Rev.
2002, 31, 12. (b) Ma, S. Acc. Chem. Res. 2003, 36, 701. (c) Ma, S. In
Topics in Organometallic Chemistry; Tsuji, J., Ed.; Springer-Verlag:
Heidelberg, 2005; pp 183ꢀ210. (d) Alcaide, B.; Almendros, P.; del Campo,
T. M. Chem.;Eur. J. 2010, 16, 5836.
1
Pd(PPh3)4
Pd(dba)2/TFPd
Pd(OAc)2/TFPe
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
DMSO
DMSO
DMSO
CH3CN
DMF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
NEt3
94(88)c
52
2
3
67
4
89
5
82
6
THF
39
7
DCE
77
8
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
22
9
66
f
10
11g
12h
13i
14j
ꢀ
75
K2CO3
K2CO3
K2CO3
K2CO3
72
36
99
83
(10) For selected examples on Pd-catalyzed cyclization reactions of
2,3-allenyl amines with organic halides, see: (a) Ohno, H.; Toda, A.;
Miwa, Y.; Taga, T.; Osawa, E.; Yamaoka, Y.; Fujii, N.; Tanaka, T.;
Ibuka, T. J. Org. Chem. 1999, 64, 2992. (b) Ohno, H.; Anzai, M.; Toda,
A.; Ohishi, S.; Fujii, N.; Tanaka, T.; Takemoto, Y.; Ibuka, T. J. Org.
Chem. 2001, 66, 4904 and references cited therein. (c) Dieter, R. K.; Yu,
H. Org. Lett. 2001, 2, 3855. (d) Shibata, T.; Kadowaki, S.; Takagi, K.
Heterocycles 2002, 57, 2261. (e) Ma, S.; Yu, F.; Gao, W. J. Org. Chem.
2003, 68, 5943. (f) Shu, W.; Yu, Q.; Jia, G.; Ma, S. Chem.;Eur. J. 2011,
17, 4720.
a The reaction was carried out on a 0.1 mmol scale of 1a in 1 mL of the
indicated solvent. b NMR yield of 3aa determined by 1H NMR analysis
of the crude reaction mixture using 1,3,5-trimethylbenzene as the
internal standard. c The value in parentheses is the isolated yield of
3aa. d Pd(dba)2 (5 mol %) and TFP (10 mol %) were used; TFP = tri-(20-
furyl)phosphine. e Pd(OAc)2 (5 mol %) and TFP (10 mol %) were used.
f No base was added. g Run at 50 °C. h Run at 90 °C. i 2a (1.2 equiv) was
used. j 2a (2 equiv) was used.
Org. Lett., Vol. 14, No. 9, 2012
2313

Table 2. Palladium-Catalyzed Cyclization of Unsubstituted 2,3-
Allenyl Amines 1aꢀd in the Presence of Propargylic Carbonates
2aꢀha
Scheme 2. Cyclization of 4-Monosubstituted 2,3-Allenyl
Amines 1e
improved the yield of 3fa to 72% by NMR (entry 3,
Table 3).
yield of
3 (%)b
entry
R1
R2, R3, R3
1
Bn (1a)
Bn (1a)
Bn (1a)
Bn (1a)
Bn (1a)
Bn (1a)
Ph, Me, Me (2a)
Ph, Me, Me (2a)
Ph, Et, Et (2b)
Ph, -(CH2)4- (2c)
Ph, -(CH2)5- (2d)
4-NO2C6H4,
92 (3aa)
90 (3aa)
90 (3ab)
85 (3ac)
86 (3ad)
85 (3ae)
2c
3
Table 3. Palladium Catalyst and Ligand Screening for the
Cyclization of 4,4-Disubstituted 2,3-Allenyl Amine 1fa
4
5
6
Me, Me (2e)
7
8
9
Bn (1a)
Bn (1a)
Bn (1a)
Me, Me, Me (2f)
n-Bu, Me, Me (2g)
CH2OTBDMS,
Me, Me (2h)
80 (3af)
83 (3ag)
70 (3ah)
10
11
12
PMB (1b)
n-Bu (1c)
H (1d)d
Ph, Me, Me (2a)
Ph, Me, Me (2a)
Ph, Me, Me (2a)
87 (3ba)
82 (3ca)
75 (3da)
[Pd]
ligand
t
yield
(%)b
entry
(mol %)
(mol %)
(h)
c
a The reaction was carried out on a 0.3 mmol scale of 1 in DMSO
(3 mL) in a Schlenk tube unless otherwise noted. b Isolated yields. c The
reaction was carried out with 6.3 mmol of 1a and 7.56 mmol of 2a in a
1
2
3
4
Pd(PPh3)4 (5)
Pd(dba)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
ꢀ
4
6
6
6
22
68
72
39
TFP (10)
TFP (10)
dppe (5)
three-necked flask. d 1d HCl was used as the starting material with
3
K2CO3 (3 equiv) as the base. Bn = benzyl, PMB = p-methoxybenzyl,
TBDMS = tert-butyldimethylsilyl.
a The reaction was carried out on a 0.1 mmol scale of 1f in DMSO
(1 mL) in a Schlenk tube. b Determined by 1H NMR analysis of the crude
reaction mixture using 1,3,5-trimethylbenzene as the internal standard.
c No ligand was added. dppe = 1,2-Bis(diphenylphosphino)ethane.
With the optimized reaction conditions in hand, the
scope of the propargylic carbonates 2 and terminal 2,3-
butadienyl amines 1 were first investigated as shown in
Table 2. The substituent on the CꢀC triple bond of pro-
pargylic carbonates R2 can be aryl (entries 1ꢀ6, Table 2) or
alkyl groups (entries 7ꢀ9, Table 2), furnishing the corre-
sponding products 3aaꢀ3ah in good to excellent yields. In
addition to 1a, secondary 2,3-butadienyl amines 1b or 1c
with a PMB or n-butyl protective group (entries 10 and 11,
Table 2) or primary 2,3-butadienyl amine 1d (entry 12,
Table 2) are also suitable substrates for the reaction. It is
noteworthy that the reaction can be easily conducted using
substrate 1a on a gram scale with 1.2 equiv of 2a, affording
3aa in 90% yield (entry 2, Table 2).
Under this set of improved conditions, 4,4-disubstituted
2,3-allenyl amines 1f and 1g underwent the reaction
smoothly, affording the corresponding products 3fa and
3ga in 70% and 72% yields, respectively (Scheme 3).
Scheme 3. Cyclization of 4,4-Disubstituted 2,3-Allenyl Amines
1f and 1g
Next, we examined the reaction of 4-monosubstituted
2,3-allenyl amine 1e with propargylic carbonate 2a. The
product 3ea was obtained as a mixture of stereoisomers
1
with a ratio of Z/E = 82:18 as determined by H NMR
analysis of the crude reaction mixture (Scheme 2).
However, when 4,4-disubstituted 2,3-allenyl amine 1f
was subjectedtothestandard conditions mentionedabove,
the corresponding product 3fa was obtainedina rather low
yield (entry 1, Table 3). Interestingly, a brief survey of the
palladium catalyst and phosphine ligand showed that the
combination of Pd(OAc)2 (5 mol %) and TFP (10 mol %)
A plausible mechanism is proposed as shown in Scheme 4.
Oxidative addition of 2 with Pd(0) would afford allenylpal-
ladium intermediate Int 1 with simultaneous generation of
2314
Org. Lett., Vol. 14, No. 9, 2012

bonding.12 The subsequent transformation involving Int 1
and Int 2 may proceed through two possible pathways:
Carbopalladation of the allene moiety of Int 2 would
generate the π-allyl palladium species Int 3, and subsequent
nucleophilic attack by the oxygen anion would afford
the product 3 and regenerate the catalytically active Pd(0)
(path a). Alternatively, anti-oxypalladation of Int 4 followed
by reductive elimination would also give 3 and regenerate
Pd(0) (path b).9
Scheme 4. A Possible Mechanism
Inconclusion, wehavedevelopedanefficient method for
the synthesis of 5-(1,3,4-alkatrien-2-yl)oxazolidin-2-ones
via palladium-catalyzed cyclization reactions of 2,3-
allenyl amines with propargylic carbonates with the in
situ generated CO2 recycled. Due to the easy availabil-
ity of the starting materials and good to excellent yields
of the reaction, this methodology will be of interest to
the scientific community. Further studies on the scope
and mechanism of the reaction as well as synthetic
applications of the products are currently underway
in our laboratory.
Acknowledgment. Financial support from National
Basic Research Program of China (2011CB808700) and
National Natural Science Foundation of China (No.
the yet unreleased molecule of CO2 probably due to its
coordination with Pd,4,5 which must have been captured by
2,3-allenyl amines 1 efficiently in the presence of a base
forming carbamate intermediate Int 2.11 The reaction of 1
with CO2 may involve a cyclic intermediate with hydrogen
€
20732005) is greatly appreciated. We thank Mr. Bo Lu in
our group for reproducing the results presented in entry 11
of Table 2 and entry 1 in Scheme 3.
(11) Sakakura, T.; Choi, J.; Yasuda, H. Chem. Rev. 2007, 107, 2365.
(12) For alkoxide/alcohol exchange of palladium alkoxide complexes
with alcohols via hydrogen bonding, see: (a) Kim, Y.-J.; Osakada, K.;
Takenaka, A.; Yamamoto, A. J. Am. Chem. Soc. 1990, 112, 1096. (b)
Gordillo, A.; Lloyd-Jones, G. C. Chem.;Eur. J. 2012, 18, 2660 and
references cited therein. For reports on the reaction of amides with CO2,
see: (c) Chen, G.; Fu, C.; Ma, S. Org. Lett. 2009, 11, 2900. (d) Chen, G.;
Fu, C.; Ma, S. Org. Biomol. Chem. 2011, 9, 105.
Supporting Information Available. Detailed experimen-
tal procedures and characterization data for all the
products. This material is available free of charge via
the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 9, 2012
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