Copper-catalyzed domino cyclization of propargylic alcohol with tosyl isocyanate to oxazolidinones

Article abstract of DOI:10.1080/00397911.2016.1258475

A copper-catalyzed domino cyclization of propargylic alcohols with tosyl isocyanate for the synthesis of oxazolidinones has been developed. Various propargylic alcohols with an aryl or alkyl substituents worked smoothly to afford the corresponding oxazoli

Full text of DOI:10.1080/00397911.2016.1258475

Copper catalyzed domino cyclization of propargylic alcohol with tosyl isocyanate to
oxazolidinones
Xiu-Shuai Chen1,2, Chuan-Jin Hou1,3, Yan-Jun Liu1,, Rui-Feng Yang1, Xiang-Ping Hu2
1School of Light Industry and Chemical Enginerring, Dalian Polytechnic University,
Dalian, China, 2Dalian Institute of Chemical Physics, Chinese Academy of Sciences,
Dalian, China, 3Post-Doctoral Research Station of Dalian Zhenbang Fluorocarbon Paint
Stock Co., Ltd., Dalian, China
Address correspondence to Chuan-Jin Hou, School of Light Industry and Chemical
Engineering, Dalian Polytechnic University, Dalian, 116034, China. E-mail:
houcj@dlpu.edu.cn
Address correspondence to Yan-Jun Liu, School of Light Industry and Chemical
Engineering, Dalian Polytechnic University, Dalian, 116034, China. E-mail:
yjliu65@sohu.com
Supplemental data (experimental details, characterization and copies of 1H and 13C NMR
spectra for all target compounds) can be accessed on the publisher’s website.
Abstract
A copper catalyzed domino cyclization of propargylic alcohols with tosyl isocyanate for
the synthesis of oxazolidinones has been developed. Various propargylic alcohols with an
aryl or alkyl substituent worked smoothly to afford the corresponding oxazolidinones in
moderate to excellent yields.
Graphical Abstract:
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KEYWORDS: Copper; cyclization; propargylic alcohol; tosyl isocyanate;
oxazolidinones
INTRODUCTION
Oxazolidinones and their derivatives are one of the most important heterocyclic
compounds, which exhibit a broad spectrum biological activities.[1-2] They have been
widely used in pharmaceutical and agricultural industry as well as in organic synthesis.
[3-4] As a result, great efforts have been devoted to develop methods for the synthesis of
oxazolidinones.[1] Among the numerous methods developed, the common way for the
oxazolidinones formation involves condensation of amino alcohols with phosgene,
chloroformate and dialkyl carbonates as carbonyl precursors. An alternative method is the
cyclization reaction of propargylic carbamates. In 2007, Chandrasekaran and co-workers
reported a based catalyzed cyclizations of propargylic carbamates.[5] Then Kang and
co-workers found that N-heterocyclic carbens were also efficient to catalyze a domino
cyclization of propargylic alcohols and benzoyl isocyanates.[6] The more important work
has focused on Au,[7,8] Pd,[9-11] and Ru[12] catalyzed cyclization of propargylic carbamates
to from oxazolidinones. Compared with the Au, Pd and Ru-catalysts used in this reaction,
copper salts has the advantage of cheap, non-toxic and easy to handle. Thus, the synthesis
of oxazolidinones with Cu-catalyst has attracted much attentions in the past decades.[13-17]
However, the substrates type in most of the Cu-catalyzed cyclization of propargylic
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compounds was limited to alkyl substrates, very few aryl-substituted propargylic alcohols
were studied. As part of our continuous research on the copper catalyzed propargylic
transformation reaction, we herein report a copper catalyzed domino cyclization of
propargylic alcohols (especially aryl-substituted propargylic alcohols[18]) with tosyl
isocyanates for the synthesis of oxazolidinones.
RESULTS AND DISCUSSION
At the outset of our investigation, the cyclization of 1-phenylprop-2-yn-1-ol (1a) with
4-methyl benzenesulfonyl isocyanate (2) was chosen as the tested model reaction to
examine the effect of several copper catalysts in the presence of Et3N as base (Table 1).
.
The results showed that all of the Cu salts, including Cu(OAc)2 H2O, Cu(OTf)2,
Cu(CH3CN)BF4, Cu(CH3CN)4ClO4, CuCl and CuI, displayed satisfactory performance
(entries 1-7). Among them, CuI afford the desired product 3a in 85% yield (entry 3). The
structure of the product 3a was confirmed by X-ray crystallography (Figure 1).[19] The
solvent effect was next examined, which showed that all solvents such as toluene, CH2Cl2,
Et2O, ClCH2CH2Cl and THF proved to be suitable for this cyclization (entries 8-11). THF
proved to be the best choice, which afforded the corresponding product in 90% yield
(entry 11). The addition of a base proved crucial to the reaction since none of the desired
product observed in its absence (entry 12). Et3N provided better result than i-Pr2NEt,
DBU and K2CO3 (entries 11, 13-15).
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Encouraged by this initial result, we explored the generality of this process by examining
the scope and limitation of the reaction with respect to propargylic alcohol 1. As shown in
Table 2, the cyclization reaction proceeded smoothly with various propargylic alcohols
bearing an aryl or alkyl substituent to furnish the corresponding oxazolidinones in
moderate to excellent yield. It appeared that the substituent position at the phenyl ring
had important effect on the reaction. Thus, substrate 1b with ortho-chloro substituent
gave lower yield in comparison with its meta- or para-chloro substituted analogues
(entries 2-4). Propargylic alcohols containing both electron-withdrawing (F, Cl, Br, CF3)
and electron-donating substituent (Me, OMe) at the para-position of the phenyl ring were
converted into the corresponding oxazolidinones with good to excellent yields (entries
5-9). In addition, 2-naphthyl substrate 1j proved to be suitable for this reaction (entry 10).
Meanwhile a heterocycles such as thiophene were able to tolerate these reaction
conditions (entry 11). Furthermore，the benzyl substrate 1l also worked smoothly to
afford the desired product in 95% yield (entry 12). However, lower yield were obtained
when alkyl substrates were employed in the reaction (entries 13-14).
CONCLUSION
In conclusion, we have developed a copper catalyzed domino cyclization of propargylic
alcohols with tosyl isocyanate to afford oxazolidinones in a mild one-step synthesis.
Under the optimized conditions, the cyclization reaction proceeded smoothly with a wide
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range of propargylic alcohols bearing an aryl or alkyl substituent to furnish the
corresponding oxazolidinones in moderate to excellent yield.
EXPERIMENTAL
All reactions were carried out under a nitrogen atmosphere using standard Schlenk
techniques. All solvents were dried and degassed by standard methods and stored under
nitrogen. 1H NMR and 13C NMR spectra were recorded at 400 MHz and 100 MHz,
respectively on a Bruker DPX400 NMR spectrometer.
General Procedure For Copper Catalyzed Domino Cyclization
A solution of CuI (3.8 mg, 0.015 mmol) in 1 mL of anhydrous tetrahydrofuran placed in
an oven-dried Schlenk flask was stirred at room temperature under a nitrogen atmosphere.
A solution of propargylic alcohol 1, (0.3 mmol) 4-methyl-benzenesulfonyl isocyanate 2
(0.33 mmol) and Et3N (50 uL, 0.36 mmol) in 2 mL of anhydrous tetrahydrofuran was
added. The mixture was stirred at room temperature for 5 h. The reaction mixture was
then concentrated under vacuum, and the residue was purified by silica gel
chromatography to afford the corresponding oxazolidinones 3.
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4-Methylene-5-Phenyl-3-Tosyloxazolidin-2-One (3a)
White solid was obtained in 90% yield after purification with column chromatography on
silica gel (petroleum ether/ethyl acetate, 20/1). M.p.: 70-72 oC. 1H NMR (400 MHz,
CDCl3): δ 7.89 (d, J = 7.5 Hz, 2H), 7.30-7.26 (m, 5H), 7.10-7.09 (m, 2H), 5.70 (s, 1H),
5.54 (s, 1H), 4.30 (s, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 150.9, 146.3,
139.5, 135.9, 134.4, 130.0, 129.9, 129.0, 128.2, 127.1, 93.9, 80.3, 21.8. HRMS calc. for
C17H16NO4S [M+H] +: 330.0800, found: 330.0767.
ACKNOWLEDGEMENTS
The authors are grateful for the financial support from the National Natural Science
Foundation of China (Nos. 21403022 and 21572226) and Natural Science Foundation of
Liaoning Province of China (No 2015020194).
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19. CCDC-1469361 (3a) contains the supplementary crystallographic data for this paper.
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Table 1. Screening of reaction conditions
a
Entry
1
[Cu]
solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
Et2O
base
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
yield(%)b
84
.
Cu(OAc)2 H2O
Cu(OTf)2
2
83
3
CuI
85
4
Cu(CH3CN)4BF4
Cu(CH3CN)4ClO4
71
5
83
.
6
Cu(OTf)2 (C6H6)0.5
66
7
CuCl
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
80
8
80
9
86
10
11
12
13
14
15
ClCH2CH2Cl
THF
86
90
THF
NR
85
THF
i-Pr2NEt
DBU
THF
trace
60
THF
K2CO3
aThe reaction was carried out with 1a (0.3 mmol), 2 (0.33 mmol), [Cu] (0.015 mmol),
base (0.36 mmol) at room temperature for 5 h. b Isolated yields.
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Table 2. Substrates scope of propargylic alcohol 1 for the synthesis of oxazolidinones
3a.
entry
1
substrate (R)
product
3a
yield (%)b
90
1a: R = Ph
2
1b: R = 2-ClC6H4
1c: R = 3-ClC6H4
1d: R = 4-ClC6H4
1e: R = 4-FC6H4
1f: R = 4-BrC6H4
1g: R = 4-CF3C6H4
1h: R = 4-MeC6H4
1i: R = 4-MeOC6H4
1j: R = 2-naphthyl
1k: R = 2-thiophenyl
1l: R = PhCH2
63
3b
3c
3
84
4
87
3d
3e
5
84
6
85
3f
7
84
3g
8
91
3h
3i
9
82
10
11
12
13
14
73
3j
78
3k
3l
95
1m: R = Me
3m
3n
62
1n: R = Cy
64
a The reaction was carried out with 1 (0.3 mmol), 2 (0.33 mmol), CuI (0.015 mmol), Et3N
(0.36 mmol) in THF at room temperature for 5 h. b Isolated yields
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Figure 1. X-ray crystallographic structure of compound 3a.
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