Catalytic Annulation of Epoxides with Heterocumulenes by the Indium-Tin System

In the synthesis of five-membered heterocycles by the annulation of epoxides with heterocumulenes such as carbon dioxide and isocyanates, we developed the indium-tin catalytic system and synthesized various cyclic adducts including novel types products under mild reaction conditions.


Synthesis of Cyclic Carbonates
Until now, various catalysts such as transition metal compounds, ionic liquid, onium salts and alkali metal salts, etc., have been developed for the reaction of epoxides with carbon dioxide [5,32,33]. However, these methods suffer from either the need for co-solvent, the requirement for high temperature, high CO 2 pressure or expensive catalyst. Indium reagents and catalysts have been applied in modern organic synthesis by their mildness and easy handling character [34]. By using the indium halide-phosphine complex, we have already developed the reaction of terminal epoxides to give cyclic carbonates under atmospheric CO 2 pressure at room temperature [35], which indicated that indium halide-based catalysts have efficient catalytic activities. As shown in Table 1, we screened indium halide catalytic systems in the reaction of epoxide 1a with CO 2 (3.9 MPa) at room temperature. The sole use of InCl 3 did not have catalytic activity (Entry 1). Interestingly, the combination of Bu 2 SnI 2 with InCl 3 increased the yield of carbonate 2a (Entry 2). The sole use of Bu 2 SnI 2 was not effective at all (Entry 3). Thus, the InCl 3 -Bu 2 SnI 2 system showed a high catalytic activity. Of particular interest is that the reaction proceeded well even at room temperature. The choice of acetonitrile as a solvent is essential because no reaction proceeded when other solvents such as hexane, benzene, CHCl 3 and THF were used. In acetonitrile, the reaction proceeded very well, and various cyclic carbonates 2 were obtained from epoxides 1b-1f catalyzed by InCl 3 -Bu 2 SnI 2 . Epoxides having aliphatic and aromatic substituents were reactive to afford the corresponding cyclic carbonates 2b-2c (Entries 4 and 5). High chemoselectivities were observed because of the mild conditions. Functionalized cyclic carbonates 2d-2f were synthesized from epoxides having halogen and oxygen substitutes (Entries 6-8).
In the reaction of epoxybutane 1b with tert-BuN=C=O (3a), a quantitative yield of 2-oxazolidinone 4a was obtained (Entry 1). Interestingly, steric hindrance of isocyanates was not a problem to give 2-oxazolidinones 4. The use of either Bu 2 SnI 2 or InCl 3 was not effective (Entries 2 and 3). Thus, it was clear that the InCl 3 -Bu 2 SnI 2 catalytic system showed a high activity even for the synthesis of 2-oxazolidinones 4. Other epoxides such as epichlorohydrin 1d and glycidylic ethers 1e, 1f also reacted well (Entries 4-6). Of course, primary aliphatic isocyanate 3b and phenyl isocyanate 3c also gave the desired products 4e and 4f, although the yields were moderate owing to the trimerization of an isocyanate as a side reaction (Entries 7 and 8) [51,57]. Thus, higher yields of 4a-d in the reaction of tert-BuN=C=O (3a) were achieved because the trimerization would be depressed by steric hindrance of 3a. In all cases, regioselective ring opening of epoxides took place at the less substituted site to give 3,5-disubstituted-2-oxazolidinones 4. In the reaction with diphenyl carbodiimide, an analogue of isocyanates, the oxazolidin-2-imine 5, was obtained in good yield (Scheme 1). Scheme 1. Catalytic synthesis of oxazolidin-2-imine 5.

Discussion
As shown in Figure 1, the structure of the Bu 2 SnI 2 -InCl 3 system could be supposed by the measurement of 119 Sn-NMR spectra in acetonitrile. The addition of equimolar InCl 3 to Bu 2 SnI 2 in acetonitrile clearly changed the 119 Sn peak from a strong one at −38 ppm to a broad one at 3 ppm. This downfield shift indicates that tin species had a positive character by the combination with InCl 3 [58,59]. The catalytic cycle is explained as shown in Scheme 2. By the interaction of tin and indium species, Lewis acidic tin species like Bu 2 SnI δ+ [InCl 3 I] δ− would be generated, which activate the epoxide ring [60][61][62][63]. This active bimetallic species is plausible because transmetallation between tin and indium reagents easily takes place [64][65][66][67][68]. The ring opening of an epoxide to A proceeds regioselectively at the less substituted carbon. Next, the tin-oxygen bond in A is added to heterocumulene to give an adduct B. In the case of isocyanates, the addition occurs at the C=N group selectively to give a stannylcarbamate B [69][70][71]. At the last stage, the Sn-X (X=O, NR) bond in the intermediate B attacks the terminal alkyl iodide [72,73]

Analysis
FTIR spectra were recorded as a thin film on a Nicolet IS5 spectrometer (Thermo Electron Scientific Instruments LLC, Madison, WI, USA). All 1 H and 13 C-NMR spectra were recorded with a JEOL JMTC-400/54/SS (400 and 100 MHz, respectively) in deuteriochloroform (CDCl 3 ) containing 0.03% (w/v) of tetramethylsilane as an internal standard. Temperatures shown in schemes or tables were controlled by a constant-temperature oil bath. Yields were determined by 1 H-NMR using 1,1,1,2-tetrachloroethane or 1,1,2,2-tetrachloroethane as an internal standard. Mass spectra were recorded on a JEOL JMS-DS-303 spectrometer (JEOL Ltd., Tokyo, Japan). Flash column chromatography was performed by Yamazen YFLC-AI-580 using Hi-Flash Silica gel 2L Hi-Flash Column 20 mL/min eluted by hexane/EtOAc with the gradation mode changing from 9/1-3/7 depending on R f values of each compound. Bulb-to-bulb distillation (Kugelrohr) was accomplished at the oven temperature and pressure indicated.
Dehydrated acetonitrile (MeCN) was purchased from commercial sources and used as obtained. Deuterated acetonitrile was also purchased and stored drying over 4 Å molecular sieves. All epoxides, isocyanates, carbodiimide and InCl 3 were also purchased and used as obtained. Bu 2 SnI 2 was prepared according to the previous report [74].

General Procedure for Synthesis of Cyclic Carbonates 2a-f from Epoxides 1 with CO 2
To a 50-mL autoclave, InCl 3 (0.5 mmol), Bu 2 SnI 2 (1.0 mmol) and epoxide 1 (10 mmol) were added in MeCN (3 mL). The autoclave was flushed with CO 2 (3.9 MPa) and stirred at room temperature for 5-10 h. After release of the CO 2 gas, the reaction mixture was quenched with H 2 O (20 mL) and extracted with Et 2 O (3 × 20 mL). The collected organic layer was dried over MgSO 4 . After filtration, the mixture was concentrated in vacuo. The residue was purified by column chromatography. Further purification was performed by Kugelrohr distillation to give a pure product 2. (2a). Colorless liquid. The NMR data of 1 H and 13 C agreed with the previous report [75]. 1 (2b). Colorless liquid. The NMR data of 1 H and 13 C agreed with the previous report [76]. 1  4-(Methoxymethyl)-1,3-dioxolan-2-one (2f). Colorless liquid. The NMR data of 1 H and 13 C agreed with the previous report [35]. 1   To a two-neck 10-mL reaction vessel, InCl 3 (0.25 mmol), Bu 2 SnI 2 (0.50 mmol), epoxide 1 (5 mmol) and isocyanate 3 (5.5 mmol) were added in MeCN (1.5 mL) under N 2 atmosphere. The reaction mixture was stirred at room temperature or 60 • C for 3-20 h. After completion of the reaction, the mixture was quenched with H 2 O (20 mL) and extracted with Et 2 O (3 × 20 mL). The collected organic layer was dried over MgSO 4 . After filtration, the mixture was concentrated in vacuo. The residue was purified by column chromatography. For some cases, further purification was performed by distillation to give a pure product 4.    5-Ethyl-3-phenyloxazolidin-2-one (4f). Colorless liquid. The NMR data of 1 H and 13 C agreed with the previous report [77]. 1

Observation of Tin-Indium System by 119 Sn NMR
To a two-neck 10-mL reaction vessel, InCl 3 (1.0 mmol) and Bu 2 SnI 2 (1.0 mmol) were added in MeCN-d 3 (1 mL) and stirred at room temperature for several minutes. After transferring of the reaction mixture into an NMR test tube and addition of tetramethyl stannane as an internal standard, 119 Sn NMR was recorded.

Conclusions
A novel type of indium-tin species Bu 2 SnI δ+ [InCl 3 I] δ− was revealed to be effective for the catalytic annulation of epoxides. In the reaction with carbon dioxide, the fixation of CO 2 proceeded well even at room temperature. In the reaction with isocyanates, novel types of 2-oxazolidiones were obtained in good yields.