Role of temperature in [3+2]-cycloaddition of isoselenocyanates with oxiranes using BF₃·Et₂O

Abstract

The [3+2]-cycloaddition reaction of isoselenocyanates with oxiranes using BF₃·Et₂O is temperature dependent affording generally either substituted 2-imino-1,3-oxaselenolanes (−5 °C) or 1,3-oxazolidinones (40 °C) in short reaction times with high yields.

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The [3+2]-cycloaddition reaction of heterocumulene with oxirane provides a powerful tool for the construction of five-membered heterocycles that are important in synthetic organic chemistry as well as in biological and medicinal sciences.^1,2 Among them, the reactions of carbodiimide, isocyanate and isothiocyanate with oxirane have been studied considerably.^3–5 In contrast, the reaction of the analogue isoselenocyanate⁶ with oxirane is yet to be investigated, which could lead to a straightforward route for the construction of polysubstituted 1,3-oxaselenolanes.⁷ In a continuation of our studies on carbon–heteroatom bond formation,⁸ we report herein a new temperature dependent selective synthesis of substituted 2-imino-1,3-oxaselenolanes (−5 °C) and 1,3-oxazolidinones (40 °C) from isoselenocyanates and oxiranes using BF₃·Et₂O with excellent regioselectivity. The method is efficient and affords a straightforward route for the construction of the target heterocyclic compounds in short reaction times. To the best of our knowledge, this is the first example of the temperature dependent selective cycloaddition reaction of heterocumulene with oxiranes as well as for the formation of 1,3-oxazolidinones from isoselenocyanates and oxiranes.

First, optimization of the reaction conditions was carried out with phenyl isoselenocyanate 1a and styrene oxide 2a as the model substrates using different Lewis acids and solvents at varied temperatures (Table 1). As anticipated, the protocol was effective and interestingly, afforded selectively either Z-phenyl-2-imino-1,3-oxaselenolane 3a (−5 °C) or 3,4-diphenyloxazolidin-2-one 4a (40 °C) as the sole product, depending on the temperature, with excellent regioselectivity. Recrystallization of the compound 4a in hexane gave crystals whose structure was confirmed by single crystal X-ray analysis (Fig. 1). Among the Lewis acids screened, BF₃·Et₂O, SnCl₄, InCl₃ and FeCl₃, all were active, and BF₃·Et₂O yielded the best results. CH₂Cl₂ was found to be the solvent of choice, while toluene and CH₃CN exhibited moderate to good results. In contrast, THF and 1,4-dioxane yielded inferior results. Using 10 mol% of BF₃·Et₂O the target molecules could be obtained in quantitative yield. The reaction at −5 °C gave complete conversion with 1.5 equiv. of styrene oxide, while the process at 40 °C required 2 equiv. of styrene oxide to give the best results. Control experiments for both processes confirmed that no reaction was observed without the Lewis acid.

Table 1 Optimization of the reaction conditions

Entry	Catalyst	Solvent	Time (h)	Conv. (%)^a
				3a ^b	4a ^c
a Determined by 400 MHz ^1H NMR. b Isoselenocyanate 1a (0.5 mmol), oxirane 2a (0.75 mmol) and catalyst (10 mol%) were stirred at −5 °C in solvent (1 mL) under a N2 balloon. c Reactions were carried out with 2 equiv. of oxirane 2a at 40 °C. d BF3·Et2O (5 mol%) was used. e 1 equiv. of oxirane 2a was used. f Catalyst was not used. n.d. = not detected.
1	BF3·Et2O	CH2Cl2	0.5	98	92
2	SnCl4	CH2Cl2	3	60	53
3	Cu(OTf)2	CH2Cl2	8	n.d.	—
4	Sc(OTf)3	CH2Cl2	18	70	68
5	InCl3	CH2Cl2	3	65	52
6	FeCl3	CH2Cl2	3	<5	—
7	BF3·Et2O	CHCl3	0.5	90	85
8	BF3·Et2O	THF	1	<3	—
9	BF3·Et2O	Toluene	1	55	41
10	BF3·Et2O	CH3CN	1	90	79
11	BF3·Et2O	1,4-Dioxane	1	<3	—
12^d	BF3·Et2O	CH2Cl2	0.5	78	71
13^e	BF3·Et2O	CH2Cl2	0.5	80	—
14^f	—	CH2Cl2	24	n.d.	n.d.

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Fig. 1 ORTEP diagram of (Z)-4-iodo-N-(4-phenyl-1,3-oxaselenolan-2-ylidene)benzenamine 3f and 3,4-diphenyloxazolidin-2-one 4a. Thermal ellipsoids are drawn at a 40% probability level. Hydrogen atoms have been omitted for clarity.

With optimized conditions in hand, the scope of the procedure was next pursued. The reactions of a series of aryl and cyclohexyl isoselenocyanates 1b–l with oxirane 2a were examined (Table 2). Aryl isoselenocyanates having electron donating as well as -withdrawing substituents on the aromatic ring readily proceeded in the reactions to give the corresponding target heterocycles in good to high yield. For example, aryl isoselenocyanates 1b–h having 2-Cl, 3-F, 4-Cl, 4-F, 4-I, 4-OMe and 4-Me substituents on the aromatic ring proceeded in the cycloaddition reactions with 2a to give the heterocyclic compounds 3b–h in 42–92% yield (−5 °C) and 4b–h in 61–84% yield (40 °C). Compound 3f in hexane gave crystals whose structure was confirmed by X-ray analysis (Fig. 1).

Table 2 Reactions of substituted isoselenocyanates with styrene oxide

Entry	Isoselenocyanate	R^1	Product (yield, %)^c
			−5 °C^a	40 °C^b
a Reaction conditions: isoselenocyanate 1a–l (0. 5 mmol), oxirane 2a (0.75 mmol) and BF3·Et2O (10 mol%) were stirred in CH2Cl2 at −5 °C for 0.5 h under N2. b Reactions were performed at 40 °C for 0.5 h under N2. c Isolated yield. n.d. = not detected.
1	1a	Ph	3a (86)	4a (73)
2	1b	2-ClC6H4	3b (42)	4b (72)
3	1c	3-FC6H4	3c (76)	4c (61)
4	1d	4-ClC6H4	3d (90)	4d (75)
5	1e	4-FC6H4	3e (92)	4e (65)
6	1f	4-lC6H4	3f (85)	4f (84)
7	1g	4-MeOC6H4	3g (88)	4g (68)
8	1h	4-MeC6H4	3h (78)	4h (70)
9	1i	4-NO2C6H4	3i (n.d.)	4i (n.d.)
10	1j	3,4-DiMeC6H3	3j (83)	4j (78)
11	1k	1-Naphthyl	3k (87)	4k (71)
12	1l	Cyclohexyl	3l (90)	3l (90)

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Under these conditions, aryl isoselenocyanate 1i with a 4-NO₂ substituent underwent no cycloaddition reaction. However, the disubstituted aryl isoselenocyanate 1j with 3,4-dimethyl groups underwent reaction with 2a to provide the heterocycles 3i and 4i in 83% and 78% yield, respectively. Similarly, 1-naphthyl isoselenocyanate 1k proceeded in reactions with 2a to afford the heterocycles 3k and 4k in 87% and 71% yield respectively. In contrast, cyclohexyl isoselenocyanate 1l, at both the reaction temperatures (−5 and 40 °C), gave 3l as the sole product.

Finally, the reactions of substituted oxiranes 2b–f with phenyl isoselenocyanate 1a were studied (Table 3). As above, the reaction was efficient and the product formation was dependent on the nature of the oxirane. For example, n-octene-1,2-oxide 2b and epichlorohydrin 2c proceeded in reactions with 1a to give the heterocyclic compounds 3m–n in 79–86% yield (−5 °C) and 4l–m in 71–73% yield (40 °C). In contrast, the reactions of α-methylstyrene oxide 2d, 4-acetoxystyrene oxide 2e and cyclohexene oxide 2f with 1a at both the reaction temperatures (−5 and 40 °C) afforded selectively heterocycles 3o–q in 62–76% yield. Among them, the compound 3q afforded single crystals in hexane whose structure was determined by X-ray analysis (see ESI†). These results suggest that the reactions of isoselenocyanates with oxiranes are regioselective and the product formation depends on the reaction temperature and nature of the oxirane.

Table 3 Reactions of substituted oxiranes with phenyl isoselenocyanate

Entry	Oxirane	Product yield^c (%)
		−5 °C^a	40 °C^b
a Reaction conditions: phenyl isoselenocyanate 1a (0. 5 mmol), oxirane 2b–f (0.75 mmol) and BF3·Et2O (10 mol%) were stirred in CH2Cl2 at −5 °C for 0.5 h under N2. b Reactions were performed at 40 °C for 1 h under N2. c Isolated yield.
1
2
3
4
5

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To reveal the mechanism, compound 3h was reacted with 1.1 equiv. of 2a and the heterocycle 4h, styrene and Se were obtained in 100% conversion along with a trace of phenyl acetaldehyde⁹ (Scheme 1). This result suggests that the oxirane 2 first undergoes reaction with isoselenocyanate 1 in the presence of the Lewis acid to give the heterocycle 3 (at −5 °C) that could further react with oxirane 2 at 40 °C to give the heterocycle 4 along with alkene and Se. Thus, the reaction of the Lewis acid with oxirane 2 can lead to the formation of a secondary carbocation that could undergo reaction with the Se of the isoselenocyanate to afford the intermediate a (Scheme 2). The cyclization of a could lead to the formation of the heterocycle 3. At 40 °C, the compound 3 may undergo further reaction with oxirane 2 to give the intermediate^4bb which could give the heterocycle 4, alkene and Se.

Scheme 1

Scheme 2 Proposed catalytic cycle.

In summary, the [3+2]-cycloaddition reaction of isoselenocyanate with oxirane has been developed. The process is efficient, regioselective, temperature dependent and affords a straightforward route for the synthesis of 2-imino-1,3-oxaselenolanes and 2-oxazolidinones in short reaction times.

Acknowledgements

We thank the Department of Science and Technology, New Delhi, and the Council of Scientific and Industrial Research, New Delhi, for financial support.

References

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Footnote

† Electronic supplementary information (ESI) available: Experimental procedures and NMR spectra (¹H and ¹³C). CCDC 843126 (3q), 843127 (4a) and 843128 (3f). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c2ra00042c

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