Rhodium-catalyzed synthesis of multi-substituted furans from N-sulfonyl-1,2,3-triazoles bearing a tethered carbonyl group

Abstract

The efficient synthesis of highly functionalized furan derivatives from 1-sulfonyl-1,2,3-triazoles with a pendent carbonyl group is reported. The process involves an intramolecular trapping of α-imino carbene and subsequent aromatization.

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Functionalized furans occur in a variety of biologically active natural products, pharmaceuticals and functional materials.¹ Moreover, they are versatile building blocks for both heterocyclic and acyclic compounds.² For this reason, the synthesis of multi-substituted furans continues to be a hot topic in modern synthetic chemistry.³ In addition to traditional methods,⁴ transition-metal-catalyzed reactions⁵ and organocatalytic approaches⁶ have been reported during the last several decades. Despite all the achievements, the development of novel and convenient methods for the synthesis of functionalized furans with readily accessible compounds is of great importance.

As one of the most important intermediates in organic chemistry, metal carbenes were traditionally prepared by the decomposition of diazo compounds and N-tosylhydrazones.⁷ In recent years, the application of alkynes as carbene precursors has attracted considerable attention.⁸ 1-Sulfonyl-1,2,3-triazole, which can be easily prepared by CuAAC reaction,⁹ was used in the formation of α-imino carbene by Fokin and Gevorgyan in 2008.¹⁰ Since then, investigation of α-imino carbene derived from N-sulfonyl triazoles has led to the development of a variety of synthetic transformations.¹¹ Cycloaddition,¹² ylide formation,¹³ ring expansion,¹⁴ and C–H or heteroatom–H insertion¹⁵ were applied in the synthesis of heterocycles or acyclic compounds. It is worth noting that in most cases, the nitrogen atom of the imino group was included in the newly formed heterocycles; the synthesis of furans or thiophenes have not been realized in this area.¹⁶ We envisioned that if we use a tethered carbonyl group to trap the α-imino carbene intermediate, furan with a tosylaminomethylene group would be formed after isomerization (Scheme 1). The tosylamino group can be used to introduce other functional groups, which offers more opportunities for the synthesis of complex cyclic compounds.

Scheme 1 Initial hypothesis.

As illustrated in Table 1, the yield of 2a was found to be highly dependent on both the dirhodium catalyst and the solvent. The treatment of a solution of triazole 1a in refluxing DCE with 1 mol% of Rh₂(OAc)₄ afforded 2,5-disubstituted furan 2a in 80% yield (entry 1). To our surprise, attempts to use Rh₂(oct)₄ as the catalyst led to only trace furan product (entry 2). The use of Rh₂(esp)₂ provided the desired product in 89% yield (entry 3). No further improvement was achieved when other catalysts such as Rh₂(Piv)₄, Rh₂(S-pttl)₄ or Rh₂(S-nttl)₄ were used (entries 4–6). Reactions performed in other solvents (entries 7–11) resulted in decreased yield.

Table 1 Optimization of reaction conditions^a

Entry	Catalyst	Solvent	t (h)	Yield^b (%)
a 0.2 mmol of 1a and 0.002 mmol of the rhodium(II) catalyst were dissolved in 2 mL solvent. b Isolated yield, average of two runs.
1	Rh2(OAc)4	DCE	1.0	80
2	Rh2(oct)4	DCE	1.0	Trace
3	Rh2(esp)2	DCE	1.0	89
4	Rh2(Piv)4	DCE	1.0	55
5	Rh2(S-pttl)4	DCE	3.0	60
6	Rh2(S-nttl)4	DCE	3.0	62
7	Rh2(esp)2	Toluene	1.0	79
8	Rh2(esp)2	CHCl3	3.0	Trace
9	Rh2(esp)2	THF	3.0	Trace
10	Rh2(esp)2	MeCN	3.0	Trace
11	Rh2(esp)2	ClCH2CHCl2	3.0	Trace

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Examination of the reaction scope with respect to the sulfonyl group of the triazole (Table 2, 1b, 1c, 1d, 1e and 1f) revealed that both the electronic nature and the steric hindrance of the substituents have great impact on the reaction. The corresponding furan products were obtained in yields ranging from 67% to 92%. Both arylsulfonyl groups and alkylsulfonyl groups were suitable for this transformation. As for the substituents of the carbonyl group, reaction of 1g and 1h bearing an alkyl chain provided 2,5-disubstituted furans 2g and 2h in good yield, whereas substrates 1i, 1j, 1k and 1l led to the aryl substituted furan in moderate yield. 2,3,5-Trisubstituted furans 2m and 2n were obtained in 66% and 61% yield, respectively, when substrates with a methyl or benzyl group at the α-position of the carbonyl group were used. Substrate 1o can be easily synthesized from cyclohexanone in two steps, and when treated with 1 mol% of Rh₂(OAc)₄, fused furan 2o was obtained in 81% yield. Of note is that 1,2-H migration products have never been observed in these transformations.

Table 2 Reaction scope^a

a 0.2 mmol of 1 and 0.002 mmol of Rh₂(esp)₂ were dissolved in 2 mL DCE, 2 was isolated by column chromatography, average of two runs. b 0.002 mmol of Rh₂(OAc)₄ was used instead of Rh₂(esp)₂.

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Interestingly, when substrate 1p, which bears a methyl group at the β-position of the carbonyl group, was treated with Rh₂(esp)₂ in refluxing DCE, furan 2p′ was obtained in 60% yield. 2p′ could be reduced to 2p smoothly by NaBH₄ (Scheme 2). We believe that the mechanism of formation of 2p′ is similar to the mechanism proposed by Lin^15d and the presence of a methyl group facilitates the elimination of hydride.

Scheme 2 Synthesis of 2p′ and 2p.

Next, we highlighted the synthetic potential of this transformation with an efficient synthesis of phenol 4a. Treatment of 2a with propargyl bromide led to the formation of 3a, which underwent gold-catalyzed rearrangement to furnish phenol 4a in 87% yield¹⁷ (Scheme 3).

Scheme 3 Synthetic derivatization of 2a.

Conclusions

In summary, intramolecular trapping of α-imino rhodium carbene with a carbonyl group has been realized; functional furan compounds with different substitution patterns were obtained in high yield. The synthetic utility of this transformation was exemplified by a gold-catalyzed phenol synthesis.

Acknowledgements

This work was generously supported by the National Natural Science Foundation of China (21002091, 21372204) and the Zhejiang Sci-Tech University 521 project.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Experimental procedures, characterization data, and NMR spectra for new compounds. See DOI: 10.1039/c4qo00273c

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