Re₂O₇ catalyzed dienone-phenol rearrangement

Abstract

The dienone-phenol rearrangement of 4,4-disubstituted cyclohexadienones catalyzed by Re₂O₇ has been described. Multi-substituted phenols can be efficiently obtained in good to excellent yields by employing this catalytic protocol.

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Although various rhenium complexes have been synthesized with some of them being commercially available,¹ their catalytic abilities for organic transformations are less explored when compared with other transition state metal complexes.² In recent years, increasing interest has been dedicated to rhenium catalysts for their stability to air and moisture and their unique Lewis acidity for the activation unsaturated hydrocarbon bonds.^3–5 Particularly, the ability to activate C(sp²)–H and C(sp³)–H bonds using rhenium carbonyl complexes has enabled them to be amenable for C–H bond functionalization reactions.^2b,3 Not only low-valent rhenium complexes, but also Re(V)⁴ and Re(VII)^2b,5 complexes are competent catalysts in a variety of organic transformations. For example, Toste and co-workers unveiled that Re(V)-oxo complexes enable the conversion of propargyl alcohols to functionalized intermediates via C–C,^4b,c C–O,^4e and C–N^4g bond formation. MeReO₃, a Re(VII) complex, is well known for its wide use as an oxidation catalyst.^5d In addition to its oxidation ability, Re(VII) also exhibits moderate Lewis acidity, which can be utilized for the generation of carbocation intermediates under mild reaction conditions. For example, Re₂O₇ and PhSiOReO₃ are popular in the stereospecific isomerization of allyl alcohols (Fig. 1, eqn (1)).^5e–h These Re(VII) complexes are also used for the generation of oxonium ions in acetalization and the Prins reaction (Fig. 1, eqn (2)).^5i–l It should be pointed out that the high efficiency of these reactions relies on the unique Lewis acid property of Re(VII), which can in turn stabilize the cation intermediates involved.

Fig. 1 Representative Re(VII) catalyzed reactions involving cationic intermediates.

The dienone-phenol rearrangement is a rearomatization reaction of 4,4-disubstituted cyclohexadienones via a bond shift, which provides facile access to multi-substituted phenols.⁶ The mechanism of the dienone-phenol rearrangement has been extensively studied and well employed in organic synthesis.⁷ Typically, the reaction can be promoted by acid, strong base or photo irradiation.⁶ In this context, the catalytic dienone-phenol rearrangement is also well described.⁸ For example, Kim has developed a domino dienone-phenol rearrangement/5-endo-dig cyclization of quinols catalyzed by PtCl₂ to afford benzofurans.^8c Fujioka also found that the transformation of dienones to benzene thioethers was efficiently achieved using catalytic TfOH.^8d More recently, the dienone-phenol rearrangement of spiro[4.5]cyclohexadienones catalyzed by Sc(OTf)₃ was described by Hamada and co-workers.^8e In this report, we disclose that Re₂O₇ is a robust catalyst for the dienone-phenol rearrangement of 4-alkoxy-substituted cyclohexadienones, which is difficult to accomplish using previously described catalysts (Fig. 1, eqn (3)).

As our interest was in the application of the dienone-phenol rearrangement towards the synthesis of phenol 2aa, we found that under the effect of an excessive amount of BF₃·OEt, cyclohexadienone 1aa was smoothly converted to phenol 2aa in 73% yield (Table 1, entry 1). Moreover, only a low yield was obtained when a catalytic amount of BF₃·OEt was employed (20%, Table 1, entry 2), which prompted us to investigate the reaction conditions to find out a catalytic protocol for this reaction. As summarized in Table 1, most of the evaluated Lewis acids (e.g. Zn(OTf)₂, Cu(TFA)₂, and AlCl₃, entry 3–9) were ineffective in the reaction with starting material being fully recovered after 12 h. Previously reported catalysts such as Sc(OTf)₃ (ref. 8e) and PtCl₂,^8c which serve as efficient catalysts for the dienone-phenol rearrangement, were also capable of facilitating the rearrangement of 1aa albeit in 45% and 55% yield, respectively (Table 1, entry 10 and 11). Other types of promoters (e.g. TMSOTf and TfOH^8d) gave unsatisfactory results (Table 1, entry 13 and 14). To our delight, Re₂O₇ worked very well for this rearrangement, providing phenol 2aa in 92% yield with an accelerated reaction rate, and other Re(VII) complexes (e.g. Phe₃SiOReO₃, MeReO₃) alleviated this reaction (Table 1, entry 14–16). Subsequently, solvent screening showed that the highest yield was observed in CH₂Cl₂ when compared to the other solvents studied (Table 1, entry 17–19). Lower or higher temperatures were detrimental to the reaction (Table 1, entry 20 and 21). Significantly, the catalyst loading could be reduced to 5 mol% without a deleterious effect on the reaction (Table 1, entry 22).

Table 1 Screening of the reaction conditions for the dienone-phenol rearrangement of quinol 1a^a

Entry	Catalyst (equiv.)	T (°C)	Solvent	Time (h)	Yield^b (%)
a Reaction conditions: quinol 1aa (0.1 mmol) in CH2Cl2 (0.5 mL) was added dropwise to a solution of catalyst (0.01 mmol) in CH2Cl2 (0.5 mL) at rt.b Isolated yield.
1	BF3·Et2O (3.0)	rt	CH2Cl2	4	73
2	BF3·Et2O (0.1)	rt	CH2Cl2	4	20
3	Cu(TFA)2 (0.1)	rt	CH2Cl2	12	ND
4	Zn(OTf)2 (0.1)	rt	CH2Cl2	12	ND
5	Cp2TiCl2 (0.1)	rt	CH2Cl2	12	ND
6	Yb(OTf)3 (0.1)	rt	CH2Cl2	12	ND
7	InCl3 (0.1)	rt	CH2Cl2	12	ND
8	AgBF4 (0.1)	rt	CH2Cl2	12	ND
9	AlCl3 (0.1)	rt	CH2Cl2	12	ND
10	Sc(OTf)3 (0.1)	rt	CH2Cl2	12	45
11	PtCl2 (0.1)	rt	CH2Cl2	4	55
12	TMSOTf (0.1)	rt	CH2Cl2	4	60
13	HOTf (0.1)	rt	CH2Cl2	4	50
14	Re2O7 (0.1)	rt	CH2Cl2	1	92
15	Ph3SiOReO3 (0.1)	rt	CH2Cl2	1	83
16	MTO (0.1)	rt	CH2Cl2	12	ND
17	Re2O7 (0.1)	rt	Toluene	12	22
18	Re2O7 (0.1)	rt	CHCl3	12	67
19	Re2O7 (0.1)	rt	EtOAc	12	16
20	Re2O7 (0.1)	0	CH2Cl2	12	50
21	Re2O7 (0.1)	40	CH2Cl2	1	76
22	Re2O7 (0.05)	rt	CH2Cl2	1	93

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Upon identification of the reaction conditions, the substrate scope in the reaction was subsequently examined. Various cyclohexadienones were prepared by phenol oxidation and subjected to the standard reaction conditions (Scheme 1). Satisfactorily, different alkoxy groups were compatible, affording the corresponding phenols in good to excellent yields (2aa to 2ag). Different protecting groups were also surveyed for exploring the functional group compatibility of the reaction. Given the fact that Brønsted acids are usually generated from the hydrolysis of Re₂O₇,⁵ acid-labile protecting groups (e.g. TBS and Boc for 2ba and 2bb) were not well tolerated, leading to low isolated yields due to substantial deprotection.⁹ Moderate yields could be obtained when acid-stable protecting groups were present (e.g. Ac, Bz, Ts for 2bd–2bf). Next, different migration groups were evaluated for this reaction. Cyclohexadienones with primary and secondary alkyl groups smoothly transferred to the corresponding phenols in very high yield (2ca–2ci). However, cyclohexadienone 1d with 4-methyl was inert under the reaction conditions, owing to the low migratory aptitude of methyl and moderate Lewis acidity of Re₂O₇. Tertiary butyl was also an unsuitable migratory group and 4-methoxyphenol was exclusively formed from 1e, presumably via an extrusion of stable tertiary carbocation (ESI†). Disappointingly, only a sluggish reaction mixture was obtained when cyclohexadienone 1f was examined. Furthermore, tetra-substituted phenols could be isolated regioselectively from multi-substituted cyclohexadienone in good yields, with the migratory group being attached to the less hindered position (2g–2i). In addition, the reaction could also be easily scaled up without influencing the isolated yields (2g and 2h).

Scheme 1 Substrate scope of the Re₂O₇ catalyzed dienone-phenol rearrangement.

To demonstrate the efficiency of Re₂O₇ in the dienone-phenol rearrangement, a direct comparison with previous protocols was carried out using cyclohexadienones 1j and 1k as the substrates (Scheme 2). In Kita's report,¹⁰ spiro-cyclohexadienone 1j could be transferred to chromane 2j quantitatively, promoted by an excess amount of montmorillonite K10 (Scheme 2, eqn (1)). Pleasingly, under the effect of catalytic Re₂O_7, chromane 2j could be furnished in a comparable yield. Furthermore, the rearrangement of cyclohexadienone 1k led to three regioisomers 2ka, 2kb and 2kc in a 1 : 2.5 : 1.6 ratio under the effect of Ac₂O/H₂SO₄ as a result of competitive [1,2]-shift and [3,3]-rearrangement of allyl (Scheme 2, eqn (2)).¹¹ In sharp contrast, under our reaction conditions only the [3,3]-shift product 2kb and 2kc¹² were obtained in a 95% combined yield and 3 : 5 ratio, showing that the reaction pathway was greatly influenced using Re₂O₇ as the catalyst.

Scheme 2 Other substrates.

Conclusions

The Re₂O₇ catalyzed dienone-phenol rearrangement reaction has been developed. Multi-substituted phenols can be conveniently prepared in good to excellent yields using this catalytic procedure. In addition, the [3,3]-shift product is exclusively formed under the effect of Re₂O₇ when the migratory group is an allyl group. The highly catalytic efficiency of Re₂O₇ in the dienone-phenol rearrangement is attributed to the moderate Lewis acidity of Re₂O₇ and its ability to stabilize the putative phenyl cation intermediate of the reaction.

Acknowledgements

We are grateful for financial support from the National Natural Science Foundation of China (grand no. 21202187, 21372239).

Notes and references

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12. The structure of 2kb and 2kc was determined by NMR analysis, see ESI.†.

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Footnotes

† Electronic supplementary information (ESI) available: General experimental procedures and spectroscopic data for all compounds. For ESI or other electronic format see DOI: 10.1039/c5ra04931h

‡ These two authors contributed equally.

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