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. 2023 Dec 1;14(1):7936.
doi: 10.1038/s41467-023-43200-7.

Selective ring expansion and C-H functionalization of azulenes

Sangjune Park  1   2 , Cheol-Eui Kim  1   2 , Jinhoon Jeong  3   4 , Ho Ryu  3   4 , Chanyoung Maeng  1   2 , Dongwook Kim  3   4 , Mu-Hyun Baik  5   6 , Phil Ho Lee  7   8   9
Affiliations

Selective ring expansion and C-H functionalization of azulenes

Sangjune Park et al. Nat Commun. .

Abstract

We report a transition metal-catalyzed ring expansion of azulene that can be contrasted with C-H functionalization. This study represents the first example of the successful ring expansion of azulene using Cu(hfacac)2 (hfacac: hexafluoroacetylacetonate) with a diazo reagent. This result is notable for extending the Buchner reaction, previously limited to benzenoid aromatics, to nonbenzenoid compounds. The chemoselectivity of the reaction can be directed towards C-H functionalization by substituting the Cu catalyst with AgOTf. This approach does not require the addition of phosphine, NHC, or related ligands, and prefunctionalization of azulenes is unnecessary. Furthermore, the method exhibits excellent functional group tolerance, allowing for the synthesis of a wide range of 6,7-bicyclic compounds and C-H functionalized azulenes. We also present a theoretical study that explains the experimental observations, explaining why copper afford the ring expansion product while silver forms the C-H alkylation product.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Transformations of Azulenes.
A Dipolar properties of azulenes and general azulene functionalizations. B Silver(I)-catalyzed C(sp2)–C(sp3) coupling of azulenes in this work. C Ring expansion reaction of benzenoid aromatic compounds (Buchner reaction). D Selective ring expansion and C–H alkylation of azulene, which is non-benzenoid aromatic compound.
Fig. 2
Fig. 2. Scope of azulenes and diazoesters in ring expansion reactiona.
a1 (0.2 mmol, 1.0 equiv), 2 (1.0 equiv), and Cu(hfacac)2 (2.0 mol %) were used in DCE (4.0 mL) at room temperature for 30 min under a N2 atmosphere. bDiazo compound (1.5 equiv) was used. cDiastereomeric ratio. dCu(hfacac)2 (4.0 mol %) was used. eDioxane was used as a solvent.
Fig. 3
Fig. 3. Scope of azulenes and diazoesters in C−H alkylationa.
a1 (0.2 mmol, 1.0 equiv), 2 (1.5 equiv), and AgOTf (2.0 mol %) were used in DCE (4.0 mL) at 25 °C for 1 h under a N2 atmosphere. b1a (2.0 equiv) and 2a (0.2 mmol, 1.0 equiv) were used. 1,3-Dialkylated product was obtained in 5% yield. cReaction temperature: 50 °C. dMethyl phenyl diazoacetate (3.0 equiv) was used. eReaction temperature: 70 °C. fDiastereomeric ratio.
Fig. 4
Fig. 4. A Proposed mechanism.
A Proposed mechanism of ring expansion and C–H alkylation pathways. B Computed reaction profiles of ring expansion and C–H alkylation pathways catalyzed by either Cu(hfacac)2 or AgOTf. The dotted lines indicate a minor pathway.
See this image and copyright information in PMC

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