One-pot synthesis of multifunctionalized m-terphenyls
Graphical abstract
Introduction
Functionalized phenyls are attractive scaffolds for synthetic material sciences and drug discovery.1 To achieve these diversified frameworks bearing different substituted groups, various kinds of approaches have been established in the past decades.2 Some functional profiles clearly indicate that polyaryl phenyl is a privileged core for synthetic design.3 Among those methods, transition metal mediated reactions have been proven to be one of the most popular tools to construct the skeleton, especially Suzuki–Miyaura cross-coupling4 or Reppe cyclotrimerization.5 Efficient synthesis of terphenyls is an important issue for organic chemists.6, 7 Some m-terphenyls are found in natural products, such as dictyoterphenyl A,3j trifucol,8, 8(a) macranthol,8b dunnialol,8c and mulberrofuran R (Fig. 1).8d
We previously reported the one-pot method for synthesizing various carbon-skeletons with different aryl substituents based on chalcones 1, such as monocyclic oxetanes and cyclohexanes, tricyclic benzo[g]indazoles, and tetracyclic azahomoisotwistanes.9 To explore the synthetic applications of substituted chalcones 1, a transition metal-free route is employed to create the skeleton of m-terphenyls 5 and 6 via a one-pot NaH-mediated tandem annulation of chalcones 1 and allyl sulfone 2. Substituted chalcones 1 are easily prepared via Claisen–Schmidt condensation of substituted aldehydes 3 (R2 group) with methyl ketones 4 (R1 group) (Scheme 1).
Section snippets
Results and discussion
To initiate the synthetic work, several chalcones 1 were prepared in nearly quantitative yields according to our recent literature methods from the NaOH-mediated Claisen–Schmidt condensation of substituted methyl ketones 4 with aldehydes 3 under the methanolic refluxing solution.9 Next, synthesis of allyl sulfone 2 was achieved from nucleophilic substitution of allyl bromide with TolSO2Na in quantitative good yields. In an attempt to develop a practical protocol of m-terphenyl with the
Conclusion
In summary, we have successfully presented a novel and one-pot cascade [C3+C3] methodology for synthesizing a series of m-terphenyls 5a–v and sulfonyl m-terphenyls 6a–v via two important steps: (1) 1,2- addition or 1,4-addition of chalcones 1a–v with the α-carbanion intermediate A of allyl sulfone 2 and (2) removal of TolSO3Na/1,6-electrocyclization/aromatization of possible intermediates (for skeleton 5) or proton exchange/six-membered ring formation/dehydration/aromatization of several
General
All other reagents and solvents were obtained from commercial sources and used without further purification. Reactions were routinely carried out under an atmosphere of dry air with magnetic stirring. Products in organic solvents were dried with anhydrous MgSO4 before concentration in vacuo. Melting points were determined with a SMP3 melting apparatus. 1H and 13C NMR spectra were recorded on a Varian INOVA-400 spectrometer operating at 200/400 and at 100 MHz, respectively. Chemical shifts (δ)
Acknowledgements
The authors would like to thank the National Science Council of the Republic of China for its financial support (NSC 102-2113-M-037-005-MY2).
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