Elsevier

Tetrahedron

Volume 69, Issue 46, 18 November 2013, Pages 9616-9624
Tetrahedron

One-pot synthesis of multifunctionalized m-terphenyls

https://doi.org/10.1016/j.tet.2013.09.036Get rights and content

Abstract

A facile one-step synthetic protocol toward multifunctionalized m-terphenyls 5 and sulfonyl m-terphenyls 6 is developed from substituted chalcones 1 and allyl sulfone 2 in good yields via a [3C+3C] annulation. The NaH-mediated annulation features transition metal catalyst-free condition. Chalcones 1 with the functional groups tolerance are easily prepared via Claisen–Schmidt condensation of substituted benzaldehydes 3 with acetophenone 4 in a qualitative yield under an aqueous alkaline methanolic solution.

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 5av and sulfonyl m-terphenyls 6av via two important steps: (1) 1,2- addition or 1,4-addition of chalcones 1av 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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