Synthesis of Conjugated Tri(hetero)aryl Derivatives Based on One-Pot Double Suzuki-Miyaura Couplings Using Bifunctional Dipotassium Phenylene-1,4-Bis(Trifluoroborate)

Abstract

An efficient one-pot double Suzuki-Miyaura cross-­coupling reaction between bifunctional phenylene-1,4-bis(potassium trifluoroborate) and aryl and heteroaryl bromides is described. The scope and limitations of this methodology that enables the synthesis of tri(hetero)aryl derivatives, potentially useful as drugs and in the field of materials science, have also been probed.

Key words

terphenyls - arylation - cross-coupling - epoxides - ­Suzuki-Miyaura reaction

References and Notes

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17

Different solvent mixtures (e.g., MeOH-H₂O, 10:1; DMF-H₂O, 10:1; dioxane-H₂O, 5:1), higher amount of H₂O (e.g., THF-H₂O, 1:1), other Pd(II) precatalysts [e.g., Pd(OAc)₂] and higher temperatures proved to be less effective and provided poor yield (15-57%) of product 4a. When Cs₂CO₃ was used as a base instead of K₂CO₃, the yield of 4a was 75%, all other conditions being identical. Comparable results in terms of yield and reaction time were also obtained by employing up to 6 equiv of K₂CO₃.

21

Similarly, the tetraazaterphenyl derivative 4o revealed an absorption at λ_max = 279 (DMSO) and fluorescence emission maximum at λ_max = 428 nm (see ref. 20b).

22

The E configuration of double bonds in terphenyl 4q was ascertained from 2D NOESY correlations.

26

In contrast to what was observed in the one-pot coupling reaction of N-Boc-2,5-dibromopyrrole with two different boronic acids (see ref. 25), in our case, the addition up to 3 equiv of LiCl had a detrimental effect on the yield of 4s which, indeed, dramatically decreased to 15%. Further investigations are currently underway to find more general conditions for effecting unsymmetrical double SM couplings employing salt 2 or different bifunctional derivatives and results will be reported in due course.

27

General Procedure for the Synthesis of Compounds 4a-s: To a suspension of dipotassium phenylene-1,4-bis-(trifluoroborate) (2; 1.0 mmol) in THF-H₂O (5.0 mL + 1.0 mL), K₂CO₃ (3 mmol), aryl(heteroaryl) bromide (2.1 mmol) (note: for the synthesis of compound 4s, 1.0 mmol of both 3s and 3b were employed instead) and PdCl₂(dppf)˙CH₂Cl₂ (5 mol%) were sequentially added under an argon atmosphere. After the mixture was stirred at 50 ˚C for 24 h in a closed reactor, the resulting solution was cooled to r.t., diluted with brine (10 mL) and extracted with Et₂O (3 × 10 mL). The solvent was finally stripped off in vacuo and the crude product so obtained was purified by silica gel column chromatography (see the Supporting Information for details) to provide the desired tri(hetero)aryl derivative.