3-(Biphenyl)acrylates by One-Pot Suzuki Cross Coupling–Wittig Olefination Reactions

: 3-(Biphenyl)acrylates are prepared in good yield by one-pot Suzuki cross-coupling (Wittig olefination reactions). The central building blocks are 4-formyl- and 3-formylphenylboronic acids and the stabilized (carbomethoxymethylene)triphenylphosphorane. Examples of one-pot Suzuki– double Wittig combinations are also shown.


Introduction
One-pot transformations can significantly reduce the time and resources needed for the experimental work-up as compared to carrying out these reactions consecutively. Important for such one-pot transformations is the compatibility of two or more reactions with one set of reaction conditions, including a common solvent system. Carbalkoxymethylenetriphenylphosphoranes (1) as stabilized phosphoranes are reactive enough to undergo Wittig olefination reactions with both aldehydes and ketones but are not sensitive towards water (and oxygen/air) and tolerate a number of solvent systems that include THF, DMSO, DME and CHCl3, aqueous systems [1], aqueous/organic solvent mixtures and even solventless conditions [2]. This makes it possible to employ these phosphoranes to run Wittig olefination reactions in parallel with C-C cross-coupling reactions, such as Suzuki [1,3], Heck [4] or Sonogashira [5] reactions in one pot. In the following, we explored the one-pot Wittig olefination-Suzuki cross-coupling reaction utilizing (carbomethoxymethylene)triphenylphosphorane (1a) to substituted 3-(biphenyl)acrylates (2) (Figure 1). This includes combinations where a Suzuki reaction is accompanied by two Wittig olefination reactions and where a hydrolysis as a follow reaction in one pot is incorporated. The work is seen as an expansion of the scope of one-pot Suzuki-Wittig olefination reactions, published by us earlier [3].

General Remarks
Melting points were measured on a Stuart SMP 10 melting point apparatus and were uncorrected. Infrared spectra were measured with a Thermo/Nicolet Nexus 470 FT-IR ESP spectrometer and a Perkin Elmer Spectrum Two spectrometer. 1 H and 13 C NMR spectra were recorded with a Varian 400 NMR spectrometer (1H at 395.7 MHz, 13 C at 100.5 MHz). The assignments of the carbon signals were aided by Distortionless Enhancement by Polarisation Transfer (DEPT) 90 and DEPT 135 experiments. The chemical shifts are relative to TMS (solvent CDCl3, unless otherwise noted). Column chromatography, where necessary, was performed on recycled silica gel (S, 0.063 mm-0.1 mm, Riedel de Haen and Merck grade 9385).

3-([1,1′-Biphenyl]-4-yl)acrylates find a number of uses. For instance, 3-(4′-alkoxy-[1,1′-biphenyl]-4-yl)acrylates have been presented as heat-resistant UV absorbers
When mixtures of bromoarenes (5, 10), formylphenylboronic acids, e.g., 14, as central building blocks, and phosphorane 1a are heated in the presence of Pd(PPh3)2Cl2/PPh3 with Na2CO3 as base in a solvent mixture of DME/H2O, methyl 3-([1,1′-biphenyl]-4-yl)acrylates 2 are produced in acceptable yields (Scheme 2). Bromoarenes clearly give equally good results as iodoarenes [3]. In all cases, the E-olefin is formed as the main isomer (E/Z > 95/5), as evidenced by the coupling constant of the acrylic protons ( 3 J = 16.0 Hz). Work-up is facile, with the cooled reaction mixture submitted to column chromatography on silica gel after aq. extraction. Care should be taken of the fact that some of the more symmetric 3-([1,1′-biphenyl]-4-yl)acrylates (2) are sparingly soluble in many solvents. In some instances, such as in the case of the preparation of 2e and 20, this can lead to a facilitation of the work-up as a simple filtration of the product directly from crude organic mixture is possible after aq. extraction of the reaction mixture. Due to the sparing solubility of some of the products in CH2Cl2, an eluant mixture of CH2Cl2/CHCl3 was used for the chromatographic separations. It is possible to use both bromobenzaldehydes (11/18) and formylphenylboronic acid (14) as building blocks in the same reaction and perform a Suzuki cross-coupling/double Wittig olefination to prepare dimethyl biphenyl-diacrylates. Again, the E,E-isomers are formed, predominately (E/Z > 95/5) (Scheme 3).   Finally, the one-pot Suzuki-Wittig reaction can be augmented by a hydrolysis step. Previously, we have communicated a Wittig olefination hydrolysis one-pot transformation of benzaldehydes to cinnamic acids [15], where the solvent system was not changed during the reaction but the temperature was elevated towards the end of the preparation. In the current case, the advertised solvent system-aq. Na2CO3/DME-was maintained during the one-pot Wittig-Suzuki reaction, where at the end of the preparation NaOH was added to the system and the reaction temperature increased (Scheme 6).

Conclusions
In conclusion, it can be said that alkyl 3-(biphenylacrylates) can be prepared facilely by one-pot Wittig olefination-Suzuki cross-coupling reaction, using either formylphenylboronic acids or bromobenzaldehydes, or both, as central building blocks. The use of bromoarenes leads to equally high yields as the use of iodoarenes. The reaction can be augmented by subsequent hydrolysis, also in one pot, to yield 3-(biphenyl)acylic acids. Similar one-pot reactions can be performed with bromocinnamaldehydes as the central building block to give 5-(biphenyl)penta-2,4-dienoates.
Author Contributions: Conceptualization, supervision, synthetic investigation, writing-original draft preparation, T.T.; synthetic investigation, A.H.; analytical work, V.P. All authors have read and agreed to the published version of the manuscript.