One-pot synthesis of m-terphenyl-2'-carbaldehydes

An efficient and straightforward one pot synthesis of m -terphenyl-2'-carbaldehyde derivatives via cascade reaction of aryl Grignard magnesium bromide with 1,3-dichloroiodobenzene is described. Via the reactions three carbon-carbon bonds are constructed and m-terphenyls are obtained in good yields


Introduction
The m-terphenyl moiety is an important structure for concave molecules. 1If a functional group is introduced into the 2'-position of a m-terphenyl, the outer benzene rings shield this functional group.The shielding is extremely efficient if the outer benzene rings carry further substituents in the ortho positions (Figure 1).

Figure 1
Some m-terphenyls with acidic substituents in the 2'-position have been introduced as selective proton donors for diastereoselective and regioselective protonations. 2In addition, these compounds are useful intermediates for constructing optical active cyclophans, 3,4 cyclic ketons, [5][6][7][8] dendrimers, 9 and liquid crystals. 10Thus, several approaches have been developed for their synthesis.Hart developed a method for the synthesis of m-terphenyls that may be substituted in all orthopositions of the outer aryl rings. 11,12The key intermediate of Hart's method is the 2'-Grignard reagent, which can be quenched by iodine to give the 2'-iodide substituted compound.Starting from the iodide compound, various 2'-substituted m-terphenyls have been synthesized via the lithium derivative.2][13] Furthermore, most reports on the synthesis of 2'-substituted m-terphenyl derivatives are limited to the two step procedure (Scheme 1).In the current study, we examine a facile one pot synthesis of m-terphenyl-2'-carbaldehydes starting from 1,3-dichloroiodobenzene. Cascade reaction of aryl magnesium bromides with 1,2,3-trihalobenzene 1 followed by quenching with electrophile gives m-terphenyls 2 in a one pot reaction.By varying the substituents of the aryl groups of the Grignard reagent, different mterphenyl derivatives can be obtained in good yields.

Results and Discussion
Our initial attempts to test the feasibility of this reaction employed readily accessible 1,3dichloroiodobenzene and phenyl magnesium bromide in THF which afforded 2,3-diphenyl magnesium bromide reagent.Then the addition of ethyl formate gave the desired product 2a in 81% yield (Table 1).We next investigated the scope of the reaction using aryl magnesium bromides with diverse substituents at ortho-, meta-and para-positions.As a result, m-terphenyl-2'-carbaldehyde derivatives were obtained in good yields (Table 1).The structures of the isolated products were confirmed by mp, IR, 1 HNMR, 13 CNMR and elemental analysis.
It should be mentioned that ortho-substituted m-terphenyls which can be further functionalized or converted to new functional groups are very important.For example, methoxy groups of the rings can be converted easily to phenol derivatives and bridged to finally give bimacrocylic concave m-terphenyl structures.Further investigation on involving these mterphenyls in the polymer backbones is under investigation.

Conclusions
summary, we have developed an efficient and straightforward one pot approach to mterphenyl-2'-carbaldehyde derivatives using readily accessible starting materials.To the best of our knowledge it is the first report on the one pot synthesis of m-terphenyl-2'-carbaldehyde derivatives.

Experimental Section
General Procedures.All substrates were purchased from Merck Company.The reactions involving organomagnesium halide reagents were carried out under argon.Solvents were dried by standard methods.Melting points were determined using a Gallenkamp melting point apparatus and are uncorrected. 1H NMR and 13 C NMR spectra were recorded on a Brucker FT-400 MHz in CDCl 3 .The Infrared absorption spectra were recorded on a FTIR Bruker-Tensor 270 spectrophotometer.Elemental analyses were carried out with Heareus CHN-RAPID instrument.

General procedure for the synthesis of m-terphenyl-2'-carbaldehyde derivatives 2a-2f
To a stirred aryl magnesium bromide solution (prepared from aryl bromides (40 mmol) and Mg (40 mmol) in dry THF (40 mL)) was added slowly 1,3-dichloroiodobenzene (4 mmol) in THF (10 mL) under argon and the mixture was refluxed for 20-25 hrs.Then ethyl formate (5 mL) was added and the reaction was refluxed for 30 min.The reaction mixture was then cooled with ice, quenched with dilute HCl (30 mL) and extracted with diethyl ether (3×50 mL).Combined organic layers were dried over MgSO 4 and concentrated in vacuo.The resulting residue was purified by recrystallization or column chromatography (diethyl ether-hexane, 20%) to afford the corresponding aldehydes.