Palladium-Catalyzed Conversion of Aryl and Vinyl Triflates to Bromides and Chlorides

Abstract

The palladium-catalyzed conversion of aryl and vinyl triflates to aryl and vinyl halides (bromides and chlorides) has been developed using dialkylbiaryl phosphine ligands. A variety of aryl, heteroaryl and vinyl halides can be prepared via this method in good to excellent yields.Aryl halides are ubiquitous synthetic intermediates in organic chemistry that are used for numerous transformations. 1 They are also present in a wide variety of natural products, pharmaceuticals and agrochemicals. 2 Therefore, the development of general and regioselective methods for the preparation of functionalized aryl halides is of great importance. Sulfonate esters, often referred to as pseudo-halides, can be employed as alternatives to aryl halides in many cross-coupling reactions. 3 Such pseudo-halides, however, cannot be used as precursors for the generation of free radicals 4 or organometallic reagents. 1 Traditional methods for the synthesis of aryl halides (bromides or chlorides) from phenols require either forcing conditions 5 or multi-step procedures. 6 Herein, we report the first example of palladium-catalyzed direct conversion of readily available aryl sulfonate esters to aryl bromides and chlorides.Although a catalytic method has not yet been reported, several mechanistically related metal-mediated carbon-halogen bond-forming processes have been published. 7 For example, the reductive elimination of aryl halides from Pt(IV), 8 Ni(III), 9 Pd(IV), 10 and Pd(III) 11 has been demonstrated. In addition, the reductive elimination of aryl halides from arylpalladium(II) halide complexes in the presence of a large excess of P(t-Bu) 3 has been reported. 12,13 A number of copper 14 -and nickel 15 -mediated halide exchange reactions have also been developed in which carbon-halogen reductive elimination processes are proposed to take place.Despite these advances in aryl-halide bond formation, to the best of our knowledge, there are few examples of the catalytic conversion of an aryl sulfonate to an aryl halide 16 including the ruthenium-catalyzed conversion of 2-naphthyl triflate to 2-bromonaphthalene 16b and our recent report of the palladium-catalyzed conversion of aryl triflates to aryl fluorides. 17 This prompted us to query whether we could uncover a catalytic process to convert aryl triflates into corresponding aryl bromides and chlorides; and results are disclosed herein.Catalysts based on dialkylbiaryl monophosphines 1-4, which have been successfully utilized as ligands in numerous transformations, 17,18 were initially examined for the conversion of sbuchwal@mit.edu.

Mechanistic insights on the Pd-catalyzed addition of C–X bonds across alkynes – a combined experimental and computational study

“…avoiding the β-H elimination). 28–32 Advances in substrate design as well as catalyst development by the Lautens group recently allowed for the reductive elimination of C(sp 2 )–X (X = I, Br, Cl) from Pd( ii ) in the carbohalogenation of alkynes (Scheme 1). 16 Interestingly, the synthetic protocol was compatible with ether, alkyl and amine tethers (Scheme 1, 1 ), but the use of an amide tether ( 4 ) required an alternative synthetic route via the chlorocarbamoylation of alkynes.…”

An Improved Synthesis of BrettPhos‐ and RockPhos‐Type Biarylphosphine Ligands

“…For example, the combination of 1 with a palladium source provides a catalyst system capable of effecting a Pd-catalyzed fluorination of aryl triflates, [6] among other important transformations. [7] A similar Pd system based on 2 allows for the intermolecular arylation of secondary and primary alcohols. [8] BrettPhos, 3 , has been used for the Pd-catalyzed amination of aryl electrophiles, [9] as well as the Pd-catalyzed trifluoromethylation of aryl chlorides.…”

Studies toward welwitindolinones: formal syntheses of N-methylwelwitindolinone C isothiocyanate and related natural products

“…38,39 Hayashi and co-workers reported a ruthenium catalyzed procedure of converting vinyl triflates to vinyl chlorides, 40 and Buchwald recently described a similar process that was catalyzed by palladium. 41 Although the vinyl triflate 75 was readily prepared in 80% yield by sequential reaction of 39 with LiHMDS and then Comins’ reagent, 42 we were unable to identify any conditions that enabled conversion of 75 into 76 . Inasmuch as Garg recently converted a closely related ketone into a vinyl halide using such a two-step method in his synthesis of 3 , 6b this failure again highlights the diabolical vagaries inherent in the chemistry of the compact welwitindolinone skeleton.…”