Phospha-adamantanes as ligands for organopalladium chemistry: aminations of aryl halides

The use of Pd₂dba₃·CHCl₃ and 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phospha-adamantane has been shown to facilitate the effective amination of aryl halides with aromatic or aliphatic amines in high yields.     

Palladium-catalyzed aminosulfonylation of aryl halides

The palladium-catalyzed three-component coupling of aryl iodides, sulfur dioxide, and hydrazines to deliver aryl N-aminosulfonamides is described. The colorless crystalline solid DABCO·(SO(2))(2) was used as a convenient source of sulfur dioxide. The reaction tolerates significant variation of both the aryl iodide and hydrazine coupling partners.     

Palladium-catalyzed direct arylation of nitro-substituted aromatics with aryl halides

Direct arylation reactions of nitrobenzenes and aryl halides occur in good yield and high ortho regioselectivity. These reactions can be performed on gram scale with as few as 3 equiv of the nitro arene relative to the aryl halide. The synthetic utility of this method is demonstrated via rapid synthesis of a Boscalid intermediate.     

Palladium-catalyzed amidation of aryl halides using 2-dialkylphosphino-2'-alkoxyl-1,1'-binaphthyl as ligands

Palladium-catalyzed intermolecular C-N bond-forming reactions between aryl halides and amides are described using 2-dialkylphosphino-2'-alkoxyl-1,1'-binaphthyl, which is both bulky and electron-rich, as the ligand. A variety of amides, including aliphatic and aromatic primary amides, lactams, and carbamates, were viable substrates for the amidation, which exhibited good functional group compatibility. By tuning the substituents at the 2,2'-position of 1,1'-binaphthyl of the ligand, the palladium-catalyzed amidation of bulky aryl halides was realized and this coupling reaction was used to synthesize 2-amino-2'-methoxy-1,1'-binaphthyl in high yield.     

Palladium-catalyzed cross-coupling of cyclopropanols with aryl halides under mild conditions

Intra- and intermolecular palladium-catalyzed cross-coupling of cyclopropanols with aryl halides can be achieved in good yields under mild conditions.     

Palladium-catalyzed carbonylative coupling of pyridine halides with aryl boronic acids

The carbonylative Suzuki cross-coupling of a variety of mono-iodopyridines and bromopyridines (1a,b, 3a-c, 5) catalyzed by palladium-phosphane systems has been studied to prepare benzoylpyridine derivatives (2, 4, 6). The selectivity and the rate of the reaction are highly dependent on the reaction conditions, i.e. nature of the palladium catalyst precursor, solvent, temperature and CO pressure. The main side-products arise from direct, non-carbonylative cross-coupling. Under optimized conditions, benzoylpyridines are recovered in high yields (80-95%). The order of reactivity decreases from iodo- to bromopyridines and from 2-, 4- to 3-substituted halopyridines. The reactivity of dihalopyridines has been investigated; 2,6-dibromopyridine (7) and 3,5-dibromopyridine (11) are selectively transformed into either the corresponding benzoyl-phenylpyridine (8, 12) or the corresponding dibenzoylpyridine (9, 13). Dissymmetric 2,5-dihalopyridines (15a,b) are transformed into 2-benzoyl-5-bromopyridine (16) or 2,5-dibenzoylpyridine (17) in high yields.     

Palladium-catalyzed cross-coupling of benzyl thioacetates and aryl halides

A method for preparing benzyl aryl thioethers utilizing an in situ deprotection of benzyl thioacetates as an alternative to free thiols as starting materials has been developed and optimized. Good to excellent yields of diverse benzyl aryl thioethers are obtained with air-stable, odor-free, and easy to prepare thioesters. A one-pot protocol for forming benzyl aryl thioethers from a benzyl halide, potassium thioacetate, and an aryl bromide has also been demonstrated.     

Palladium-catalyzed cross-coupling reaction of tricyclopropylbismuth with aryl halides and triflates

The palladium-catalyzed cross-coupling reaction of tricyclopropylbismuth with aryl and heterocyclic halides and triflates is reported. The reaction tolerates numerous functional groups and does not require anhydrous conditions. The method was successfully extended to the cross-coupling of triethylbismuth.     

Palladium-catalyzed decarboxylative coupling of potassium nitrophenyl acetates with aryl halides

A palladium-catalyzed decarboxylative cross-coupling of potassium 2- and 4-nitrophenyl acetates with aryl chlorides and bromides has been developed. Because the nitro group can be readily converted to many other functional groups, the new reaction provides a useful method for the preparation of diverse 1,1-diaryl methanes and their derivatives.     

Palladium-catalyzed coupling of ammonia and lithium amide with aryl halides

A mild, palladium-catalyzed coupling of aryl halides with ammonia or lithium amide to form primary arylamines as the major product is described. These reactions occurred with excellent selectivity for formation of the primary arylamine over formation of the diarylamine (9.5:1 to over 50:1 ratios of arylamine to diarylamine). In addition, the first organopalladium complex with a terminal -NH2 ligand has been isolated. This complex reductively eliminates to form arylamines.     

Palladium-catalyzed cross-coupling reactions of 2-indolyldimethylsilanols with substituted aryl halides

[reaction: see text] A mild and general cross-coupling reaction of 2-indolylsilanols has been developed. The experimental variables that lead to successful coupling are (1) the use of sodium tert-butoxide as the activator, (2) the use of copper(I) iodide in stoichiometric quantities, and (3) the use of Pd2(dba)3.CHCl3 as the catalyst. Under these conditions N-(Boc)-2-indolyldimethylsilanol reacts with a variety of aromatic iodides to afford the coupling products in good yield (70-84%).     

Palladium-catalyzed regiocontrolled alpha-arylation of trimethylsilyl enol ethers with aryl halides

Inter- and intramolecular arylations of trimethylsilyl enol ethers with aryl halides are accomplished regiospecifically in the presence of a palladium catalyst and tributyltin fluoride in refluxing benzene or toluene. The optimal catalyst system called for the use of Pd2(dba)3 and tri-tert-butylphosphine in ca. 1:2 ratio. Aryl iodides, bromides, and chlorides are all effective arylation partners in this reaction. [reaction: see text]     

Palladium-catalyzed benzylic direct arylation of benzyl sulfones with aryl halides

An effective palladium catalyst system for the direct arylation of benzyl sulfones with aryl halides has been developed. The catalytic reaction provides a facile route to diarylmethyl sulfones. The products can be transformed further via desulfonylative functionalization mediated by aluminum compounds.     

Palladium-catalyzed amination of aryl halides on solid support

[reaction: see text] The first examples of the Pd(0)-catalyzed amination of aryl halides using Rink-resins as nitrogen source are described. Pd(2)dba(3)/BINAP/NaO-t-Bu was found to be the most efficient catalyst/base system, while a solvent mixture of dioxane and tert-butyl alcohol was shown to enhance the selectivity toward the desired monoarylation. Moderate to good yields and excellent purities of the amination products were found with electron-poor aryl halides, while electon-rich aryl halides failed to react under these conditions.     

Palladium-catalyzed intermolecular coupling of aryl halides and amides

[formula: see text] The first general intermolecular C-N bond-forming reactions between aryl halides and amides were realized using a palladium catalyst with Xantphos as the ligand. Aryl triflates, carbamates, and sulfonamides are also viable substrates for the amidations, which proceed at 45-110 degrees C with 1-4 mol% of Pd catalyst in 66-99% yields and exhibit good functional group compatibility.     

Discovery and synthesis of novel phosphine-based ligands for aryl aminations

Three families of ligands were prepared for use in Pd-catalyzed aryl aminations and possibly other Pd-catalyzed reactions. The first series is derived from diarylsulfones, the second from trityl imidazole, and the third from 2-bromobenzophenone. While these ligands were not very general in terms of substrate scope, they do work fairly well under certain specific conditions. Additionally, the preparation of these ligands is amenable to bulk synthesis.     

Palladium-catalyzed direct arylation of aryl(azaaryl)methanes with aryl halides providing triarylmethanes

Direct arylation of aryl(azaaryl)methanes with aryl halides takes place at the benzylic position in the presence of a hydroxide base under palladium catalysis to yield triarylmethanes.