P(i-BuNCH2CH2)3N: an effective ligand in the palladium-catalyzed amination of aryl bromides and iodides

It is shown that the bicyclic triaminophosphine P(i-BuNCH2CH2)3N serves as an effective ligand for the palladium-catalyzed amination of a wide array of aryl bromides and iodides. Other bicyclic or acyclic triaminophosphines, even those of similar basicity and/or bulk, were inferior.     

Scope and limitations of Pd2(dba)3/P(i-BuNCH2CH2)3N-catalyzed Buchwald-Hartwig amination reactions of aryl chlorides

Proazaphosphatrane ligands in combination with Pd(2)(dba)(3) generate highly active catalysts for Buchwald-Hartwig amination of aryl chlorides. In particular, commercially available P(i-BuNCH(2)CH(2))(3)N is a highly general and efficient ligand, allowing the coupling of an electronically diverse set of aryl chlorides, including chloropyridines, with a wide variety of amines using 1 mol % of Pd at 100 degrees C. Either a 1:1 or 2:1 ratio of ligand to Pd was found to be effective. This catalyst system performs exceptionally well for sterically hindered substrates, even with only 0.25 mol % of Pd. It is shown that NaOH can also be used as the base (instead of NaO-t-Bu) allowing functionalized substrates to participate in these reactions.     

P(i-BuNCH2CH2)3N: an efficient ligand for the direct alpha-arylation of nitriles with aryl bromides

A new catalyst system for the synthesis of alpha-aryl-substituted nitriles is reported. The bicyclic triaminophosphine P(i-BuNCH(2)CH(2))(3)N (1b) serves as an efficient and versatile ligand for the palladium-catalyzed direct alpha-arylation of nitriles with aryl bromides. Using ligand 1b, ethyl cyanoacetate and primary as well as secondary nitriles are efficiently coupled with a wide variety of aryl bromides possessing electron-rich, electron-poor, electron-neutral, and sterically hindered groups.     

Efficient palladium-catalyzed amination of aryl chlorides using di(dicyclohexylamino)phenylphosphine as a PN2 ligand

The palladium-catalyzed amination of a variety of aryl chlorides has been accomplished by using di(dicyclohexylamino)phenylphosphine (1) as a bulky electron-rich monoaryl phosphine ligand. The optimized condition for the palladium-catalyzed amination of aryl chloride is the followings: aniline (3.0 mmol, 1.0 equiv), chlorobenzene (3.15 mmol, 1.05 equiv), ligand 1 (1 mol %, 0.03 mmol), KO^tBu (4.5 mmol, 1.5 equiv), Pd₂(dba)₃ (1 mol %, 0.03 mmol), and toluene as solvent at reflux temperature. We report on couplings of various amines or chloroamines with chlorobenzenes and heteroaryl chloride.     

Pd2(dba)3/P(i-BuNCH2CH2)3N-catalyzed Stille cross-coupling of aryl chlorides

[reaction: see text] The Pd(2)(dba)(3)/P(i-BuNCH(2)CH(2))(3)N (1d) catalyst system is highly effective for the Stille cross-coupling of aryl chlorides with organotin compounds. This method represents only the second general method for the coupling of aryl chlorides. Other proazaphosphatranes possessing benzyl substituents also generate very active catalysts for Stille reactions. Noteworthy features of the method are: (a) commercial availability of ligand 1d, (b) the wide array of aryl chlorides that can be coupled, and (c) applicability to aryl, vinyl, and allyl tin reagents.     

Transition metal dinitrogen complexes supported by a versatile monoanionic [N2P2] ligand

By adjusting to the steric and electronic requirements of differing metal centers, the new multidentate monoanionic ligand [N(2)P(2)] has demonstrated a unique ability to stabilize a range of transition metal-dinitrogen complexes in a variety of oxidation states and coordination geometries.     

Zur solvensfreien Darstellung von Tetramethylammoniumsalzen: Synthese und Charakterisierung von [N(CH3)4]2[C2O4], [N(CH3)4][CO3(CH3)], [N(CH3)4][NO2], [N(CH3)4][CO2H] und [N(CH3)4][O2C(CH2)2CO2(CH3)]

Solvent-free Synthesis of Tetramethylammonium Salts: Synthesis and Characterization of [N(CH₃)₄]₂[C₂O₄], [N(CH₃)₄][CO₃CH₃], [N(CH₃)₄][NO₂], [N(CH₃)₄][CO₂H], and [N(CH₃)₄][O₂C(CH₂)₂CO₂CH₃] A general procedure to synthesize tetramethylammonium salts is presented. Several tetramethylammonium salts were prepared in a crystalline state by solvent-free reaction of trimethylamine and different methyl compounds at mild conditions: [N(CH₃)₄]₂[C₂O₄] (cubic; a = 1 114.8(3) pm), [N(CH₃)₄][CO₃CH₃] (P2₁/n; a = 813.64(3), b = 953.36(3), c = 1 131.3(4) pm, β = 90.03(1)°), [N(CH₃)₄][NO₂] (Pmmn; a = 821.2(4), b = 746.5(3), c = 551.5(2) pm), [N(CH₃)₄][CO₂H] (Pmmn; a = 792.8(7), b = 791.7(3), c = 563.3(4) pm) and [N(CH₃)₄][O₂C(CH₂)₂CO₂CH₃] (P2₁; a = 731.1(2), b = 826.4(3), c = 1 025.2(3) pm, β = 110.1(1)°). The tetramethylammonium salts were characterized by IR-spectroscopy and X-ray diffraction. The crystal structures of the methylcarbonate and the nitrite are described.     

Application of a new bicyclic triaminophosphine ligand in Pd-catalyzed Buchwald-Hartwig amination reactions of aryl chlorides, bromides, and iodides

The new bicyclic triaminophosphine ligand P(i-BuNCH2)3CMe (3) has been synthesized in three steps from commercially available materials and its efficacy in palladium-catalyzed reactions of aryl halides with an array of amines has been demonstrated. Electron-poor, electron-neutral, and electron-rich aryl bromides, chlorides, and iodides participated in the process. The reactions encompassed aromatic amines (primary or secondary) and secondary amines (cyclic or acyclic). It has also been shown that the weak base Cs2CO3 can be employed with ligand 3, allowing a variety of functionalized substrates (e.g., those containing esters and nitro groups) to be utilized in our amination protocols. This ligand provides a remarkably general, efficient, and mild palladium catalyst for aryl iodide amination. Although 3 is slightly air and moisture sensitive, easy procedures can be adopted that avoid the need of a glovebox. Comparisons of the efficacy of 3 in these reactions with that of the proazaphosphatrane P(i-BuNCH2CH2)3N (2) reveal that in addition to the opportunity for transannulation in 2 (but not in 3), other significant stereoelectronic contrasts exist between these two ligands which help account for differences in the activities of the Pd/2 and Pd/3 catalytic systems.     

P(MeNCH2CH2)3N: a highly selective reagent for synthesizing trans-epoxides from aryl aldehydes

In contrast to its acyclic analogue P(NMe2)3 (1), which in benzene at room temperature reacts with two aryl aldehyde molecules bearing electron-withdrawing groups to give the corresponding diaryl epoxide as an isomeric mixture (trans/cis ratios: 72/28-51/49), P(MeNCH2CH2)3N (2a) under the same reaction conditions is found to be a highly selective reagent that provides epoxides with trans/cis ratios as high as 99/1. These reactions are faster with 2a, because its phosphorus atom is apparently more nucleophilic than that in 1. Thus, it is found that 2a more easily forms 1:1 and 1:2 adducts with one or two molecules of aldehyde, respectively. These adducts apparently are intermediates in the formation of the product epoxide and the corresponding phosphine oxides of 1 and 2a.     

A Tri-Coordinate-Magnesium Silylamide Complex: {[(CH3)3Si]2N}2MgO(CH2CH2)2OMg{N[Si(CH3)3]2}2

The reaction of diethylmagnesium dioxane adduct solution with 1,1,1,3,3,3-hexamethyldisilazan ((CH₃)₃SiNHSi(CH₃)₃) gives {[(CH₃)₃Si]₂N}₂MgO(CH₂CH₂)₂OMg{N[Si(CH₃)₃]₂}₂ (1); this alkoxomagnesium silylamide in the solid state contains unprecedented three-coordinate magnesium and oxygen atoms.     

(t-Bu)2PN=P(i-BuNCH2CH2)3N: new efficient ligand for palladium-catalyzed C-N couplings of aryl and heteroaryl bromides and chlorides and for vinyl bromides at room temperature

By employing Pd(OAc)2, Cs2CO3, or NaOH, and the new ligand (t-Bu)2PN=P(i-BuNCH2CH2)3N (3a), an electronically diverse array of aryl bromides and chlorides possessing base-sensitive substituents (nitro, ester, and keto) provide coupling products with bulky aryl amines in good to excellent yields. Aryl halides possessing other functional groups including cyano, amino, trifluoromethyl, and phenol, coupled with equal ease, producing highly functionalized amines in good to excellent yields. Moreover, an aryl chloro group can be preserved in the presence of a bromo substituent under our reaction conditions. BOC-protected amines also participated efficiently. Heterocyclic bromides and chlorides underwent clean couplings with amines in excellent yields. An important strength of our protocol is the use of lower palladium loadings than those reported earlier, without compromising yields. The air-stable palladium complex (eta3-cinnamyl)PdCl.(3a) (5) was also employed successfully in C-N coupling reactions while the crotyl analogue was less efficacious. The 3a/Pd(OAc)2 catalyst system promotes, for the first time, efficient coupling of vinyl bromides with a variety of amines to produce imines and enamines at room temperature.     

2,6-Diazaspiro[3.3]heptanes: synthesis and application in Pd-catalyzed aryl amination reactions

A concise and scalable synthesis of a 2,6-diazaspiro[3.3]heptane building block is reported. The usefulness of this structural surrogate of piperazine is shown in arene amination reactions yielding a variety of N-Boc- N'-aryl-2,6-diazaspiro[3.3]heptanes.     

Synthesis of triamidoamine ligands of the type (ArylNHCH(2)CH(2))(3)N and molybdenum and tungsten complexes that contain an [ArylNCH(2)CH(2))(3)N]3- ligand

Aryl bromides react with (H(2)NCH(2)CH(2))(3)N in a reaction catalyzed by Pd(2)(dba)(3) in the presence of BINAP and NaO-t-Bu to give the arylated derivatives (ArylNHCH(2)CH(2))(3)N [Aryl = C(6)H(5) (1a), 4-FC(6)H(4) (1b), 4-t-BuC(6)H(4) (1c), 3,5-Me(2)C(6)H(3) (1d), 3,5-Ph(2)C(6)H(3) (1e), 3,5-(4-t-BuC(6)H(4))(2)C(6)H(3) (1f), 2-MeC(6)H(4) (1g), 2,4,6-Me(3)C(6)H(2) (1h)]. Reactions between (ArNHCH(2)CH(2))(3)N (Ar = C(6)H(5), 4-FC(6)H(4), 3,5-Me(2)C(6)H(3), and 3,5-Ph(2)C(6)H(3)) and Mo(NMe(2))(4) in toluene at 70 degrees C lead to [(ArNHCH(2)CH(2))(3)N]Mo(NMe(2)) complexes in yields ranging from 64 to 96%. Dimethylamido species (Ar = 4-FC(6)H(4), 3,5-Me(2)C(6)H(3)) could be converted into paramagnetic [(ArNHCH(2)CH(2))(3)N]MoCl species by treating them with 2,6-lutidinium chloride in tetrahydrofuran (THF). The "direct reaction" between 1a-f and MoCl(4)(THF)(2) in THF followed by 3 equiv of MeMgCl yielded [(ArNHCH(2)CH(2))(3)N]MoCl species (3a-f) in high yield. If 4 equiv of LiMe instead of MeMgCl are employed in the direct reaction, then [(ArNHCH(2)CH(2))(3)N]MoMe species are formed. Tungsten species, [(ArNHCH(2)CH(2))(3)N]WCl, could be prepared by analogous "direct" methods. Cyclic voltammetric studies reveal that MoCl complexes become more difficult to reduce as the electron donating ability of the [ArylNCH(2)CH(2))(3)N]3- ligand increases, and the reductions become less reversible, consistent with ready loss of chloride from ([(ArNHCH(2)CH(2))(3)N]MoCl)(-). Tungsten complexes are more difficult to reduce, and reductions are irreversible on the CV time scale.