The reactions of aryl bromides with amines occurs at room temperature when using Pd(0) and P(t-Bu)(3) in a 1:1 ratio, and the reactions of aryl chlorides occur at room temperature or 70 degrees C. The arylation of indoles and the new arylation of carbamates also occur when using P(t-Bu)(3) as ligand.
Mild, selective 1:1 reactions of amines with dienes to form allylic amines are rare 1 and limited to the reaction of cyclic dialkylamines catalyzed by nickel. 2 Late transition metalcatalyzed, amine-induced telomerizations of butadiene 1 and oxidative 1,4 addition of nucleophiles to dienes 3 are now well known, and the palladium-catalyzed additions of amines to more reactive eneynes 4 and allenes 5 have been reported. However, reactions of dienes with amines generally occur at high temperatures and produce isomeric mixtures. 1c,f,g We report the use of a high-throughput colorimetric assay to identify catalysts for the regioselective 1:1 hydroamination of dienes at room temperature. 6,7 The scope of the diene hydroamination is broad and includes enantioselective examples.To evaluate simultaneously a large number of potential catalysts for the hydroamination, we developed a colorimetric method to monitor the presence or absence of anilines. Furfural undergoes a condensation and ring opening with 2 equiv of aniline, but not with the allylic amine product, in the presence of acid to create a red product. 8 Thus, addition of furfural and acid to catalytic reactions of aromatic amines will reveal which catalysts are most active; reactions that consume the largest amount of aniline will show an absence of the red color. Typically, the reactions were diluted to distinguish the colors. Figure 1 displays the results of this colorimetric assay for the reaction of aniline with cyclohexadiene. A set of potential catalysts generated from commercially available coordination complexes and common phosphines was assembled from stock solutions in a 96-well glass plate prior to the addition of reactants. Acids have been shown to inhibit telomerization of butadiene, eneynes, and allenes. Thus, we conducted reactions in the presence and absence of 10 mol % of TFA. After 4 h, some reactions conducted in the presence of acid showed, by the colorimetric assay, complete conversion of aniline, while reactions in the absence of acid required longer times to observe reaction. GC/MS analysis of solutions showing conversion of aniline indicated formation of 1:1 adducts without telomerization. These experiments showed that complexes formed from [Pd(π-allyl)Cl] 2 and PPh 3 were the most active ( Figure 1). These two materials are known to form PPh 3 -ligated Pd(0), 9 and NMR experiments in THF showed formation of Pd(PPh 3 ) 4 immediately upon mixing. Thus, we used the readily available Pd(PPh 3 ) 4 for preparative-scale reactions. Table 1 shows results from preparative reactions containing 2 mol % Pd(PPh 3 ) 4 and 10 mol % TFA as catalyst and cocatalyst. Reactions were typically run at room temperature in toluene for 24 h, but shorter times could be used. All reactions occurred in high yield regardless of the presence of an electron-withdrawing, electron-donating, or ortho substituent on the aniline. Both the electron-rich (entries 7, 9) and electron-poor anilines (entries 5, 6) gave the addition products in high yields, although reactions (1) (...
The transition metal-catalyzed anti-Markovnikov hydroamination of unactivated vinylarenes with a rhodium complex of DPEphos is reported. The reaction of electron-neutral or electron-rich vinylarenes with a variety of secondary amines in the presence of catalyst forms the products from anti-Markovnikov hydroamination in high yields. Reactions of morpholine, N-phenylpiperazine, N-Boc-piperazine, piperidine, 2,5-dimethylmorpholine, and perhydroisoquinoline reacted with styrene to form the amine product in 51-71% yield. Reactions of a variety of vinylarenes with morpholine generated amine as the major product. Reactions of morpholine with electron-poor vinylarenes gave lower amine:enamine ratios than reactions of electron-rich vinylarenes at the same concentration of vinylarene, but conditions were developed with lower concentrations of electron-poor vinylarene to maintain formation of the amine as the major product. Reactions of dimethylamine with vinylarenes were fast and formed amine as the major product. Mechanistic studies on the hydroamination process showed that the amine:enamine ratio was lower for reactions conducted with higher concentrations of vinylarene and that one vinylarene influences the selectivity for reaction of another. A mechanism proceeding through a metallacyclic intermediate that opens in the presence of a second vinylarene accounts for these and other mechanistic observations.
A simple colorimetric assay of various transition-metal catalysts showed that the combination of DPPF, Ni(COD)(2), and acid is a highly active catalyst system for the hydroamination of dienes by alkylamines to form allylic amines. The scope of the reaction is broad; various primary and secondary alkylamines react with 1,3-dienes in the presence of these catalysts. Detailed mechanistic studies revealed the individual steps involved in the catalytic process. These studies uncovered unexpected thermodynamics for the addition of amines to pi-allyl nickel complexes: instead of the thermodynamics favoring the reaction of a nickel allyl with an amine to form an allylic amine, the thermodynamics favored reaction of a nickel(0) complex with allylic amine in the presence of acid to form a Ni(II) allyl. The realization of these thermodynamics led us to the discovery that nickel and some palladium complexes in the presence or absence of acid catalyze the exchange of the amino groups of allylic amines with free amines. This exchange process was used to reveal the relative thermodynamic stabilities of various allylic amines. In addition, this exchange reaction leads to racemization of allylic amines. Therefore, the relative rate for C-N bond formation and cleavage influences the enantioselectivity of diene hydroaminations.
Several types of imidazolium salt ionic liquids were prepared derived from poly(oxyethylene)alkyl sulfate and used as an additive or coating material for lipase-catalyzed transesterification in an organic solvent. A remarkably increased enantioselectivity was obtained when the salt was added at 3-10 mol % versus substrate in the Burkholderia cepacia lipase (lipase PS-C)-catalyzed transesterification of 1-phenylethanol by using vinyl acetate in diisopropyl ether or a hexane solvent system. In particular, a remarkable acceleration was accomplished by the ionic liquid coating with lipase PS in an iPr(2)O solvent system while maintaining excellent enantioselectivity; it reached approximately 500- to 1000-fold acceleration for some substrates with excellent enantioselectivity. A similar acceleration was also observed for IL 1-coated Candida rugosa lipase. MALDI-TOF mass spectrometry experiments of the ionic-liquid-coated lipase PS suggest that ionic liquid binds with lipase protein.
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