Oxidative addition initiates most palladium-catalyzed cross-couplings [1] and is often rate-limiting for reactions of aryl chlorides [2] and deactivated aryl bromides. [3] This addition usually occurs to an unsaturated complex formed from ligand dissociation or after transformation of a precatalyst to the true catalyst.[ [7±10]Here we describe the catalytic activity of air-stable, readily accessible, alkyl di-tert-butylphosphane ligated palladium(i) dimers toward selected couplings of amines with aryl chlorides on the time scale of minutes at room temperature. Furthermore, these dimers catalyze a range of aminations and Suzuki±Miyaura couplings of aryl bromides even more readily. In addition to providing a convenient catalyst for synthetic chemistry, these results indicate that the elementary step of oxidative addition of an aryl chloride to the reactive Pd 0 intermediate ligated by PtBu 3 or P(1-Ad)tBu 2 (1-Ad ¼ 1-adamantyl) occurs with rates that are unparalleled for this step.[11±14]We and others have reported several times that the rates for cross-couplings catalyzed by palladium complexes of PtBu 3 are faster when a 1:1 ratio of phosphane to palladium is used. [7±10, 15] [16] are formally Pd I complexes that contain a 1:1 ratio of metal to ligand. They are readily prepared from [Pd 2 (dba) 3 ]¥C 6 H 6 , [PdBr 2 (cod)], and the corresponding ligand in good yield (cod ¼ (Z,Z)-cycloocta-1,5-diene). Complex 1 a is air-stable indefinitely as a solid, and 1 b is stable enough to be weighed in air. These dimers could cleave into two different monomeric units, such as a highly reactive monoligated palladium (0) To evaluate the potential of 1 a and 1 b as catalysts for the aminations of aryl halides, we studied the prototype reaction of p-chlorotoluene with dibutylamine in the presence of sodium tert-butoxide as base and 0.5 mol % of 1 b in toluene at room temperature. This reaction was complete within 15 min and formed N,N-dibutyl-p-toluidine in 86 % yield of isolated product. The reaction occurred at a similar rate and in a higher 95 % yield when conducted in THF, most likely because of the greater solubility of 1 b in THF. Although the combination of [Pd(dba) 2 ] with carbene 2[18] and the combination of Pd(OAc) 2 with biphenylyl phosphane 3 [19] have been used for amination of aryl chlorides at room temperature, reactions catalyzed by these species required longer times at higher catalyst loadings.[20] Table 1 summarizes results on the room-temperature amination of aryl chlorides and bromides catalyzed by palladium(i) dimers 1 a and 1 b. All of these reactions, except that in entry 11, were quenched after 15 min. In some cases, reactions catalyzed by 1 a gave higher conversions with 1 mol % catalyst. For example, the reaction of cyclic secondary amines with p-chlorotoluene occurred to only 88 % completion after 15 min when catalyzed by 1 b, but to full completion when catalyzed by the 1 a (entry 2). Higher activity of 1 a was also observed for the amination of o-substituted aryl chlorides. The reaction of o-c...

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.

The amination of aryl halides in the presence of inexpensive and air-stable alkali metal hydroxide bases and Pd[P(t-Bu)3]2 as catalyst gave arylamines in high yields. The reactions were conducted with a catalytic amount of cetyltrimethylammonium bromide as phase-transfer agent and either aqueous hydroxide or solid hydroxide in the presence of water. This combination of alkali metal hydroxide base, H2O, and the ammonium salt performed as well as NaO-t-Bu in the amination of p-chlorotoluene with dibutylamine. Hydroxide base was suitable for reactions of a wide range of aryl chlorides and bromides with aliphatic and aromatic amines. Some functional groups that were intolerant of tert-butoxide base, such as esters, enolizable ketones, nitriles, and nitro groups, were tolerated by the combination of hydroxide base, H2O, and cetyltrimethylammonium bromide in toluene solvent.

Catalytic asymmetric hydrogenations of prochiral unsaturated compounds, 1 olefin, 2 ketone, 3 and imine, 4 have been intensively studied and are considered as a versatile method of creating a chiral carbon center. 5 However, no highly enantioselective hydrogenation of heteroaromatic groups has so far been reported except that of 2-methylquinoxaline to our knowledge. 6 Resonance stability of heteroaromatic compounds might impede the enantioselective hydrogenation, 7 which may find potentially wide applicability in stereoselective organic synthesis. 8,9 Herein, we describe the highly enantioselective hydrogenation of heteroaromatic compounds, indoles.We recently disclosed that the rhodium complex generated from Rh(acac)(cod) and PPh 3 is a good catalyst for the hydrogenation of five-membered heteroaromatic compounds. 10 Thus chiral rhodium complexes prepared in situ from Rh(acac)(cod) and various commercially available chiral bisphosphines (1 mol %) were examined for asymmetric hydrogenation of N-acetyl-2-butylindole (1a) at 60°C for 2 h with 5.0 MPa of H 2 in 2-propanol (eq 1), resulting in non-enantioselective hydrogenation (0-1% ee). 11 Fortunately, the successful asymmetric hydrogenation has been achieved by use of a trans-chelating chiral bisphosphine ligand, (S,S)-(R,R)-PhTRAP, 12,13 giving (R)-N-acetyl-2-butylindoline (2a) with 85% ee (77% conversion). No reduction of the fused aromatic ring of 1a was observed.On further investigation into the asymmetric hydrogenation, [Rh(nbd) 2 ]SbF 6 was found to be superior to Rh(acac)(cod) as catalyst precursor (Table 1). It is noted that addition of base is necessary for achievement of high enantioselectivity as well as high catalytic activity. The [Rh(nbd) 2 ]SbF 6 -(S,S)-(R,R)-PhTRAP catalyst scarcely promoted the hydrogenation in the absence of base, giving a trace of 2a with only 7% ee (S) (entry 1). Addition of 10 mol % of Et 3 N or Cs 2 CO 3 brought remarkable improvement of the enantioselectivity and catalytic activity (100% conversion, 94% ee (R)) (entries 2 and 3). 14 Both the enantioselectivity and catalytic activity were significantly dependent upon base: K 2 -CO 3 gave (R)-2a with 76% ee, and pyridine did not activate the cationic PhTRAP-rhodium complex at all (entries 4 and 5). The amount of Cs 2 CO 3 did not affect the selectivity: 20 mol %, 94% ee; 1 mol %, 93% ee. It is possible to carry out the asymmetric hydrogenation at lower pressure (1.0 MPa) without significant decrease of the selectivity and reaction rate (entry 6). The amount of PhTRAP-rhodium complex can be reduced to 0.1 mol %, and the reaction was completed within 20 h to give (R)-2a of 93% ee in 92% isolated yield (entry 7).Although 2-propanol has frequently been used as a hydrogen source in the transfer hydrogenation of unsaturated compounds (1) For reviews, see: (a) Takaya, H.; Ohta, T.; Noyori, R. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH Publishers: New York

A ruthenium-catalyzed intermolecular, anti-Markovnikov hydroamination of vinylarenes with secondary aliphatic and benzylic amines is reported. The combination of Ru(cod)(2-methylallyl)2, 1,5-bis(diphenylphosphino)pentane, and triflic acid was the most effective catalyst of those tested. Control reactions conducted without ligand or acid did not form the amine. The reaction of morpholine, piperidine, 4-phenylpiperazine, 4-BOC-piperazine, 4-piperidone ethylene ketal, and tetrahydroisoquinoline with styrene in the presence of 5 mol % of this catalyst formed the corresponding beta-phenethylamine products in 64-96% yield, with 99% regioselectivity, and without enamine side products. Acyclic amines such as n-hexylmethylamine and N-benzylmethylamine reacted with styrene in 63 and 50% yields, respectively. Alkyl-, methoxy-, and trifluoromethyl-substituted styrenes reacted with morpholine in the presence of this catalyst or a related one containing 1,1'-bis(diisopropylphosphino)ferrocene as ligand to give the products in 51-91%. Further, the hydroamination of alpha-methyl styrene was observed for the first time with a homogeneous transition metal catalyst. Preliminary mechanistic studies showed that the reaction occurred by direct, irreversible, anti-Markovnikov hydroamination and that the mechanism of the ruthenium-catalyzed hydroamination is likely to be distinct from that of the recently reported rhodium-catalyzed reaction.