Matthias Beller

The Catalytic Amination of Alcohols

In this Minireview, the synthesis of amines by the amination of alcohols, by means of the so‐called borrowing hydrogen methodology, is presented. Compared to other synthetic methodologies for the synthesis of amines, these transformations are highly attractive because often alcohols are readily available starting materials, some of them on a large scale from renewable sources. In addition, the amination of alcohols produces water as the only by‐product, which makes the process potentially environmentally benign. Already today, lower alkyl amines are produced in bulk by the chemical industry with this synthetic method. In particular, the recent progress applying organometallic catalysts based on iridium, ruthenium, and other metals will be discussed. Notable recent achievements include the conversion of challenging substrates such as diols, the development of recyclable catalysts, milder reaction temperatures, and the direct alkylation of ammonia or its equivalents with alcohols.

First efficient palladium-catalyzed Heck reactions of aryl bromides with alkyl methacrylate☆

Abstract An efficient palladium-catalyzed coupling reaction of aryl bromides with butyl methacrylate has been developed. Depending on the reaction conditions various amounts of butyl 3-aryl-2-methylpropenoate and butyl 3-aryl-2-methyliden-propenoate as well as double arylated products were produced. Superior turn over numbers up to 8300 and turn over frequencies up to 1000 h −1 for Heck reactions of aryl bromides with methacrylic acid ester have been obtained for the first time.

Phosphapalladacycle-Catalyzed Heck Reactions for Efficient Synthesis of Trisubstituted Olefins: Evidence for Palladium(0) Intermediates

The coupling reaction of 1,1-disubstituted olefins (α-methylstyrene, n-butyl methacrylate) with various aryl bromides (Heck reaction) has been studied as a new concept to synthesize trisubstituted olefins. Surprisingly, the nature of the base dramatically influences the product distribution. Thus, a systematic investigation on the role of base in Heck reactions of 1,1-disubstituted olefins was performed. Less coordinating bases like NaOAc, NaOBz or Na2CO3 yield a statistical distribution of regioisomers with the terminal olefin 10 as the major product. However, by using amines like Bu3N or diisopropylethylamine (DIPEA) as base internal olefins can be synthesized with high selectivities. With phosphapalladacycle 3 as catalyst precursor, we were able to obtain catalyst turnover numbers up to 1000, while Pd(OAc)2/2PPh3 was one order of magnitude less active. Analysis of the reaction profile by kinetic investigations led to the postulation of a reduction and subsequent oxidative addition of the catalyst precursor 3 to form 12 as catalytically active intermediate.

First palladium-catalyzed aminations of aryl chlorides☆

Abstract The palladium-catalyzed coupling reaction of aryl chlorides with various amines has been studied for the first time. Crucial for the success of this Cue5f8N bond forming reaction is the use of potassium tert-butoxide as base. Turn over numbers up to 900 and yields up to 80% have been obtained.

Palladium-catalyzed carbonylation of benzyl chlorides to phenylacetic acids : a new two-phase process

Palladium-catalyzed carbonylation of substituted benzyl chlorides in a two-phase system at atmospheric carbon monoxide pressure generates the corresponding phenylacetic acids in 80–94% yield. The palladium catalyst is dissolved in the aqueous phase by using water-soluble phosphine ligands. The turnover numbers (TON) are higher than 1500 and turnover frequencies (TOF) of 135 h−1 are reached. The length of the induction period observed is in inverse order to the phosphine-palladium ratio. The reaction rate is strongly dependent on the temperature and the initial substrate concentration. Continuous addition of substrates is increasing the life time of the catalyst. The proposed active species is generated via chloride- and hydroxy-bridged palladium dimers.

Rhodium-Catalyzed Amination of Vinylpyridines: Hydroamination versus Oxidative Amination

Cationic rhodium complexes catalyze the amination of 2- and 4-vinylpyridine with secondary amines. Depending on the substrate and the reaction conditions either oxidative amination to yield the corresponding enamines 1a–8a or hydroamination to give 2-aminoethylpyridines 1b–8b occurs. In all cases products with anti-Markovnikov regioselectivity are obtained. For mechanistic studies novel cationic complexes of rhodium(I)-containing cyclooctadiene and vinylpyridine 12 as well as complexes containing cyclooctadiene, vinylpyridine, and morpholine 13 were prepared and characterized by NMR spectroscopy and X-ray diffraction analysis.

Palladium–catalyzed C–C– and C–N–coupling reactions of aryl chlorides

In this paper we report a brief review of the palladium–catalyzed olefination and amination of aryl chlorides. Special emphasis is given on the efficiency of known catalysts. Best turnover numbers (TON up to 40,000) known to date for Heck reactions are displayed by palladacycle catalysts, e.g., 1 in the presence of salts as co–catalysts. Model studies show that the catalyst productivity is strongly influenced by the nature of the added salt. In addition, the ability of mixtures of Pd(OAc)2 and phosphines to catalyze the reaction of styrene with 1–chloro–4–trifluoromethylbenzene was studied dependent on the Pd:P ratio. It was found that apart from the palladacycle 1 a number of established phosphines permit efficient C–Cl activation. Amination of aryl chlorides is also possible in the presence of palladacycles as catalyst precursors. Crucial for the success of the C–N bond forming reaction is the use of potassium tert–butoxide as base and reaction temperatures > 120°C. Turnover numbers up to 900 and yields up to 80% have been obtained for the amination of 1–chloro–4–trifluoromethylbenzene.

Base-catalyzed hydroamination of aromatic olefins-an efficient route to 1-aryl-4-(arylethyl)piperazines

Abstract An efficient synthesis of pharmaceutically interesting 1-aryl-4-(arylethyl)piperazines by base-catalyzed hydroamination is presented. Starting from substituted aryl olefins and various N -arylpiperazines, the desired products 3 – 12 were obtained in one step under mild conditions in the presence of a catalytic amount of n -butyllithium in yields up to 99%.

Cobalt-catalyzed biphasic hydroformylation of internal short chain olefins

Hydroformylation of short chain internal olefins to linear aldehydes is an interesting subject due to the enormous importance of the resulting oxo products. Here we report a systematic study of the hydroformylation of 2-pentenes in an aqueous two-phase system with a Co/TPPTS catalyst. At elevated temperatures and pressures good yields of the desired aldehydes were obtained. Linear to branched ratios (n/iso) of up to 70:30 were observed. Recycling of the catalyst and reuse up to four times without loss of activity has been demonstrated.

Palladium‐Catalyzed Hydroamidocarbonylation of Olefins to Imides

Carbonylation reactions allow the efficient synthesis of all kinds of carbonyl-containing compounds. Here, we report a straightforward synthesis of various imides from olefins and CO for the first time. The established hydroamidocarbonylation reaction affords imides in good yields (up to 90u2009%) and with good regioselectivity (up to 99:1) when applying different alkenes and amides. The synthetic potential of the method is highlighted by the synthesis of Aniracetam by intramolecular hydroamidocarbonylation.