Benzylamine rhodium

Ruthenium complexes of (129) and (130)336 were investigated for the asymmetric hydrogenation of prochiral 2-R-propenoic acids (Scheme 62a) rhodium complexes of these ligands were used for hydrogenation of acetoamido-cinnamic acid methyl ester (Scheme 62c) and hydrogenation of acetophenone-benzylamine (Scheme 62b). The results obtained with these... 

Similarly, ketimines (benzylimines of aromatic ketones) undergo the rhodium-catalyzed ortho-alkenylation with alkynes to give or/ o-alkenylated aromatic ketones after hydrolysis.61 This method is applied to an efficient one-pot synthesis of isoquinoline derivatives by using aromatic ketones, benzylamine, and alkynes under Rh catalysis (Equation (55)). 

James and coworkers found that one benzylamine is actually bound to the rhodium in the active catalyst in hydrogenations of PhCH=NRCH2Ph using [Rh(COD)(PPh3)2]PF6 as catalyst precursor. However, the addition of more than two equivalents of benzylamine inhibited the catalysis [63]. 

Gyclization/hydrosilylation of enynes catalyzed by rhodium carbonyl complexes tolerated a number of functional groups, including acetate esters, benzyl ethers, acetals, tosylamides, and allyl- and benzylamines (Table 3, entries 6-14). The reaction of diallyl-2-propynylamine is noteworthy as this transformation displayed high selectivity for cyclization of the enyne moiety rather than the diene moiety (Table 3, entry 9). Rhodium-catalyzed enyne cyclization/hydrosilylation tolerated substitution at the alkyne carbon (Table 3, entry 5) and, in some cases, at both the allylic and terminal alkenyl carbon atoms (Equation (7)). 

Rhodium-catalyzed hydroformylation of 2-amino-/V-(but-3 -enyl)- and -A-(3 -rnethylbut-3 -enyi)benzylamines (381) in the presence of rho-dium(II) acetate dimer and triphenylphosphine in deoxygenated ethyl acetate gave mixtures of 5,5a,6,7,8,9-hexahydro-llH-pyrido[2,l-b]quinazo-line (382), isomeric 6-methyl-5,5a,6,7,8,10-hexahydropyrrolo[2,l-b]quina-zolines (383), and 6-methyl-6,7,8,10-tetrahydropyrrolo[2,l-ft]quinazoline (384), as well as a stereoisomeric mixture of 7-methyl-5,5a,6,7,8,9-hexahy-dro-ll//-pyrido[2,l-b]quinazolines (385) and 15% of 7-methyl-6,7,8,9-tetrahydro-llH-pyrido[2,l-fr)quinazolme (386), (95AJC2023). When the bulky tricyclohexylphosphine was used instead of triphenylphosphine, a 3 7 mixture of compounds 382 and 383 and a 3 1 mixture of isomeric 385 were formed. 

Rhodium-catalyzed hydroformylation of -(substituted amino)benzyl-amines (387, X = H2) and -(substituted amino)benzamides (387, R = H, X = O) in the presence of rhodium(II) acetate dimer and triphenylphos-phine in deoxygenated ethyl acetate gave a 7 3 mixture of 1,2,3,4,4 ,5-hexahydro-6//-pyrido[l,2-a]quinazolines (388, X = H2,0) and isomeric 3-methyl-l,2,3,3fl,4,5-hexahydropyrrolo[l,2-a]quinazolines (389, X = H2, O) (94AJC1061). The methyl derivative of benzylamine 387 (R = Me, X = H2) afforded a mixture of diastereoisomers 390 and 391 (X = H2). Their ratio depended on the reaction time. Longer reaction times gave more 391 (X = H2), containing the methyl group in an equatorial position. Compound 390 isomerized into 391 (X = H2), under the aforementioned conditions. The benzamide derivative (387, R = Me, X = O) yielded only one isomer (391, X = O), independent of the reaction period. 

The asymmetric hydrogenation of C—O bonds have now been achieved in optical yields up to 95%, rivalling the performance of alkenes. Here also, rhodium complexes have been used almost exclusively, but some success has been obtained with cobalt catalysts. Using [Co(HDMG)2] in presence of optically active bases, benzil could be reduced to benzoin (equation 54) in an optical yield of 78%. Quinine or quinidine were the chiral bases employed. The best optical yields were obtained with quinine (60). It was found that when benzylamine was also present, the rate of hydrogenation was greatly enhanced without any decrease in the optical yield.276... 

A rhodium catalyst [Rh(cod)Cl]2 was applied at 140°C and 100 bar to achieve a yield of 99% in hydroaminomethylation of ethyl oleate and morpholine. Several amines were tested in the reaction with fatty compounds hexylamine, benzylamine, aspartic diethyl acid, valinol, and diisopropylamine are further amines which can be employed in hydroaminomethylation. The conversion with primary amines showed that hydroaminomethylation can proceed twice on the amine. The dimer fatty acid ester bridged with an amine is a highly functionalized molecule with various applications. An excess of the primary amine during the reaction prohibits the reaction of the hydroformylation product with a secondary amine which is the product of hydroaminomethylation with the primary amine (Scheme 19). 

An efficient single-step synthesis of isoquinolines was achieved by a three-component reaction of aromatic ketone with benzylamine and alkyne. Rhodium (I) is used as the catalyst and o-functionalization of the aromatic rings is not necessary, indicating an extended scope for this method <03OL2759>. The reaction is complicated by a sizable amount of phenethyl-substituted side product. 

TriarylimidazoIes have been isolated from reactions of alkenes, carbon monoxide and ammonia in the presence of a rhodium catalyst, while benzylamines react with catalytic quantities of metal carbonyls to form the same compounds [69, 70]. 4-Aminoimidazolium salts have been made by assembling iminochloro sulfides, benzaldimines and isocyanides in a process believed to involve a transient 7V-imidobenzylideniminium halide intermediate. Yields of 25-76% are reported [71]. 

There have been reports of a novel synthesis of 2,4,5-trialkyl-imidazoles by the rhodium-catalyzed reactions of alkenes with carbon monoxide and ammonia. Yields are 50-60%. Benzylamine and derivatives react with carbon tetrachloride in the presence of a catalytic amount of metal carbonyls to yield 2,4,5-triarylimidazoles and -imidazolines. The suggested reaction mechanism implicates an initially formed radical species which coordinates with the metal carbonyl. 

Aromatic nitriles hydrogenate to primary amine over palladium-on-carbon in ethanol-HCl or acetic acid" finely divided Ni (Raney Ni) in ethanol/NH3 [equation (f)]. Rhodium hydroxide and (7 3) rhodium-platinum oxide inhibited by LiOH convert ben-zonitrile to benzylamine, and isophthalonitrile or terephthalonitrile to the corresponding diamines [equation (g)]. ... 

Related Reagents. Bis(bicyclo[2.2.1]hepta-2,5-diene)rho-dium Perchlorate [l,4-Bis(diphenylphosphino)butane](norbora-diene)rhodium Tetrafluroborate Catecholborane (1,5-Cycloocta-diene)[ 1,4-Bis(diphenylphosphino)butane]iridium(I) Tetrafluoro-borate (1,5-Cyclooctadiene)(tricyclohexylphosphine)(pyridine) iridium(I) Hexafluorophosphate Octacarbonyldicobalt Palladium (II) Chloride Tetrakis(triphenylphosphine)palladium(0) 2-Amino-3-picoline Benzylamine. 

Scheme 6.3 Easy cyclometalation reactions with a benzylamine proceed via agostic interaction as shown in agostic intermediate 6.6 Equation (6.4) Chelation-Assisted Carbon-Halogen Bond Activation by a Rhodium(I) Complex ...

In 2006, EUman, Bergmann, and coworkers reported the synthesis of a PKC inhibitor by using a rhodium-catalyzed intramolecular C-H alkenylation at the C2 position of the indole moiety (Scheme 16.4) [13]. Imine 19, which was prepared from the corresponding aldehyde and a benzylamine, was treated with a rhodium complex and phosphoramidite ligand 20 in toluene, followed by hydrolysis of the imine group under acidic conditions to afford 22 in 61% yield with 90% ee (over two steps). Mechanistically, imine 19 directed the rhodium-catalyzed C-H activation via intermediate 21, with subsequent intramolecular alkylation to give the desired product 22. Thereafter, the synthesis of the target PKC inhibitor from 22 over several steps has been accomplished. 

Efficient synthesis of chiral amines is very important to the pharmaceutical industry and there are several different approaches using asymmetric hydrogenation that can be employed, some of which have been discussed in previous sections. For example, ot-methyl benzylamine derivatives, common to many pharmaceuticals, can be synthesised in excellent yields and enantioselectivities from the corresponding vinyl acetamide usually employing rhodium catalysis. 

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