Arylation, allylamine derivatives

Our first applications of this new method have allowed the successful regio- and stereoselective arylation of acyclic allylic esters and A -protected allylamine derivatives. As a consequence of the high synthetic value of the arylated products, they were applied in the total synthesis of several bioactive compounds. Starting from allyUc esters, the synthesis of kavalactones such as the yagonine (27), methysticin (28), and dehydromethysticine (29) was accomplished in a straightforward way. Additionally, the y-arylated allylamine derivatives were applied to the total synthesis of the bioactive compounds naftifine (68), abamine (75), abamine SG (77), cinacalcet hydrochloride (85), and alverine (91). 

Palladium-catalysed reactions of allylamine derivatives with aryl halides Palladium-catalysed intramolecular aiylative cyclisation reactions of iV-Allylanilines with aryl halides to yield aziridines 44 (Z=Ph) and a similar reaction of iV-Allylacet-amides resulted in the selective formation of 5-benzyl-substituted oxazolines 45 without contamination by the corresponding aziridines 44 (Z=CH3CO) [79-82] (Scheme 12.9). 

While aryl halides are the substrates of choice for the neutral Heck arylations of allylamine derivatives, aryl triflates are the most used for the catimiic mode. However, as oxidative addition of Pd(0) to aryl triflates is usually slower than that with aryl bromides and iodides, bidentate ligands are commonly used to increase the stability and nucleophilicity of the Pd(0) catalyst, thus preventing the formation of Pd black (an inactive form of Pd(0)). 

SCHEME 14 Arylation of allylamine derivatives under neutral ctmditions. 

In summary, the stereoselective arylation of allylamine derivatives was accomplished by a substrate-directed Heck-Matsuda strategy. The data we obtained from these studies suggest that the origin for the regiocontrol in favor... 

The synthesis of 7-azaindoles is a challenging task and there are few efficient routes to substituted derivatives. In the laboratory of C. Thibault, the concise and efficient synthesis of 4-fluoro-1/-/-pyrrolo[2,3-jb]pyridine was achieved. The fluorination was carried out using the Balz-Schiemann reaction. The aromatic amine precursor was prepared via the Buchwald-Hartwig coupling of the aryl chloride with A/-allylamine followed by deallylation. The diazonium tetrafluoroborate intermediate was generated at 0 C and it decomposed spontaneously in 48% HBF4 solution to afford the desired aromatic fluoride. 

Prior chapters have covered the use of transition metals in asymmetric hydrogenations ( 6.2 and 7.1), hydroborations ( 7.3), hydrosilylations and hydro-cyanations ( 6.3, 6.4, 7.4 and 7.5), cyclopropanations ( 7.19), aldol reactions ( 6.11), allylations of carbanions ( 5.3.2), and some sigmatropic rearrangements ( 10.3). This chapter covers other reactions catalyzed by transition metal complexes including coupling of organometallic reagents with vinyl, aryl or allyl derivatives, Heck reactions allylamine isomerizations, some allylation reactions, car-bene insertions into C-H bonds and Pauson-Khand reactions. 

The synthesis of allylamines and corresponding a-amino-acids as inhibitors of clinically relevant enzymes has been reported. Seventeen 2-aryl-3-haloallylamine derivatives were prepared and evaluated as potential monoamine oxidase inhibitors, and found to be enzyme-activated irreversible inhibitors whose selectivity for... 

Amines also react with P-keto-esters to give the corresponding amino acid derivative. When 1.133 was treated with ethylamine in reaction 4, ethyl 3-(N-ethyl-amino)-3-phenylprop-2-enoate (1.134) was obtained. Several other 3-aryl derivatives (piperonyl, p-bromophenyl, p-methylphenyl, and p-nitrophenyl) were prepared by this method. The use of different amines (methylamine, isopropylamine, benzyl-amine, allylamine, aniline) led to several different N-substituted derivatives. ... 

Scarborough and Stahl also described a carboamination reaction for the synthesis of pyrroUdine derivatives. They used iV-tosyl allylamines and vinyl ether or styrene derivatives as the electrophiUc carbon source in place of aryl bromide to obtain 2,4-disubstituted pyrrolidine derivatives in good yield and moderate diastereoselectivity (Scheme 40.7). This reaction was performed in the presence of Cu(II) salt and molecular O2 as the co-catalyst for the reoxidation of Pd(0) to Pd(II). ... 

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