Acetylenic amines, alkylation preparation

The synthesis can be conducted both in solution and without solvents. The reaction in solvent (e.g., methanol, ethanol, dioxane, dimethylformamide) is recommended for volatile 1,3-diynes and amines in this case the pyrroles are purer and the yield is higher. With disubstituted diacetylenes, ammonia and primary alkyl- and arylamines produce 1,2,3-trisubstituted pyrroles under the same conditions (65CB98 71MI1). Since disubstituted diacetylenes are readily obtained by oxidative coupling of acetylenes (98MI2), this reaction provides a preparative route to a wide range of pyrroles. 

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

JV-heterocycles can be prepared by inserting olefins or acetylenes with pendant electrophiles. Typical electrophiles used are alkyl halides and epoxides. The latter do not react with the zirconaaziridine, but with the amine generated... 

Alkylphthalimides, preparation, 676 reaction with hydrazine, 676 Alkyl sulfates, alkylation, of acetylenes by, 80 of alcohols by, 228 of amines by, 667-669 of 6-keto esters by, 347 of ketones by, 339 of malonic esters by, 489 of nitriles by, 600... 

Addition of amines to acetylene carboxylates 246 in ball mill was studied by Stolle and Thorwirth (Scheme 3.65) [44]. Employing solvent-free protocol in planetary ball mill in conjunction with quartz sand as inert grinding auxiliary, a number of enamines 247 were prepared in high yield (Table 3.33). No further catalysts or additives was required to accomplish reaction within 5 min. Obtained E/Z ratios vary with amine applied in the case of dicarboxylates, mainly the E-isomers have been identified. In contrast, reactions with propiolates and anilines yielded favorably the Z-isomer, whereas secondary alkyl amines furnished the E-isomer preferably. Simple stirring of DMAD and aniline in flask afforded only 80% conversion and chemoselectivity was lower (E/Zratio of 87 13) in comparison to ball milling. A common method for synthesis is the reaction in solvent, for which was found to have a strong influence on the E/Z ratio of the product, while this influence is not present in solvent-free milling. 

Another efficient method to prepare chiral propargylamines 42 using a multicomponent process is by alkylation of in situ formed propargyl imines from alkynals 40 and o-phenoxy aniline (11c) by dialkylzinc derivatives 41 in the presence of a chiral ligand, for instance a dipeptide, and a Lewis acid salt, as depicted in Scheme 11.16 [48], Furthermore, the synthesis of A-aryl propargyl amines can be also performed by the alkynylation using dimethylzinc and terminal acetylenes of several aldehydes and o-methoxyaniline catalyzed by (l/ ,25)-A-bis(p-methoxybenzyl)norephedrine and phenylacetylene (52-93%, 79-97% ee) [49],... 

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