Alkenes aminohalogenation reactions

The enantioselective alkene aminohalogenation reaction using 2-iodopropane as iodine source was also realized in this group. A range of chiral 2-iodomethyl indolines and pyrrolidines could be formed in good to excellent yield and enantioselectivity. In addition, 1,1-dichloroethene and (2,2-dibromo-l-methylcyclopropyl)benzene ako could lead to aminochloride and aminobromide products in moderate yield and good enantioselectivity [61] (Scheme 8.25). 

Recent development of regio- and stereoselective aminohalogenation reaction of alkenes, particularly, aziridinium mechanism of the reaction 07EJO2745. 

While such a process had initially been observed as an undesired side-reaction in transformations where copper salts were employed as re-oxidants [13], Chemler demonstrated that various aminohalogenation reactions proceed in THF or acetonitrile in the presence of potassium carbonate as base [14]. These reactions employ palladium trifluoroacetate or palladium dibromide as catalyst source and require a moderate excess of the copper oxidant (3-4 equiv) giving moderate to excellent yields. However, they usually suffer from rather low selectivity, either in the initial aminopalladation or via subsequent rearrangement pathways to provide mixtures of pyrrolidines and piperazines (Scheme 4.2, Eq. (4.3)). A stoichiometric control reaction in the presence of palladium bromide led only to the Wacker cydization together with an alkene isomerization product, suggesting that the presence of copper(II) salts is crucial for the overall process. The exact role of the copper(II) salts has not yet been darified and palladium intermediates of different oxidation states may be involved in the final stage of carbon-halogen bond formation. 

The potential of palladium-catalyzed aminochlorination reactions of alkenes dates back to their isolation as side products in aminocarbonylation reactions under copper(II)dichloride cocatalysis [47d]. These reactions were later developed further using copper(II) salts as co-oxidants or reoxidants, respectively, and concomitantly as halide sources. For example, Chemler showed that various aminohalogenation reactions proceed under palladium catalysis in the presence of potassium carbonate as base in moderate to excellent yields in the presence of an excess of the copper oxidant [80]. Both five- and six-membered rings 115 and 116 were formed under these conditions from allyl anilines 114 (Scheme 16.28). Among other examples... 

In recent years, a number of novel palladium-catalyzed diaslereoselective alkene difunctionalization reactions, such as aminohalogenation [34], aminoacetoxylation [35], aminofluorination [36], and diamination [37], have been studied intensively by the combination of other reactions with an amino- or oxopaUadation reaction. In some of these transformations, a Pd(IV) species is believed to be the key intermediate (Scheme 6.21). 

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