Aminohalogenation reactions

Intramolecular aminopalladations constitute a particularly versatile approach to the generation of alkyl palladium intermediates [12]. These compounds were reacted 

Michael recently described aminochlorination reactions from intramolecular aminopalladation follotved by reaction tvith N-chlorosuccinamide (NCS) [17]. Initial reactions made use of Michael s earlier observation on stabilization of aminopallada-tion intermediates starting from 5 mol% ligated Pd complex A [18], but further tvork shotved that simple palladium salts such as Pd(NCMe)2Cl2 could also be employed, albeit in higher catalyst loadings of 10 mol% (Eq. (4.7)). The reaction tvorks well for a series of amides and carbamates, but not for tosylates. 

---

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

In 2010, Brenner-Moyer and co-workers [80] reported an organocatalytic enantioselective olefin aminofluorination reaction, in which an iminium-catalyzed aza-Michael addition preceded an enamine-catalyzed a-fluorination reaction (Scheme 13.41) [80]. This reaction was a rare example of a catalytic enantioselective olefin aminohalogenation reaction, and it furnished precursors to enan-tioenriched a-fluoro-(3-amino acids. 

Related aminohalogenation reactions of allenes, such as the conversion of 72 to 73, can be effected under similar reaction conditions (Eq. (1.32)) [59]. However, these... 

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. 

Scheme 4.2 Aminohalogenation reactions employing copper salts as halogen source.

Scheme 4.3 Aminohalogenation reactions employing N-halogenated amides.

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... 

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). 

The ionic liquid [bmim][NTf2] catalyzed the aminohalogenation of electron-deficient aUcenes in good yields. This is the first time that this reaction was performed in the absence of a metal catalyst. A representative example is presented in Scheme 79. The authors found that the major regiomer was 71 [201]. 

The aminohalogenation of electron-deficient olefins with NCS can be promoted by hypervalent iodine reagents. First, the NXS may react with TSNH2 to generate TsNHCl, which can be oxidized by PhI(OAc)2 to form I-N bond. The chloro anion can dissociate and the generated nitrenium intermediate can immediately react with the double bond of olefins to form an aziridinium ion. A series of substrates are tolerable under the reaction conditions and are aminochlorinated or brominated in good yields with high diastereoselectivities (eq 42). ... 

Carbon-carbon and carbon-nitrogen double bonds were utilized as an entry point to A-functionalization by formation of new carbon-nitrogen bond in mechanosynthetic reactions such as aza-Michael reaction and aminohalogenation of olefins. 

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). 

Copper Cyclization via aminohalogenation of (195), affording pyrrolidine derivatives (196) at <93% ee, has been reported to proceed upon catalysis with [(7 ,7 )-Ph-box]Cu(OTf)2 in the presence of Pr X (X = I, Br, Cl) as the source of the halogen atom and Mn02. The reaction is believed to proceed via iyn-aminocupration, followed by atom transfer, to form the C-X bond. ... 

---