Hydroamination of Simple Alkenes

Since more reactive alkenes, such as vinyl arenes or sterically strained polycycles, react more readily in the hydroamination reaction, several asymmetric hydroami nation reactions utilizing these substrates have been disclosed. Weakly basic anilines can react with vinyl arenes to give the Markovnikov addition products 6 and 7 with good yields and enantioselectivities in the presence ofa chiral phosphine ligand Pd complex as demonstrated by Hartwig (Eq. 11.3) [13] and later by Hii (Eq. 11.4) [14]. 

Equations 11.3 and 11.4. Palladium catalyzed asymmetric Markovnikov addition of aniline to vinyl arenes [13, 14]. 

The range of amines involved may be expanded to more basic alkylamines (Eq. 11.5) [16]. Compound 10 was obtained in moderate yield and enantioselectivity utilizing the R,R) Et FerroTANE ligand. Note that almost stoichiometric amounts of a strong Bronsted acid are required to afford the Markovnikov hydroamination product of the vinyl arene. 

Equation 11.6. Iridium catalyzed asymmetric hydroamination of norbornene [26]. 

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While intermolecular hydroamination of simple alkenes remains a great challenge as of now, addition of amines to alkynes, allenes, and dienes proceeds more easily. However, the addition of an amine to a polyene moiety may not necessary result in the formation of a new stereocenter, if an imine is generated (Scheme 11.18). 

Preparation of aliphatic amines by direct hydroamination of alkenes with amines is a highly desirable reaction. However, except for the well-established hydroamination of 1,3-dienes via 7r-allylpalladiums, no smooth hydroamination of simple alkenes is known. As a breakthrough, Kawatsura and Hartwig reported that the hydroamination of styrene derivatives with aniline is catalyzed by Pd(TFA)2 and DPPF in the presence of trifluoroacetic acid (TFA) or triflic acid as a cocatalyst to afford the branched amine 24 regioselectively in 99 % yield. Formation of the branched amine 24 offers an opportunity of asymmetric amination. They obtained the (5)-amine 25 in 80 % yield with 81 % ee using (/ )-BINAP as a chiral ligand [14]. The reaction is explained by insertion of styrene to the H-Pd bond and nucleophilic attack of amine on an fj -benzylpalladium complex [15]. Hii and coworkers obtained the amine 24 with 70 % ee in 75 % yield using the dicationic Pd complex, [Pd(MeCN)(H20)(/ -BINAP)](0Tf)2 [16]. 

Multiple efficient catalysts were reported for the intramolecular process, while the intermolecular process has been studied predominantly for alkynes. The reactivity of the unsaturated fragment decreases in the order alkyne > allene diene > vinyl arene unactivated alkene with the intermolecular hydroamination of simple alkenes representing the most difficult transformation. The hydroamination of all types of carbon-carbon unsaturated fragments will be covered in this chapter. 

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