Allylic amination reactions

A non-covalently functionalized dendrimer was also applied in a continuous allylic amination reaction.[33] PPI dendrimers functionalized with urea adamantyl groups can act as host molecules for phosphorus ligands equipped with acetyl urea groups (Figure 4.18). The so formed supramolecular complex was reacted with a palladium precursor... 

The amination of styrene, however, led to two products (1-phenyl-1-ethylamine and 2-phenyl-l-ethylamine) in a 1 3 ratio [113], indicating that the hydrozirconation was not completely regioselective [114,115]. Since it is well known that hydrozirconation of trisubsti-tuted alkenes places zirconium at the least hindered carbon of the chain by a process involving zirconium migration, this class of alkenes was not investigated [5,116], On the other hand, hydrozirconation/amination of 3-methyl-l,2-butadiene gave an allylic amine. Reaction of the latter could either occur at the terminal carbon or proceed with... 

More recently, Hartwig and coworkers reported iridium-catalyzed, asymmetric aminations of allylic alcohols in the presence of Lewis acid activators [103]. The addition of molecular sieves and Nb(OEt)5 or catalytic amounts of BPh3 activated the allylic alcohol sufficiently to allow allylic amination reactions to occur in high yield, branched-to-linear selectivity, and enantioselectivity (Scheme 29). Without the activators, only trace amounts of product were observed. 

Table 9.1 Data summary Screening SALs 21XY in the palladiun catalyzed allylic amination reaction with TsN(H)l /le.

The resulting noncovalently immobilized complexes have been used as ligand systems for both the Pd-catalyzed allylic amination reaction and the Rh-catalyzed hydroformylation. A glycine-urea functionalized PPh3 ligand, 4(S), was noncovalently attached to the immobilized dendritic support, and the application of this system in the Pd-catalyzed allylic amination attains similar yields and product distributions as the homogeneous analogue for the... 

Other types of allylic amination reactions include a variety of indirect approaches such as reduction of a,P-unsaturated imines and oximes, rearrangement of aziridines, and elimination of water from vicinal amino alcohols. However, these reactions will not be considered in this chapter [2]. 

The reaction type (a) in Scheme 1 for the allylic amination reaction uses substrates which have an allylic C-X (X = heteroatom, halide) bond and is mainly nucleophilic amination of functionalized alkenes, whereas reaction type (b) is a direct allylic amination of an alkene, based on electrophilic amination of nonfunctionalized alkenes and involves a cleavage of a C-H bond. 

In 1965, Tsuji et al. observed that palladium could catalyze the allylic alkylation reaction [18]. This discovery, which is a very attractive way to expand the scope of the allylic amination reactions mentioned above, has stimulated an intense research in this field, and even though complexes of nickel, platinum, rhodium, iron, ruthenium, molybdenum, cobalt, and tungsten have been found also to catalyze the alkylation, palladium complexes have received by far the greatest attention [19]. 

In the palladium-catalyzed allylic amination reaction, primary and secondary amines can be used as nucleophiles, whereas ammonia does not react. Therefore, many ammonia synthons have been developed, and a variety of protected primary allyl amines can now be prepared using azide, sulphonamide, phthalimide, di-f-butyl iminocarbonate ((Boc)2NLi), and dialkyl A-(rerr-butoxycarbonyl)phosphoramide anions as the nucleophile [20], An example of the use of ((Boc)2NLi) 30 as the amine nucleophile in the palladium-catalyzed allylic amination reaction is shown in Eq. (9). This reaction also illustrates the problem with the regioselectivity in the reaction as a mixture of the products 31-33 are obtained [21]. 

Two examples using azo compounds in allylic amination reactions will be presented in the following. Leblanc et al. have used the more reactive trichloro derivative 82 of DEAD, 81, and found that the ene reaction proceeds at various temperatures and without any Lewis acid catalyst present, for both cyclic and acyclic alkenes to give allyl amines in good yields. The reaction of the alkene 85 with 82 gave the allylic aminated compound 86 in 85 % yield (trans. cis = 85 15) (Eq. (21)) [53f. The allyl amine 87 was formed in good yield after treatment with a suspension of zinc powder in acetic acid solution. 

Sharpless et al. found that heating a solution of 109 with 2-methyl-2-hexene 110 afforded an allylic amination reaction leading to the formation of 111 in 57 % yield together with high yields of the parent molybdenum dioxo complex 107 (Eq. (26)). 

A variety of different metal complexes have been screened as catalysts for allylic amination using phenyl hydroxylamine 108 as the nitrogen fragment donor, and it was found that iron-complexes have better redox capacity compared to molybdenum [64]. With the iron compounds, higher yields and a lower amount of hydroxylamine-derived byproducts are obtained. These byproducts constitute one of the problems in this type of allylic amination reactions in general, as their formation is difficult to suppress. The allylic amination reaction of a-methyl styrene 112 with 108 can, e.g., be catalyzed by the molybdenum dioxo complex 107, iron phthalocyanine 114, or by the combination of the iron chlorides 115 [64,65]. It appears from the results in... 

This book is arranged in seven chapters which cover the following aspects of amination - even if the order of the contributions is somewhat arbitrary. Chapter 1 (K. A. Jprgensen) deals with modem aspects of allylic amination reactions for preparing fundamental building blocks which have either distinct important properties or can be used for further transformations in organic synthesis. Two approaches - the... 

E)-Allylic amines. Reaction of the lithiated methylphosphonate ester with a nitrile, followed by addition of an aldehyde, furnishes a conjugated imine with an ( )-configuration. Immediate reduction (e.g., with NaBH4) gives the allylic amine. 

For asymmetric allylic amination reactions, chiral sulfur diimides and selenium diimides are efficient chiral reagents (Sections D.7.4. and D.7.6.). The synthesis uses (S)-l-phenylethylamine as a chiral auxiliary26. 

A synthesis of Agelastatin A by Weinreb and co-workers featured the use of a 13 bis[2-(trimethylsilyl)ethylsuifonyl] sulfodiimide 137 2 as an enophile in a two-step allylic amination reaction [ heme 8.137]. The initial ene reaction produced a dipolar intermediate 1373 that underwent a [2,3] Sigmatropic shift to afford the SES-protected allylic amine derivative 137,4. Reductive cleavage of the N-S bond followed by cleavage of the Boc group with trifluoroacetic acid gave the sulfonamide 1373 in 50-60% overall yield. Final deprotection of the SES group with TBAF returned the desired amine 137,6 in 90% yield. 

Treatment of the diamide 77 with dibutyltin dichloride affords the 2,2-bis(2-[4(/ ),5(5)-diphenyl-1,3-oxazolinyl])propane 78, while successive reaction of 77 with mesyl chloride and aqueous ethanolic sodium hydroxide yields the diastereomer 79 <96TI3649>. The (+)- and (-)-forms of the chiral oxazoline 80 were used as ligands for palladium catalysed allylic amination reactions thus the acetate 81 and benzylamine gave the optically active amine 82 in excellent enantiomeric excess <97JOC55Q8>. The enantioselective catalytic alkylation of aldehydes RCHO (R = n-heptyl, Ph, cyclohexyl or PhCH=CH) with allyluibutyltin in the presence of chiral bis(oxazolinyl)zinc complexes, c.g., 83, leads to alcohols 84 in 40 6% enantiomeric excess <97TL145>. 

Draw the structures of the intermediates in the following allylic amination reactions and hence explain the difference in the outcome of these two reactions. 

Mechanistic studies suggested that the reaction proceeds by way of trifluoroacetic acid protonation of Ni(0), followed by hydrometallation of the 1,3-diene to generate a 7t-allyl intermediate (Scheme 3-108). An external attack of the amine to the Ji-allyl intermediate then generates the product allylic amine. Reaction of the Jt-allyl intermediate with the amine is thermodjmamically favorable only in the presence of additional diene. 

Flubacher, D. and Helmchen, G. (1999) Enantioselective domino Heck-allylic amination reactions. Tetrahedron Lett., 40, 3867-8. 

SCHEME 11.37, Asymmetric allylic amination reaction of imides with MBH carbonates. 

---