Amination palladium catalyzed allylic

N-Unsubstituted aziridines can be elaborated by taking advantage of the nucleophilicity of the nitrogen center. One noteworthy example is the palladium-catalyzed arylation of aziridine 201 with /i-bromonitrobenzene 202 using a 

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Palladium complexes are general and versatile catalysts for allylic amination.1,la lh The palladium-catalyzed allylic aminations of 1,3-symmetrically disubstituted substrates, including enantioselective versions, have been widely studied.1, a h It has been important to control the regioselectivity in allylic amination of unsymmetrical substrates 1 or 2 (Equation (1)). In general, palladium-catalyzed allylic amination gives the ( )-linear product 3Tla lh regiocontrol in amination has recently attracted much attention in approaches toward the branched product 4. 

An unusually high regioselectivity was observed by Cook s group in palladium-catalyzed allylic amination of 5-vinyloxazolidinone 10 (Scheme 2).5 An imide-type nucleophile was directed to the internal carbon, whereas... 

Palladium-catalyzed, Allylic Amination. Allylic substitution of mono-saccharidic hex-2-enopyranoside 4-acetates with secondary amines in the presence of tetrakis (triphenylphosphine)palladium(O) liad led to a large variety of 4-aminated 2-enosides, with retention of configuration (56-58). The method was applied to the disaccaridic enoside 1 to give, with benzylmethylamine or dibenzylamine, the 4-amino sugar derivatives g in yields of 92 and 67% (46). Studies concerning hydrox-ylation of t)ie double bond and subsequent deprotection are incomplete. 

In a subsequent paper (87), the same authors investigated the palladium-catalyzed allylic aminations with pyrphos-functionlized PPI and PAMAM dendrimers as multidentate ligands. Zero to four generation PPI-(pyrphosPdCl2)x and PAMAM-(pyrphosPdCl2)x neutral dendrimers (97) showed a strong positive dendritic effect on the selectivity of the allylic amination of 1,3-diphenyl-1-acetoxypropene with morpholine (at 45°C in DMSO). 

The resulting peripheral phosphine-functionalized dendrimers were used as a ligand in the palladium-catalyzed allylic amination of crotyl acetate in a CFMR. The active catalysts were prepared by mixing all three components the dendrimer, the phosphine ligand and a suitable palladium precursor [(crotyl)PdCl]2. The catalytic activity and selectivity of 16 in a batch process... 

Fig. 6 Schematic representation of the Meijer-Reek noncovalently immobilized phosphine ligands applied in palladium-catalyzed allylic aminations...

Table 2 Palladium-catalyzed allylic amination using catalysts that are noncovalently anchored in the core of a carbosilane dendrimer...

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]. 

Palladium, benzylchlorobis(triphenylphosphine)-, trans-, 67, 86 Palladium-catalyzed aryl-aryl coupling, 66, 70 PALLADIUM-CATALYZED ALLYLIC AMINATION, 67,105 PALLADIUM-CATALYZED CHLOROACETOXYLATION, 67, 105 PALLADIUM-CATALYZED COUPLING OF ACID CHLORIDES WITH ORGANOTIN REAGENTS, 67, 86 PALLADIUM-CATALYZED COUPLING OF ARYL HALIDES, 66, 67 PALLADIUM-CATALYZED syn-ADDITION OF CARBOXYLIC ACIDS,... 

N-Allylation of aziridines is often complicated by side reactions. The classical solution to this problem, reductive amination, can also be problematic due to the increased strain energy of the aziridinium intermediate. A way to avoid this difficulty was developed by Yudin and co-workers <2005JA17516, 2004JA5086>. The results obtained showed that NH-aziridines such as 197 or 198 underwent a palladium-catalyzed allylic amination with various allyl acetates affording the desired allylated product 199 and 200 with high levels of regioselectivity and in high isolated yields (Scheme 54). 

The key step of the synthesis was palladium -catalyzed allylic amination/[2,3]-Stevens rearrangement. Amathaspiramides A-F (129-134) were synthesized by Chiyoda et al. [67]. They started the synthesis by taking 3-methoxyphenacyl bromide and the key step was the reduction of lactam moiety to the cyclic imine by Schwartz s reagent, [Cp2Zr(H)Cl]. 

Scheme 15.43 Switch in diastereoselectivity for palladium catalyzed allylic amination/[2,31-rearrangement. 

More recently, Alper and colleagues described a convenient protocol for the synthesis of substituted benzazepine derivatives (Scheme 2.44) [286]. This protocol is based on the sequential palladium-catalyzed allylic amination and a subsequent intramolecular carbonylation reaction. The substrates were obtained by a Baylis-HiUman reaction. 

Scheme 10.6 Comparative study on isostructural NHC-phosphine and amino-phosphine chelate complexes in palladium-catalyzed allylic amination.

SCHEME 22.11 Palladium-catalyzed allylic amination of 1,3-diphenylallyl acetate. 

This one-step transformation of an alkene to an allylic acetate compares well with other methods of preparation such as hydride reduction of a, 8-unsaturated carbonyl compounds followed by esterification. The scope and limitations of the reaction have been investigated. The allylic acetoxylation proceeds via a TT-allylpalladium intermediate, and as a result, substituted and linear alkenes generally give several isomeric allylic acetates. With oxygen nucleophiles the reaction is quite general, and reactants and products are stable towards the reaction conditions. This is normally not yet the case with nitrogen nucleophiles, although one intramolecular palladium-catalyzed allylic amination mechanistically related to allylic acetoxylation has been reported. ... 

Kawatsura M, Hrrakawa T, Tanaka T, Dceda D, Hayase S, Itoh T. Regioselective synthesis of trifluoromethyl group substituted allylic amines via palladium-catalyzed allylic amination. Tetrahedron Lett. 2008 49 2450-2453. 

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