Allyl transfer amine protection

The mild and selective nature of the palladium-catalysed allylation reaction has made it suitable for protection. Allyl ethers, esters, amines and carbamates can usually be easily formed by standard procedures. The allyl group can be removed later by exposme to a palladium catalyst and a competitive nucleophile, Y (Scheme 9.68). This is an allyl transfer reaction. Commonly used competitive nucleophiles for allyl esters of carboxylic acids include sodium 2-methylhexanoate, secondary amines such as pyrrolidine (Scheme 9.69) and morpholine, and dimedone. ... 

The allylsulfonyl group, introduced by reaction with aUylsulfonyl chloride in the presence of a totiary amine, has been shown to be a useful new hydroxyl protecting group. While stable towards deacetyladon, desilylation, and acetal hydroly it is selectively removed under mild conditions by palladium (0)-mediated allyl transfer m morpholine. ... 

Another method for deallylation of ally esters is the transfer of the allyl group to reactive nucleophiles. Amines such as morpholine are used[415-417], Potassium salts of higher carboxylic acids are used as an accepter of the allyl group[418]. The method is applied to the protection and deprotection of the acid function in rather unstable /f-lactam 664[419,420]. 

The [2,3]- or [3,3]-sigmatropic rearrangements (Scheme 24) provide a means to introduce either the protected amine or the carbon atom which will become the carboxylic acid, while also positioning the double bond in the correct position for the alkene isosteres. Moreover, when starting from homochiral allyl alcohols, a very effective chirality transfer assures the stereospecific construction of the R1 and R2 side-chain stereochemistries. 

Various allylic amines and protected allylic alcohols were tested using different cyclodextrins. Although only low to moderate enantioselectivity was obtained, the method demonstrated for the first time an enantioselective inverse phase-transfer catalysis hydration reaction via an oxymercuration-demercuration process. 

The increasing application of direct metallation methods and the importance of primary amines as synthetic intermediates have created a need for new aminating reagents. In particular, reagents that could directly transfer an N-protected group rather than a free amino group. In this context several N.O-diprotected hydroxyl-amines have been recently reported (Scheme 2) terr-butyl and allyl iV-[(arylsul-fonyl)oxy]carbamate 6 [5] and the Af,0-bis(trimethylsilyl)hydroxylamine 7 [6]. 

To compare the transfer of chirality in a [2,3]-rearrangement from carbon to carbon versus nitrogen to carbon, Bonin and coworkers devised a clever series of experiments f Scheme 1521). Allylic amines 94 were prepared from N-protected phenylglycinoL Oxidation with m-CPBA yielded stable amine JV-oxides 96, which were isolated in 51-74% de (confirmed by NMR analysis). Ammonium zwitterions 95 proved to be highly stable in dichloromethane... 

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