Morpholine allyl transfer

The alternative selective cleavage of the allyl ester was achieved by Pd(0)-catalyzed allyl transfer. Because the Fmoc group is sensitive to morpholine, a very weak base must be used as the allyl-trapping nucleophile. IV-Methyl aniline was favorable, and its use as a scavenger nucleophile gave rise to the acid 29 in a high yield. 

As has already been detailed for the allyloxycarbonyl (Aloe) moiety, allyl esters also proved to be very versatile and useful carboxy-protecting groups. They can be easily constructed by azeotropic esterification or nucleophilic displacement on allylic halides. For the cleavage of these esters lithium di-methylcuprate can be used. However, a much milder method is found in the Rh -catalyzed isomerization of the allyl moiety to a propenyl ester which immediately hydrolyzes under the reaction conditions (Scheme 67). Even milder is the Pd°-catalyzed allyl transfer to morpholine as an accepting nucleophile. The removal of allyl ester protection has earlier been used in particular in -lactam anti-... 

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 Pd(0)-catalyzed transfer of the allyl moiety to dimedone [23], morpholine [22], or N,N -dimethyl barbituric acid [27] resulted in the completely selective cleavage of the Aloe group, whereas the numerous other protecting groups and the glycosidic bonds,... 

Another method for deallylation is the Pd-catalyzed transfer of the allyl group to reactive nucleophiles. Sodium 2-ethylhexanoate [141], morpholine [142], dimedone [143] and AA-dimethylbarbituric acid [144] are used as allyl scavengers. It is claimed that benzenesulfinic acid 331 or sodium toluenesulfinate are the best allyl scavengers [145]. 

Representative procedure [11] a round-bottomed flask was charged with 8mL morpholine (30 mmol) and dimethylacetamide dimethyl acetal (3.8 mL, 10mmol) and the mixture was slowly heated to 190 °C over 5 h under a steady stream of N2. After cooling to room temperature, dry benzene (10 mb) and 3-methyl-but-3-en-2-ol 11 (430 mg, 5 mmol) were added. The reaction mixture was transferred to a sealed tube and the solution was refluxed until the allylic alcohol was consumed (24 h) as determined by TLC (30% hexanes in ethyl acetate, v/v). The solvent was removed in vacuo and the residue was purified by column chromatography (hexa-nes ethyl acetate 2 1—> 1 1) to afford the pure product 12 as a colorless oil (870 mg, 4.5 mmol, 90%). 

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