JV-Protecting groups

Farwick and Helmchen [28] prolonged the alkyl chain of chiral allylamines by a hydroformylation-(Wittig olefination) sequence (Scheme 5.139). Particular attention was paid to the choice of the JV-protective group. As expected in the Wittig olefination step, mainly the Z-configured olefins were formed. After selective removal of only one Af-protective group, the obtained Af-Boc protected methyl esters were converted via a diastereoselective aza-Michael reaction into the corresponding fi-proline derivatives. 

Since the use of N,iV-dimethylacetamide and triethylamine improved the rate and extent of cleavage of the JV-benzyloxycarbonyl group in several difficult cases, these additives have been incorporated into the submitters standard procedure and are included in the present procedures. Deprotection with this method has been carried out with as much as 25 g. of the protected peptide. 

Protecting group abbreviations are as follows JV-benzyloxycarbonyl (Z), N-tert-butyloxycarbonyl (Boc), tert-butyl ether (Bu ), and S-tert-butyl (Bu ). 

Syntheses of A-alkyl-1,2,4-triazoles and AT-alkylbenzotriazoles have been carried out with the aid of the JV-phenylsulfonyl protecting group [9]... 

Boc) and 7V-(benzyloxycarbonyl) (Z) protective groups are stable under these conditions. In contrast to that, the jV-(4-methoxybenzyloxycarbonyI) (Moz) protecting group can readily be cleaved by the cation radical of tris(2,4-dibromophenyl)amine (Table 11, No. 13) ° >. 

The enone 445 was then converted to ( )-oxocrinine (415) by a sequence that commenced with the bromination of 445 using excess 5,5-dibromo-2,2-di-methyl-4,6-dioxo-l,3-dioxane to provide a mixture of bromo ketones 446. Removal of the jV-carbobenzyloxy protecting group according to the protocol previously detailed gave 448 as a mixture (a-Br (3-Br = 3 1) of diastereomers, but only the a-bromo isomer underwent dehydrobromination on heating with lithium bromide and lithium carbonate in dry DMF to furnish 415. Interestingly, treatment of the (3-bromo derivative of 448 under similar conditions afforded the debrominated product 447 (200). 

The JV-formyl group is stable providing hot aqueous acid or alkaline conditions are avoided. Deprotection is affected by prolonged hot alkaline hydrolysis, or in the case of protected amino acids, by oxidative225 or reductive procedures.226... 

The hydroboration of ( )-baikiain (4,5-dehydro-( )-pipecolinic acid) via its JV-benzyloxycarbonyl methyl ester derivative (134) led, after oxidation and removal of the protecting groups, to 72% trans-5-hydroxy-( + )-pipecolinic acid (136) and 28% (raw.s-4-hydroxy-( + )-pipecolinic acid (135), separable by preparative ion-exchange column chromatography.118... 

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