Resolution amines, ethyl isocyanate

Resolution of sec-amines. Reaction of sec-amines with (+)- or (- )-l results in two diasteriomeric ureas, R2NCONH(CH3)C6H5, which can usually be resolved by either chromatography or crystallization. The resolved sec-amine is obtained by alcoholysis of the optically pure urea. The method is particularly valuable where both optical isomers of the amine are desired see also (R)-( - )-(l-naphthyl)ethyl isocyanate (6, 416) for a similar reagent. 

Resolution of alcohols (c/., l-(naphthyl)ethyl isocyanate, 8, 356-357). A practical synthesis of the methyl ester of (S)-5-HETE (1) from arachidonic acid involves chromatographic separation of the diastereomeric urethanes prepared" from the isocyanate derived from dehydroabietylamine (hydrogen chloride and phosgene).1 Urethanes from other chiral amines are less useful. The urethanes are cleaved with triethylamine and trichlorosilane to give the corresponding pure enantiomeric esters, which can be hydrolyzed by base. 

A significant advance in the resolution of asymmetric alcohols has been the formation of carbamates from the reaction with a chiral isocyanate. Isocyanates are highly reactive and are widely used for the derivatization of hydroxyl and amine functional groups. Alcohols react relatively slowly and require heating for several hours, whereas phenols react rapidly, even at room temperature. Reagents used have included (R(-P)/S(—) phenylethyl isocyanate (15) and R(-p)/S( —)- -( -naphthyl)ethyl isocyanate (16) the diastereomeric carbamates are stable and no evidence for racemization has been recorded. The individual enantiomers can be recovered by refluxing the dias-tereomeric carbamates... 

Other diamide sub-units have been coupled to polysiloxane backbones leading, for example, to resolution of trifluoroacetyl derivatives of secondary amines and the resolution of alcohols and a-hydroxy acids as their isopropylurethane derivatives after derivatisation with isopropyl isocyanate. Such a method established that commercial (5)-ethyl lactate contained 1.67% of the R enantiomer, i.e. it had an e.e. of 96.66%. 

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