Highly Efficient Synthesis of Enantiomerically Pure (S)-2-Amino-1,2,2-triphenylethanol. Development of a New Family of Ligands for the Highly Enantioselective Catalytic Ethylation of Aldehydes

The reaction of ( S )-triphenylethylene oxide ( 3 ) with diisopropoxytitanium(IV) diazide in benzene solution at 70 °C takes place readily in a completely regioselective and stereospecific manner to afford ( S )-2-azido-1,2,2-triphenylethanol ( 6 ). Reduction of the azide by catalytic hydrogenation leads to ( S )-2-amino-1,2,2-triphenylethanol ( 5 ) that, by N,N-dialkylation with 1,4-dibromobutane, 1,5-dibromopentane, 1,5-dibromo-3-oxapentane, α,α‘-dibromo- o -xylene, and methyl iodide, affords the corresponding ( S )-2-dialkylamino-1,2,2-triphenylethanols ( 7a − e ). On the other hand, the reaction of 5 with benzyl bromide or 1-iodobutane takes place as a monoalkylation, leading to the corresponding ( S )-2-alkylamino-1,2,2-triphenylethanols ( 8f, g ). The performance of amino alcohols 7a − e as ligands for the catalytic enantioselective addition of diethylzinc to benzaldehyde has been studied, with enantioselectivities of 94−97% being recorded. The best performing ligands in this family, 7a [( S )-1,2,2-triphenyl-2-(1-pyrrolidinyl)-ethanol] and 7c [( S )-2-morpholino-1,2,2-triphenylethanol] have been studied in the addition of Et 2 Zn to a representative family of aldehydes. With 7a, a 96.6% mean ee is recorded for a family of 16 α-substituted aldehydes and a 92.8% mean ee for a family of six α-unsubstituted aldehydes. With 7c working on the same families of aldehydes, the mean enantioselectivities are 96.8% and 91.8%, respectively.