Application of Ã-aminoorganostannanes to the preparation of ß-aminoalcohols

Abstract

Preparation of non-conjugated dipole-stabilized a-aminoorganolithiums by tilithium exchange is explored. The configurational stability of enantiomerically enriched a-aminoorganolithiums is also investigated. These organolithiums can react with aldehydes to provide both racemic and chiral non-racemic ~-aminoalcohols.

N-(1-tn'butylstannyl)alkyl-N,N' ,N'-trimethylureas are prepared from stannyl phthalimides which, in turn are prepared from hydroxystannanes generated from aldehydes and tributyltinlithium. The trimethylurea organostannanes transmetalate completely with n-BuLi at -78oC. The resulting organolithiums do not trap with electrophiles; instead, the amide group migrates from the nitrogen to the carbanion (1,2 migration) to give the more stable lithium amides.

N-alkyl 2-(trimethylsilyl)ethoxycarbonyl (Teoc) protected a-aminoorganostannanes are also prepared from stannyl phthlimides. These a-aminoorganostannanes undergo complete tin-lithium exchange with n-BuLi at -78oC. Reaction of the resulting organolithiums with either CO2 or benzaldehyde give low yield of isolated product, presumably due to decomposition of the organolithiums. The Teoc group seems to be a poor protecting group for stabilizing a-aminoorganolithiums.

N-t-Butylthiomethyl t-Boc protected a-aminoorganostannanes transmetalate with n-BuLi at -78oC to give a-aminoorganolithiums which can react with different aldehydes to give b-aminoalcohols in good yields. Aromatic aldehydes give approximately a 2:1 ratio of the anti:syn diastereomers, where aliphatic aldehydes give almost a 1:1 mixture of the two diastereomers. The enantiomerically enriched N-t-butylthiomethyl t-Boc protected a-aminoorganolithiums racemize very slowly at -95oC (2-33%) and they react with aldehydes with complete retention of stereochemistry to give b-aminoalcohols in high enantiomeric excess (91-94%). The protected b-aminoalcohols may be converted to oxazolidinones which are then hydrolyzed to primary b-aminoalcohols. Oxazolidinones with straight chains alpha to the nitrogen (R=n-C3H7, n-C4H9 and n-C5H11) give low yields of the primary b-aminoalcohols. The b-aminoalcohols with these groups may be deprotected via aminoacetal intermediates, which can undergo transacetalization with 1,3-propanedithiol to the primary b-aminoalcohols. Hydrolysis of enantiomerically enriched oxazolidinones give primary b-aminoalcohols with high enantiomeric excess. Anti b-aminoalcohols can cyclize with inversion under Mitsunobu conditions, to trans oxazolidinones which can then hydrolyze to give syn primary b-aminoalcohols.

Finally, stannylimines are prepared from the acylstannanes and (r)-a-methylbenzylamine and a-naphthylethylamine as chiral auxiliaries. The stannylimines undergo diastereoselective reduction with DIBAL-H at -78oC to give stannylamines with moderate diastereomeric excess (56-62%). Removal of the chiral auxiliaries when tin is still present in the molecule is difficult. When t-Boc protected stannylamines (with the chiral auxiliary still in place) are treated with n-BuLi or t-BuLi, the t-Boc group is attacked instead of transmetalation.