Azasteroids. Reaction of Chiral N,N-Maleoyl Amino Acids with 1-(1-Trimethylsiloxyvinyl)-3,4-dihydronaphthalene

The cycloaddition between N,N-maleoyl amino acid esters and 1-(1-trimethylsiloxyvinyl)-3,4-dihydronaphthalene gave 11-(trimethylsiloxy) derivatives of 16-azaestra-1,3,5(10)-trienes. These were transformed by desilylation into the parent 11-oxo-derivatives, which reacted with hydroxylamines to 11-hydroxyimino derivatives. The stereochemistry of the products was elucidated using different NMR methods, HPLC, CD, X-ray structure analysis, and calculations. It was found that mixtures of diastereoisomers were obtained from these cycloadditions. Reactions using chiral maleoyl amino acid derivatves did not change this result. The chiral center did not provoke stereoselectivity, probably caused by the flexibility of the chiral side chain. A directing influence of the side chain was found only in reactions with derivatives of phenylalanine. This might be explained as an interaction between the aromatic system and the carbonyl groups of the imide moiety. This interaction kept the aromatic ring in its position in the final product, and was found in the X-ray crystallographic analysis, and agreed with results of calculations.