Diastereoselective Ritter reactions of chiral secondary benzylic alcohols

摘要

An acid-catalysed Ritter reaction of chiral secondary benzylic alcohols enables diastereoselective access to chiral amides, which represent inter alia valuable intermediates for the synthesis of chiral 1,2-diamines and β-amino acids.rnThe introduction of an amino group into an organic molecule proceeds typically via an S_N2-type displacement of a suitable leaving group by an appropriate strong nitrogen nucleophile. The reaction is stereospecific and-if applicable-the question of facial diastereoselectivity must be addressed when establishing the stereogenic center at the leaving group. An alternative reaction mode for the creation of a C-N bond is the acid-catalysed Ritter reaction, i.e. the reaction of nitriles as weak nitrogen nucleophiles with suitable electrophile precursors. Carbenium ions have been invoked as intermediates in this S_N1-type reaction. The facial diastereoselectivity of this process, however, has not yet been studied. We have now investigated the reaction of the title compounds, which serve as precursors for chiral benzylic cations. Suitable conditions for the Ritter reaction were established and the reactions were shown to proceed with remarkable diastereoselectivities.