Diastereoselective Amidoalkylation Reactions of Electrochemically Methoxylated Chiral 2-Oxazolidinones with Organocopper Reagents

Article abstract of DOI:10.1021/jo00098a025

(4RS,5R)-4-Methoxy-5-methyl-2-oxazolidinone (2ab), easily obtained by electrochemical decarboxylative methoxylation of the cyclic L-threonine derivative (4S,5R)-5-methyl-2-oxazolidinone-4-carboxylic acid (1), acts as effective diastereoselective amidoalkylation reagent.The methoxy group exchange in 2ab can be performed with higher order organocuprates (R3Cu2Li) in the presence of BF3*OEt2.The 4-alkyl- or 4-aryl-substituted 2-oxazolidinones 3-6 can be obtained with trans diastereoselectivities between 75 and 98percent in S_N1 fashion via the intermediate N-acylimine.On the contrary, the N-methylated (4RS,5R)-4-methoxy-3,5-dimethyl-2-oxazolidinone (7ab) undergoes methoxy group exchange under identical conditions mainly via the S_N2 mechanism.Thus, starting from trans-7a mainly cis-8b is formed with 76percent ds.The described procedures make cis- or trans-4-alkyl-5-methyl-2-oxazolidinones and the respective dichiral 2-amino alcohols selectively available by a short reaction sequence.