Asymmetric Synthesis of 3-Substituted 2-exo-Methylenealkanones by Addition-Elimination Reaction Using a Chiral Leaving Group and Organometallic Nucleophiles

Article abstract of DOI:10.1021/jo00044a026

A novel diastereodifferentiating addition-elimination reaction of (S)-2-<<2-(methoxymethyl)-1-pyrrolidinyl>methyl>-2-alken-1-ones with organometallic reagents such as organocuprates and organozincates afforded optically active 3-substituted 2-methylenealkanones with high enantiomeric purity.The enantiomeric excess (ee) of the products in this asymmetric induction reaction involving 1,5-transfer of stereogenicity was highly dependent on the structure of the enone substrates and the type of organometallic reagents, chiral auxiliaries, and added Lewis acids: (i) the use of lithium diorganocuprates (R2CuLi) led to the highest ee's, (ii) in the reaction with R2CuLi the ee decreased in the following order by varying their structure of the main framework of the enones, cycloheptenones (96-97 percent ee) > cyclohexenones ( 95 percent ee) > cyclopentenones ( 82-85 percent ee) > acyclic enones (55-70 percent ee), (iii) the addition of LiBr as the external Lewis acid in the reaction with R2CuLi did not affect the ee, whereas that of ZnBr2 or MgBr2 decreased the ee by 5 percent or considerably more, respectively, and (iv) the existence of the methoxy oxygen atom in the chiral auxiliary was essential to achieve high ee's.The origin of the observed high and low ee's was rationalized by considering plausible transition state models.