External reagents enantioselective additions

The cyclopropanation of alkenes using external stoichiometric chiral additives can be divided according to their general mechanistic scheme into two classes. The enantios-elective cyclopropanation of allylic alcohols, in which a pre-association between the corresponding zinc alkoxide and the zinc reagent probably takes place, constitutes the first class. The second class involves the enantioselective cyclopropanation of unfunctionalized alkenes. The latter implies that there will be no association between the reagent and the alkene through alkoxide formation. 

The first report of an external chiral ligand-mediated enantioselective addition of an organolithium reagent to an imine appeared in 1990 (Tomioka, in this volume) [27]. Tomioka and coworkers found that 1,2-addition of MeLi, n-BuLi and vinyllithium to the 4-methoxyphenylimine of benzaldehyde 15 gave, in the presence of tridentate aminoether 16, the corresponding tertiary amines 17 in excellent yields and good ees (71-77%) (Scheme 6). 

The ligand 108 has activity as an external controller of stereochemistry in the enantioselective addition of methyllithiiun to imines derived from veratralde-hyde with up to 41% ee [87]. (-)-Sparteine (19)-mediated reaction of organo-hthium reagents afforded isoquinoUne alkaloid 107 directly from 3,4-dihydroi-soquinoline 106 with up to 47% ee (Scheme 32) [88]. 

The Michael-type addition reaction of a carbonucleophile with an activated olefin constitutes one of the most versatile methodologies for carbon-carbon bond formation [1]. Because of the usefulness of the reaction as well as the product, many approaches to the asymmetric Michael-type addition reactions have been reported, especially using chirally modified olefins [2-8]. However, the approach directed towards the enantioselective Michael-type addition reaction is a developing area. In this Chapter, the recent progress of the enantioselective Michael-type addition reaction of active methylene compounds and also organometallic reagents with achiral activated olefins under the control of an external chiral ligand or chiral catalysts will be summarized [9]. 

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