Stereoselective alkylation of cyclic ketones by dialkylamino- and aryloxy(methyl)magnesium compounds

Synthesis and characterisation of a series of alkylmagnesium amide and related oxygen-contaminated “alkoxy” compounds

“…33f , 41 Bailey's isolation of the b-diketiminate magnesium alkylperoxide species, 33f [HC{C(CH 3 )NAr'} 2 Mg(l-g 2 :g 1 -OOCH 2 Ph)] 2 , which co-crystallises with the alkoxide analogue, [HC{C(CH 3 )NAr'} 2 Mg(OCH 2 Ph)] 2 (Ar' = Dipp), suggests that the mechanism for this Mg-C bond formation proceeds via an alkylperoxide intermediate, which then undergoes r-bond metathesis with a further molecule of the alkylmagnesium starting material to generate the alkoxide species (eqn. ( 5)), (5) though the mechanism of the alkylperoxide formation is still debated. In our system the dimeric alkylmagnesium alkoxide, [Bu t OMgBu t •THF] 2 (11), was isolated from the reactions of Bu t MgCl in THF solution with both NaTMP and NaHMDS.…”

“…4 Since then, only a trickle of research into this area has been forthcoming, most commonly as a small part of a larger paper on related compounds, as in the case of work by Ashby and Willard on the alkylation of ketones by MeMgX complexes, where X was selected from alkoxides, alkyl, halide and amide groups. 5 This trend was continued by groups such as Reetz and co-workers in the investigation of the reactivity of compounds of the form RMgL (R = alkyl or aryl), which focused on Grignard reagents (L = halide) and organomagnesium carboxylate salts [L = OC(O)R'], though alkylmagnesium amides were also mentioned. 6 It is only in the past few years that these compounds have gained new attention as possible reagents in organic synthesis for reactions as varied as deprotonation, halogen-magnesium exchange, alkylation and reduction.…”

“…9 Studies of alkylmagnesium amides have now been extended to enantioselective deprotonation through the use of the chiral amide ligand (R)-N-benzyl-a-methylbenzylamide, with good selectivites obtained using cyclohexanone derivatives as the substrates. 10 The aforementioned early work by Ashby 5 and later by Reetz 6 on stereoselective alkylation by alkylmagnesium amides was expanded by Chong et. al.…”

Novel Enantiomerically Pure Heteroleptic Magnesium Complexes for Use in Enantioselective Deprotonation Reactions.

“…5 In addition, this type of complex has previously been used as a reducing reagent, 6 and also as a stereoselective alkylation reagent. 7 However, to date, there are no examples of the use of this type of complex as a base in asymmetric synthesis. Herein, we outline the application of such complexes as reagents in the enantioselective deprotonation of conformationally locked cyclic ketones.…”

Novel Enantiomerically PureHeteroleptic Magnesium Complexes for Use in Enantioselective DeprotonationReactions

“…heteroleptic complexes. 7 However, to date, there are no examples of the use of this type of complex as a base in asymmetric synthesis. Hence, in addition to the reactive anion, the steric and electronic nature of the spectator may be varied in order to optimise the performance of the reagent.…”