Reinhard W. Hoffmann

The quest for chiral Grignard reagents

The involvement of single electron transfer, i.e. of free radicals in the reactions of organomagnesium reagents could be detected with the aid of a chiral secondary Grignard reagent, in which the magnesium-bearing carbon atom is the sole stereogenic centre. So far, however, such reagents have not been accessible, because the standard preparation of Grignard reagents proceeds via free radicals. We review and summarize here our efforts to generate such a Grignard reagent 36 by asymmetric synthesis starting from an enantiomerically pure alpha-chloroalkyl-sulfoxide 30b using a sulfoxide/magnesium exchange reaction to give 33 followed by a carbenoid homologation reaction. Grignard reagent 36 turned out to be an ideal probe to learn about the extent to which SET is involved in reactions of organomagnesium reagents.

Discrimination of Enantiotopic Iodine Atoms by an Iodine/Magnesium Exchange Reaction

Differentiation of enantiotopic groups is an alternative in stereoselective synthesis to the standard way of differentiating enantiotopic faces. Chiral Grignard reagents are able to differentiate the enantiotopic iodine atoms of 1,1-diiodoalkanes and lead to enantiomerically enriched configurationally stable α-iodoalkylmagnesium reagents [Eq. (1)].

Diastereoselective bromine/lithium exchange reactions of 3-alkoxy-1,1-dibromo-alkanes☆

Abstract The diastereoselectivity in the bromine/lithium exchange reaction on chiral 3-alkoxy-1,1-dibromo-alkanes has been investigated. The differentiation of the two diastereotopic bromine atoms was found not to depend solely on a conformational preorganisation of the substrate, as surmised previously. It became apparent that steric crowding at the δ-center controls the spatial orientation of a C-3-oxygen substituent at the chiral center, which may be the cause of the asymmetric induction observed.

Kumada-Corriu coupling of Grignard reagents, probed with a chiral Grignard reagent

The Grignard reagent 2, in which the magnesium-bearing carbon atom is the sole stereogenic centre has been coupled with vinyl bromide under Pd(0) or Ni(0)-catalysis to give compound 3 with full retention of configuration. Coupling using Fe(acac)3 or Co(acac)2 as catalyst was accompanied by considerable racemisation. These findings are discussed with respect to a dichotomy between concerted polar and stepwise SET transmetallation pathways.

The stereochemistry of a retro-carbolithiation reaction

Ring-opening of the cyclopropylmethyl lithium compound 7 to give the α-duryl thio-substituted alkyllithium compound 8 proceeds in a stereochemically defined manner at the lithium-bearing stereocentre.

Stereochemistry of the intramolecular carbolithiation of vinyl sulfides

Intramolecular carbolithiation of vinyl sulfides to generate configurationally stable α-durylthioalkyllithium compounds at –105 °C in THF showed carbolithiation to be non-stereospecific regarding the newly formed lithium bearing stereocentre.