The quest for chiral Grignard reagents

Abstract

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.

Transformations of benzothiadiphosphole system: General one‐pot synthesis of 1,2,5‐dithiaphosphepines and their precursor phosphanethiols

“…This observation may be in agreement with our hypothesis that in the first step, the reaction of a bisGrignard reagent with 1 may not be a conventional [10] double S N 2 substitution, which would give the expected form C, but might prefer to give the intermediate A with a hypervalent phosphorus atom as shown in Scheme 2. In the intermediate A, the formation of another additional ring around the P 1 atom, obtained by attack of the bis-Grignard, is a factor of further stability.…”

Reactions of the Bornyl and Fenchyl Grignard Reagent with Chlorophosphanes – Diastereoselectivity and Mechanistic Implications

“…The stoichiometric reactions of the (epimerized) bornyl and fenchyl Grignard reagents with the chlorophosphanes, Ph 2 PCl, PCl 3 and (Et 2 N) 2 PCl, respectively, provided diastereomeric mixtures of bornylphosphanes and isobornylphosphanes (1-6) as well as α-fenchylphosphanes and β-fenchylphosphanes (7)(8)(9)(10)(11)(12), which were quantitatively and qualitatively assessed by 1D and 2D 31 P-, 31 C-and 1 H NMR spectroscopy (see Schemes 1 and 2). The assignment of the endo and exo configurations was supported by comparison of indicative 3 J( 31 P-CC-13 C) couplings with those of endo-and exo-norbornyldimethylphosphane oxide based on the Karplus relation.…”

“…Isobornyl chloride or β-fenchyl chloride were obtained from commercially available (1S)-(-)-endo-borneol and (1R)-(+)-endo-α-fenchol by the Appel reaction using CCl 4 /PPh 3 . Bis(diethylamino)chlorophosphane (Et 2 N) 2 PCl was prepared according to a published procedure. [14] 31 P-, 13 C-and 1 H NMR spectra were collected using a Jeol JNM-LA 400 FT spectrometer and a Jeol Eclipse+ 500 FT spectrometer.…”

“…[2] We turned our attention to diastereomeric Grignard reagents prepared by the direct method from Mg and sec-alkyl chlorides derived from naturally occurring inexpensive monoterpenes, such as menthol, [3] borneol and fenchol. [4] These Grignard reagents have three chiral centers and consist of configurationally stable mixtures of diastereomers, which differ only in the configuration of the α-carbon atom.…”

The Alkylation of Carbanions

“…The configurational stability of Grignard reagents has been the subject of numerous investigations [312,540,[561][562][563][564]. Unfunctionalized, secondary Grignard reagents isomerize at -10 C in ethers with a half-life of about 5 h (Scheme 5.77), and are thus significantly more stable toward racemization than the corresponding organolithium compounds.…”