Amination of Grignard Reagents with Retention of Configuration

Abstract

[see reaction]. The stereochemistry of electrophilic amination has been probed using the chiral Grignard reagent 5, in which the magnesium-bearing carbon atom is the sole stereogenic center. Amination with azidomethyl phenyl sulfide 1 and with O-sulfonyloxime 2 were found to proceed with full retention of configuration.

The quest for chiral Grignard reagents

“…38 (cf. Scheme 18) These expected and unexpected insights regarding the mechanisms of Grignard reactions became possible only after we succeeded in the first asymmetric synthesis of a Grignard reagent 39 (36), in which the magnesium-bearing carbon atom is the sole stereogenic centre.…”

Mechanistic Studies of the Copper-Catalyzed Electrophilic Amination of Diorganozinc Reagents and Development of a Zinc-Free Protocol

“…This limitation has been overcome through the pioneering work of Hoffmann, who has developed the unbiased chiral Grignard reagent 4 and successfully used it to investigate various oxidations, 9 including electrophilic amination. 10 Transmetalation of an equilibrium mixture of 3 to zinc and further reaction with an excess of 1b yielded a 65:35 endo:exo mixture of amine 5 in 55% yield (Scheme 1). This is similar to published ratios obtained for carbonation, 8a mercuration, 8a and amination.…”

Alkaline Earth Organometallics

“…In the absence of halide ions, the configurational stability extends to À20 C. 112 A review 113 documents how the asymmetric synthesis of the related Grignard reagent ((S)-1benzylpropylmagnesium chloride) (eqn [9]) was used as a probe to examine the extent to which SET is involved in reactions of organomagnesium reagents, including amination, 114 allylation, 115,116 oxidation, 117 and transmetallation. There are also possibilities for studying single-electron transfer (SET) in the reaction of Grignard reagents, in which the metal-bearing carbon is the only stereogenic center.…”