Reaction of 2-norbornyl- and 3,3-dimethyl-2-norbornylmagnesium bromide with acetone

Abstract

Attempts to determine the stereochemistry of electrophilic addition of acetone to two configurationally rigid Grignard reagents [2-norbornylmagnesium bromide (3) and 3,3-dimethyl-2-norbornylmagnesium bromide (9)] are described. Evidence is presented which suggests that the reaction of 9 with benzophenone proceeds via an electrontransfer pathway. In addition, results describing an improved synthesis of camphenilone and the stereospecific synthesis of exo-2-bromo-3,3-dimethylnorbornane are presented.Despite its long-standing synthetic importance, a detailed understanding of the reaction of Grignard reagents with carbonyl compounds has only recently begun to emerge.2'3 The products of such reactions indicate that several, frequently competitive reaction pathways are available: (a) direct 1,2addition, (b) electron transfer, (c) reduction (when a ß hydrogen is present in the Grignard reagent), and (d) enolization

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

“…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 ). This is similar to published ratios obtained for carbonation,8a mercuration,8a and amination . After establishing that both isomers react similarly, we examined the resolved isomer.…”

“…We next examined the fate of a stereodefined R* 2 Zn reagent when subjected to the amination conditions. The Grignard reagents 3 -endo and 4 were chosen to conduct the study (Scheme ). Though conveniently prepared, the use of 3- endo is not completely unbiased, as the reaction of interest must proceed through diastereomeric transition states.…”

General stereoretentive preparation of chiral secondary mixed alkylmagnesium reagents and their use for enantioselective electrophilic aminations

“…To date, only one example of a non-heteroatom-stabilized α-chiral Grignard reagent has been reported, which was prepared via a sulfoxide-magnesium exchange. 2 Furthermore, deracemization of a mixture of endo- and exo- norbornylmagnesium bromide using benzophenone 3 or exploiting the different reactivities of menthylmagnesium chloride epimers 4 have been reported. Recently, we have shown that various enantiomerically enriched secondary alkyl iodides of type 1 underwent an I/Li-exchange 5 at −100 °C in pentane:ether mixtures furnishing the corresponding chiral alkyllithiums of type 2 with retention of configuration ( Scheme 1a ).…”

Concerted and stepwise Grignard additions, probed with a chiral Grignard reagent

“…Therefore, the stereochemical probes such as 4 12,13 and 5 14 have been used to probe the mechanism of Grignard additions. 15,16 Yet in the case of 4 and 5 it is a moot point, to what extent the stereochemical outcome is influenced by the presence of the additional stereogenic centres (only one case of epimerisation 13 has been so far observed). The ideal probe would be a Grignard reagent such as 6, in which the magnesium-bearing carbon atom is the sole stereogenic centre.…”

“…This is in line with the finding for the carboxylation of 5. 14 As the addition of formaldehyde to 5 proceeded as well without epimerisation, 15 we looked at the addition of 6 to aromatic aldehydes, where the intervention of electron transfer steps is more likely. Addition of 6 to aldehydes generates two diastereomeric adducts (D1; D2), which were derivatized with Mosher's reagent and analysed by 1 H-NMR spectroscopy.…”