Grignard reaction stereoselectivity

Total syntheses have been reported by E.J. Corey (1978B, 1979). We outline only the stereoselective synthesis of a protected fragment (A) which contains carbon atoms 1—9. This fragment was combined with fragment (B) by a Grignard reaction and cyclized by one of the methods typical for macrolide formation (see p. 146). 

A useful extension of the in situ anomerization process involves the employment of C-nucleophiles such as vinyl and allyl magnesium bromides. Grignard reactions to per-O-benzylated glycosyl iodides proceed stereoselectively when a strong nucleophile like allyl magnesium bromide is used, giving [1-C-allyl fucosides (95% P-only)... 

There is still much to explore. For example, quantitative solid-state Wittig and Grignard reactions await exploration (see less than quantitative examples in [67]). First experiments are promising, but the authors did not yet care for running the reactions to completion or they did not assess the solid state even though interesting stereoselectivities emerged (review in [67]). 

Direct substitution reaction of 125 <1995EJM697> with organozinc reagents derived from allyl, benzyl, phenyl, vinyl, and -butyl Grignard reagents stereoselectively produced C-lO-substituted deoxoartemisinins 142 in good to moderate yields (Scheme 17 Table 12) <2002TL2891>. 

The stereoselectivity in the Grignard reaction,97 complementary to that in the methyllithium109 and diazomethane156 reactions, of methyl 3,4-0-isopropylidene-a-L-en/thro-pentopyranosid-2-ulose (62), and that between the Grignard and diazomethane reactions of the / ano-mer107 of 62, methyl 2,3-0-isopropylidene-/ -L-en/thro-pentopyranosid-... 

The stereoselectivities in nucleophilic additions to various hexopyran-osid-2-163, -3-164, and -4-ulosesI6S 167 were extensively examined (see Tables II and III). The results in the Grignard reactions in Table III were commonly explained by the approach of the reagent from the sterically favored direction to the magnesium-coordinated conformations (left-hand side in the equilibration formulas), but the concept for the methyl-... 

A different type of reaction, in which the intermediate formation of a chelate ring is crucial, is the reaction of pyridyl thioates with Grignard reagents, which achieves an overall conversion of an alkyl or aryl halide to a ketone (Scheme 105).378 Grignard reactions are highly susceptible to chelation factors and stereoselectivity is observed in the addition of organomagnesium or... 

Earlier work further illustrates the influence of both size and basicity of the amine-protecting group on the direction and degree of stereoselectivity of nucleophilic additions. While some excellent selectivities are observed in the Grignard reaction to amino aldehydes such as (33 equation 13), no general model adequately explains all of the results shown in Table 9. 

The stereoselective total synthesis of ( )-lepadiformine was accomplished in the laboratory of S.M. Weinreb. The introduction of the hexyl chain in a stereoselective fashion was achieved by a Grignard reaction to an iminium salt during the last steps of the synthetic sequence. The iminium salt was generated in situ from an a-amino nitrile with boron trifluoride etherate, and the addition of hexylmagnesium bromide gave a 3 1 mixture of alkylated products favoring the desired stereoisomer. Removal of the benzyl group completed the total synthesis. 

Temperature effects. The stereoselectivity of Grignard reactions is influenced by conformational mobility of substrates. Thus, at low temperatures the maintenance of one conformation favors the formation of one product. 

Scheme 7. Stereoselective vinyl Grignard reaction of galactosyl iodide...

Phosphoryl chloride-Stannous chloride-Pyridine [1, 881, before references], Johnson20 states that the stereoselectivity of the Cornforth olefin synthesis can be improved by carrying out the Grignard reaction (the first step) at a low temperature... 

Nickel and Grignard catalyzed stereoselective synthesis of cis and trans 2-alkyl-vinylcyclopentanes from telemerization of butadiene. Cyclization (ene reaction) of unsaturated allyl Grignard reagents, see also Feldman (see 1st edition). 

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