Enantioselectivity Grignard reactions

Kinetic resolution. By an enantioselective Grignard reaction of cyclic allylic ethers... 

Magnesium alkoxides prepared from 1,2 5,6-di-O-isopropylidene-a-D-glucofuranose and 1,6-dideoxy-3,4-0-isopropylidene-2,5-di-C-methyl-L-threo-hexitol have been reported to form chiral complexes with Grignard reagents, leading to enantioselective Grignard reactions. The stereochemical results of such reactions were discussed. 

The first reports on enantioselective addition reactions of achiral organometallic reagents, modified by aprotic chiral additives, described the addition of Grignard reagents to prostereogenic carbonyl compounds in the presence of ( + )-(/ ,/J)-2,3-dimethoxybutane (l)4 5, (-)-tetrahydro-2-methylfuran (2)6, (-)-l-[(tetrahydro-2-furanyl)methyl]pyrrolidine (3)7 or (-)-sparteine (4)8. The enantioselectivity, however, was poor (0-22% ee). 

Enantioselective protonation. (R)- and (S)-a-Damascone (4) have been prepared by a Grignard reaction followed by enantioselective protonation with l1 and 2,3 both available from (-)- or (+ )-ephedrine. Thus protonation of the ketone enolate 3 with (+ )-l or (- )-2 furnishes (S)- or (R)-a-damascone (4), respectively. 

The starting point forthe preparation ofenantiomerically-enriched a-damascone was the synthesis of the racemate already described above, and the idea of carrying out enantioselective protonation using ephedrine derivatives. The Grignard reaction of methyl cyclogeraniate gave the keto-enolate with an... 

These experiments also enabled the discovery of catalytic enantioselective protonation. [46] Highly ( )- enriched, pure hthium enolate (98 2) was obtained hy a Grignard reaction, addition of chlorotrimethylsilane, fractional distillation and treatment with methyllithium. For the stereoselective protonation, 0.2-0.3 equivalents of isopropylephedrine were sufficient, because this was re-... 

One approach to ent-4 -tetrahydrocannabinol, which is independent ofthe chiral pool, was developed by David Evans (reaction scheme see next page). [143] Via enantioselective Diels-Alder reaction on a copper-bis-(oxazoline) complex, there is obtained a cyclohexenecarboxamide, which after conversion into its benzyl ester and an exhaustive Grignard reaction gives ent-menth-l-ene-3,8-diol. Also this isomer can be converted in an analogous matmer stepwise into tetrahydrocannabinol. A -Tetrahydrocannabinol would be correspondingly accessible by use ofthe antipode ofthe catalyst. 

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