Achiral Grignard reagents

By treatment of a racemic mixture of an aldehyde or ketone that contains a chiral center—e.g. 2-phenylpropanal 9—with an achiral Grignard reagent, four stereoisomeric products can be obtained the diastereomers 10 and 11 and the respective enantiomer of each. 

An alternative approach17 is to attach a chiral auxiliary, (phenyl ethylamine, available by resolution, chapter 22, and used repeatedly in chapters 22-28, to the anhydride 100 in the form of a chiral imide 108. This auxiliary is very close to the two carbonyl groups of the anhydride in 108 and directs the achiral Grignard reagent 109 to one of them to give adduct 110 immediately reduced and hydrolysed to the lactone 106. One recrystallisation gives 106 in >98% ee. This time a Horner-Wadsworth-Emmons reaction (chapter 15) adds the side chain as a conjugated unsaturated acid reduced to the saturated side chain in 111, a common intermediate in most syntheses of ifetroban. The formation of the oxazole and the rest of the synthesis is described by R. N. Misra and the Bristol-Meyers Squibb team.16... 

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). 

An alternate route to chiral binaphthyls involves displacement of a chiral l-alkoxy group from an achiral naphthyloxazoline with a-naphthyllithium or an a-naphthyl Grignard reagent. The optical yields in this process depend on the choice of the leaving group. 

Cram [2] and Prelog [3] to explain the addition of achiral nucleophiles such as Grignard reagents to the diastereotopic faces of ketones and aldehydes having a proximal stereocenter. In the decades since, there has been a steady stream of additional contributions to the understanding of these phenomena. 

Another case that falls within the scope of the definition is the generation of an excess of one configuration at a new chiral center in the reaction between a chiral molecule and an achiral reagent. The control of the stereochemistry of addition of Grignard reagents to carbonyl centers adjacent to a chiral carbon is exemplary. In... 

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