Grignard reagents with ortho esters

Eliel, E. L. Nader, F. W. Conformational analysis. XX. The stereochemistry of reaction of Grignard reagents with ortho esters. Synthesis of 1,3-dioxanes with axial substituents at C-2.]. Am. Chem. Soc. 1970, 92, 584-590. 

Uncatalyzed nncleophihc snbstitution reactions of Grignard reagents with aromatic compounds is much more difficult than with alkyl species, unless the leaving gronp (sometimes halide nsnally alkoxide is preferred) is activated by one or more potent electron-withdrawing substituents, snch as an oxazoline, nitro, or ester moiety, most often at the ortho... 

Acetals, " ketals, and ortho esters react with Grignard reagents to give, respectively, ethers and acetals (or ketals). The latter can be hydrolyzed to aldehydes... 

Cleavage of acetals or ortho esters with Grignard reagents... 

Reduction of acetals or ortho esters 0-80 Reduction of epoxides 0-92 Cleavage of acetals or ortho esters with Grignard reagents... 

An alternative to the Meyers or Cram oxazoline methods is the use of 2-menthoxybenzoates for the synthesis of axially chiral biaryls. Treatment of the ester 34 with Grignard reagent 35 provides the (M)-biphenyl 36 in 94% e.e (ref. 23). However, poor enantioselectivities were observed in cases where an ortho chelating substituent on the Grignard reagent was absent. 

Ortho esters have found occasional use as carboxyl blocking groups in some syntheses [73, 74, 75, 76, 96] particularly where it is necessary to prevent reaction at a carboxyl group with a Grignard reagent at a subsequent stage in a synthesis. An example of an application of this type is in the preparation of (57) in studies allied to the synthesis of the antibiotic mycomycin (33) [96]. An alternative use is illustrated by the synthesis of the amino-sugar muramic acid (58) [74]. 

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