Grignard reagents reaction with ethyl orthoformate

Apart from the technical route described to p-apo-8 -carotenal, readily available vitamin A alcohol (Cjo) has served as an intermediate in the form of the phosphonium salt by reaction with the monodiethyl acetal of a Cio dial (ref. 54). The required Cjo monodiethylacetal was obtained (ref.5, p409) by the reaction of the mono aldehyde-protected derivative, the enol ether of methylmalonaldehyde, (C4) with the acetylenic Grignard reagent from trans 3-methyl-2-penten-4-yn-l-ol (C ) followed by acidic dehydration and partial reduction with Lindlar catalyst to give firstly 8-hydroxy-2,6-dimethylocta-2, 4,6-triene-l-al (Cio). Protection of the hydroxyl group by acetylation in pyridine solution with acetyl chloride and formation of the diethyl acetal with ethyl orthoformate followed by hydrolysis of the acetyl group and oxidation afforded the final CIO aldehyde component (D)shown in Scheme 15a. 

Grignard reagents can also act as sources of negative carbon in displacement reactions, e.g. in the synthetically useful reaction with triethoxymethane (ethyl orthoformate, 58) to yield acetals (59) and, subsequently, their parent aldehydes (60) ... 

The preparation of acetals is effected by refluxing an ethereal solution of ethyl orthoformate and a Grignard reagent. Prolonged heating is necessary for maximum yields. The reaction mixtures are then carefully processed by the addition of ice and dilute acetic acid followed by extraction with ether and distillation to give the acetal (80-90%). Further studies have been made in conjunction with the preparation of aldehydes (method 165). ... 

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