Reagents Ortho Esters

Strong nucleophiles such as Grignard reagents. In general, ortho esters are difficult to prepare directly from acids and are therefore more often prepared from the nitrile. Simple ortho esters derived from normal alcohols are the least stable in terms of acid stability and stability toward Grignard reagents, but as the ortho ester becomes more constrained its stability increases. 

It will be recalled that lactone-derived enol triflate 102 was expected to serve as a substrate for a Murai coupling37 with the mixed cuprate reagent derived from iodo ortho ester 103 (see Scheme 17c). If successful, this C-C bond forming process would accomplish the introduction of the remaining carbon atoms needed for the annulation of the seven-membered D-ring lactone. 

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

Reaction between Grignard reagents and ortho esters... 

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

We might have recognised this as a Claisen-Cope product since it is a y > < -unsaturaLed ester. Disconnecting and inverting the allylic group from the ester enolate gives the start ing material 32), Ortho esters are usually used as the reagents. 

Transetherification 0-79 Reduction of ortho esters 0-92 Reaction between Grignard reagents and ortho esters... 

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

Ortho-esters at position 1,2- of sugars are more easily prepared than the corresponding acetals as an exchange of both functional groups is possible, 1,2-O-alkylidene derivatives can be prepared by the reaction of these ortho-esters with the appropriate carbonyl reagent in strictly anhydrous conditons and in the presence of an acid [87]. 

Amino groups react very easily with aldehydes or ketones, and with aldehydes in the presence of amines, they can be acylated by the usual acylating agents, and they react with amidacetals, Vilsmeier reagents and nitroso compounds (Scheme 12). As mentioned earlier, alkylation leads mainly to AT(2)-alkylated products. The hydrazino group reacts in the same way as the amino group with aldehydes or ketones, with acyl chlorides or carboxylic anhydrides, with sulfonyl chlorides, ortho esters, carbon disulfide and with nitrous acid. The last three reactions have mainly been used for the synthesis of condensed 1,2,4-triazines. 

Dihydrazones of cyclic 1,2-diketones react with ortho esters and similar reagents to form aza macrocycles, which coordinate as for (31). 

Regioselective endocyclic cleavage of the ortho ester cw-2-methoxy-4-methy 1-1,3 -dioxane by Grignard reagents, involving rupture of the less congested C(2)—0(1) bond remote from the 4-methyl substituent, has been discussed.115... 

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. 

Ortho esters have been frequently used as cyclization agents. Generally, heating the reagents together is sufficient to effect cyclization, but Kanaoka isolated the intermediate 1-ethoxymethylene-thiosemicarbazide (33) from the reaction between thiosemicarbazide... 

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