2.2- Dimethoxypropane acetonide formation

Acetonide formation 2,2-Diethoxypropane. 2,2-Dimethoxypropane. Ion-exchange resins. 

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

The superiority of di-p-nitrophenyl hydrogen phosphate as catalyst for the reaction is partly because its lipophilic area is approximately twice that of p-toluene-sulfonic acid and hence its salts with nucleosides are correspondingly more soluble in acetone. A further advantage of the procedure is that the formation of a nucleoside acetonide can be coupled with phosphorylation to produce the corresponding nucleotide. Thus, after the preparation of adenosine-2, 3 -acetonide (4) in solution, the acetone and 2,3-dimethoxypropane can be removed by distillation and the residue treated with tetra-p-nitrophenyl pyrophosphate for conversion into the nucleotide acetonide. 

Anhyd copper sulfate is also an excellent catalyst for the formation of acetonides from glycols and acetone (eq 2). Either 2,2-dimethoxypropane or 2-methoxypropene can sometimes improve the efficiency. The regiochemistry of the copper-catalyzed process is different from that found in the proton-catalyzed reaction. 

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