Cleavage of an Unsymmetric Ether

Unsymmetric ethers, ROR , react with HI by a protonation-substitution mechanism that can lead to two different product combinations. 

Interestingly, some unsymmetric ethers undergo selective cleavage and give only one of the two possible product combinations. 

Consider the reaction of ethyl propyl ether with HI. Write the two different possible product combinations. Compare e energies of the two products 1-propanol and ethyl iodide-, ethanol and 1-propyl iodide). Which is the lower-energy combination Is the energy difference significant ( .002 au or 1 kcal/mol) Based on thermochemistry alone, is this reaction Likely to be selective Explain. 

Selective ether cleavage comes about during the substitution step, which obeys an Sn2 mechanism. Therefore, selective cleavage requires selective attack by Y on one of the electrophilic carbons in the protonated ether. Determine if selective attack is likely by examining the shape of the lowest-unoccupied molecular orbital (LUMO) in protonated ethyl propyl ether. Is this orbital larger near one carbon than the other If so, what product combination will result What other atom(s) contribute to the LUMO What would happen if 1 attacked this atom(s)  

Repeat this analysis for the reaction of phenyl methyl ether with HI leading to phenol and methyl iodide or methanol and phenyl iodide and involving protonated phenyl methyl ether as an intermediate. (Note In this case, the appropriate empty molecular orbital is LUMO+2 the LUMO is concentrated primarily on the CO bond.) Which reaction, with ethyl propyl ether or phenyl methyl ether, appears to be more likely to give selective ether cleavage  

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In anhydrous media cleavage occurs more slowly than in aqueous media, and the process resembles an Sn2 displacement rather than a carbonium ion reaction. Thus the first products in the cleavage of an unsymmetrical ether by a halogen acid are the less highly branched halide and the more highly branched alcohol.15 This would be the expected result of a collision between a protonated ether molecule and, for example, a halide ion, since attack should occur at the less substituted position ... 

The cleavage of an unsymmetrical acyclic ether yields two alkyl phenyl tellurium products. The product distribution is determined by the relative ease of the cleavage of the ether bond by an SN2 process2 ... 

The cleavage of an unsymmetrical acyclic ether yields two alkyl phenyl tellurium products. 

Unsymmetrically substituted benzylidene acetals can be cleaved regioselectively in some cases using Lewis acidic metal hydride reducing agents.317 The cleavage results in the formation of a benzyl ether (more hindered position) and an alco-... 

The use of an acetal to tether the diene and dienophile has been investigated by Craig and co-workers [15], Preparation of the unsymmetrical acetal precursor was best achieved via the corresponding enol ether. For example, the isopropylidene-linked triene 28 was synthesized in two steps from acetate 29. Tebbe methylenation of 29 afforded enol ether 30, which was used directly in a Pd -catalyzed addition of the dienophile 3 to form 28 (acid-catalyzed addition with pTSA proved inferior). Thermolysis of 28 in toluene at 165°C allowed a remarkably facile and completely regiospecific cyclization to take place. Acidic methanolysis of the Diels-Alder adducts resulted in cleavage of the tether and isolation of a 2.7 1 mixture of lactones 31 and 32 in 72% yield (Scheme 10-9). 

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