Retro-Michael reaction pathway

Phenoxypropanoic acid, 3-(phenylthio)propanoic acid, 4-phenylbutanoic acid and the corresponding ethyl and methyl esters have been pyrolysed between 520 and 682 K.10 Analysis of the pyrolysates showed the elimination products to be acrylic acid and the corresponding arene. The thermal gas-phase elimination kinetics and product analysis have been found compatible with a thermal retro-Michael reaction pathway involving a four-membered cyclic transition state. 

As in the uncatalyzed reactions with enamines (vide supra), there is potentially more than one point where stereochemical differentiation can occur (Scheme 59). Selectivity can occur if the initial addition of the enol ether to the Lewis acid complex of the a,/J-unsaturated acceptor (step A) is the product-determining step. Reversion of the initial adduct 59.1 to the neutral starting acceptor and the silyl enol ether is possible, at least in some cases. If the Michael-retro-Michael manifold is rapid, then selectivity in the product generation would be determined by the relative rates of the decomposition of the diastereomers of the dipolar intermediate (59.1). For example, preferential loss of the silyl cation (or rm-butyl cation for tert-butyl esters step B) from one of the isomers could lead to selectivity in product construction. Alternatively, intramolecular transfer of the silyl cation from the donor to the acceptor (step D) could be preferred for one of the diastereomeric intermediates. If the Michael-retro-Michael addition pathway is rapid and an alternative mechanism (silyl transfer) is product-determining, then the stereochemistry of the adducts formed should show little dependence on the configuration of the starting materials employed, as is observed. 

A retro-Michael reaction to open the pyrrolidine ring and undesired lactone or lactam ring formation were some of the side reactions (21b-c). In order to avoid unproductive pathways, Sakaguchi and coworkers discovered that bulky heptamethyldisilazane in large excess could provide the desired product 21a reproducibly in 50% yield. Phenol 21a was subsequently dibrominated and converted to amathaspiramide F in three steps. 

It was suggested that this reaction proceeds via the DKR-mediated Michael-retro-Michael-Michael-Michael cascade reaction pathway the initially formed Michael adduct undergoes a DKR process in the presence of catalyst 81b, where the deprotonation of the highly acidic proton of 109 by the quinuclidine base of the catalyst leads to a reversible and stereoselective retro-Michael-Michael-Michael process. This proposal was supported by the observation that the reaction of racemic 109 with nitrostyrene under identical conditions depicted in Scheme 9.36... 

Deprotection of secondary (7) (eq 5) and tertiary Dios-amides (8) (eq 6) is achieved by acid-catalyzed hydrolysis of the acetal moiety to aldehyde in a hot aqueous solution of TEA followed by spontaneous retro-Michael reactiorr, giving the corresponding primary and secondary amines in excellent yields. Secondary Dios-amide (7) can be cleaved more easily than tertiary Dios-amide (8). A plausible reaction pathway is shown in eq 7. Acrolein generated as a co-product is not troublesome under these aqueous conditions. 

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