An intramolecular oxa-Michael reaction on α,ß-unsaturated α-amino-δ-hydroxycarboxylic acid esters. Synthesis of functionalized 1,3-dioxanes.

A highly diastereoselective intramolecular oxa-Michael reaction on α,ß-unsaturated α-amino-δ-hydroxycarboxylic acid esters is presented; 1,3-dioxanes functionalized in positions 2,4 and 6 were obtained in good yields and with excellent selectivities; an experimental and computational study was carried out to understand the reaction course in terms of yields and selectivities. This reaction proceeds under mild reaction conditions using highly electrophilic aldehydes and ketones.

3-bromozinc propenyl esters: an experimental and theoretical study of the unique stereocrossover observed in their addition to aromatic and aliphatic aldehydes.

We report the results of a combined experimental and theoretical study on the reaction of 3-bromopropenyl acetate in the presence of zinc with three different aldehydes (i.e., benzaldehyde, 2-methylpropanal, and cyclohexanecarboxaldehyde). A 80% de in favor of the anti product has been experimentally observed with both saturated aldehydes, while for benzaldehyde, a 1:1 syn/anti ratio has been found. DFT computations show the existence of three eta1-allylic organozinc complexes [gamma-(Z)-5a, gamma-(E)-5a, and alpha-5a], very close in energy. Only gamma-(Z)-5a and gamma-(E)-5a lead to the observed product. The computational investigation of the reaction of these allylic organozinc complexes with benzaldehyde and 2-methylpropanal demonstrates in both cases the existence of two competitive reaction paths leading to the syn and anti adducts, respectively. An anti preference has been found for 2-methylpropanal with both gamma-(Z)-5a and gamma-(E)-5a species (a diastereoselectivity larger than 80% is predicted), in agreement with the experiment. With benzaldehyde, while the reaction of gamma-(Z)-5a retains an anti-stereopreference (de = 70%), that involving gamma-(E)-5a is characterized by two degenerate transition states. In this case, the agreement between computations and experiments would be satisfactory under the assumption that the initial oxidative addition affords the gamma-(E)-5a zinc complex only. Additional MP2 computations have demonstrated that pi-stacking interactions can play a significant role in determining the relative energy of the transition states leading to the syn and anti products.