Reaction of α-diketones with 2-amino alcohols. Intramolecular competitive 6-exo-trig vs 5-endo-trig processes. A systematic and kinetic study

Abstract

2-Aminoethanol and C-substituted derivatives 1 react with diacetyl, benzil, and 1-phenyl-1,2-propanedione, models of α-diketones 2 to give with remarkable regio- and stereoselectivity 2-hydroxy-5,6-dihydro-2H-1,4-oxazines 3, cis-octahydro[1,4]oxazino[3,2-6]oxazines 4, α-imino ketones 6, 2-acetyl-1,3-oxazolidines 7, N,N′-bis(2-hydroxy-2-methylpropyl)-2,3-butanediimines 8, and 2,2′-dimethyl-2,2′-bioxazolidines 9 depending on the nature of the reagents and the reaction conditions. On the basis of isolated intermediates, a reasonable mechanism taking into account the stereoelectronic effects observed on the cyclization has been proposed for these processes. In addition, a kinetic study of the ring-chain-ring tautomeric equilibrium of oxazines 3a-c, 3i-k, and 3o-q has been studied by 1H NMR and 13C NMR. In solution, compounds 3a-c and 3i-k exhibit a three-component tautomeric equilibria consisting of the following: the β-iminohemiacetal 3, the β-hydroxyimino ketone 6, and the 2-acetyl- or 2-benzoyl-1,3-oxazolidine 7. The calculated rate constants for this process show that the equilibrium is shifted toward the formation of the five-membered ring by 0.4-4.8 kJ mol-1 over the six-membered ring depending on the substitution patterns. Compounds 3p-q exist in solution as equimolar mixtures of the ring and open-chain tautomers. Compound 3o exists predominantly in the open-chain form. In addition, 2-acylthiazolidines 13a-c do not evidence any dynamic processes in solution. © 1992 American Chemical Society.