5-Phenylthio-1,3-oxazinan-4-ones via hetero Diels–Alder reactions: synthesis of (R)- and (S)-Duloxetines and Fluoxetines

Metal-Free Synthesis of Oxazinones and Their Reductive Ring Opening to Provide Cyclopropyl Carbinols

“…Following this, hetero Diels-Alder reactions were used to generate 1,3-oxazinan-4-ones 8 in 33-55% yield from heterodienes 6 and aldehydes 7. 8 This reaction forgoes the use of elevated temperatures, and instead facilitates the reaction with the use of strong Lewis acids. However, only a limited number of examples using this method have been reported: four electron-rich aromatic substituents (furanyl, N-tertbutyloxyindolyl, thiophenyl, 4-methoxyphenyl), and two electron-neutral substituents (phenyl, methyl) were disclosed.…”

EuFOD-Catalyzed Hetero-Diels-Alder (HDA) Reaction under Microwave Heating

“…No Comments on Table 1 a) Although the formation of the cycloadducts 2 and 3 takes place even under classical heating conditions (CH, 21,22 in all cases, immaterial of the final goal of the production of 1,3-aminols, scaffolds of CNS drugs like Prozac ® , and its congeners.…”

“…It was gratifying to find out that the above reported procedure must be considered efficient and valuable in view of the possibility to build up a small library of oxazinan-2-ones, which may in turn, be elaborated to a 1,3-aminols according to already published protocols. 21,22 Hetero-Diels-Alder Reaction of Azadienes 1, 4 with Aromatic Aldehydes; trans-2,6-Diphenyl [1,3] AcCl (0.430 mL, 6 mmol) in hexane (2 mL), and the mixture was stirred for 2 h at r.t. The mixture was filtered through a Celite pad and the solvent was evaporated.…”

“…[17][18][19][20] The HDA-cycloadducts thus obtained have been demonstrated to serve as useful intermediates for the preparation of 1,3-aminols, scaffolds of a wide range of biologically active compounds including CNS drugs as Prozac ® . 21,22 The synthesis of the target compounds was extensively optimized using azadiene 1 and benzaldehyde as test sub-strata (Scheme 1 and Table 1). As underlined in Table 1, entry 5, the best conversion of azadiene 1 into HDA adduct was achieved in chlorobenzene as solvent and Eu-FOD as lanthanide catalyst.…”

Synthesis and Biological Evaluation of Cruentaren A Analogues

“…The synthesis for 5-phenylthio-1,3-oxazinan-4-ones is based on the hetero Diels-Alder reaction between an azadiene and an aldehyde. [40] Other 1,3-oxazinanones are known as well. [41,42,43] Biological testing: The described analogues as well as the diyne 53 were tested for cytotoxicity against the L929 cell line and the inhibitory efficacy on F-ATPase in mitochondrial preparations of bovine heart.…”