An improvement in Seebach's method for the synthesis of α-alkylprolines is reported wherein the hydrolysis of the chiral oxazolidinone 2 is performed on a suspension of silica gel in MeOH/H2O. Following hydrolysis, the pure α-alkylproline can be obtained by filtration thereby avoiding a tedious ion exchange purification.
In the process of synthesizing N-propynoyl-(4S)-4-benzyl-1,3-oxazolidin-2-one (1) by Evans' conditions to prepare analogues of locostatin, an N-crotonyl oxazolidinone that inhibits cell migration and disrupts specific protein–protein interactions involved in the regulation of cell signaling, we unexpectedly discovered that the reaction underwent a secondary transformation to yield the bis-oxazolidinone enamine 2 (). The structure was confirmed by one- and two-dimensional NMR and ESI-MS (). In addition, compound 2 was hydrolyzed under acidic conditions and found to react sluggishly, suggesting that the presence of the electron-withdrawing group adversely affects the ability of the enamine to undergo hydrolysis.
(S)-(-)-4-Benzyl-2-Oxazolidinone For Synthesis
Enamines have become widely used intermediates in organic synthesis since the development of facile methods for their use in the alkylation and acylation of carbonyl compounds by Stork. These substrates are able to form carbon–carbon bonds easily, and the use of chiral amines provides an entry into asymmetric syntheses. Over the past decade, there has been an expansion of the reactions that may undergo enamine organocatalysis, such as α-oxidations and alkylations, aldol condensation, Michael additions, and enantioselective reductions. These developments have been showcased in the recent syntheses of (−)-anisomycin and (+)-conicol. The present report describes a method for preparing enamine products from N-propynoyl oxazolidinones and tosyl imides through tertiary amine catalysis.
Periodate Cleavage of 1,2-Diols - ChemTube3D
An efficient, cost-effective and large-scale synthesis of ezetimibe 1, an antihypercholesterolemia drug, is described. Chiral oxazolidinone chemistry was used to fix the required stereochemistry of the β-lactam ring, and the chiral oxazaborolidine chemistry was used to fix the hydroxyl group stereochemistry. The synthesis significantly lowers the cost and provides easy access to ezetimibe on large scale.