Biorenewable Resources in the Biginelli Reaction: Cerium(III)-Catalyzed Synthesis of Novel Iminosugar-Annulated Perhydropyrimidines

Abstract

An unprecedented version of the Biginelli reaction using an unprotected aldose as a biorenewable aldehyde component and 2-phenyl-1,3-oxazol-5-one as a novel active methylene building block with urea/thiourea is reported. The reaction is cerium(III)catalyzed, expeditious, and effected under solvent-free microwave irradiation conditions to yield diastereoselectively, iminosugar-annulated polyfuntionalized perhydropyrimidines via ring transformation of an isolable intermediate followed by cyclodehydration.

Synthetic Approaches to α,β‐Diamino Acids

“…Recently, Yadav et al have reported the one-pot synthesis of 4-amino perhydropyrimidines 10 upon a Biginelli reaction. Upon microwave irradiation and in the presence of a Ce(III) salt, D-xylose and D-glucose react with ureas 8 and thioureas generating aldose-derived C¼N species that are attacked in situ by an 1,3-oxazol-5-one 9 and finally evolve to the perhydropyrimidine 10 diastereoselectively (Scheme 9.2) [9]. p-Toluenesulfinimines 11 can participate as chiral inductors in the BF 3 ÁEt 2 O-mediated addition of lithiated a-imino glycinates to afford enantiopure 4,5-trans 4-carbomethoxy N-sulfinylimidazolidines 12 (Scheme 9.2).…”

Multicomponent reactions in chiral ionic liquids: A stereocontrolled route to mercaptopyranothiazoles

“…As part of our ongoing research programme and continued interest in devising new solvent-free cyclization processes [35][36][37][38][39], we had to develop an efficient synthetic approach to pyranothiazoles incorporating a thiol function at C-6. For this purpose, we utilized the mercaptoacetyl transfer agent, 2-methyl-2-phenyl-1,3oxathiolan-5-one ( Figure 1) [38], which leads to the desired mercaptoacetylative heteroannulation and is the key element in the present successful synthetic strategy for the target compounds 4 (Scheme 1).…”

Urea: A Useful and Inexpensive Chemical for Organic Synthesis

“…This easily accessible chemical has been used as building block in the synthesis of N-carbamoyl-L-amino acids, 1 cyclic carbonates, 2 and many nitrogen-containing heterocycles such as pyridines, 3 pyrimidines, 4 3,4-dihydropyrimidinones, 5 oxazines, 6 1,3-ox-azin-3-ones, 7 and iminosugars. 8 Another application of urea in carbohydrate chemistry was described earlier. 9 Urea is also employed as source of ammonia in the syntheses of triarylamines, 10 imides, 11 and amides.…”

“…(F) Iminosugars are compounds with great pharmacological importance. Yadav et al8 reported that the reaction of 2-phenyl-1,3-oxazol-5-one, urea, and unprotected aldoses following the Biginelli protocol under solvent-free conditions leads to the formation of functionalized iminosugars in good yields and high trans diastereoselectivity. (G) Recently, Artamkina et al10 developed a new method for triarylamine synthesis using a palladium-catalyzed C-N bond formation (Buchwald-Hartwig reaction).…”