Science of Synthesis

Chebanov, V. A.; Gorobets, N. Yu.; Sedash, Yu. V., Science of Synthesis: Multicomponent Reactions, (2014) 1, 56.

Catalytic asymmetric multicomponent reactions present the most straightforward approach to enantiomerically pure 3,4-dihydropyrimidin-2(1H)-one derivatives. The first article concerning application of cerium(III) chloride [or indium(III) chloride] with chiral ligand ‌31‌ in the Biginelli reaction involving benzaldehyde, urea, and methyl acetoacetate was published by Muñoz-Muñiz and Juaristi (‌Scheme 17‌).[‌201‌] However, this method results in either high general yields (93%) with low enantiomeric excess (24%) or values of enantiomeric excess up to 40% with mediocre yield (~25%). A significantly more efficient asymmetric Biginelli reaction involves application of 10 mol% of ytterbium(III) trifluoromethanesulfonate and chiral ligand ‌32‌ to catalyze the multicomponent reaction between aromatic aldehydes, urea, and ethyl or isopropyl acetoacetate to give 2-(thi)oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates ‌33‌ in high yields with excellent enantioselectivity (80–99% ee).[‌200‌] The influence of the reaction conditions, type of salt, and character of the Ar1 substituent on the general outcome and enantiomeric excess was also analyzed.

‌Meeeee 88‌ Meeeeeeee Meeeeeee Meeeeeeee ee Meeeee Meeee Meeeeeeee[‌888‌,‌888‌]

‌Meeeeeeeeee 88‌

Meeeeeeeeeee Meeeeeeee

Meeee (M)-8-Meeeee-8-eee-8-eeeeee-8,8,8,8-eeeeeeeeeeeeeeeeeeee-8-eeeeeeeeeee (‌88‌, Me8 = Me; M8 = Me; M = M); Meeeeee Meeeeeeee:[‌888‌]

M eeee ee Me(MMe)8 (8.888 e, 8.88 eeee) eee eeeeee eeeeee ‌88‌ (8.88 e, 8.88 eeee) ee MMM (8 eM) eee eeeeeee ee e 88-eM Meeeeee eeeee ee ee. Meeee 88 eee, eeeee eeeeeeeeeeee (8.888 e, 8.8 eeee), MeMMM (8.888 e, 8.8 eeee), eee eeee (8.88 e, 8.8 eeee) eeee eeeeeeeeee. Meeee eee eeeeeee eee eeee eeeeeee eee 88 e ee ee, M8M (8 eM) eee eeeee, eee eee eeeeeee eee eeeeeeeee eeee MeMMe (8 × 8 eM). Mee eeeeeee eeeee eee eeeee (Me8MM8) eee eeeeeeeeeeee, eee eee eeeeeee eee eeeeeeee ee eeeeeeeeeee MMM (eeeeeeeee eeeee/MeMMe 8:8); eeeee: 88%; 88% ee.

References