Improved Protocol for the Three‐Component Biginelli Reactions and Biginelli‐Like Mannich Reactions of Carbamates, Aldehydes, and Ketones

Abstract

A mild, convenient, and improved method for the direct three‐component Biginelli and Biginelli‐like Mannich‐type reactions of carbonyl compounds in the presence of inexpensive FeCl3⋅6 H2O and Me3SiCl as catalysts is described. Reactions performed with carbamates can be used to directly access N‐protected β‐amino carbonyl compounds in a single step.

Iron Catalysis in Organic Synthesis

“…953 In addition, under these conditions the authors could extend the substrate scope to ketones (Scheme 649). 1139 A variety of 5-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones could be synthesized in high yields.…”

“…953 They conducted a threecomponent reaction of aldehydes, ketones, and carbamates in the presence of catalytic amounts of iron(III) chloride hexahydrate and substoichiometric amounts of trimethylchlorosilane. Under very mild conditions, in a solvent mixture of dichloromethane and diethyl ether at room temperature, they obtained β-(benzyloxycarbonylamino)aldehydes or ketones in moderate to good yields.…”

Recent Uses of Iron (III) Chloride in Organic Synthesis

“…However, a Mannich-type reaction takes place (Scheme 22) [54], using 10 mol% of FeCl 3 ·6H 2 O with respect to aldehyde. However, a Mannich-type reaction takes place (Scheme 22) [54], using 10 mol% of FeCl 3 ·6H 2 O with respect to aldehyde.…”

“…Ni(acac) 2 , Yb(TfO) 3 and FeCl 3 ·6H 2 O have been studied in [bmim]PF 4 , focusing on the addition of acetoacetone (5 3 ) to methylvinylketone (54), to give 55 as a model reaction (Scheme 28) [67]. Ni(acac) 2 , Yb(TfO) 3 and FeCl 3 ·6H 2 O have been studied in [bmim]PF 4 , focusing on the addition of acetoacetone (5 3 ) to methylvinylketone (54), to give 55 as a model reaction (Scheme 28) [67].…”

Heterogeneous liquid phase synthesis of 3,4-dihydropyrimidine-2(1H)-ones using aluminated mesoporous silica

“…Many Lewis acids such as Cu(OTf) 2 , CuCl 2 , Ag 3 PW 12 O 40 , FeCl 3 ⋅6H 2 O, Me 3 SiCl [6][7][8][9][10], and protic acids such as NH 2 SO 3 H, NH 4 Cl [11,12] were employed for this reaction. Other special methods including ionic liquids, microwave irradiation, trimethylsilyl-triflate, polyaniline-bismoclite complex, L-proline, grindstone chemistry, and I 2 were also employed [13][14][15] for this transformation, but all these processes suffer from many drawbacks such as purification of the product, the reaction yield and the use of hazardous organic synthesis.…”