Synthesis of β^2,2‐Amino Esters via Rh‐Catalysed Regioselective Hydroaminomethylation

Abstract

The synthesis of β 2,2 -amino esters was successfully achieved via Rh-catalysed regioselective hydroaminomethylation of methyl methacrylate with secondary amines using the neutral precursor [Rh(acac)(CO) 2 ]. In this process, the presence of molecular sieves revealed crucial in order to access the final amino ester. For the synthesis of products containing aniline derivatives, the use of the cationic precursor [Rh(COD) 2 ]BF 4 and Me CgPPh phosphine as ligand was necessary in a mixture of toluene/ DCE as solvent. Effects of the steric and electronic properties of the amines were observed during this study. Interestingly, poisoning effect of CO in the hydrogenation of the imine intermediate was observed when benzyl amine was used.

Comprehensive Chirality

“…The authors had previously published very interesting results on the regioselectivity of the reaction of α-substituted acrylates to access β 2,2 -amino esters 142 . In this case, the products were not chiral, but provided β 2,2 -amino acid derivatives containing a quaternary carbon center which are scaffolds present in various medicinal drugs 143 In this study, the authors focused on the [Rh(COD)2]BF4/(R,R)-QuinoxP* catalytic system to access chiral γ-aminobutyric esters in poor to high yields (up to 98%) and high enantioselectivities (up to 86%).…”

2‐Arylpropylamines from 1‐Propenylbenzenes in a New One‐Pot Metathesis–Hydroaminomethylation Protocol

“…Rh-catalyzed HAM has been recently used for the synthesis of indoles or indoline-2-ols, [13] gamma-aminobutyric esters, [14] beta-aminoesters [15] in homogeneous catalysis. Also, in several recent studies the catalyst was supported on an immiscible liquid phase [16][17][18][19] or on polymers [20,21] to facilitate the recycling.…”

Hydroaminomethylation of Natural Allylic and Homoallylic Alcohols: A Ligand‐Controlled Route to New Amines

“…Due to the further development of more efficient cobalt and rhodium catalysts and the introduction of phosphorus ligands, HAM has become a powerful method for the synthesis of amines. [4][5][6][7][8][9][10][11][12][13][14][15] As HAM is a tandem catalytic process in which various catalytic cycles occur simultaneously, the conditions can be good for one catalytic cycle and deleterious for the other. For this reason, care in the choice of appropriate conditions is critical for the successful reaction sequence.…”

“…However, selectivity for amines was low and the reaction required harsh conditions (T>300 °C and pressures up to 150 bar). Due to the further development of more efficient cobalt and rhodium catalysts and the introduction of phosphorus ligands, HAM has become a powerful method for the synthesis of amines [4–15] . As HAM is a tandem catalytic process in which various catalytic cycles occur simultaneously, the conditions can be good for one catalytic cycle and deleterious for the other.…”