Hydroaminomethylation with Novel Rhodium–Carbene complexes: An Efficient Catalytic Approach to Pharmaceuticals

Abstract

Starting from [{Rh(cod)Cl}(2)] and 1,3-dimesitylimidazole-2-ylidenes the novel [RhCl(cod)(carbene)] complexes 1-5 have been synthesized, characterized, and tested in the hydroaminomethylation of aromatic olefins. The influence of different ligands and reaction parameters on the catalytic activity was investigated in detail applying 1,1-diphenylethylene and piperidine as a model system. The scope and limitations of the novel catalysts is shown in the preparation of 16 biologically active 1-amino-3,3-diarylpropenes. In general, high chemo- and regioselectivity as well as good yields of the desired products were achieved.

Synthesis of Fexofenadine via Rhodium-Catalyzed Hydroaminomethylation

“…This one-carbon homologation can be applied to the synthesis of secondary and tertiary amines. Hydroaminomethylation has been applied to the synthesis of fine chemicals [2][3][4] and several pharmaceuticals [5][6][7]. In addition to the use of unmodified rhodium carbonyl catalysts, rhodium complexes of phosphines and heterocyclic carbene ligands catalyze the hydroaminomethylation sequence.…”

Selective Catalytic Reductions of Amides and Nitriles to Amines

“…Examples include the aminations of olefins and alkynes [16][17][18][19][20][21][22][23], catalytic hydroaminomethylations [24][25][26][27][28][29][30], and more recently amination of alcohols as well as amines [31][32][33][34][35][36][37][38]. Our work on the development of novel catalytic reductions to give amines started around 2007 when we got interested in the ruthenium-catalyzed hydrogenation of nitriles.…”

Recent Advances in Amine Synthesis by Catalytic Hydroaminomethylation of Alkenes

“…The introduction of the triphenylphosphine ligand in the coordination sphere of rhodium results in the n/iso ratio increase since the hydridic character of the RhÀ H bond is higher and favors the formation of the linear alkyl moiety. Hydroaminomethylation with N-Heterocyclic carbene ligands has first been reported by Beller et al [44,45] Scheme 12. [40] Operating at somewhat higher temperatures (60 to 100 8C) the reaction converted all the styrene and morpholine to reach a selectivity for the branched amine of 85.5 %.…”