A Multicatalytic Approach to the Hydroaminomethylation of α‐Olefins

Abstract

We report an approach to conducting the hydroaminomethylation of diverse α‐olefins with a wide range of alkyl, aryl, and heteroarylamines at relatively low temperatures (70–80 °C) and pressures (1.0–3.4 bar) of synthesis gas. This approach is based on simultaneously using two distinct catalysts that are mutually compatible. The hydroformylation step is catalyzed by a rhodium diphosphine complex, and the reductive amination step, which is conducted as a transfer hydrogenation with aqueous, buffered sodium formate as the reducing agent, is catalyzed by a cyclometallated iridium complex. By adjusting the ratio of CO to H2, we conducted the reaction at one atmosphere of gas with little change in yield. A diverse array of olefins and amines, including hetreroarylamines that do not react under more conventional conditions with a single catalyst, underwent hydroaminomethylation with this new system, and the pharmaceutical ibutilide was prepared in higher yield and under milder conditions than with a single catalyst.

Glycerol Boosted Rh‐Catalyzed Hydroaminomethylation Reaction: A Mechanistic Insight

“…Taking into account the remarkable effect of glycerol and given the fact that hydrogenation of the imine‐, iminium‐ or enamine‐type intermediates is generally accepted as the rate‐determining step for Rh‐catalyzed HAM, we considered that a hydrogen transfer (glycerol as reducing agent) could be operative in addition to the hydrogenation reaction, enabling low‐pressure conditions while overriding the need for a metal‐based co‐catalyst . Thus, the nature of the hydrogen donor was further assessed with glycerol and butan‐1‐ol at 80 °C, revealing that enamine reduction was faster in the latter, albeit with moderate 1 a selectivity (Table , entries 1 and 2).…”

“…Overall, the results reported herein stress the fact that glycerol enables a Rh‐based catalytic system working under molecular regime, to perform one‐pot HAM cascade reaction to reach a reactivity behavior that was to date limited to multi‐catalytic systems, in particular those based on Rh/Ir bimetallic catalysts for the synthesis of linear amines …”

“…10:1) in the presence of an excess of tris(3‐sulfophenyl)phosphine trisodium salt (TPPTS), taking advantage of the known performance of Ir‐based systems in the hydrogenation of imines and enamines, leading to primary amines from terminal alkenes and ammonia (total pressure 78 bar; 110–130 °C; 5–10 h) with high regioselectivity (linear amines) and good chemoselectivity (primary amines) (Scheme a) . More recently, Hartwig's group also reported a Rh/Ir catalytic system constituted by [Rh(acac)(CO) 2 ]/BISBI (BISBI=2,2′‐bis(diphenylphosphinomethylene)‐1,1′‐biphenyl) and Xiao's catalyst, an Ir III organometallic complex that is stable in the presence of carbon monoxide; this catalytic system permits reactions to be performed under milder conditions (total pressure 3.4 bar; 80 °C; 20 h), producing secondary linear amines from good to high yields, using a mixture of solvents (toluene/methanol) and an aqueous buffer solution of NaHCO 2 (Scheme b). Notably, the role of bidentate ligands, such as the diphosphine BISBI, has proven to be key to achieving such high regioselectivities…”

Reusable Catalysts for Hydroformylation‐Based Reactions

“…[27] In addition, many efforts have been devoted to improving the efficiency of hydroformylation-based sequential processes, both in batch and continuousflow, which directly transform olefins into alcohols, acetals, and amines without isolating the aldehyde intermediates (Figure 3). [28] In general, sequential reactions carried out under hydroformylation conditions take advantage of the reactivity of the carbonyl group to obtain highly functionalized synthons through sustainable one-pot processes, avoiding the consumption of solvents and purification materials. [33] Bearing in mind that the most active and selective hydroformylation catalysts are transition metal complexes, mainly those based on rhodium or cobalt, which in addition to being toxic, are extremely expensive, several strategies have been implemented to develop reusable catalysts, in order to increase the reaction sustainability.…”

Catalytic and biophysical investigation of rhodium hydroformylase

“…[1][2][3][4][5][6][7][8][9][10] Design of ArMs that promote higher selectivity and activity is challenging. Strategies to achieve this have included, supramolecular assembly, 11,12 creating metal binding sites in vivo and reconstituted with a metal ion, 13,14 metal substitution, [15][16][17] incorporation of unnatural metal binding amino acids, 10,[18][19][20] computational or in silico 21 and covalent attachment including phosphonate ester and thioester linkage, 22,23 alkylation or maleimide conjugation. 24,25 One of the major advantages of ArMs is the great scope for tuning the catalyst activity and selectivity by genetic optimization i.e.…”