Ruthenium‐Catalyzed Highly Chemoselective Hydrogenation of Aldehydes

Abstract

The use of a [(ethylenediamine)(dppe)Ru(OCOtBu) 2 ] [dppe = 1,2-bis(diphenylphosphino)ethane] complex under base-free conditions allowed highly efficient and selective hydrogenation of aldehydes in the presence of ketones in addition to olefins. Even in the case of highly sensitive 1,6-ketoaldehydes, the desired ketoalcohols were obtained in high yields with 94-99 % overall selectivity at complete aldehyde conversion with a TON up to 30 000. The lack of requirement for strong basic co-catalysts and polar protic solvents also allowed efficient and highly chemoselective reduction of aldehydes bearing other functional groups, such as epoxides, carboxylic acids, esters, amides, and nitriles emphasizing the potential synthetic utility of the catalyst.The search for highly enantioselective chemical processes has been the main driving force towards the development of new synthetic catalytic methodologies for many years, probably related to the ever-growing number of optically pure drugs produced in the pharmaceutical industry.[1] Nevertheless, if astonishingly high enantiocontrol was achieved for a large number of chemical transformations, it was quite often done at the expense of process efficiency in terms of catalyst loadings and reaction scope. Initially introduced and further developed as a concept by Trost, [2] chemoselectivity was more recently claimed by Baran and co-workers [3] to be the key for further synthetic efficiency, especially to access highly complex molecules. Discovery of new chemoselective transformations should indeed allow some traditional retrosynthetic approaches to be reconsidered and avoid some tedious protection/deprotection sequences. New transformations should also be able to efficiently meet some increasing industrial requirements related to the environment with the potential to decrease the E-factor.Research towards highly efficient chemoselective processes has been nicely illustrated by recent developments in the reduction of carbonyl groups into alcohols. Noyori-type catalysts are widely used for the hydrogenation of ketones in the presence of olefins, even in the case of achiral transformations, thanks to their amazingly high catalytic activity.[4] Nevertheless, such catalysts were never reported for selective reduction of aldehydes in the presence of ketones, such a transformation represents a step further in chemoselectivity. This could be related to the general requirement for a strongly basic co-catalyst to achieve high catalytic efficiency, such conditions favoring the aldol side reaction. In addition to this, if aldehydes are known to be more reactive than ketones, some with only a slight difference in bond energy (about 5 kcal mol À1 ), it is a true obstacle to achieve high chemoselectivity results at complete aldehyde conversion. Also, several homogeneous catalysts, such as [Ir(H 3 )(PPh 3 ) 3 ], [RuCl 2 (PPh 3 ) 3 ], [Rh(cod)Cl] 2 / TPPTS (cod = 1,5-cyclooctadiene; TPPTS = tris(3-sulfophenyl)-phosphine trisodium salt), developed earlier were reported to exhibit some decent a...

Catalytic (de)hydrogenation promoted by non-precious metals – Co, Fe and Mn: recent advances in an emerging field

“…These results render the B-Fe catalysts among the most active systems reported to date for the selective hydrogenation of aldehydes and rival the performance of noble metal catalysts. 57 The utility of iron-catalysed hydrogenation was later extended to unactivated esters with the development of the aminopincer Fe catalysts based on the ligand family C (Scheme 6). The groups of Beller 58 and Guan 59 independently reported the use of catalyst C-Fe-1 for the conversion of various esters to the corresponding alcohols at 1-3% mol catalyst loading under 10-50 bar H 2 pressure and a temperature of 100-135 1C.…”

Hydrogenation and Reductive Amination of Aldehydes using Triphos Ruthenium Catalysts

“…Low catalyst loadings of S/C = 10 000:1, as electiono fs olvents and solvent-free conditions were tested.F ull conversion was observed in most cases and, pleasingly,improved selectivity was observed, up to 98:2 in favour of cinnamyl alcohol (entries [11][12][13][14][15][16][17]. The low catalyst loading and high selectivity for the allylic alcohol comparef avourably with the best homogenous catalysts under hydrogenation conditions, for example: (Ir) S/C = 500:1, [41] (Ru) S/C = 500:1, [8] (Ru) S/C = 200:1, [42] (Ru) S/ C = 200:1, [43] (Ru) SC = 500:1, [44] (Ru) S/C = 1000:1, [45] (Fe) S/C = 200:1, [46] (Fe) S/C = 500:1, [47] (Fe) S/C = 20 000:1, [48] (Ru) S/C = 10 000:1.…”

“…and the use of phenylacetylide complexes, H−Ru−(CCPh), reported by Morris et al . More recently, ruthenium carboxylates have been developed by Dupau and co‐workers and are employed under neutral or weakly acidic conditions . Additionally, an efficient catalytic hydrogenation of aldehydes using a ruthenium glycinate complex has been reported by Zhang and co‐workers …”

Unexpected Role of Anionic Ligands in the Ruthenium‐Catalyzed Base‐Free Selective Hydrogenation of Aldehydes

“…Starting from readily available [(cod)Ru(OCOR) 2 ]‐type precursors (cod=1,5‐cyclooctadiene),17 we synthesized [(diamine)(diphosphine)Ru(OCOR) 2 ] complexes 3 , generally as a cis / trans mixture of biscarboxylate isomers, through sequential ligand‐coordination steps, as described in the Supporting Information. We tested a very large variety of complexes of type 3 without isomer separation in the selective hydrogenation of aldehydes16 and report herein the use of a limited number of these catalysts with the substrates shown in Scheme .…”