Homogeneous Hydrogenation of Aldehydes, Ketones, Imines and Carboxylic Acid Derivatives: Chemoselectivity and Catalytic Activity

Abstract

414Scheme 15.1 Hydrogenation of n-butyraldehyde. Table 15.1 Hydrogenation of aldehydes with [IrH 3 (PPh 3 ) 3 ] in acetic acid. Substrate Catalyst [mol.%] Temperature [8C] Yield [%] TON TOF [h -1 ] 0.022 80 73 3280 492 0.023 110 82 3540 177 0.032 90 64 2000 89 0.039 110 80 2030 81 0.013 110 98 7780 259 examined for a,b-unsaturated aldehydes (Scheme 15.2). Using the [IrH 3 (PPh 3 ) 3 ] complex in acetic acid for the hydrogenation of crotonaldehyde resulted in the formation of the saturated alcohol (Scheme 15.3). It was also noted that this catalyst did not allow for ketone hydrogenation at 10 bar. Other attempts to use iridium PPh 3 complexes such as [IrCl(PPh 3 ) 3 ], [IrCl(CO)(PPh 3 ) 2 ], [Ir(ClO 4 )(CO)(PPh 3 ) 2 ] and [Ir(CO)(PPh 3 ) 3 ]ClO 4 to hydrogenate unsaturated aldehydes did not yield great results [3], mainly because these catalysts suffered from low activity and selectivity.The catalytic system of [Ir(COD)Cl] 2 with an excess of the bulky phosphine P(o-MeOPh) 3 under transfer hydrogenation conditions of propan-2-ol and KOH was used successfully in the selective hydrogenation of cinnamaldehyde (Scheme 15.4) [4]. Selectivity and activity were found to increase with increasing P/Ir ratios, and complete conversion was achieved in as little as 5 minutes (turnover frequency (TOF) *6000 h -1 ). Hydrogenation of Aldehydes 415Scheme 15.2 Distribution of products in the hydrogenation of a,b-unsaturated aldehydes. Scheme 15.3 Hydrogenation of crotonaldehyde with [IrH 3 (PPh 3 ) 3 ] in acetic acid. Scheme 15.4 Transfer hydrogenation of cinnamaldehyde.Using molecular hydrogen as the reducing agent, [Ir(COD)(OCH 3 )] 2 with an excess of tertiary phosphine was better than [Ir(COD)Cl] 2 for the selective hydrogenation of cinnamaldehyde [5]. In these studies, a great dependence on solvent and ligand was reported. A variety of different phosphines, which were markedly different in their steric and electronic properties, were examined in this reaction. In propan-2-ol the most effective phosphine was PCy 2 Ph which gave 94% yield (TOF 235 h -1 ) of the unsaturated alcohol in a 2 h reaction under 30 bar H 2 at 100 8C. Phosphines such as PCyPh 2 , PPhPr i 2 , PPh 2 Pr i and PEtPh 2 were also effective in giving over 95% selectivity. The less-effective phosphines were PEt 2 Ph, PMePh 2 , PBu i 3 and PMe 2 Ph. Reactions that were performed in toluene were generally less effective.More recent advances in iridium-catalyzed aldehyde hydrogenation have been through the use of bidentate ligands [6]. In the hydrogenation of citral and cinnamaldehyde, replacing two triphenylphosphines in [IrH(CO)(PPh 3 ) 3 ] with bidentate phosphines BDNA, BDPX, BPPB, BISBI and PCP ( Fig. 15.1) led to an increase in catalytic activity. a) Selectivity of allylic alcohol formed as a percentage of total hydrogenation products. b) TOF (h -1 ) expressed for conversion of starting material. Hydrogenation of Aldehydes 419Scheme 15.5 Preparation of cationic DiPFc catalyst.

Mechanochemical Metal-Free Transfer Hydrogenation of Carbonyls Using Polymethylhydrosiloxane as the Hydrogen Source

“…The reduction of carbonyls to alcohols is a key reaction in the chemical industry, spanning from the production of commodity chemicals to pharmaceutical compounds . On the lab scale, this is often done using stoichiometric amounts of hydrides, such as NaBH 4 or LiAlH 4 .…”

“…The reduction of carbonyls to alcohols is a key reaction in the chemical industry, spanning from the production of commodity chemicals to pharmaceutical compounds. 1 On the lab scale, this is often done using stoichiometric amounts of hydrides, such as NaBH 4 or LiAlH 4 . 2 Catalytic methods relying on transition metals allowed us to unravel the potential of molecular hydrogen gas for this reaction, via the development of highly active and chemo-, regio-, and enantioselective systems, with high atom-economy.…”

Selective, Base-Free Hydrogenation of Aldehydes Catalyzed by Ir Complexes Based on Proton-Responsive Lutidine-Derived CNP Ligands

“…Herein, we report the synthesis of Ir complexes incorporating new CNP ligands having di- tert -butylphosphino side arms and their application to the chemoselective hydrogenation of commercial-grade aldehydes under neutral conditions. Aldehyde hydrogenation represents an environmentally friendly alternative to the use of alumino- and borohydrides commonly used in organic synthesis laboratories and industrial settings for the reduction of carbonyl groups . Although hydrogenation of carbonyl derivatives, particularly ketones, is usually regarded as a well-developed technology, relatively few examples of catalytic systems have been described for the hydrogenation of aldehydes to primary alcohols, , most of them requiring previous extensive substrate purification and the use of a base as a catalyst activator, which is an important limitation to the reaction scope due to the sensitivity of aldehydes to basic conditions.…”

Transition Metal Complexes of an (S,S)-1,2-Diphenylethylamine-Functionalized N-Heterocyclic Carbene: A New Member of the Asymmetric NHC Ligand Family

“…Enantiopure alcohols and amines are essential building blocks for the synthesis of drugs, fragrances, and agrochemicals. One of the many ways to efficiently generate such molecules is via the asymmetric hydrogenation of the corresponding ketones or imines using a transition metal catalyst. − However, most hydrogenation catalysts, including recently reported iron-based catalysts, contain asymmetric chelating phosphine ligands, which can potentially introduce harmful contaminants into products destined for medical applications. ,− A possible solution to this problem is to replace the phosphines with N-heterocyclic carbenes (NHC) since these organic ligands might be less toxic while maintaining a σ-donor strength that is similar or greater than that of a phosphine. , Our group previously reported achiral NHC-Q-NH 2 ligands with linking groups Q for use with precious metals such as Ru ( 1 , 2 , and 4 ) and Ir ( 3 ) (Scheme ). − The complexes of these ligands showed moderate to exceptional catalytic reactivity under mild conditions (25–50 °C, 9–26 atm) toward the complete hydrogenation of ketones, imines (only 2 ), and esters (only 2 ).…”