The reduction of amides gives access to a wide variety of important compounds such as amines, imines, enamines, nitriles, aldehydes and alcohols. The chemoselective transformation into these functional groups is challenging due to the intrinsic stability of the amide bond; nevertheless, the ability to reduce highly stable carboxamides selectively in the presence of sensitive functional groups is of high synthetic value for academic and industrial chemists. Hydride-based reagents such as LiAlH or diboranes are today the most commonly used compounds for amide reductions, and apart from the substantial amount of waste generated using these methods, they lack tolerance to most other functional groups. This tutorial review provides an overview of the recent progress made in the development of chemoselective protocols for amide reduction and gives an insight to their advantages and drawbacks.

Herein, a practical and mild method for the deoxygenation of a wide range of benzylic aldehydes and ketones is described, which utilizes heterogeneous Pd/C as the catalyst together with the green hydride source, polymethylhydrosiloxane. The developed catalytic protocol is scalable and robust, as exemplified by the deoxygenation of ethyl vanillin, which was performed on a 30 mmol scale in an open-to-air setup using only 0.085 mol % Pd/C catalyst to furnish the corresponding deoxygenated product in 93 % yield within 3 hours at room temperature. Furthermore, the Pd/C catalyst was shown to be recyclable up to 6 times without any observable decrease in efficiency and it exhibited low metal leaching under the reaction conditions.

In this study, two stereocomplementary ω-transaminases from Arthrobacter sp. (AsR-ωTA) and Chromobacterium violaceum (Cv-ωTA) were immobilized via iron cation affinity binding onto polymer-coated controlled porosity glass beads (EziG™). The immobilization procedure was studied with different types of carrier materials and immobilization buffers of varying compositions, concentrations, pHs and cofactor (PLP) concentrations. Notably, concentrations of PLP above 0.1 mM were correlated with a dramatic decrease of the immobilization yield. The highest catalytic activity, along with quantitative immobilization, was obtained in MOPS buffer (100mM, pH 8.0, PLP 0.1 mM, incubation time 2 h). Leaching of the immobilized enzyme was not observed within 3 days of incubation. EziG-immobilized AsR-ωTA and Cv-ωTA retained elevated activity when tested for the kinetic resolution of rac-α-methylbenzylamine (rac-α-MBA) in single batch experiments. Recycling studies demonstrated that immobilized EziG 3 -AsR-ωTA could be recycled for at least 16 consecutive cycles (15min per cycle) and always affording quantitative conversion (TON ca. 14,400). Finally, the kinetic resolution of rac-α-MBA with EziG 3 -AsR-ωTA was tested in a continuous flow packed-bed reactor (157 µL reactor volume), which produced more than 5 g of ( S )-α-MBA (> 49% conversion, > 99% ee) in 96 h with no detectable loss of catalytic activity. The calculated TON was more than 110,000 along with a space-time yield of 335 g L −1 h −1 .

The chemoselective reduction of amides in the presence of other more reactive reducible functional groups is a highly challenging transformation, and successful examples thereof are most valuable in synthetic organic chemistry. Only a limited number of systems have demonstrated the chemoselective reduction of amides over ketones. Until now, the aldehyde functionality has not been shown to be compatible in any catalytic reduction protocol. Described herein is a [Mo(CO)6 ]-catalyzed protocol with an unprecedented chemoselectivity and allows for the reduction of amides in the presence of aldehydes and imines. Furthermore, the system proved to be tunable by variation of the temperature, which enabled for either C-O or C-N bond cleavage that ultimately led to the isolation of both amines and aldehydes, respectively, in high chemical yields.

Compared with biocatalysis in aqueous media, the use of enzymes in neat organic solvents enables increased solubility of hydrophobic substrates and can lead to more favorable thermodynamic equilibria, avoidance of possible hydrolytic side reactions and easier product recovery. ω-Transaminases from Arthrobacter sp. (AsRÀ ωTA) and Chromobacterium violaceum (CvÀ ωTA) were immobilized on controlled porosity glass metal-ion affinity beads (EziG) and applied in neat organic solvents for the amination of 1phenoxypropan-2-one with 2-propylamine. The reaction system was investigated in terms of type of carrier material, organic solvents and reaction temperature. Optimal conditions were found with more hydrophobic carrier materials and toluene as reaction solvent. The system's water activity (a w ) was controlled via salt hydrate pairs during both the biocatalyst immobilization step and the progress of the reaction in different nonpolar solvents. Notably, the two immobilized ωTAs displayed different optimal values of a w , namely 0.7 for EziG 3 À AsRÀ ωTA and 0.2 for EziG 3 À CvÀ ωTA. In general, high catalytic activity was observed in various organic solvents even when a high substrate concentration (450-550 mM) and only one equivalent of 2propylamine were applied. Under batch conditions, a chemical turnover (TTN) above 13000 was obtained over four subsequent reaction cycles with the same batch of EziG-immobilized ωTA. Finally, the applicability of the immobilized biocatalyst in neat organic solvents was further demonstrated in a continuous flow packedbed reactor. The flow reactor showed excellent performance without observable loss of enzymatic catalytic activity over several days of operation. In general, ca. 70% conversion was obtained in 72 hours using a 1.82 mL flow reactor and toluene as flow solvent, thus affording a space-time yield of 1.99 g L À 1 h À 1 . Conversion reached above 90% when the reaction was run up to 120 hours.

Tertiary amides are efficiently reduced to their corresponding enamines under hydrosilylation conditions, using a transition-metal-free catalytic protocol based on t-BuOK (5 mol %) and (MeO)3SiH or (EtO)3SiH as the reducing agent. The enamines were formed with high selectivity in good-to-excellent yields.

Tertiary amides were efficiently reduced to their corresponding tertiary amines in high isolated yields by using the commercially available and inexpensive polymeric silane polymethylhydrosiloxane (PMHS) as the reducing agent. The reaction is efficiently catalyzed by an in situ generated iron/N‐heterocyclic carbene complex (1 mol‐%) obtained from iron(II) acetate and 1‐(2‐hydroxy‐2‐phenylethyl)‐3‐methylimidazolium triflate ([PhHEMIM][OTF]). A catalytic amount of lithium chloride (1 mol‐%) present in the reaction mixture significantly reduced the reaction time and increased the chemoselectivity of the reduction process.

Broadly applicable methods for efficient and catalytic additions of easy-to-handle allyl–B(pin) (pin = pinacolato) compounds to ketones and acyclic α-ketoesters have been developed. Accordingly, a large array of tertiary alcohols can be obtained in up to >98% yield and 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, as Me-substitution leads to substantially higher enantioselectivity, the sense of induction is reversed as well.