Site-Selective Hydrogenation of Electron-Poor Alkenes and Dienes Enabled by a Rh-Catalyzed Hydride Addition/Protonolysis Mechanism

The transition metal catalyzed hydrogenation of alkenes is a well-developed technology used on a lab scale as well as on large scales in the chemical industry. Site- and chemoselective mono-hydrogenations of polarized conjugated dienes remain challenging. Instead, stoichiometric main-group hydrides are used rather than H2. As part of an effort to develop a scalable route to prepare geranylacetone, we discovered that Rh(CO)2acac/xantphos based catalysts enable the selective monohydrogenation of electron-poor 1,3-dienes, enones, and other polyunsaturated substrates. D-labeling and DFT studies support a mechanism where a nucleophilic Rh(I)-hydride selectively adds to electron-poor alkenes and the resulting Rh-enolate undergoes subsequent inner-sphere protonation by alcohol solvent. The finding that (Ln)Rh(H)(CO) type catalysts can enable selective mono-hydrogenation of electron-poor (poly)enes provides a valuable tool in the design of related chemoselective reduction processes of unsaturated substrates

Study of Precatalyst Degradation Leading to the Discovery of a New Ru⁰ Precatalyst for Hydrogenation and Dehydrogenation

The complex Ru-MACHO (<b>1</b>) is a widely used precatalyst for hydrogenation and dehydrogenation reactions under basic conditions. In an attempt to identify the active catalyst form, <b>1</b> was reacted with a strong base. The formation of previously unreported species was observed by NMR and mass spectrometry. This observation indicated that complex <b>1</b> quickly degraded under basic conditions when no substrate was present. X-ray crystallography enabled the identification of three complexes as products of this degradation of complex <b>1</b>. These complexes suggested degradation pathways which included ligand cleavage and reassembly, along with reduction of the ruthenium atom. One of the decomposition products, the Ru⁰ complex [Ru­(N­(CH₂CH₂PPh₂)₃)­CO] (<b>5</b>), was prepared independently and studied. <b>5</b> was found to be active, entirely additive-free, in the acceptorless dehydrogenation of aliphatic alcohols to esters. The hydrogenation of esters catalyzed by <b>5</b> was also demonstrated under base-free conditions with methanol as an additive. Protic substrates were shown to add reversibly to complex <b>5</b>, generating Ru^II–hydrido species, thus presenting a rare example of reversible oxidative addition from Ru⁰ to Ru^II and reductive elimination from Ru^II to Ru⁰

Ru(II)-Triphos Catalyzed Amination of Alcohols with Ammonia via Ionic Species

An active and selective system for the amination of primary alcohols to primary amines with ammonia based on ruthenium and triphos as the tridentate phosphine ligand was developed. On the basis of detailed mechanistic studies, we propose that the active catalyst is, unlike the previously reported systems on this reaction, a cationic ruthenium complex. The experimental findings are supported by detailed density functional theory (DFT) calculations on the catalytic cycle. Because of the cationic nature of the active catalyst, strong anion and solvent effects were observed in the catalytic amination reaction when using the ruthenium triphos complexes. Therefore, a higher activity could be achieved when the nonpolar solvent toluene is used in this amination instead of tetrahydrofuran. Our findings can help to develop and optimize the system systematically for an application to relevant target molecules

Selective Alkylation of Amines with Alcohols by Cp*–Iridium(III) Half-Sandwich Complexes

[Cp*Ir(Pro)Cl] (Pro = prolinato) was identified among a series of Cp*–iridium half-sandwich complexes as a highly reactive and selective catalyst for the alkylation of amines with alcohols. It is active under mild conditions in either toluene or water without the need for base or other additives, tolerates a wide range of alcohols and amines, and gives secondary amines in good to excellent isolated yields

Alcohol Amination with Aminoacidato Cp*Ir(III)-Complexes as Catalysts: Dissociation of the Chelating Ligand during Initiation

The use of aminoacidato Cp*Ir­(III)-complexes in catalytic alcohol amination reactions of primary and secondary alcohols with amines permits to carry out these transformations at very mild reaction conditions without the use of an additional base. Herein we discuss the fate of the chelating aminoacidato ligands upon initiation of Cp*Ir­(III)-complexes from a mechanistic perspective. Catalyst initiation has been followed by NMR using isotopically labeled ¹³C,¹⁵N-glycinato complexes

Alcohol Amination with Aminoacidato Cp*Ir(III)-Complexes as Catalysts: Dissociation of the Chelating Ligand during Initiation

The use of aminoacidato Cp*Ir­(III)-complexes in catalytic alcohol amination reactions of primary and secondary alcohols with amines permits to carry out these transformations at very mild reaction conditions without the use of an additional base. Herein we discuss the fate of the chelating aminoacidato ligands upon initiation of Cp*Ir­(III)-complexes from a mechanistic perspective. Catalyst initiation has been followed by NMR using isotopically labeled ¹³C,¹⁵N-glycinato complexes

Alcohol Amination with Ammonia Catalyzed by an Acridine-Based Ruthenium Pincer Complex: A Mechanistic Study

The mechanistic course of the amination of alcohols with ammonia catalyzed by a structurally modified congener of Milstein’s well-defined acridine-based PNP-pincer Ru complex has been investigated both experimentally and by DFT calculations. Several key Ru intermediates have been isolated and characterized. The detailed analysis of a series of possible catalytic pathways (e.g., with and without metal–ligand cooperation, inner- and outer-sphere mechanisms) leads us to conclude that the most favorable pathway for this catalyst does not require metal–ligand cooperation

Iminosugar C‑Glycoside Analogues of α‑d‑GlcNAc-1-Phosphate: Synthesis and Bacterial Transglycosylase Inhibition

We herein describe the first synthesis of iminosugar C-glycosides of α-d-GlcNAc-1-phosphate in 10 steps starting from unprotected d-GlcNAc. A diastereoselective intramolecular iodoamination–cyclization as the key step was employed to construct the central piperidine ring of the iminosugar and the C-glycosidic structure of α-d-GlcNAc. Finally, the iminosugar phosphonate and its elongated phosphate analogue were accessed. These phosphorus-containing iminosugars were coupled efficiently with lipophilic monophosphates to give lipid-linked pyrophosphate derivatives, which are lipid II mimetics endowed with potent inhibitory properties toward bacterial transglycosylases (TGase)