Palladium-Catalyzed Synthesis of Alkylated Amines from Aryl Ethers or Phenols

Synthesis of alkylated amines is an important and attractive task in organic chemistry. Herein, we demonstrate a general protocol to produce alkylated amines via the catalytic coupling of amines with aromatic ethers or phenols. This transformation is performed in the presence of a heterogeneous palladium catalyst, and the key to its success is the use of a Lewis acid (LA) co-catalyst. This method shows broad substrate scope and a variety of phenols, including lignin-derived fragments, can be converted to the desired products smoothly. Preliminary mechanistic investigations reveal that this straightforward domino transformation occurs via a hydrogenolysis/reduction/condensation/reduction process

Direct Catalytic N‑Alkylation of Amines with Carboxylic Acids

A straightforward process for the N-alkylation of amines has been developed applying readily available carboxylic acids and silanes as the hydride source. Complementary to known reductive aminations, effective C–N bond construction proceeds under mild conditions and allows obtaining a broad range of alkylated secondary and tertiary amines, including fluoroalkyl-substituted anilines as well as the bioactive compound Cinacalcet HCl

Toward a Practical Catalyst for Convenient Deaminative Hydrogenation of Amides under Mild Conditions

Amide bond reduction is a versatile transformation offering access to various alcohols and amines that could be used as valuable precursors in the chemical and pharmaceutical industries, e.g., for manufacturing plastics, textiles, dyes, agrochemicals, etc. Over the last two decades, catalytic amide hydrogenation employing homogeneous catalysis has gained more attention due to the atom efficiency and low environmental impact of this transformation. Owing to the inherent strength of amide bonds, amide hydrogenation procedures often involve high temperatures and pressures, which is why efforts are being channeled to finding protocols with lower-energy input. Here, we report a mild amide hydrogenation method involving commercially available precursors Ru(acac)3 and 1,2-bis(di-tert-butylphosphinomethyl)benzene (L4), which under basic conditions, at 80 °C and under 30 bar of H2, can selectively hydrogenate a series of 2°-benzamides to anilines and alcohols with yields of 36–98% and 29–92%, respectively. Additionally, 1°- and 3°-amides proved to be appropriate substrates; however, low to moderate yields were obtained. The catalyst is believed to operate via an inner-sphere mechanism with a hemiaminal being the likely intermediate during the hydrogenation process

Selective Hydrogenation of Ruthenium Acylphosphine Complexes

Hydrogenation of a benzene ruthenium chloride dimer in the presence of novel acyl­phosphine (phosphomide) ligands resulted in the formation of corresponding ruthenium­(II)–benzyl phosphine complexes. Here, selective reduction of the carbonyl group to a methylene unit takes place with molecular hydrogen under mild conditions in good yield. This approach provides an alternative synthesis of ruthenium phosphine complexes of benzyl and heterobenzyl phosphine ligands

Acrolein Hydrogenation on Ni(111)

Acrolein hydrogenation via allyl alcohol, propanal, and enol into propanol on the Ni(111) surface has been investigated using the spin-polarized periodic density functional theory method. On the basis of the computed adsorption energies and effective hydrogenation barriers, acrolein hydrogenation into propanal and allyl alcohol obeys the Langmuir–Hinshelwood mechanism and propanal formation is more favored kinetically and thermodynamically than allyl alcohol formation. Hydrogenation of propanal and allyl alcohol should follow the Eley–Rideal mechanism. The adsorption energies of acrolein, allyl alcohol, and propanal along with the partial hydrogenation selectivity on Ni, Au, Ag, and Pt catalysts have been compared and discussed

Selective Hydrogenation of Ruthenium Acylphosphine Complexes

Hydrogenation of a benzene ruthenium chloride dimer in the presence of novel acyl­phosphine (phosphomide) ligands resulted in the formation of corresponding ruthenium­(II)–benzyl phosphine complexes. Here, selective reduction of the carbonyl group to a methylene unit takes place with molecular hydrogen under mild conditions in good yield. This approach provides an alternative synthesis of ruthenium phosphine complexes of benzyl and heterobenzyl phosphine ligands

Selective Palladium-Catalyzed Aminocarbonylation of 1,3-Dienes: Atom-Efficient Synthesis of β,γ-Unsaturated Amides

Carbonylation reactions constitute important methodologies for the synthesis of all kinds of carboxylic acid derivatives. The development of novel and efficient catalysts for these transformations is of interest for both academic and industrial research. Here, the first palladium-based catalyst system for the aminocarbonylation of 1,3-dienes is described. This atom-efficient transformation proceeds under additive-free conditions and provides straightforward access to a variety of β,γ-unsaturated amides in good to excellent yields, often with high selectivities

General and Regioselective Synthesis of Pyrroles via Ruthenium-Catalyzed Multicomponent Reactions

A general and highly regioselective synthesis of pyrroles via ruthenium-catalyzed three-component reactions has been developed. A variety of ketones including less reactive aryl and alkyl substrates were efficiently converted in combination with different type of amines and vicinal diols into various substituted pyrroles in reasonable to excellent isolated yields. Additionally, α-functionalized ketones gave synthetically interesting amido-, alkoxy-, aryloxy-, and phosphate-substituted pyrroles in a straightforward manner. The synthetic protocol proceeds in the presence of a commercially available ruthenium catalyst system and catalytic amount of base. It proceeds with high atom-efficiency and shows a broad substrate scope and functional group tolerance, making it a highly practical approach for preparation of various pyrrole derivatives

Synthesis of <i>N</i>‑Lauroyl Sarcosine by Amidocarbonylation: Comparing Homogeneous and Heterogeneous Palladium Catalysts

An improved system for the synthesis of <i>N</i>-acyl amino acids via Pd-catalyzed amidocarbonylation is reported. Utilizing inexpensive Pd black gives the industrially important surfactant <i>N</i>-lauroyl sarcosine in excellent yields (95%) on a multi-gram scale. Advantages of the new system include reusability, decreased process temperature, and, importantly, drastically decreased co-catalyst loading

Relay Iron/Chiral Brønsted Acid Catalysis: Enantioselective Hydrogenation of Benzoxazinones

An asymmetric hydrogenation reaction of benzoxazinones has been accomplished via a relay iron/chiral Brønsted acid catalysis. This approach provides a variety of chiral dihydrobenzoxazinones in good to high yields (75–96%) and enantioselectivities (up to 98:2 er). It is noteworthy that challenging 3-alkyl-substituted substrates underwent highly enantioselective reduction. A key to success is the utilization of a nonchiral phosphine ligand to reduce disadvantageous background reactions through tuning the catalytic activity of Fe₃(CO)₁₂