A robust Fe-based heterogeneous photocatalyst for the visible-light-mediated selective reduction of an impure CO2 stream.

The transformation of CO2 into value-added products from an impure CO2 stream, such as flue gas or exhaust gas, directly contributes to the principle of carbon capture and utilization (CCU). Thus, we have developed a robust iron-based heterogeneous photocatalyst that can convert the exhaust gas from the car into CO with an exceptional production rate of 145 µmol g-1 h-1. We characterized this photocatalyst by PXRD, XPS, ssNMR, EXAFS, XANES, HR-TEM, and further provided mechanistic experiments, and multi-scale/level computational studies. We have reached a clear understanding of its properties and performance that indicates that this highly robust photocatalyst could be used to design an efficient visible-light-mediated reduction strategy for the transformation of impure CO2 streams into value-added products.

Straightforward synthesis of functionalized γ-Lactams using impure CO2 stream as the carbon source.

Direct utilization of CO2 into organic synthesis finds enormous applications to synthesize pharmaceuticals and fine chemicals. However, pure CO2 gas is essential to achieve these transformations, and the purification of CO2 is highly cost and energy intensive. Considering this, we describe a straightforward synthetic route for the synthesis of γ-lactams, a pivotal core structure of bioactive molecules, by using commercially available starting materials (alkenes and amines) and impure CO2 stream (exhaust gas is collected from the car) as the carbon source. This blueprint features a broad scope, excellent functional group compatibility and application to the late-stage transformation of existing pharmaceuticals and natural products to synthesize functionalized γ-lactams. We believe that our strategy will provide direct access to γ-lactams in a very sustainable way and will also enhance the Carbon Capture and Utilization (CCU) strategy.

Strecker-Derived Methodology for Library Synthesis of N-Acylated α-Aminonitriles.

The Strecker reaction is a three-component condensation of an aldehyde, an amine, and hydrogen cyanide, delivering an α-amino carbonitrile. Despite extensive investigations, the possibility to use amides instead of amines as one of the three condensation partners has been largely neglected. Nonetheless, the N-acylated α-aminocarbonitriles that are obtained in this way are of direct interest for drug discovery, because they make up a well-known class of mechanism-based inhibitors of serine- and cysteine-type hydrolases. In response, we have thoroughly explored the corresponding variant of the Strecker reaction, focusing on catalyst use, solvent, reaction time, and cyanide source. Optimized parameters were combined in a sequential one-pot protocol for which the scope was found to be compatible with library synthesis applications. Product yields ranged from 7 to 90%, and conditions were found to be mild and tolerant to a wide range of functional groups, including moieties that are typically present in druglike molecules.

Dual effect of halides in the Stille reaction: in situ halide metathesis and catalyst stabilization.

Halide anions can increase or decrease the transmetallation rate of the Stille reaction through in situ halide metathesis. Although the influence of the halogen present in oxidative addition complexes on the transmetallation rate with organostannanes was already known, the application of in situ halide metathesis to accelerate cross-coupling reactions with organometallic reagents is not described in the literature yet. In addition a second unprecedented role of halides was discovered. Halide anions stabilize the [Pd(0)(L)(2)] catalyst in Stille reactions, by means of [Pd(0)X(L)(2)](-) formation (X=Cl, I), hereby preventing its leaching from the catalytic cycle. Both arene (iodobenzene) and azaheteroarene (2-halopyridine, halopyrazine, 2-halopyrimidine) substrates were used.

Concise Xanthine Synthesis through a Double-Amidination Reaction of a 6-Chlorouracil with Amidines using Base-Metal Catalysis.

A new and concise route towards xanthines through a double-amidination reaction is described; consecutive intermolecular C-Cl and intramolecular oxidative C-H amidination. N-uracil amidines are obtained through SN AE on a 6-chlorouracil with amidines. Direct Cu-catalyzed oxidative C-H amidination on these N-uracil amidines yields polysubstituted xanthines. Sustainable oxidants, tBu2 O2 or O2 , can be used in this oxidase-type reaction. The protocol allows for the introduction of N1, N3, N7, and C8 substituents during the xanthine-scaffold construction, thus avoiding post-functionalization steps. Both 6-chlorouracils and amidines are readily available commercially or through synthesis.

Copper(I)-Catalyzed Ketone, Amine, and Alkyne Coupling for the Synthesis of 2-Alkynylpyrrolidines and -piperidines.

A Cu(I)-catalyzed coupling of a ω-chloro ketone, a primary amine, and an alkyne is described. This protocol allows for the synthesis of α-quaternary carbons in 2-alkynyl-substituted N-heterocycles. The key step is the in situ generation of a cyclic ketiminium species, which has enhanced reactivity for alkynylation compared to acyclic ketiminium species.

Amine Activation: Synthesis of N-(Hetero)arylamides from Isothioureas and Carboxylic Acids.

A novel method for N-(hetero)arylamide synthesis based on rarely explored amine activation, rather than classical acid activation, is reported. The activated amines are easily prepared using a three-component reaction with commercial reagents. The new method shows a broad scope including challenging amides not (efficiently) accessible via classical protocols.

2,6-Di(arylamino)-3-fluoropyridine Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors.

New non-nucleoside reverse transcriptase inhibitors (NNRTI), which are similar in structure to earlier described di(arylamino)pyrimidines but featuring a 2,6-di(arylamino)-3-fluoropyridine, 2,4-di(arylamino)-5-fluoropyrimidine, or 1,3-di(arylamino)-4-fluorobenzene moiety instead of a 2,4-disubstituted pyrimidine moiety, are reported. The short and practical synthesis of novel NNRTI relies on two sequential Pd-catalyzed aminations as the key steps. It is demonstrated through direct comparison with reference compounds that the presence of a fluorine atom increases the in vitro anti-HIV activity, both against the wild type virus and drug-resistant mutant strains.

"Base effect" in the auto-tandem palladium-catalyzed synthesis of amino-substituted 1-methyl-1H-α-carbolines.

An auto-tandem Pd-catalyzed process consisting of an intramolecular direct arylation and an intermolecular Buchwald-Hartwig reaction for C-ring amino-substituted 1-methyl-1H-α-carboline synthesis has been developed. A mechanistic study of the direct arylation reaction revealed a rate effect of the inorganic base on the C-H activation step ("base effect"). The amines, reagents in the tandem protocol, appear to have a similar effect on the direct arylation.