Protocol for olefin metathesis reactions of hydrophobic substrates performed in aqueous emulsion with mechanical stirring or with microwaves support.

In the presented protocol, we describe the olefin metathesis of hydrophobic substrates in water emulsions using ruthenium catalysts in the presence of air. We detail the testing of mechanical foaming for emulsification and the use of microwave heating to optimize metathesis reaction efficiency. By utilizing relatively low catalyst loading and ensuring simple product isolation, the steps outlined in this protocol extend known methods for the aqueous metathesis techniques. For complete details on the use and execution of this protocol, please refer to Tyszka-Gumkowska et al. (2022).

Testing enabling techniques for olefin metathesis reactions of lipophilic substrates in water as a diluent.

Olefin metathesis reactions of diverse polyfunctional substrates were conducted in water emulsions using two hydrophobic ruthenium catalysts in the presence of air. Instead of using surfactants to increase the efficiency of the metathesis reaction in water, ultrasound and microwave techniques were tested on a small-scale reaction, whereas conventional heating and mechanical stirring were effective enough to provide high conversion and selectivity on a larger scale. The developed conditions extend known protocols for the aqueous metathesis methodology, utilizing relatively low catalyst loadings and allowing for simple product isolation and purification. The established synthetic protocol was successfully adopted in the large-scale synthesis of a pharmaceutically related product - sildenafil (Viagra) derivative.

Highly Enantioselective Epoxidation of α,ß-Unsaturated Ketones Using Amide-Based Cinchona Alkaloids as Hybrid Phase-Transfer Catalysts.

A series of 20 one chiral epoxides were obtained with excellent yields (up to 99%) and enantioselectivities (up to >99% ee) using hybrid amide-based Cinchona alkaloids. Our method is characterized by low catalyst loading (0.5 mol %) and short reaction times. Moreover, the epoxidation process can be carried out in 10 cycles, without further catalyst addition to the reaction mixture. This methodology significantly enhance the scale of the process using very low catalyst loading.

Static Combinatorial Chemistry: A High-Pressure Approach to the Synthesis of Macrocyclic Benzoamide Libraries.

We investigated the yield and distribution of macrocyclic products formed in combinatorial libraries (CLs) obtained via double-amidation reactions of methyl diesters with α,ω-diamines. The application of the static combinatorial chemistry (SCC) approach allowed us to generate a large number of macrocyclic diamides and tetraamides in single experiments. We show that high-pressure conditions accelerate the macrocyclization process but also have a great impact on the distribution of macrocyclic products in the presented libraries, promoting the formation of macrocyclic compounds and eliminating the linear ones. The distribution of macrocyclic products was also found to be strongly dependent on the structural features of the substrates employed. Furthermore, in three- and four-substrate CLs we observed the formation of a new type of hybrid tetraamides consisting of three different components.

A General Method for High-Pressure-Promoted Postfunctionalization of Unclosed Cryptands: Potential Phase-Transfer Catalysts.

We report a high-pressure approach to facile late-stage functionalization of unclosed cryptands (UCs) (11 examples, yield up to 99%). Direct comparison of classic and high-pressure conditions of the quaternization reaction in a sterically crowded intraannular position is investigated, and differences in the reactivity of tertiary amine substrates are discussed. Finally, we demonstrated the application of UCs as catalysts for synthetically important alkylation reactions under phase-transfer conditions.

Chiral Recognition of Carboxylate Anions by (R)-BINOL-Based Macrocyclic Receptors.

Three (R)-BINOL-based macrocyclic receptors obtained via double-amidation reaction were used for chiral recognition of four anions derived from α-hydroxy and α-amino acids. The structural factors of hosts and guests that affect chiral recognition processes were also investigated, indicating that the proper geometry of both receptor and guest molecules plays a crucial role in effective enantio-discrimination.