The combination of the metal-catalyzed cycloisomerization of alkynes containing a tethered nucleophile as substituent in aqueous media (followed by the spontaneous hydrolysis, hydroalkoxylation, or aminolysis of the transiently formed five-membered heterocycles) with the subsequent enantioselective ketone bioreduction (mediated by KREDs) has been achieved. The overall transformations, which formally involve a three-step one-pot reaction, provide a variety of enantiopure valuable molecules (e.g., 1,4-diols, lactones, and γ-hydroxy-carbonyl compounds (carboxylic acids, esters, and amides)) with high conversions and enantioselectivities and under mild reaction conditions, disclosing the concept of integrated metal-catalyzed cycloisomerizations of alkynes and enzymatic catalysis in water.

New iminophosphorane-phosphine Au complexes [AuCl(κ -P-Ph PCH P{=NP(=S)(OR) }Ph )] (3 a,b) and [Au Cl (μ -P,S-Ph PCH P{=NP(=S)(OR) }Ph )] (4 a,b) proved to be general, very efficient, and recyclable (up to four consecutive runs) catalysts for the cycloisomerization of alkynyl amides in water or choline chloride-based eutectic mixtures as green solvents. Remarkably, this cycloisomerization reaction took place under mild conditions (low catalyst loading, at room temperature, and in the absence of cocatalysts or protecting atmosphere) to give the corresponding alkylidene lactams by employing an efficient and sustainable methodology.

The subsequent double-bond isomerization in the synthesis of dibenzocycloheptenes and their heteroaromatic analogues was investigated. In the case of biphenyls, a basic additive completely prevented an isomerization to the thermodynamic product. With electron-rich intramolecular heteroaromatic nucleophiles, the isomerization was still observed, but the kinetic product can be obtained by careful control of the reaction times in most cases. Mechanistic studies demonstrated that a slow isomerization is also possible with the gold catalyst at elevated temperatures, but much faster isomerization rates were observed with acidic additives. An observed initiation period for the gold-catalyzed isomerization indicates that not the homogenous catalyst, but a decomposition product of it may be the catalytically active species.

The synthesis of four different monofunctional vinyl cyclopropane (VCP) derivatives and their polymerization behavior is presented. The different VCPs have different capabilities to form hydrogen bonds in their side chain. A preorganization due to these hydrogen bonds should lead to a fast polymerization. Kinetic studies, hydrogen-bond strength, and theoretical calculations were used to correlate the degree of conversion and the amount of preorganization. While VCPs capable of hydrogen bonding did not show a huge difference, a general effect of hydrogen bonds on polymerization behavior could be observed.

The synthesis of four different monofunctional vinyl cyclopropane (VCP) amides and their photopolymerization behavior are presented. All VCPs can form hydrogen bonds, with one being the amide linkage of the VCP unit and the other one being the side chain. The number of additional hydrogen bonds is regulated by the different side chains being, carbonate, urethane, urea, and amide. Hydrogen bonds should lead to a preorganization of the monomers, leading to a fast polymerization. Kinetic studies of the photopolymerization, analysis of hydrogen bond strength via solid-state nuclear magnetic resonance (NMR) experiments, and theoretical calculations are used to correlate the degree of conversion and the amount of preorganization. A fast polymerization could be observed due to hydrogen bonding near the active site, while hydrogen bonds in the side chain make a minor difference.