Carsten Bolm

Mechanochemistry: opportunities for new and cleaner synthesis

The aim of this critical review is to provide a broad but digestible overview of mechanochemical synthesis, i.e. reactions conducted by grinding solid reactants together with no or minimal solvent. Although mechanochemistry has historically been a sideline approach to synthesis it may soon move into the mainstream because it is increasingly apparent that it can be practical, and even advantageous, and because of the opportunities it provides for developing more sustainable methods. Concentrating on recent advances, this article covers industrial aspects, inorganic materials, organic synthesis, cocrystallisation, pharmaceutical aspects, metal complexes (including metal-organic frameworks), supramolecular aspects and characterization methods. The historical development, mechanistic aspects, limitations and opportunities are also discussed (314 references).

Vanadium-catalyzed asymmetric oxidations

Chirally modified vanadium complexes have been used as catalysts in enantioselective epoxidations of allylic alcohols and asymmetric sulfide to sulfoxide oxidations. For both reactions various combinations of chiral ligands and vanadium sources have been tested. The results of previous work and those of current investigations are discussed and details of the catalysis with respect to enantioselectivity and catalyst turnover is presented.

Catalyzed Asymmetric Arylation Reactions

Addition and substitution reactions with carbon nucleophiles are fundamental processes in organic synthesis, and the development of general catalytic asymmetric variants thereof is still a major challenge today. In contrast to enantioselective alkyl transfer reactions, the corresponding arylations have not yet reached a high level of maturity. The existing protocols are either of no general applicability or are limited in terms of selectivity. This article summarizes established routes for catalytic asymmetric aryl transfer together with the latest developments in this area. The scope and limitations of this reaction are discussed.

Direct addition of alkynes to imines and related C=N electrophiles: A convenient access to propargylamines

Propargylic amines are highly useful building blocks in organic synthesis, and the corresponding structural motif has been found in various natural products and compounds of pharmaceutical relevance. This article provides an overview of the most significant advances in the preparation of propargylic amines via the direct addition of alkynes to imines and related carbon-nitrogen electrophiles in the presence of metal catalysts or promoters.

Anaerobic oxidation of short-chain hydrocarbons by marine sulphate-reducing bacteria

The short-chain hydrocarbons ethane, propane and butane are constituents of natural gas. They are usually assumed to be of thermochemical origin, but biological formation of ethane and propane has been also observed. Microbial utilization of short-chain hydrocarbons has been shown in some aerobic species but not in anaerobic species of bacteria. On the other hand, anaerobic utilization of short-chain hydrocarbons would in principle be expected because various anaerobic bacteria grow with higher homologues (≥C6). Indeed, chemical analyses of hydrocarbon-rich habitats with limited or no access of oxygen indicated in situ biodegradation of short-chain hydrocarbons. Here we report the enrichment of sulphate-reducing bacteria (SRB) with such capacity from marine hydrocarbon seep areas. Propane or n-butane as the sole growth substrate led to sediment-free sulphate-reducing enrichment cultures growing at 12, 28 or 60 °C. With ethane, a slower enrichment with residual sediment was obtained at 12 °C. Isolation experiments resulted in a mesophilic pure culture (strain BuS5) that used only propane and n-butane (methane, isobutane, alcohols or carboxylic acids did not support growth). Complete hydrocarbon oxidation to CO2 and the preferential oxidation of 12C-enriched alkanes were observed with strain BuS5 and other cultures. Metabolites of propane included iso- and n-propylsuccinate, indicating a subterminal as well as an unprecedented terminal alkane activation with involvement of fumarate. According to 16S ribosomal RNA analyses, strain BuS5 affiliates with Desulfosarcina/Desulfococcus, a cluster of widespread marine SRB. An enrichment culture with propane growing at 60 °C was dominated by Desulfotomaculum-like SRB. Our results suggest that diverse SRB are able to thrive in seep areas and gas reservoirs on propane and butane, thus altering the gas composition and contributing to sulphide production.

Organocatalytic reactions: effects of ball milling, microwave and ultrasound irradiation

Ball milling, microwave heating and ultrasound irradiation can be used to support conventional laboratory techniques. By applying them, a number of organocatalytic processes could be improved and superior results have been achieved compared to reactions performed under standard conditions. The purpose of this overview is to highlight recent advances by presenting selected examples.

Catalytic asymmetric approaches towards enantiomerically enriched diarylmethanols and diarylmethylamines

Enantiopure diarylmethanols and diarylmethylamines are important intermediates for the synthesis of pharmaceutically relevant products with antihistaminic, antiarrhythmic, diuretic, antidepressive, laxative, local-anesthetic and anticholinergic properties. Furthermore, they have been used as precursors for 1,1-diarylalkyl moieties, which occur in other antidepressants as well as in antimuscarinics and endothelin antagonists. In this critical review catalytic strategies towards enantioenriched diarylmethanols and diarylmethylamines are discussed, including methods for asymmetric carbon-carbon bond formations by aryl transfer reactions to aldehydes and arylimines, respectively, and enantioselective reductions of diarylketones.

Copper‐Catalyzed Cross‐Couplings with Part‐per‐Million Catalyst Loadings

Due to the importance of functionalized arenes as scaffolds in applied organic materials and biologically relevant molecules, metal-catalyzed cross-couplings have gained significant attention in recent years. 2] Among them Ullmann type C X bond formations are particularly attractive because they often allow the use of low-cost starting materials in combination with readily available copper salts. Whereas the initial protocols required high temperatures and over-stoichiometric quantities of metal, recent approaches involving wellchosen and optimized metal–ligand combinations allow for milder reaction conditions and catalytic turnover. Despite these significant advances it has to be noted that commonly in these catalytic Ullmann type reactions both TONs (turnover numbers) as well as TOFs (turnover frequencies) remain rather limited resulting in the requirement of metal salt amounts in the range of 5 to 10 mol%. Lowering the catalyst loading leads to extended reaction times and decreased product yields. Here, we report on Ullmann type reactions with “homeopathic amounts” of copper salts. During investigations of iron-catalyzed cross-coupling reactions 8] it was noted that for some substrate combinations the catalyst activity depended on the metal salt source and its purity. Those observations suggested a closer look into the effects of metal traces under the applied reaction conditions. Taking into account the results by Taillefer and others on Fe/Cu co-catalyses, copper became the prime metal of choice. To our surprise we found that even with catalyst loadings in the 0.01 mol% range of copper(II) salts N-, O-, and S-arylations were possible to provide the corresponding products in yields > 90%. As a representative example, the coupling between pyrazole (1) and phenyliodide (2, 1.5 equiv) to provide N-arylated product 3 [Eq. (1)] was studied in detail. Further reaction components were N,N’dimethylethylenediamine (DMEDA) as (potential) ligand (20 mol %), K3PO4·H2O as base (2 equiv) [12] and toluene as solvent. The reaction mixture was kept under inert atmosphere at 135 8C in a sealed microwave tube for 24 h.

Ring closing enyne metathesis: A powerful tool for the synthesis of heterocycles

The ring closing metathesis (RCM) is a powerful method in organic synthesis for the preparation of cyclic compounds by formation of new carbon-carbon bonds. In the past years a particular subclass of the RCM, the ring closing enyne metathesis (RCEYM), has attracted attention due to its synthetic potential in the generation of ring structures with 1,3-diene moieties, which can subsequently be further functionalised. In this tutorial review mechanistic considerations will be described and the synthetic power of this useful and attractive carbon-carbon bond forming reaction will be illustrated by recent examples of RCEYM applications in the preparation of heterocyclic compounds.

Copper-catalyzed direct sulfoximination of azoles and polyfluoroarenes under ambient conditions.

The direct dehydrogenative C-N coupling of azoles or polyfluoroarenes with N-H sulfoximines proceeds effectively in the presence of a copper catalyst at room temperature under air to afford the corresponding N-arylsulfoximines in good to high yields.