Machines vs Malaria: A Flow-Based Preparation of the Drug Candidate OZ439.

An efficient preparation of the antimalarial drug candidate OZ439, which was obtained by integrating a machine-assisted approach with batch processes, is reported. This approach allows a rapid and cost-effective production of the key intermediates that were readily elaborated into the target molecule.

Batch versus flow photochemistry: a revealing comparison of yield and productivity.

The use of flow photochemistry and its apparent superiority over batch has been reported by a number of groups in recent years. To rigorously determine whether flow does indeed have an advantage over batch, a broad range of synthetic photochemical transformations were optimized in both reactor modes and their yields and productivities compared. Surprisingly, yields were essentially identical in all comparative cases.

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow.

The application of a monolithic form of triphenylphosphine to the Ramirez gem-dibromoolefination reaction using flow chemistry techniques is reported. A variety of gem-dibromides were synthesised in high purity and excellent yield following only removal of solvent and no further off-line purification. It is also possible to perform the Appel reaction using the same monolith and the relationship between the mechanisms of the two reactions is discussed.

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors.

Herein we describe the application of a monolithic triphenylphosphine reagent to the Appel reaction in flow-chemistry processing, to generate various brominated products with high purity and in excellent yields, and with no requirement for further off-line purification.

Sequential ortho-lithiations; the sulfoxide group as a relay to enable meta-substitution.

Sulfoxides are known to be powerful directing groups for ortho-lithiation, even in competition with other directors. This has been utilised to introduce substituents meta- to a methoxy-group by sequential lithiation, reaction with Me tert-butylsulfinate, and a second lithiation. Electrophilic trapping of the ensuing lithio-compound with a range of electrophiles followed by reductive removal of the sulfoxide led to meta-substituted anisoles.

A practical flow reactor for continuous organic photochemistry.

[reaction: see text] Compact flow reactors have been constructed and optimized to perform continuous organic photochemistry on a large scale. The reactors were constructed from commercially available or customized immersion well equipment combined with UV-transparent, solvent-resistant fluoropolymer (FEP) tubing. The reactors were assessed using the [2 + 2] photocycloaddition of malemide 1 and 1-hexyne forming the cyclobutene product 2 and the intramolecular [5 + 2] photocycloaddition of 3,4-dimethyl-1-pent-4-enylpyrrole-2,5-dione 3 to form the bicyclic azepine 4.

Silenes as novel synthetic reagents: identification of a practical method for silene generation and trapping.

The elucidation of a robust and reliable sequence for the generation of highly reactive transient silenes from simple aldehydes is described. The key step involves a silyl-modified Peterson olefination which critically depends on the presence of a sub-stoichiometric amount of soluble lithium salts (LiBr).

Lewis acid mediated cyclisations of silylated methylenecyclopropyl hydrazones.

Silylated methylenecyclopropyl hydrazones on treatment with BF3 x Et2O cyclise to give heterocyclic products involving a novel sequence of hydride and silyl shifts via a series of increasingly stable cationic intermediates.