Continuous Flow Homolytic Aromatic Substitution with Electrophilic Radicals: A Fast and Scalable Protocol for Trifluoromethylation.

We report an operationally simple and rapid continuous flow radical C-C bond formation under Minisci-type reaction conditions. The transformations are performed at or below room temperature employing hydrogen peroxide (H2 O2 ) and dimethylsulfoxide (DMSO) as reagents in the presence of an FeII catalyst. For electron-rich aromatic and heteroaromatic substrates, C-C bond formation proceeds satisfactorily with electrophilic radicals including . CF3 , . C4 F9 , . CH2 CN, and . CH2 CO2 Et. In contrast, electron-poor substrates exhibit minimal reactivity. Importantly, trifluoromethylations and nonafluororobutylations using CF3 I and C4 F9 I as reagents proceed exceedingly fast with high conversion for selected substrates in residence times of a few seconds. The attractive features of the present process are the low cost of the reagents and the extraordinarily high reaction rates. The direct application of the protocol to dihydroergotamine, a complex ergot alkaloid, yielded the corresponding trifluoromethyl ergoline derivative within 12 seconds in a continuous flow microreactor on a 0.6 kg scale. The trifluoromethyl derivative of dihydroergotamine is a promising therapeutic agent for the treatment of migraines.

Shifting chemical equilibria in flow--efficient decarbonylation driven by annular flow regimes.

To efficiently drive chemical reactions, it is often necessary to influence an equilibrium by removing one or more components from the reaction space. Such manipulation is straightforward in open systems, for example, by distillation of a volatile product from the reaction mixture. Herein we describe a unique high-temperature/high-pressure gas/liquid continuous-flow process for the rhodium-catalyzed decarbonylation of aldehydes. The carbon monoxide released during the reaction is carried with a stream of an inert gas through the center of the tubing, whereas the liquid feed travels as an annular film along the wall of the channel. As a consequence, carbon monoxide is effectively vaporized from the liquid phase into the gas phase and stripped from the reaction mixture, thus driving the equilibrium to the product and preventing poisoning of the catalyst. This approach enables the catalytic decarbonylation of a variety of aldehydes with unprecedented efficiency with a standard coil-based flow device.

A modular and organocatalytic approach to gamma-butyrolactone autoregulators from Streptomycetes.

A general synthesis of optically active gamma-butyrolactone autoregulators is developed by a two-step sequence to assemble 2,3-trans-disubstituted butyrolactones in high yields and enantioselectivities; the scope of this reaction was elaborated by setting up a library of alkyl-substituted butyrolactones and the synthesis of the autoregulators IM-2 and VB-D.

Organocatalytic asymmetric conjugate addition to allenic esters and ketones.

The first example of an organocatalytic enantioselective conjugate addition of cyclic beta-ketoesters and glycine imine derivatives to electron-deficient allenes is described. We disclose that the corresponding chiral beta,gamma-unsaturated carbonyl compounds are formed exclusively under phase-transfer conditions using either cinchona-alkaloid-derived or biphenyl-based chiral quaternary ammonium salts as catalysts. The scope of the reaction for beta-ketoesters is outlined for allenes having a ketone or ester motif as electron-withdrawing group as well as different substituents in the 3-position, giving the optically active products in high yields and excellent diastereo- and enantioselectivities (90-96% ee). The conjugate addition also proceeds for a number of cyclic beta-ketoesters having different ring sizes, ring systems, and substituents in high yields and enantioselectivities. Glycine imine derivatives also undergo the asymmetric conjugate addition to electron-deficient allenes in high yields and with enantioselectivities in the range of 60-88% ee, thus providing a rapid entry to optically active alpha-vinyl-substituted alpha-amino acid derivatives. It is shown that the enantioselectivity is strongly dependent on the size of the ester moiety of the nucleophile in combination with the catalytic system used. The high synthetic value of the chiral products arising from these new catalytic processes is demonstrated by two straightforward transformations leading in one case to optically active hexahydrobenzopyranones and in the other to substituted pyroglutamates (gamma-lactames).

Formation of volatile iodinated alkanes in soil: results from laboratory studies.

Volatile iodinated organic compounds play an important role in the tropospheric photochemical system, but the current knowledge of the known sources and sinks of these alkyl iodides is still incomplete. This paper describes a new source of alkyl iodides from the pedosphere. Different organic-rich soils and humic acid were investigated for their release of volatile organoiodides. Six volatile organoiodides, iodomethane, iodoethane, 1-iodopropane, 2-iodopropane, 1-iodobutane and 2-iodobutane were identified and their release rates were determined. We assume an abiotic reaction mechanism induced by the oxidation of organic matter by iron(III). The influence of iron(III), iodide and pH on the formation of alkyl iodides was investigated. Additionally, different organic substances regarded as monomeric constituents of humus were examined for the production of alkyl iodides. Two possible reaction pathways for the chemical formation of alkyl iodides are discussed. As humic acids and iron(III) are widespread in the terrestrial environment, and the concentration of iodide in soil is strongly enriched (compared to seawater), this soil source of naturally occurring organoiodides is suggested to contribute significantly to the input of iodine into the troposphere.