A cheap, easy-to-build, and effective resistively heated reactor for continuous flow synthesis at high temperature and pressure is herein presented. The reactor is rapidly heated directly using an electric current and is capable of rapidly delivering temperatures and pressures up to 400 °C and 200 bar, respectively. High-temperature and high-pressure applications of this reactor were safely performed and demonstrated by selected transformations such as esterifications, transesterifications, and direct carboxylic acid to nitrile reactions using supercritical ethanol, methanol, and acetonitrile. Reaction temperatures were between 300 and 400 °C with excellent conversions and good to excellent isolated product yields. Examples of Diels−Alder reactions were also carried out at temperatures up to 300 °C in high yield. No additives or catalysts were used in the reactions.
The
palladium(0)-catalyzed intramolecular annulation of 12 1,3-disubstituted
cyclopentenes, derived from (+)-vince lactam, resulted in 5-exo cyclizations
which furnished a series of 2,5-dimethyl-1-((3R,4′S)-2H-spiro[benzofuran-3,1′-cyclopentan]-2′-en-4′-yl)-1H-pyrroles
in excellent diastereoselectivities and useful isolated yields. The
double bond migration process that followed the arylpalladium insertion
was controlled by a fine-tuning of the reaction system, which provided
regioselectivities of up to 98:2. The selective Mizoroki–Heck
reaction was used as the key transformation for preparing two new
spirocyclic monoprotected amino acids as single stereoisomers.
A method for highly regio- and stereoselective intramolecular Mizoroki–Heck 5-exo cyclization of aryl iodides to the corresponding spirooxindoles has been developed. Electron-rich and electron-deficient aryl iodide precursors were selectively ring-closed with high stereoselectivity and good yields. The double-bond position in the cyclopentene ring was controlled by careful choice of reaction conditions. These rare spiro compounds were further functionalized to rigidified unnatural amino acid derivatives by a subsequent gas-free Pd(0)-catalyzed alkoxycarbonylation, followed by selective O- and N-deprotections.
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