Scale‐Up Studies for the Asymmetric Juliá–Colonna Epoxidation Reaction

Abstract

The asymmetric Juliá -Colonna epoxidation reaction under triphasic/PTC conditions has been successfully scaled-up to a one-hundred gram substrate level providing the corresponding epoxy ketone with high optical purity (up to 97% ee) and in good yield (75 -78%). The amount of polyamino acid catalyst could be reduced leading to a simplified reaction work-up. In order to minimise the overall reaction time baffled reactors with pitched-blade impellers have been employed.Keywords: amino acids; asymmetric catalysis; epoxidation; heterogeneous catalysis; phase-transfer catalysisThe poly-a-amino acid-catalysed asymmetric Juliá -Colonna epoxidation has emerged as an efficient synthetic method for the enantioselective functionalisation of a,b-unsaturated ketones. Since its discovery in 1980, [1] the heterogeneous catalyst and the oxidant/solvent system has been optimised further so that now a broad range of substrates containing a substituted enone system can be epoxidised in high yield and with high enantioselectivity.[2]Recently, we have developed a new protocol for the Juliá -Colonna epoxidation reaction under triphasic conditions [3] employing our own polyamino acid catalyst. The addition of small amounts of tetrabutylammonium bromide (TBAB) as a phase-transfer catalyst (PTC) to the heterogeneous reaction mixture resulted in a significant acceleration of the epoxidation reaction.[4] With this new protocol we could obtain complete conversion of chalcone 1 into epoxy ketone 3 with high chemo-and enantioselectivity (94% ee) within 7 minutes at room temperature. In contrast to our new procedure less than 60% conversion has been observed without TBAB under otherwise identical epoxidation conditions after 1.5 hours.Some time ago we became interested in preparing enantiomerically pure epoxy ketone 4 as a valuable synthetic intermediate. Using our newly developed triphasic/PTC conditions 4 could be obtained successfully from enone 2[5] with 97%ee on a small scale.

Catalytic Asymmetric Oxygenations with the Environmentally Benign Oxidants H2O2and O2

“…An inconvenience of the original system was the need for a prolonged preactivation period, which could be avoided by using the high-temperature polypeptide preparation procedure developed by Geller and co-workers; moreover, the resulting catalyst exhibited very high activities, so that the reaction (under triphasic conditions) required only 7–30 min in the presence of phase-transfer agent tetra- n -butylammonium bromide. , Also, the oxidant excess was reduced to only 1.3 equiv. , A scaled-up epoxidation procedure (100 g scale) was proposed . A recyclable catalyst (based on imidazolium-modified poly- l -leucine), requiring no preactivation, and recoverable by filtration, was developed …”

Cα‐Tetrasubstituted amino acid based peptides in asymmetric catalysis

“…Subsequently, this reaction was explored in more detail by several groups, especially that headed by S. M. Roberts, 41,42 allowing the development of more efficient and general protocols that greatly expanded its scope. [43][44][45] Thus, a series of L-(-Me)Val-and L-(-Me)Leubased homopeptides with an increasing number of amino acid residues was prepared, protected with the Z (benzyloxycarbonyl) and -OtBu (tert-butyloxy) groups at the N-and C-termini, respectively. N--deprotected and N-acetylated [L-(Me)Val] n -OtBu homopeptides were also studied for comparison.…”

Industrial Catalysts for Regio‐ or Stereo‐Selective Oxidations and Reductions. A Review of Key Technologies and Targets

“…Optically active epoxides with high ees are obtained from facile processes that use small amounts of catalyst and simple reagents. Gerlach and Geller [71] have reported the process development studies that allow the reaction to be run on pilot plant scale. The resulting epoxides can be converted into a wide range of interesting products, [72] …”