Recyclable L-proline organocatalyst for Wieland–Miescher ketone synthesis

Abstract

Wieland-Miescher ketone 4 was synthesised using L-proline catalyst in the ionic liquid medium via non-selective conjugated addition reaction followed by an enantioselective intermolecular Aldol condensation reaction of triketone 3 intermediate. Short reaction time, recycling of the catalyst, good yield and selectivity are major outcomes of this proposed protocol.

Organocatalyst Design for the Stereoselective Annulation towards Bicyclic Diketones and Analogues

“…Srivastava tested a series of ionic liquids as alternative solvents for this reaction, comparing them with classic organic solvents or with water [36]. Ketone (S)-1 was obtained with moderate or good yield (42-88%) and selectivity (61-93% ee) employing 1 mol% of L-Pro in different ionic liquids at room temperature for 2 h. The best results were found with [pyC 4 ]NTf 2 reaction medium (88% chemical yield, 93% ee), which also proved to be better than conventional solvents or neat conditions.…”

Biocatalytic Approaches to the Enantiomers of Wieland–Miescher Ketone and its Derivatives

“…The enantiomerically enriched form of 1 was firstly described in 1971, when two different groups of industrial chemists independently proposed an asymmetric version of the Robinson annulation catalyzed by proline [5–7] . Since then, the enantioselective synthesis of one of the enantiomers of 1 ((8a S )‐ 1 a and (8a R )‐ 1 b ) has become a model target to evaluate the performances of new chiral organocatalyst, [8–10] as it has been recently carefully reviewed [11,12] …”

“…[4] The enantiomerically enriched form of 1 was firstly described in 1971, when two different groups of industrial chemists independently proposed an asymmetric version of the Robinson annulation catalyzed by proline. [5][6][7] Since then, the enantioselective synthesis of one of the enantiomers of 1 ((8aS)-1 a and (8aR)-1 b) has become a model target to evaluate the performances of new chiral organocatalyst, [8][9][10] as it has been recently carefully reviewed. [11,12] The unselective reduction of the C 1 carbonyl moiety of 1 should theoretically afford a complex mixture of stereoisomeric alcohols (5-hydroxy-4a-methyl-4,4a,5,6,7,8-hexahydronaphthal-en-2(3H)-one) which exist as two couples of cis-and transenantiomers (compounds (4aS, 5S)-2 a, (4aR, 5R)-2 b and (4aS, 5R)-3 a, (4aR, 5S)-3 b in Scheme 1).…”

Aspects in the Total Syntheses of Higher Terpenoids Starting From Wieland–Miescher Ketone and Its Derivative: A Review

“…Starting from known decalone 31, 29 introduction of a formyl group at C-8 followed by Robinson annulation provided tricyclic enone 32. Treatment with excess amount of Copper(II) bromide promoted the aromatization of the enone 32 in high yield, which was followed [8][9][10][11][12][13][14][15][16][17][18][19] by deprotection and Dess-Martin periodinane (DMP) oxidation to furnish ketone 35. Regioselective Baeyer-Villiger oxidation and subsequent lactone ring opening furnished the target compound 37 in 35% yield from Wieland-Miescher ketone (1) in 14 linear steps.…”

“…Figure2. Some representative prolineamide organocatalysts for the syntheses of optically active Wieland-Miescher ketone (1) [8][9][10][11][12][13][14][15][16][17][18][19]. …”