Imidazolium Ion‐Tagged Proline Organocatalyst for α‐Aminoxylation of Aldehydes and Ketones in Ionic Liquids

Abstract

A novel imidazolium ion-tagged l-proline catalyst has been developed. The asymmetric aaminoxylation of aldehydes and ketones with excellent enantioselectivities, up to 99% ee, and high yields in ionic liquids has been achieved. The system can be easily recycled and reused for at least six times without significant loss of yields and enantioselectivity.Keywords: aldehydes and ketones; a-aminoxylation reaction; asymmetric organocatalysts; ionic liquids; recyclability Optically active a-hydroxy carbonyl moieties, important intermediates in organic synthesis, are commonly found in numerous biologically active natural products. Different diastereoselective and enantioselective methods have been developed for their synthesis.[1]The direct proline-catalyzed asymmetric a-aminoxylation of carbonyl compounds with nitrosobenzene has recently increasingly attracted the attention of organic chemists. In 2003, Zhong [2] , MacMillan [3] and Hayashi [4a] independently reported the a-aminoxylation of aldehydes catalyzed by proline for the first time. Shortly after, the scope of this aminoxylation reaction was extended to ketones by the groups of Hayashi [4b] and Córdova [5] at the same time. However, there has been no progress in developing new organocatalysts [6] for this reaction up to now. Some other similar work was just focused on changing different substrates and solvents [7] and efforts were devoted to the reaction mechanism [8] and applications.[9]Recently, chiral ionic liquids [10] (CILS), especially functional ionic liquids [11] or task-specific ionic liquids have been introduced in many publications due to their unique characteristics and environmentally benign practices. But so far, there are very few reports on CILS as organocatalyst for asymmetric reactions and most of them were used as reaction media for inducing asymmetric synthesis.[12] Miao and Chan first reported an asymmetric aldol reaction catalyzed by the trans-4-hydroxy-l-proline derivative 1a (Figure 1) in DMSO or acetone with medium values (catalyst loading: 30%, up to 87% ee).[11d] After that, Lombardo and co-worker also reported a cross-aldol reaction catalyzed by onium ion-tagged proline 1b and reached a satisfactory result.[13] Luo and Chengs group[11c] got a good result (up to 99% ee for the Michael addition to nitroolefins) by using pyrrolidinetype chiral ionic liquid 2 (Scheme 1). Recently, Liebscher et al. also reported task-specific ionic liquids as catalysts for Michael additions.[14] Nevertheless, we thought that compounds 1a and 1b both contained a carboxylic ester, which was prone to be decomposed, leading to a reduction of the catalytic efficiency. In addition, Chengs catalyst 2 did not retain the active carboxylic acid group playing a crucial role in many asymmetric reactions, which maybe confined its general application.Herein, we designed a more stable imidazolium ion-tagged 3, which comprised both the chiral proline scaffold as a catalytic site and the ionic liquid moiety. We replaced the unstable carboxylic ester by an ion...

Multiphase Homogeneous Catalysis: Common Procedures and Recent Applications

“…A recent effective a-aminoxylation of a carbonyl compound catalyzed by ion-tagged proline 26 has been reported to proceed within the order of minutes in [bmim][BF 4 ] (BF 4 = tetrafluoroborate) (Scheme 19). 73 Product 27 is extracted with diethyl ether, then the IL phase is dried under vacuum (30 min at 60 °C) and reused seven times with very similar results.…”

Recent Advances on Asymmetric Nitroso Aldol Reaction

“…Proline was also incorporated covalently to the ionic liquid by preparing imidazolium ion tagged prolines 71 59 and 72. 60 As an example the α-aminoxylation of 3-methylbu-tanal (73) using an ionic liquid as the solvent afforded, after in situ reduction, the corresponding diol 74 in good yield and high enantioselectivity for both catalysts (Scheme 18).…”

“…Catalyst 71 was reused up to seven times in the α-aminoxylation of cyclohexanone and >99% ee was obtained in all runs. 59 The addition of urea 75 61 and thioureas 76 and 77 62 (Figure 6) as cocatalysts to the nitroso aldol reaction catalyzed by L-proline (45) resulted in higher reaction rates in more benign solvents. O-Selectivity as well as high yields and enantioselectivities are maintained (Table 11).…”

Synthesis and application of azolium ionic liquid tagged TADDOL catalysts

“…Ionic liquids (IL) have shown interesting ability as phase tags for organocatalysts. [6][7][8][9][10][11][12][13][14][15] Ionic liquid tagged catalysts can be tuned to attain a required physical property, such as solubility, or compatibility with the reaction medium and thermal stability. 16 In this way improved recovery and recycling and sometimes even better catalytic activity can be attained.…”