Enantioselective allylations of α-nitro ketones (3) and α-nitro esters (15) with allyl acetate were carried out in the presence of 2 equiv of alkali metal fluorides (KF, RbF, CsF) and 1 mol % of palladium catalysts prepared in situ from Pd2(dba)3·CHCl3 and chiral phosphine ligands. Moderate enantioselectivities were observed in the reaction of nitro ketones 3, giving products 4 (4a, 49% ee; 4b, 58% ee; 4c, 44% ee) when rubidium fluoride and ferrocenylphosphine ligands bearing monoaza-15-crown-5 (1b) or monoaza-18-crown-6 (1c) moieties were used as a base and a chiral ligand, respectively. Optically active allylation product 4a was converted into 1-methyl-1-azaspiro[4.5]decan-10-amine (13), a precursor to opioid receptor binding agents. Enantioselectivity in the reaction of nitro esters 15 increased in accord with increasing steric demand of the ester alkyl group (Me < Et < t-Bu). The highest selectivity (80% ee) for the reaction of tert-butyl ester 15c was observed when the reaction was carried out at −40 °C in the presence of the palladium catalyst with the ligand (1c) bearing a monoaza-18-crown-6 moiety, RbF (2 equiv), and RbClO4 (1 equiv). The pronounced effect of the crown ether moiety for both enantioselection and rate acceleration can be explained by assuming the formation of a ternary complex involving the crown ether, rubidium cation, and enolate anion at the stereodifferentiating transition state. Optically active nitro ester (R)-16c was converted into (R)-α-methylglutamic acid (20).

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...

Enantioselective Allylation of Nitro Group-Stabilized CarbanionsCatalyzed by Chiral Crown Ether Phosphine-Palladium Complexes.-The scope and limitations of the Pd-catalyzed asymmetric allylation of α-nitro ketones and α-nitro esters are investigated to achieve the highest enantioselectivity possible. The allylation products are useful synthetic intermediates for optically active . alpha.-methylated α-amino acids, such as (R)-(IX). - (SAWAMURA, M.; NAKAYAMA, Y.; TANG, W.-M.; ITO, Y.; J. Org. Chem. 61 (1996) 26, 9090-9096; Dep. Chem., Sch. Sci., Univ. Tokyo, Bunkyo, Tokyo 113, Japan; EN)

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