The nitroaldol (Henry) reaction is an important carbonyl addition process that affords products that may be transformed into valuable building blocks. 1 Therefore, it is not surprising that recent efforts have focused on the development of catalytic enantioselective reaction variants. The current contributions to this area have been highlighted by the recent studies of Shibasaki and Trost. [2][3][4][5] The purpose of this Communication is to report a new catalyst system for the nitroaldol reaction (eqs 1,2; M ) Cu, X ) OAc). The basis for the current study was to identify a weakly Lewis acidic metal complex bearing moderately basic charged ligands (X) that would facilitate the deprotonation of nitroalkanes (eq 1) as a prelude to the aldol addition process (eq 2). It was felt that divalent metal acetate-ligand complexes of the general structure A might meet these requirements because acetate has been employed as a Brønsted base in the racemic nitroaldol reaction. 1 A series of divalent metal acetates in combination with chiral bidentate ligands were screened as enantioselective catalysts for the nitroaldol process. 6,7 From this survey, bis(oxazoline) 8 (box) complexes derived from Cu(OAc) 2 emerged as promising catalyst candidates. The results from the ligand survey with this metal acetate are summarized in Table 1. The five box ligands (1a-d, 2) with the illustrated absolute configurations that were evaluated with Cu(OAc) 2 ‚H 2 O afforded promising levels of enantioselection (entries 1-5). 8,9 In each instance, the reactions carried out at ambient temperature were complete within 24 h. From this comparison, the indabox ligand 2 proved to be the ligand of choice, 9 providing the nitro alcohol product in 74% ee (Table 1, entry 5). With ethanol as the solvent (Table 1, entry 6), the nitro alcohol product was isolated in 81% ee. Further optimization of this process showed that the reaction may be performed with lower catalyst loadings (1-5 mol %), while the use of 10 equiv of nitromethane was found to be sufficient for the reaction to proceed to completion. Reaction concentrations could also be increased to as high as 1.0 M with no change in enantioselectivity. Cu(II) carboxylate structure was also evaluated with ligand 2, and it was concluded that this catalyst variable is subordinate to ligand architecture. 10 In all instances, the only side reaction observed in these reactions was the accompanying dehydration product.With optimized conditions in hand, the scope of the reaction was explored (Table 2). In general, high enantiomeric excesses (87-94% ee) are observed at room temperature for aromatic aldehydes bearing either electron-withdrawing or electron-donating groups (entries 1-9). 11 Aliphatic branched and unbranched aldehydes are also acceptable substrates, affording nitro alcohol adducts in good yields and enantioselectivities (entries 10-15, 90-94% ee).Reaction enantioselectivity can be further improved by lowering the temperature at the accompanying expense of increasing the reaction time. In one insta...

A chiral auxilliary-based direct aldol reaction is reported. The reactions are catalytic in magnesium salts and are facilitated by silylation with chlorotrimethylsilane. The adducts isolated are in high diastereoselectivity (up to 32:1 dr) and favor the anti-aldol diastereomer B. Reactions are operationally simple and can be run under ambient atmosphere without rigorous exclusion of water. Many of the adducts are highly crystalline and a single diastereomer can be isolated without chromatography.

An enantioselective aldol reaction of N-propionylthiazolidinethione and representative aldehydes is disclosed. The reaction is catalyzed by [Ni(S,S)-t-BuBox](Otf)2. Enolization is effected by 2,6-lutidine, and TMSOTf facilitates catalyst turnover. Syn diastereoselectivities range from 88:12 to 97:3, and enantioselectivities are 90% or greater. Both aromatic and enolizable aliphatic aldehydes are included within the scope of this aldol addition process.

[reaction: see text] Diastereoselective direct aldol reactions of chiral N-acylthiazolidinethiones occur in high yield with preference for the illustrated anti diastereomer. This reaction is catalyzed by 10% MgBr2.OEt2 in the presence of triethylamine and chlorotrimethylsilane. Yields range from 56 to 93% with diastereoselectivity up to 19:1 for a variety of N-acylthiazolidinethiones and unsaturated aldehydes.

An effective method has been developed for the kinetic resolution of racemic azomethine imines via [3 + 2] cycloadditions with alkynes catalyzed by a chiral copper complex. Efficient kinetic resolution is observed for a variety of N1 and C5 substituents on the dipole, thereby furnishing a wide array of useful enantioenriched azomethine imines, which can readily be transformed into monocyclic and bicyclic pyrazolidinones.