Tandem methods for the catalytic asymmetric preparation of enantioenriched β-hydroxy (E)-enamines and cyclopropylamines are presented. The diastereoselective hydrogenation of enantioenriched (E)-trisubstituted hydroxy enamines to generate 1,2-disubstituted 1,3-amino alcohols is also outlined. These methods are initiated by highly regioselective hydroboration of N-tosyl substituted ynamides with diethylborane to generate β-amino alkenyl boranes. In situ boron to zinc transmetalation generates β-amino alkenyl zinc reagents. These functionalized vinylzinc intermediates were subsequently added to aldehydes in the presence of catalyst derived from an enantioenriched amino alcohol (morpholino isoborneol, MIB). The catalyst promotes highly enantioselective C–C bond-formation to provide β-hydroxy enamines in good isolated yields (68–86%) with 54–98% enantioselectivity. The intermediate zinc β-alkoxy enamines can be subjected to a tandem cyclopropanation to afford amino cyclopropyl carbinols with three continuous stereocenters in a one-pot procedure with good yields (72–82%), enantioselectivities of 76–94% and diastereomeric ratios >20:1. Diastereoselective hydrogenation of isolated enantioenriched β-hydroxy enamines over Pd/C furnished syn-1,2-disubstituted-1,3-amino alcohols with high yields (82–90%) and moderate to excellent diastereoselectivities. These methods were used in an efficient preparation of the enantioenriched precursor to PRC200-SS derivatives, which are potent serotonin-norepinephrine-dopamine reuptake inhibitors.

A simple and efficient method to convert aldehydes into α,β-unsaturated aldehydes with a two-carbon homologation is presented. Hydroboration of ethoxy acetylene with BH 3 •SMe 2 generates tris (ethoxyvinyl) borane. Transmetallation with diethylzinc, addition to aldehydes or ketones, and acidic workup affords enals. When the addition is quenched with anilinium hydrochloride, 1,2-dithioglycol, or acetic anhydride the unsaturated imine, dithiolane, or 1,1-diacetate is isolated in high yield. These transformations can be performed in a one-pot procedure.The field of organocatalysis has witnessed explosive growth in the last decade and will continue to be a dynamic area of chemical research. 1 A wide variety of organocatalysts and reaction classes have been recently advanced, and many of these are based on α,β-unsaturated aldehydes as substrates. As a result, enals have arguably become the single most important class of substrates for development and applications of organocatalytic transformations 2 while remaining a mainstay of metal-based catalytic asymmetric processes. 1a,3 To keep pace with the ever-increasing demand for enals, current synthetic methods must be reevaluated and optimized or supplanted with new, direct and more efficient approaches. Herein we disclose a simple and practical yet broadly applicable one-pot method for the conversion of aldehydes and ketones into α,β-unsaturated aldehydes.A practical synthesis of enals would meet the following criteria: it must be general, employ commercially available and inexpensive reagents, use common laboratory techniques, be functional group compatible, and be tolerant of α-stereogenic centers in enantioenriched aldehydes and ketones. Furthermore, the transformation should be amenable to a one-pot procedure to enable rapid generation of an array of enals.Existing methods for conversion of aldehydes and ketones to enals do not satisfy these criteria (Scheme 1). For example, cross aldol reactions with acetaldehyde enolates are not general, yielding self-condensation products with aliphatic aldehyde partners (Scheme 1, A). 4 This difficulty can be circumvented with C-silated imines (B and C), 5 but these imines must be prepared, silylated, and distilled, adding additional steps. Methods employing commercially available ethoxy acetylene are most attractive (Scheme 1, E and F). Hydrostannylation of ethoxy acetylene provides a vinylstannane. Transmetallation with n-BuLi leads to a highly reactive vinyllithium that readily adds to aldehydes and ketones to afford enals on acidic workup. 9 The drawback of such methods is the incompatibility of the vinyllithium with most functional groups. Suzuki introduced a method that combines the twosteps above into one and circumvents the highly reactive vinyllithium intermediate in E. 10 Thus, hydrozirconation of ethoxy acetylene, in situ transmetallation of the vinylzirconocene intermediate with catalytic AgClO 4 , addition to aldehydes and elimination provides enals (F). Although this method has advantages over those outl...

New chiral N,N-bidentate 2,2′-bis-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one) ligands have been prepared and characterised by their 1 H and 13 C NMR spectra and/or optical rotation. The ligands prepared were then tested for their ability to form complexes with copper(II) salts. It was found that the most stable complex is formed from the 2,2′-bis-(4-isopropyl-1,4-dimethyl-4,5-dihydro-1H-imidazol-5-one) ligand and copper(II) chloride.The structure of this complex was determined by means of quantum-chemical computations at the B3LYP or UB3LYP/6-31G(d,p) level. According to the computations, the geometry of the copper atom most resembles a tetrahedral arrangement, which was also confirmed by means of X-ray structural analysis. It was found that the structure of this copper(II) complex does not allow the copper atom to coordinate to additional ligands; therefore, it is catalytically inactive in the asymmetric Henry reaction. Graphical abstractNew chiral N,N-bidentate ligands derived from substituted 2,2′-bis-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one) have been prepared and characterised by means of 1 H and 13 C NMR spectroscopy and optical rotation.Their Cu(II) complexes have been prepared and their structures have been studied by computational methods and by X-ray diffraction. The catalytic activity of some complexes have been studied.

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