Highly diastereo- and enantioselective direct aldol reactions of aldehydes and ketones catalyzed by siloxyproline in the presence of water

Proline-based organocatalysts have been developed for a highly enantioselective, direct aldol reaction of aldehydes and ketones in the presence of water. While several surfactant-proline combined catalysts have proved effective, proline derivatives with a hydrophobic moiety such as trans-siloxy-L-proline and cis-siloxy-D-proline, both of which are easily prepared from the same commercially available 4-hydroxy-L-proline, have been found to be the most effective organocatalysts examined in this study, affording the aldol product with excellent diastereo- and enantioselectivities, these two catalysts generating opposite enantiomers. Water affects the selectivity, and poor results are obtained under neat reaction conditions or in dry organic solvents. More than three equivalents of water are required for the best diastereo- and enantioselectivities, while three equivalents is the recommended amount from a synthetic point of view. The reaction proceeds in the organic phase, and also proceeds in the presence of a large amount of water. The large-scale preparation of aldols with the minimal use of an organic solvent, including in the purification step, is described.     

Enantioselective copper(II)‐catalyzed Henry reaction utilizing chiral aziridinyl alcohols

A family of enantiopure β‐aminoalcohols based on aziridine backbones were synthesized, and examined as chiral ligands for the copper(II)‐catalyzed asymmetric Henry reaction of aromatic aldehydes with nitromethane, giving β‐nitroalcohols in excellent yields (up to 93%) and moderate to good enantioselectivities (up to 82%). Moreover, possible transition states of the reaction are proposed. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis and applications in Henry reactions of novel chiral thiazoline tridentate ligands

Several novel chiral tridentate ligands containing thiazoline were efficiently synthesized from commercially available l=cysteine in high yield. These ligands were subsequently applied to the asymmetric Henry reaction of nitromethane and various aldehydes. It was found that the structures of the thiazoline ligands had a significant influence on the enantioselectivity. It was shown that the optimal catalyst for this reaction was a ligand complexed with CuCl, which was formed from chiral thiazoline with chiral aminoalcohol. At ?20°C, with 10 mol% of this ligand, a product with (S)‐configuration was isolated in 93% yield and 98% enantiomeric excess. Copyright © 2015 John Wiley & Sons, Ltd.     

A new copper(I)-tetrahydrosalen-catalyzed asymmetric Henry reaction and its extension to the synthesis of (S)-norphenylephrine

A new chiral hydrogenated salen catalyst has been developed for the asymmetric Henry reaction which produces the expected products in moderate to high yields (up to 98 %) with excellent enantioselectivities (up to 96 % ee). A variety of aromatic, heteroaromatic, enal, and aliphatic aldehydes were found to be suitable substrates in the presence of hydrogenated salen 1 f (10 mol %), (CuOTf)(2)C(7)H(8) (5 mol %), and 4 A molecular sieves. This process is air-tolerant and easily manipulated with readily available reagents, and has been successfully extended to the synthesis of (S)-norphenylephrine in 67 % overall yield, starting from commercially available m-hydroxybenzaldehyde. Based on experimental investigations and MM+ calculations, a possible catalytic cycle including a transition state (8 or A) has been proposed to explain the origin of reactivity and asymmetric inductivity.     

Highly enantioselective synthesis of organic compound using right- and left-handed helical silica

Highly enantiomerically enriched (up to 96-97% ee) 5-pyrimidyl alkanol was obtained by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde in the presence of the artificially designed chiral inorganic material, right- and left-handed helical silica.     

Highly enantioselective aldol reactions catalyzed by a recyclable fluorous (S) pyrrolidine sulfonamide on water

Fluorous (S) pyrrolidine sulfonamide serves as an efficient promoter for highly enantioselective aldol reactions of ketones and aldehydes with aromatic aldehydes on water. A notable feature of the organocatalyst is that it can be recovered from the reaction mixtures by simple fluorous solid-phase extraction and subsequently reused (up to seven cycles) without a significant loss of catalytic activity and stereoselectivity.     

Highly diastereoselective and enantioselective preparation of homoallylic amines: application for the synthesis of beta-amino acids and gamma-lactams

Reactions of N-silyl- and N-aluminoimines with B-allyldiisopinocampheylborane in the presence of methanol, followed by oxidative workup furnished homoallylic amines in good yields and high ee. A 11B NMR spectroscopy study revealed that the reactions do not proceed, even at room temperature, unless a molar equivalent of water or methanol is added. The first reagent-controlled asymmetric crotylboration and alkoxyallylboration of aldimines furnishing beta-methyl or beta-alkoxy homoallylic amines in very high diastereoselectivity and enantioselectivity are reported herein. Crotylboration and alkoxyallylboration of imines proceed only with the "allyl"-boron "ate" complexes, instead of the "allyl"-dialkylboron reagents used with aldehydes. The addition of methanol is necessary for these reactions as well. Application of this methodology for the conversion of representative nitriles to beta-amino acids in two steps has been described. Additionally, a procedure for the preparation of chiral delta-amino alcohols and gamma-lactams from nitriles is also reported.     

Highly exo-selective and enantioselective cycloaddition reactions of nitrones catalyzed by a chiral binaphthyldiimine-Ni(II) complex

[reaction: see text] Significant levels of exo-selectivity (exo:endo = >99:1 to 86:14) and enantioselectivity (95-82% ee) were obtained in the 1,3-dipolar cycloadditions of a number of nitrones with 3-(2-alkenoyl)-2-thiazolidinethiones, using the chiral binaphthyldiimine-Ni(II) complex (5-20 mol %), which was easily prepared form N,N'-bis(3,5-dichrolo-2-hydroxybenzylidene)-1,1'-binaphthyl-2,2'-diamine and Ni(ClO4)2 x 6H2O in CHCl3 in the presence of 4 A molecular sieves, as a chiral Lewis acid catalyst.