Direct Asymmetric Aldol Addition Research Articles

A Squaramide‐Tagged Proline‐Mediated Direct Asymmetric Aldol Addition in the Presence of Water

A squaramide moiety introduced at the C‐4 position of proline produced an organocatalyst that promoted the direct asymmetric aldol addition in the presence of water. A variety of aldol adducts, majorly from the reaction cyclohexanone with aldehydes, were obtained in yields generally in the range of 53‐99%, accompanied by 71‐97% ee and 82:18 to >99:1 diastereomeric ratios. An asymmetric desymmetrization of 4‐alkyl cyclohexanones was also achieved using the transformation.

Cooperative assistance of a sulfonamide in a proline-mediated direct asymmetric aldol addition

A sulfonamide moiety was introduced at the C-4 position of proline, cis to the –COOH group, to examine a possible synergistic interaction between the two groups and the consequent influence on the enamine mediated asymmetric aldol reaction.

Direct Catalytic Asymmetric Aldol Addition of an α-CF3 Amide to Arylglyoxal Hydrates.

Direct asymmetric aldol addition of an α-CF3 amide to arylglyoxal hydrates was promoted by a chiral catalyst comprising a soft Lewis acidic Cu(I), a chiral bisphosphine ligand, and DBU. The 7-azaindoline moiety of the amide facilitates its enolization and stabilizes the thus-generated Cu enolate, furnishing enantioenriched aldol adducts.

ChemInform Abstract: Influence of a Remote Sulfinyl Group on L‐Proline‐Catalyzed Direct Asymmetric Aldol Addition of Acetone.

Abstract The addition of acetone to rac-2-methylsulfinyl-benzaldehyde, catalyzed by secondary amines (morpholine, piperidine, l -proline, l -prolinamide and (S)-(–)-α,α-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether), was realized. Interesting aspects, such as 1,4-asymmetric induction by the remote sulfinyl group of the aldehyde but also the stereochemical control and kinetic resolution of the racemic substrate by the chiral organocatalyst were examined. Finally, an unexpected stereoselective retro-aldol reaction catalyzed by l -proline was pointed out.

L-Hydroxyproline Immobilized on MCM-41 by Ionic Liquid as a Hetero - geneous Organocatalyst for Direct Asymmetric Aldol Addition

A new heterogenized silica-based organocatalyst was prepared via anion exchange of imidazolium ionic liquid with L– hydroxyproline material. This was evaluated as a heterogenous organocatalyst for the asymmetric aldol reaction of nitrobenzaldehydes, cyclohexanone and cyclopentanone by performing the reaction under different conditions by using several solvents and reaction temperatures. Excellent isolated yields of the aldol products of up to %90 were achieved. In addition, excellent selectivity (ee up to %98) was obtained. In one case, dr reached up to > 99:1. Keywords: Asymmetric synthesis, imidazolium ionic liquid, hydroxy proline, aldol addition, organocatalyst, MCM-41.

Influence of a remote sulfinyl group on l-proline-catalyzed direct asymmetric aldol addition of acetone

The addition of acetone to rac-2-methylsulfinyl-benzaldehyde, catalyzed by secondary amines (morpholine, piperidine, l-proline, l-prolinamide and (S)-(–)-α,α-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether), was realized. Interesting aspects, such as 1,4-asymmetric induction by the remote sulfinyl group of the aldehyde but also the stereochemical control and kinetic resolution of the racemic substrate by the chiral organocatalyst were examined. Finally, an unexpected stereoselective retro-aldol reaction catalyzed by l-proline was pointed out.

ChemInform Abstract: Synthesis of Zirconium Phosphonate Supported L‐Proline as an Effective Organocatalyst for Direct Asymmetric Aldol Addition.

AbstractThe catalyst is easily recoverable and can be used at least 6 times without any significant loss in activity.

Synthesis of Zirconium Phosphonate Supported L‐Proline as an Effective Organocatalyst for Direct Asymmetric Aldol Addition

AbstractStable L‐proline‐functionalized zirconium methyl‐ and/or phenylphosphonates have been prepared as amorphous solids by the precipitation of (4R)‐4‐[(4′‐phosphonobenzyl)oxy]‐L‐proline and methyl‐ and/or phenylphosphonic acid with ZrOCl2. The supported L‐proline catalysts were tested in the direct asymmetric aldol addition between several ketones and p‐substituted benzaldehydes. High yields, diastereoselectivities (anti/syn up to 92:8) and enantiomeric excesses (up to 99 % ee) have been achieved. Moreover, an easy protocol for the efficient recovery of the catalytic system by simple centrifugation has been defined, and the effective reuse of the catalyst has been reported in the representative aldol addition of cyclohexanone with p‐nitrobenzaldehyde. This study has shown that these L‐proline immobilized catalytic systems can be used at least six times without loss of activity and with reproducible anti/syn and ee values.

Validity of Inorganic Nanosheets as an Efficient Planar Substituent To Enhance the Enantioselectivity of Transition‐Metal‐Catalyzed Asymmetric Synthesis

Effectively enhancing the enantioselectivity is a persistent challenge in heterogeneous asymmetric catalysis. Here, the validity of a layered double hydroxides (LDH) nanosheet as an efficient planar substituent to enhance the enantioselectivity has been investigated theoretically; first in vanadium-catalyzed asymmetric epoxidation of allylic alcohols, and then in zinc-catalyzed direct asymmetric aldol addition. The computational predication is further confirmed experimentally in zinc-catalyzed direct asymmetric aldol addition by controlling the location of catalytic sites.

ChemInform Abstract: Direct Asymmetric Aldol Addition—Isomerization of α,β‐Unsaturated γ‐Butyrolactam with Aryl α‐Ketoesters: Synthesis of MBH‐Type Products.

AbstractThe title reaction affords Morita—Baylis—Hillman type adducts containing a quaternary stereocenter in high yields and with excellent enantioselectivities.

Direct asymmetric aldol addition–isomerization of α,β-unsaturated γ-butyrolactam with aryl α-ketoesters: synthesis of MBH-type products

A highly efficient direct asymmetric aldol addition-isomerization reaction at the α-position of α,β-unsaturated γ-butyrolactam and aryl α-ketoesters by using a bifunctional thiourea catalyst was achieved. Morita-Baylis-Hillman type adducts containing a quaternary stereocenter can be obtained in high yields and with excellent enantioselectivities (up to 99% ee).

D-Glucosamine in a chimeric prolinamide organocatalyst for direct asymmetric aldol addition

O-TBDPS d-glucosamine coupled with l-proline is reported to act as an efficient organocatalyst in the accomplishment of direct aldol reactions. Excellent results, in terms of chemical yields, as well as diastereomeric and enantiomeric ratios, are reported for the catalyzed additions of cyclohexanone and acetone to variously substituted benzaldehydes.

Isoleucine-Catalyzed Direct Asymmetric Aldol Addition of Enolizable Aldehydes

Isoleucine-catalyzed direct enantioselective aldol additions between enolizable aldehydes are reported. Intermediate acetal structures dictate the configurative outcome and were supported by a hydrogen bond. This direct isoleucine-catalyzed aldol addition represents a welcome complement to both proline- and histidine-catalyzed aldol additions of enolizable aldehydes.

Supported l-proline on zirconium phosphates methyl and/or phenyl phosphonates as heterogeneous organocatalysts for direct asymmetric aldol addition

Zirconium phosphates methyl and/or phenyl phosphonates-supported l-proline have been prepared as amorphous solids by precipitation of (4 R)-4-(phosphonooxy)- l-proline, methyl and/or phenyl phosphonic acid with ZrOCl 2. The supported l-proline catalysts were tested on the direct asymmetric aldol addition of cyclohexanone to p-nitrobenzaldehyde in DMF/H 2O (9:1) and in sole water. The hydrophobic groups on solid surface favor reagents’ diffusion toward proline chiral moiety increasing the catalytic activity of supported l-proline. High diastereoselectivity ( anti/syn up to 94:6) and high enantiomeric excess up to 97% have been obtained.

Direct Asymmetric Aldol Reaction of Aryl Ketones with Aryl Aldehydes Catalyzed by Chiral BINOL-Derived Zincate Catalyst

Direct asymmetric aldol reaction of aryl ketones with aryl aldehydes catalyzed by chiral metal complex is reported for the first time herein. Two novel semicrown chiral ligands 1a and 1b were synthesized from (S)- and (R)-BINOL, respectively, and then employed to catalyze the direct asymmetric aldol addition of aryl ketones to aryl aldehydes. Introduced with 2.0 equiv of diethylzinc, 1b had higher enantioselectivity than 1a. Up to 97% yield and up to 80% enantioselectivity were achieved.