Double diastereoselection in anti aldol reactions mediated by dicyclohexylchloroborane between an l-erythrulose derivative and chiral aldehydes

Anti aldol reactions of an l-erythrulose derivative with several α-chiral aldehydes mediated by dicyclohexylboron chloride are examined. Good yields and stereoselectivities are observed. The results are best explained when the reactions are assumed to occur via boat-like transition states with minimization of 1,3-allylic strain and avoidance of syn pentane interactions.     

Aldol reactions between L-erythrulose derivatives and chiral alpha-amino and alpha-fluoro aldehydes: competition between Felkin-Anh and Cornforth transition states

Both matched and mismatched diastereoselection have been observed in aldol reactions of a boron enolate of a protected L-erythrulose derivative with several chiral alpha-fluoro and alpha-amino aldehydes. Strict adherence to the Felkin-Anh model for the respective transition structures does not account satisfactorily for all the observed results, as previously observed in the case of alpha-oxygenated aldehydes. In some cases, only the Cornforth model provides a good explanation. The factors that influence this dichotomy are discussed and a general mechanistic model is proposed for aldol reactions with alpha-heteroatom-substituted aldehydes. Additional support for the model was obtained from density functional calculations.     

Double diastereoselection in aldol reactions mediated by dicyclohexylchloroborane between chiral aldehydes and a chiral ethyl ketone derived from L-erythrulose. synthesis of a C1-C9 fragment of the structure of the antifungal metabolite soraphen A1alpha

[Chemical reaction: See text] Both matched and mismatched diastereoselections have been observed in the aldol reactions of a range of chiral aldehydes with the dicyclohexylboron enolate of a chiral ethyl ketone related to L-erythrulose. As was previously observed in the corresponding aldol reactions with L-erythrulose derivatives, the Felkin-Anh model provides an adequate explanation for the stereochemical outcome of reactions with chiral alpha-methyl aldehydes. However, a satisfactory account of the results observed with alpha-oxygenated aldehydes was only possible with the Cornforth model. As a practical application of the methodology described herein, a C1-C9 fragment of the structure of the antifungal macrolide soraphen A1alpha has been prepared in a convergent and stereoselective way.     

Acyclic stereoselection. 27. Simple diastereoselection in the lewis acid mediated reactions of enolsilanes with aldehydes.

The Lewis acid mediated reactions of enolsilanes 1–11 with benzaldehyde and isobutyraldehyde have been investigated. With the exception of compound 4, essentially no stereoselectivity is observed.     

syn-Selective asymmetric cross-aldol reactions between aldehydes and glyoxylic acid derivatives catalyzed by an axially chiral amino sulfonamide

syn-Selective asymmetric cross-aldol reactions of aldehydes with tert-butyl glyoxylate and glyoxamide were realized by the use of an axially chiral amino sulfonamide (S)-1. The cross-aldol products obtained are densely functionalized and readily converted to synthetically useful and important chiral building blocks such as γ-lactone and γ-lactam.     

Stereoselective anti aldol reactions of erythrulose derivatives. Functionalized chiral d3 and d4 synthons

An improved procedure for the synthesis of anti aldols from protected erythrulose derivatives is reported. The preparation of functionalized d3 and d4 synthons with various stereochemical arrays by means of this methodology is described and subsequently applied to a stereoselective formal synthesis of the natural metabolite goniothalesdiol.     

The first example of aldol reactions between trimethylsilyl enol ethers and aldehydes by the aid of rhodium complex

Crossed aldol reaction of trimethylsilyl enol ether with aldehyde is successfully performed with the aid of catalytic amount of rhodium complex, [(COD)Rh(DPPB)]⁺X⁻ (X = PF₆ and ClO₄) or Rh₄(CO)₁₂, under neutral conditions.     

Rational combination of two privileged chiral backbones: highly efficient organocatalysts for asymmetric direct aldol reactions between aromatic aldehydes and acylic ketones

A new class of organocatalysts has been designed by rational combination of proline with cinchona alkaloids. The chiral amine 3a, prepared from l-proline and cinchonidine, has been found to be an efficient catalyst for the direct aldol reactions of acetone or 2-butanone with a wide range of aldehydes (up to 98% ee). The cinchonidine backbone is essential to the reaction efficiency and enantioselectivity.     

Steric factors direct Baylis-Hillman and aldol reactions in titanium tetrachloride mediated coupling between alpha-keto esters and cyclohex-2-enone derivatives

The titanium tetrachloride mediated reaction of alpha-keto esters with 5,5-dimethylcyclohex-2-enone provides the corresponding Baylis-Hillman adducts exclusively whereas a similar reaction of alpha-keto esters with cyclohex-2-enone furnishes the corresponding aldol adducts (with high syn-diasteroeselectivity) as the major product (along with the Baylis-Hillman adducts as the minor product), thus clearly demonstrating the role of the steric factors in directing the reaction pathway.     

Asymmetric construction of quaternary carbon stereocenters: high stereoselection in Mukaiyama aldol reactions of 2-siloxyindoles with chiral aldehydes

[reaction: see text] A new synthesis of enantiopure 3,3-disubstituted oxindoles by stereoselective Mukaiyama aldol reaction of 3-substituted 2-siloxyindoles and chiral, enantiopure aldehydes having nitrogen or oxygen substituents at the alpha carbon is described. When the C3 substituent of the prochiral nucleophile is aryl or heteroaryl, stereoselectivity is high (10-80:1).     

手性胺催化不对称水相aldol反应研究进展

Aldol反应作为最重要的碳碳键形成反应之一,在有机合成中有着重要作用,本文综述了手性伯胺,仲胺催化剂催化的水相aldol反应的最新研究进展。     

L-Proline catalyzed aldol reactions between acetone and aldehydes in supercritical fluids: An environmentally friendly reaction procedure

The direct asymmetric aldol reaction between various aldehydes and acetone catalyzed by l-proline catalyst was successfully carried out in supercritical CO₂ (scCO₂) and 1,1,1,2-tetrafluoroethane (R-134a) fluids. The enantioselectivity of 84% ee to the targeted product was achieved under 20 MPa, 40 °C, and 15 mol% of the catalyst in supercritical CO₂ (scCO₂) fluid. The effects of reaction parameters, such as temperature, pressure, catalyst loading and different substituted aldehydes on both enantioselectivity and aldol yield were discussed. The titled reaction was also performed in 1,1,1,2-tetrafluoroethane, and the obtained results were compared with those in scCO₂. This new reaction procedure provides an environmental asymmetric aldol reaction system as compared with that in organic solvents.     

Double bond formation by one pot palladium induced reactions between aldehydes,allylic alcohols and triphenylphosphine

The reactions between several aldehydes, two allylic alcohols and triphenylphosphine under palladium catalysis leads to double bond formation, synthetically parallelizing the Wittig reaction.     

Novel chiral bifunctional l-thiazoline-amide derivatives: design and application in the direct enantioselective aldol reactions

Several novel chiral bifunctional l-thiazoline-amide derivatives were simply synthesized from commercially available l-cysteine and l-proline in high yield. These catalysts were subsequently applied to the direct enantioselective aldol reactions of various aldehydes, which are rarely reported in the literature. The products with anti configuration were obtained up to 97% ee and 99% dr when the l-thiazoline-amide derivatives were used. A plausible transition state model was proposed to explain the observed enantio and diastereoselectivities.     

Lewis Acid mediated reactions of zirconacyclopentadienes with aldehydes: one-pot synthetic route to indene and cyclopentadiene derivatives from aldehydes and benzyne or alkynes

One-pot procedures for the preparation of highly substituted indenes, tetrahydroindenes, and cyclopentadienes have been developed by using a combination of zirconocene-mediated Cbond;C-bond-forming reactions with Lewis acid mediated activation of carbonyl groups. The carbonyl groups of aldehydes were deoxygenated in the reaction and behaved formally as a one-carbon unit. A variety of Lewis acids were checked and showed different reactivities in this reaction.     

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.     

Highly diastereo- and enantioselective direct aldol reactions of cycloketones with aldehydes catalyzed by a trans-4-tert-butyldimethylsiloxy-l-proline amide

An organocatalyst derived from trans-4-hydroxy-l-proline and (1S,2S)-1,2-diphenyl-2-aminoethanol catalyzes the direct aldol reactions of cycloketones with a wide scope of aldehydes in high yields and with excellent diastereoselectivities of up to >99:1 and enantioselectivities of up to >99% ee.