Desymmetrization of diols by a tandem oxidation/Wittig olefination reaction

Diols are desymmetrized by a tandem oxidation/Wittig olefination to give alpha,beta-unsaturated hydroxy esters without the requirement for protecting group strategies; the alpha,beta-unsaturated hydroxy esters are transformed into dienyl diesters using a second oxidation/Wittig olefination sequence using PCC.     

A one-pot silyl-Reformatsky olefination

A novel one-pot olefination reaction has been developed, involving the stereoselective formation of (E)-α,β-unsaturated esters/ketones from the reaction of α-bromocarbonyl compounds with aromatic aldehydes. The reactions use a reagent combination of trichlorosilane, and triethylamine and may proceed via the in situ formation of a trichlorosilyl ketene acetal. The general procedure offers key advantages (high conversions, low quantities of organic soluble by-products) over the conventional Wittig reaction.     

Lewis acid-catalyzed Meyer-Schuster reactions: methodology for the olefination of aldehydes and ketones

In principle, the most efficient and atom-economical means of converting an aldehyde or ketone into the homologated α,β-unsaturated ester is through addition/rearrangement sequences involving acetylenic π-bonds (Scheme 1). Implementation of such a strategy for the synthesis of α,β-unsaturated esters is presented: addition of ethoxyacetylene followed by scandium(III) triflate-catalyzed Meyer-Schuster rearrangement reaction. Stereoselectivities range from good to excellent in the formation of disubstituted α,β-unsaturated esters from aldehydes (Table 3). The two-stage olefination of even the most hindered ketones proceeds with near perfect efficiency (Table 4).     

A facile one-pot synthesis of α-fluoro-α,β-unsaturated esters from alkoxycarbonylmethyltriphenylphosphonium bromides

A convenient one-pot synthesis of α-fluoro-α,β-unsaturated esters from ethoxy- and tert-butoxycarbonylmethyltriphenylphosphonium bromide was developed. The fluorinated phosphoranes, generated in situ from alkoxycarbonylmethyltriphenylphosphonium bromides and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor^®), undergo a Wittig reaction with aldehydes to yield α-fluoro-α,β-unsaturated esters with (Z)-selectivity.     

Total synthesis of (+)-synargentolide A

The highly stereoselective total synthesis of polyacetate α,β-unsaturated δ-lactone natural product (+)-synargentolide A has been accomplished from inexpensive d-1,5-gluconolactone. Key reactions involved in the synthesis are hydroboration, Wittig olefination, Brown’s asymmetric allylation, and a ring closing metathesis reaction.     

The direct preparation of functionalised cyclopropanes from allylic alcohols or α-hydroxyketones using tandem oxidation processes

New manganese dioxide-mediated tandem oxidation processes (TOPs) have been developed, which facilitate the direct conversion of allylic alcohols and α-hydroxyketones into polysubstituted functionalised cyclopropanes. In the simplest version, the oxidation of an allylic alcohol is carried out in the presence of a stabilised sulfurane, and the intermediate α,β-unsaturated carbonyl compound undergoes in situ cyclopropanation. By using a combination of stabilised phosphorane and sulfurane, the direct conversion of allylic alcohols or α-hydroxyketones into functionalised cyclopropanes is achieved, with in situ cyclopropanation being followed by Wittig olefination, or vice versa. The application of these methods to a formal synthesis of the lignan (±)-picropodophyllone, and to novel analogues of the insecticide allethrin II, is described.     

Asymmetric dihydroxylation of vinyl sulfones: routes to enantioenriched α-hydroxyaldehydes and the enantioselective syntheses of furan-2(5H)-ones

The asymmetric dihydroxylation of α,β-unsaturated sulfones under Sharpless conditions affords enantioenriched α-hydroxyaldehydes in a complex mixture of dimeric species. These mixtures undergo olefination generating the corresponding α,β-unsaturated esters or furan-2(5H)-ones with high levels of enantiomeric excess. The application of this method for the rapid stereoselective synthesis of the furanone natural products; quercus lactone and maritolide, are described.     

Polymer-Assisted Solution-Phase Synthesis Under Combined Ultrasound and Microwave Irradiation: Preparation of α,β-Unsaturated Esters and Carboxylic Acids,Key Intermediates of Novel Sigma Ligands

The optimal conditions to prepare α,β-unsaturated methyl esters via Wittig reaction combining polymer-assisted solution-phase synthesis (PASPS) methodology and simultaneous ultrasound and microwave irradiation were established. The effects of temperature, solvent, and irradiation time were discussed. Results clearly indicated the superiority of combined ultrasound and microwave-assisted procedure over microwave-assisted methodology. Moreover, an efficient PASPS procedure to prepare α,β-unsaturated carboxylic acids via tandem Wittig olefination and hydrolysis reaction was developed under combined ultrasound and microwave irradiation. Generally, a good conversion of aldehydes to acids was observed. The optimized protocols allowed us to quickly prepare a small collection of either α,β-unsaturated esters or carboxylic acids, key intermediates for the drug-discovery process of new sigma ligands.     

A highly stereospecific synthesis of (E)-α,β-unsaturated esters

CrCl₂-induced olefination of aldehydes using methyl dichloroacetate exclusively generates (E)-α,β-unsaturated esters in excellent yields. The intermediate α-chloro-β-hydroxy adducts could also be isolated in good yields under conditions of limited reagent.     

Gold-mediated synthesis of α-ionone

A simple and convenient synthesis of α-ionone, an important component of flowers and fragrances, is reported. The key step in the formation of the α,β-unsaturated ketone moiety involves an NHC-Au^I catalyzed Meyer-Schuster-like rearrangement of readily prepared propargylic esters. The complex [{Au(IPr)}₂(μ-OH)][BF₄] proved to be the most efficient catalyst leading to α-ionone in 70% yield from a propargylic benzoate. This optimized procedure represents a valuable and attractive alternative to classical methods leading to α,β-unsaturated ketones, such as the Wittig or aldol reactions.     

Enantioselective photodeconjugation of α,β-unsaturated esters: Effect of the nature of the chiral agent

A synergism exists between the effect of the amino and hydroxy groups of chiral amino alcohols on the enantiomeric excess of the photodeconjugation of α,β-unsaturated esters.     

Iodine-mediated Z-selective oxidation of ketones to α,β-unsaturated esters: synthesis and mechanistic studies

The Z-selective oxidation of simple acyclic ketones to Z-2,3-trisubstituted α,β-unsaturated esters is described. Enolates generated under the reaction conditions undergo double iodination followed by a Favorskii-related rearrangement to the unsaturated ester. This reaction represents the first stereoselective one-step transformation of ketones to α,β-unsaturated esters. Mechanistic studies suggest that an electrocyclic reaction governs the Favorskii-related rearrangement.     

TiCl4-mediated olefination of aldehydes with acetic acid and alkyl acetates: a stereoselective approach to (E)-α,β-unsaturated carboxylic acids and esters

A new method has been developed for the preparation of α,β-unsaturated carboxylic acids and corresponding esters with (E)-stereoselectivity via the TiCl₄-mediated olefination of aldehydes. The method, which uses readily available acetic acid or its alkyl esters as active methylene partners, is more flexible and complementary to conventional routes in the preparation of (E)-cinnamic acid derivatives.     

Tandem reduction-olefination for the stereoselective synthesis of (Z)-α-fluoro-α,β-unsaturated esters

A tandem stereoselective reduction-olefination reaction of ethyl 2-acyl-2-fluoro-2-diethylphosphonoacetate employing NaBH₄ in EtOH was developed. The one-pot reaction gave α-fluoro-α,β-unsaturated esters with excellent (Z)-selectivity. A plausible mechanism involving a diastereoselective reduction predicted by the Felkin-Anh model, followed by olefination similar to the Horner-Wadsworth-Emmons reaction, has been proposed.     

PDC-Mediated Tandem Oxidative–Wittig Olefination

A convenient tandem oxidative–Wittig olefination of a primary alcohols to α,β-unsaturated compounds using pyridinium dichromate (PDC) is described.     

微波促进立体选择性高效合成糖基α,β-不饱和酯类化合物

利用微波促进糖醛与叶立德(Ph3P=CHCOOEt)发生Wittig反应,立体选择性地合成了含有α,β-不饱和酯的糖烯类化合物,反应效率显著提高,使用不同的反应溶剂可实现对反应立体选择性的控制.并通过1H NMR中双键氢的偶合常数确定了产物的构型.     

Convenient procedure of Horner-Wadsworth-Emmons olefination for the synthesis of simple and functionalized α,β-unsaturated nitriles

A mild and practical procedure of Horner-Wadsworth-Emmons olefination promoted by lithium hydroxide and α-cyano phosphonates has been set up for the synthesis of α,β-unsaturated nitriles. The reaction conditions are tolerated by functionalized ketones and the exclusive formation of E-γ-hydroxy α,β-unsaturated nitriles has been observed.     

A novel and efficient procedure for the preparation of allylic alcohols from α,β-unsaturated carboxylic esters using LiAlH4/BnCl

A new and efficient method for the reduction of α,β-unsaturated carboxylic esters to allylic alcohols utilizing LiAlH₄/BnCl is described. Various α,β-unsaturated esters, including the coumarins bearing α,β-unsaturated lactone skeleton, can be converted smoothly into their corresponding allylic alcohols in high yields under mild conditions with short reaction times.     

Total Synthesis and Biological Evaluation of Seiricuprolide and Pestalotioprolide B

The first total syntheses of seiricuprolide and pestalotioprolide B, rare 14-membered α,β-unsaturated macrolides embedding a chiral epoxide motif, were achieved in 17 steps with 1.9 % and 1.6 % overall yields, respectively. Our synthesis featured the key Shiina macrolactonization to construct the 14-membered macrocyclic skeleton, Wittig olefination to generate the (E)-α,β-unsaturated ester and selective reduction of advanced chiral propargylic alcohol intermediate to enable the exclusive formation of Z- or E-olefin at C8−C9. Synthetic seiricuprolide and pestalotioprolide B were evaluated for their cytotoxic activity against the HCT116 colon cancer cell line as well as their inhibitory effect on CFTR chloride channel activity in human intestinal epithelial (T84) cells. Preliminary structure–activity relationship suggested that the C5−C6 β-epoxide moiety suppressed both biological activities.     

New Preparation of α,β-Unsaturated Esters from 1-Alkenes Via Two Carbon Homologation Route. Synthesis of Queen Substance

2-Methylthio-4-alkenoic esters prepared from 1-alkenes and ethyl methylsulfinylacetate are converted into α,β-unsaturated esters via hydrogenation, oxidation, and thermolysis. This method was applied to the synthesis of queen substance.