Baylis-Hillman product, formation

Very good enantioselectivities were recently reported by Hatakeyama and coworkers [33]. The reaction of a variety of aldehydes 28 with the highly reactive 1,1,1,3,3,3-hexafluoro iso-propylacrylate 27 using modified Cinchona-alkaloids as the catalyst resulted, at a temperature of-55 °C, in formation of the Baylis-Hillman-products 30 in 31-58% yields with 91-99% ee (Scheme 6). The use of the tricyclic derivative 29, which was prepared from quinidine in one step [34], proved crucial in order to obtain high enantioselectivities. The success of catalyst 29 can be explained by the (compared with quinidine) increased nucleophilicity, by the... 

An alkene activated by an electron-withdrawing group—often an acrylic ester 2 is used—can react with an aldehyde or ketone 1 in the presence of catalytic amounts of a tertiary amine, to yield an a-hydroxyalkylated product. This reaction, known as the Baylis-Hillman reaction, leads to the formation of useful multifunctional products, e.g. o -methylene-/3-hydroxy carbonyl compounds 3 with a chiral carbon center and various options for consecutive reactions. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

The conversion rate in aza-Baylis-Hillman reactions is generally low, which leads to extended reaction times [87]. Heating is normally used to increase the reaction speed however, it also promotes the formation of side products. Alternatively, microwave heating was successfully used as a way of promoting the reaction [92]. However, microwaves-promoted reactions are not easy to scale-up. Guided by this, the Stevens research group [89, 93] used the commercial CYTOS College System [18] to perform these reactions on a microscale in a continuous manner in order to improve the reaction rates and make it industrially more applicable. 

The Morita-Baylis-Hillman (MBH) reaction is the formation of a-methylene-/ -hydroxycarbonyl compounds X by addition of aldehydes IX to a,/ -unsaturated carbonyl compounds VIII, for example vinyl ketones, acrylonitriles or acrylic esters (Scheme 6.58) [143-148]. For the reaction to occur the presence of catalytically active nucleophiles ( Nu , Scheme 6.58) is required. It is now commonly accepted that the MBH reaction is initiated by addition of the catalytically active nucleophile to the enone/enoate VIII. The resulting enolate adds to the aldehyde IX, establishing the new stereogenic center at the aldehydic carbonyl carbon atom. Formation of the product X is completed by proton transfer from the a-position of the carbonyl moiety to the alcoholate oxygen atom with concomitant elimination of the nucleophile. Thus Nu is available for the next catalytic cycle. 

The stereoselective formation of carbon-carbon bonds is an important problem in organic chemistry. The Baylis-Hillman-reaction allows the direct preparation of oc-methylene-/ -hydroxycarbonyl compounds by base-catalyzed reaction of a,/ -unsaturated carbonyl compounds with aldehydes [1-3]. The first step of this reaction involves nucleophilic attack of the catalyst onto the Michael-acceptor 1 under formation of the zwitterionic intermediate 2. Subsequently, this intermediate reacts in the rate-determing step of the Baylis-Hillman-reaction with the aldehyde 3 under formation of the alcoholate 4 (Scheme 1). The product 5... 

Product formation and yields in the Baylis-Hillman reaction also depend on a balance between the reactivities of the carbonyl and olefin partners as was shown, for example, for reactions of fluorine-containing carbonyl compounds [13]. 

A case of anomalous 1,3-dioxolane formation has been reported when the sesquiterpene lactone parthenin 9 is treated under Baylis-Hillman conditions with aromatic aldehydes and affords products of type 10 <07TL955>. A computational study of copper-catalysed carbonyl... 

Propose a mechanism for the following formation of the aza Morita Baylis Hillman reaction product that is obtained from an a hydroxypropargylsilanc (1) and the N tert butanesulfinyl imine. Provide the structure of intermediate A obtained upon slow addition of n BuLi to ( ) 1. 

Some polyfunctional isoxazolines of generic structure 44 were obtained in 78-91% yields by treatment of aryl aldoximes 42 with Baylis-Hillman adducts 43 in the presence of diacetoxy iodobenzene (DIB). The reaction is completely diastereoselective and involves the formation of nitrile oxides from aldoximes followed by 1,3-DC with the activated alkenes. Under the same conditions, ketoximes afforded only deoximation products <04TL7347>. 

In a reversal of this intramolecularized side-chain reactivity (effecting annulation of a five-membered ring to the N/C-2-position of pyridine) the Baylis-Hillman reaction of pyridine-2-aldehydes with acceptor-substituted alkenes, e.g. acrylates, in the presence of DABCO gives rise to formation of products 74, which can be cyclized to 2-substituted indolizines, e.g. indolizine-2-carboxylates 75 [54]. 

Baylis-Hillman adducts are readily available building blocks, which upon stereoselective OYE-catalyzed reduction afford synthetically important chiral products [42]. The first example to be reported involves the formation of the Roche ester (4a) from the Baylis-Hillman adduct 3a especially the allyl and benzyl ethers (3b and 3c, respectively) can be reduced stereoselectively using several different OYEs, with results (99% ee) rivaling and surpassing synthetic catalysts (Eigure 5.6) [42]. 

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