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Journal ArticleDOI

Studies in claisen rearrangement : Novel thermal transformation of α-aryloxymethylacrylic acids and their derivatives

01 Jan 1985-Tetrahedron (Pergamon)-Vol. 41, Iss: 15, pp 3153-3159

Abstractα-Aryloxymethylacrylic acids and their derivatives have been found to undergo some novel thermal transformations leading to the formation of ‘ene’ dimers. The structure of the dimer has been revised on the basis of degradation studies, extensive spectral data and isolation of intermediates. more

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Reference EntryDOI
Abstract: In a patent application published in 1972, Baylis and Hillman reported the reaction of acetaldehyde with ethyl acrylate and acrylonitrile in the presence of catalytic amounts of 1,4-diazabicyclo[2.2.2]octane to give the α-hydroxyethylated products in good yields. No structure proof was given. The assignment eventually was shown to be correct, but since the initial disclosure was not followed by a journal publication, this remarkably simple, atom-efficient, and useful reaction was ignored for a number of years, and it has been only fairly recently that its potential has begun to be explored. The transformation is now commonly referred to as the Baylis–Hillman reaction. This is unfortunate because credit for its invention clearly belongs to Morita, who five years earlier, in patents and a brief paper reported the same reaction with the exception that tertiary phosphines were used as the catalysts; he also proposed the currently accepted mechanism. Baylis and Hillman made reference to Morita's work in their patent application. It is true that tertiary amines in general are cheaper, less toxic, and more readily removed than tertiary phosphines. However, the latter sometimes give higher yields in shorter reaction times, and there are a number of examples where they are the only useful catalysts. The DABCO-catalyzed reaction is slow, and reaction times at room temperature of days or even weeks are common. Attempts to remedy this situation by use of other amine catalysts, change of reaction temperature, high pressure, or microwave irradiation have been partially successful. Activated olefins other than acrylonitrile and acrylic esters that have now been shown to undergo the reaction include α,β-unsaturated aldehydes and ketones, vinyl sulfoxides, vinyl sulfones, vinylsulfonates, and vinylphosphonates. β-Substituted activated olefins do not normally react. Among electrophiles other than aldehydes, unactivated ketones undergo the Morita–Baylis–Hillman reaction only under high pressure, but activation such as in α-halo ketones, α-keto esters, α-keto lactones, and nonenolizable α-diketones often produces very reactive substrates. Imines also can be employed, provided they carry a sufficiently electronegative group on nitrogen. This chapter covers catalyzed α-hydroxyalkylations and α-aminoalkylations of activated olefins. Transition metal catalyzed reactions of this type, are also included even though they proceed by a different mechanism. Transformations that require stoichiometric amounts of reagents or more than one step are summarized in the section on Comparison With Other Methods but are not included in the Tabular Survey. The Morita–Baylis–Hillman reaction has been reviewed before. Keywords: catalysts; hydroxyalklyation; aminoalkylation; activated olefin; acrylates; allenic esters; acrylamides; acrylonitrile; acrolein; unsaturated ketones; vinyl sulfoxides; vinyl sulfones; vinylsulfonates; vinylphosphonates; substituted activated olefins; electrophile; intramolecular reactions; side reactions; aldehydes; diketones; keto esters; keto lactones; imines; iminium salts; Aldol and Michael reactions; Morita-Baylis-Hillman reaction; comparison of methods; synthetic utility; experimental conditions; experimental procedures; tabular survey

85 citations

08 Dec 2009
Abstract: The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF recptor TrkA.

64 citations

Journal ArticleDOI
Abstract: Ozonolysis of mono-substituted alkenes A-1 followed by reacting with a preheated mixture of CH2Br2–Et2NH affords α-substituted acroleins A-2 in good yields. Under very mild reaction conditions, these α-substituted acroleins A-2 can be easily converted to α-methylene esters A-4 , which could be further converted to the corresponding α-keto esters A-5 . This methodology can be also applied to the preparation of α-methylene lactones B-4 , α-methylene lactams, and α-keto lactones B-5 with various ring sizes.

38 citations

Journal ArticleDOI
Abstract: The addition of various substituted phenols [XC6H4OH, X=H, o-CHO, o-CO2Me, o-CO2CH2Ph, o-CN, m-NHCOMe, m-OMe, p-OMe, p-CHO, p-Cl] to allylic acetates obtained from Baylis–Hillman adducts [RCH(OAc)C(CH2)CO2Et, R=H, n-Pr] has been studied in the presence of a Pd(0) catalyst and/or KF/alumina. In some cases, the use of one of these two reagents was sufficient to promote the OAc/OAr exchange but in general, faster reactions and higher yields were achieved when both reagents were used together. Evidence for two routes, an η3-allylpalladium intermediate and a Michael addition/elimination, was then obtained while a Heck type reaction could be involved under neutral conditions.

37 citations

Journal ArticleDOI
TL;DR: Bronsted acids induced the intramolecular cyclisation of 3-aryloxypropanoic esters affording 3-methyl-4-chromanones, which have been transformed into the corresponding racemic benzyl β-oxoesters.
Abstract: Bronsted acids induced the intramolecular cyclisation of 3-aryloxypropanoic esters affording 3-methyl-4-chromanones, which have been transformed into the corresponding racemic benzyl β-oxoesters. These latter esters, in the presence of hydrogen and catalytic amounts of both palladium and (endo, endo) aminoborneol, led to optically active chromanones with up to 75% ee through a deprotection–decarboxylation–protonation cascade reaction.

34 citations

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Journal ArticleDOI
Abstract: Bei Wiederauinahme meiner Arbeiten iiber die 0 A l k y l d e r i v a t e d e s A c e t e s s i g e s t e r s und verwandter Verbindungen hat sich ein bemerkenswerter Unterschied gezeigt, der zwischen den 0-Alkylderivaten mit den gewiihnlichen gesLt t ig ten A l k g l e n (Methyl, Athyl, Propyl usw.) einerseits und den %All yl'derivaten andererseits besteht. Wahrend die ersteren so gut wie gar keine Neigung zeigen, sich in die isomeren C-Derivate umzulagern, tritt diese Neigung bei den 0 A 11 y lderivaten i n stitrkstem Mn5e hervor. 0Al ly 1acetessigester wird beim Destillieren uber etwas Salmiak fast vollstiindig in 0Ally l ace t ess iges t e r verwandelt :

306 citations

Journal ArticleDOI
Abstract: N-Allyl-2-methylaniline (12) forms on heating at 140° in xylene in the presence of zinc chloride 2-allyl-6-methylanline (19) as major compound and 4-allyl-2-methylaniline (20) as well as 2,7-dimethyl-indoline (21) as minor products. Compound 21 is also formed when 19 is heated in the presence of zinc chloride (scheme 2). That 19 arises from a charge-induced [3s, 3s] sigmatropic rearrangement of 12 – and 20 from two consecutive [3s, 3s]-sigmatropic transformations – follows from the reaction of N-crotyl-2-methylaniline (13) in the presence of zinc chloride at 140°. 2-(1′-Methylallyl)-6-methylaniline (22) and 4-crotyl-2-methylaniline (23) are formed exclusively. Small amounts of 2,3,7-trimethyl-indoline (24) and 2-(cis- and trans-1′-methyl-propenyl)-6-methylaniline (cis- and trans-25) are observed as by-products. Compound 24 arises from 22 in the presence of zinc chloride (scheme 3). Similar results are obtained when N-allyl and N-(2′-methylallyl)-N-methyl-aniline (14 and 15, respectively) are heated in the presence of zinc chloride. Whereas 14 gives nearly exclusively 2-allyl-N-methyl-aniline (28) and only small amounts of the corresponding 1, 2-dimethyl-indoline (29) and of 2-(cis- and trans-propenyl)-N-methyl-aniline (cis- and trans-27), 15 forms comparable amounts of 2-(2′-methylallyl)-N-methyl-aniline (30), 1,2,2-trimethyl-indoline (31), and 2-isobutenyl-N-methyl-aniline (32) (scheme 4). Compound 30, and also 32, are transformed into 31 on heating in the presence of zinc chloride. Charge-induced aromatic amino-Claisen rearrangements are also observed when N-allylated anilinium tetraphenylborates are heated at 100–105° in hexamethyl phosphoric acid triamide. Thus, N-allyl- and N-crotyl-N, N-dimethyl-anilinium tetraphenylborate (16 and 17, respectively) yield 2-allyl- and 2-(1′-methylallyl)-N,N-dimethyl-aniline (33 and 34, respectively) besides small amounts of N, N-dimethyl-aniline. N-Cinnamyl-N, N-dimethyl-anilinium tetraphenylborate (18) gives, besides appreciable amounts of N,N-dimethyl-aniline, a mixture of 2-(1′-phenylallyl)-,2-cinnamyl-, and 4-cinnamyl-N, N-dimethyl-aniline (35, 36, and 37, respectively) in which the first two compounds predominate.

44 citations