Acid catalysed reaction of indanones, tetralones and benzosuberone with neopentyl glycol and other alkanediols under forced conditions (original) (raw)
The Journal of Organic Chemistry, 2009
When treated with Ac 2 O at rt in the presence of 4-6 mol % FeCl 3 , 2-alkylcinnamaldehydes are converted to 2-alkyl-1H-inden-1-yl acetates through the intermediacy of gemdiacetates. Methanolysis of the indenyl acetates yields the corresponding indenols. Saponification yields 2-alkylindanones, providing, in effect, an intramolecular acylation employing catalytic levels of acid. Geminal dicarboxylates, or acylals, are prepared by the acid-catalyzed reaction between aldehydes and noncyclic anhydrides of carboxylic acids. The reaction is easily accomplished under mild conditions using a variety of Brønsted or Lewis acid catalysts. 1,2 A convenient, solventless procedure is to treat aldehydes with excess acetic anhydride and catalytic quantities of FeCl 3 at 0°C. 3 Acylals have been proposed as aldehyde protecting groups. 2,4 Other synthetic uses are concerned mainly with substitution reactions of a carboxylate group with carbon nucleophiles. 1,5 Acetic acid elimination from the diacetate acylals of R,β-unsaturated aldehydes produces 1-acetoxy-1,3-dienes, which have been used in Diels-Alder reactions. 6 Acylals of R,β-unsaturated aldehydes also have been employed as substrates in Pd-catalyzed allylic substitutions. 7 In the presence of Lewis acids, the acylals of acrolein and 2-alkylacroleins will alkylate aromatic rings, yielding the enol acetates of 3-arylpropanals, the Scriabine reaction. 8 This reaction, which provides a route to 3-arylpropanals, was described by Igor Scriabine in 1961. The transformation was effected by treating the unsaturated acylals with an excess of arene and 1 equiv of TiCl 4 in combination with BF 3 3 Et 2 O. More recent procedures developed for industrial purposes accomplish the reaction using substoichiometric levels of Lewis acid. 8e,8f Recently, we reported that in situ generated dimethyl acetals of (E)-2-alkylcinnamaldehydes cyclize in the presence of catalytic quantities of FeCl 3 , yielding 1-alkoxy-2-alkyl-1H-indenes (1). 9,10 Typically, indene formation was effected using 5-10 mol % FeCl 3 in refluxing MeOAc. These indenes were then transformed in two steps (base-catalyzed doublebond migration to form the enol ether and acid-catalyzed hydrolysis) into 2-alkylindanones (2). Formally, the transformation corresponds to an intramolecular Friedel-Crafts acylation achieved with catalytic quantities of Lewis acid. 11 Traditional Friedel-Crafts acylations require stoichiometric amounts of Lewis acid to proceed to completion because of coordination of Lewis acid with the resulting aryl ketones. On the basis of the precedents of our acetal cyclization and the Scriabine reaction, it seemed plausible that
Metal-free synthesis of indanes by iodine(III)-mediated ring contraction of 1, 2-dihydronaphthalenes
Journal of the Brazilian Chemical Society, 2011
Um protocolo livre de metais foi desenvolvido para sintetizar indanos através da contração de anel de 1,2-di-hidronaftalenos promovida por PhI(OH)OTs (HTIB ou reagente de Koser). Este rearranjo oxidativo pode ser realizado em diversos solventes (MeOH, CH 3 CN, 2,2,2-trifluoroetanol (TFE), 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), e uma mistura 1:4 de TFE:CH 2 Cl 2 ) em condições brandas. A contração de anel fornece indanos trans-1,3-dissubstituídos diastereosseletivamente, os quais são difíceis de obter em química orgânica sintética.
Synthetic studies in dihydroindole and indole alkaloids
1973
A synthetic approach toward the synthesis of vindoline (3) and a reinvestigation of the total synthesis of vincaminoridine (4) and epivincaminoridine (4a) is described. The synthetic sequence involves alkylation with benzyl chloride of the monosodium salt of propane-l,3-diol to give y-benzyloxypropanol (197). Treatment of 197 with thionyl chloride afforded benzyl-ychloropropyl ether (198). Alkylation of ethyl diethyl malonate with 198 provided diethyl Y~D enz yl ox yP ro Pyl etn yl malonate (134). Basic hydrolysis of 134 gave y-benzyloxypropylethyl malonic acid (199), which upon decarboxylation provided 2-(y-benzyloxypropyl)-butanoic acid (200). The monoacid (200) was esterified with ethanol to provide ethyl tx-(y-benzyloxypropyl)-butanoate (135). Alkylation of 135 with allyl bromide gave ethyl-a-(y-benzyloxypropyl)-a-allylbutanoate (201), which upon treatment with osmium tetroxide and sodium periodate gave ethyl a(y-benzyloxypropyl)-a-(a-formylmethyl)butanoate (140). Condensation of 140 with 6-methoxy tryptamine afforded the tetracyclic lactam (150). Lithium aluminum hydride reduction of the latter, followed by hydrogenolysis of the benzyl group gave two isomeric tetracyclic alcohols (204). These intermediates were converted via their mesylate derivatives to the quaternary salts (205), which upon treatment with potassium cyanide gave the isomeric cyanides (216). Acid hydrolysis of 216 gave the corresponding carbomethoxy derivative (151). Alkylation of 151 i i iwith methyl iodide provided dl-vincaminoridine (4) and dlepivincaminoridine (4a). Transannular cyclization of the latter substances gave the pentacyclic aspidosperma-type system (195). The degradation sequence involved acid hydrolysis of vindoline (3) to provide desacetyl vindoline (224), which upon catalytic hydrogenation gave desacetyldihydrovindoline (225). Pyrolysis of 225 afforded the ketone (86), which upon treatment with dimethyl carbonate provided the g-ketoester (226). Treatment of the sodium enolate of 226 with oxygen-hydrogen peroxide gave the hydroxy ketoester (227). Treatment of desacetyldihydrovindoline (225) with N,Nthiocarbonyldiimidazole gave the thiocarbonate derivative (230), which upon desulfurization with Raney nickel afforded the unsaturated ester (231). Catalytic hydrogenation of 231 gave the saturated ester (232) , which upon treatment with lithium diisopropyl amide and oxygen-hydrogen peroxide provided the hydroxyester (234). The saturated ester 232 was converted to the alcohol derivative (237) by reduction with aluminum hydride. Oppenauer oxidation of 237 gave the aldehyde (238). Finally potassium permanganate oxidation of the unsaturated ester (231) gave 5-membered lactam (240), 6-membered lactam (241), N-formyl-5-membered lactam (242), ct and N Q-formyl-6-membered lactam (243) .
Novel Synthesis of 1H-Inden-1-Ones and Thienylpropenones in Aqueous Medium
Journal of the Chinese Chemical Society, 2006
Condensation of acetylacetone with 4-methoxybenzaldehyde, 2,4-dimethoxybenzaldehyde, 3,4-dimethoxybenzaldehyde, 4-nitrobenzaldehyde and 2,4-dinitrobenzaldehyde in water and in the presence of cetyltrimethylammonium bromide (CTABr) as cationic surfactant in dilute sodium hydroxide at room temperature did not afford the expected arylideneacetylacetone but yielded 1H-inden-1-one derivatives 1, while, with piperonaldehyde under the same conditions afforded dipiperonylideneacetone 2. Also 3-acetylthiophene condensed with some aromatic aldehydes under the same conditions gave the expected stereoselective thienylpropenones 4. The structures of the products were identified by IR, NMR, Mass spectral data and elemental analysis.
This is the sixth chapter in the series published by the same authors: “The Organic Chemistry Notebook Series, a Didactical Approach”. Here we offer the mechanistic views of the synthesis of alkenes by oxidative decarboxylation of carboxylic acids. The aim of this series of studies is to help students to have a graphical view of organic synthesis reactions of diverse nature. The oxidative decarboxylation of carboxylic acids is a useful method for generating alkenes. Here we propose the mechanism and its discussion for the application of the method of decarboxylation of diacids lacking nearby double bonds. Also, the route is explained mechanistically for the preparation of Dewar benzene. The thermal or photolytic decomposition of di-t-butyl per-esters is described. The treatment of monocarboxylic acids to afford alkenes in the presence of lead tetraacetate and copperII acetate is briefly discussed. The alkylation-decarboxylation of aromatic acids is also explained. The oxidative decarboxylation of carboxylic acids can eventually conduct to the obtaining of ketones instead of alkenes. We have used a series of reactions reviewed by W. Carruthers, and we have proposed didactical and mechanistic views for them. This latest approach is included in the synthetic methods reviewed by W. Carruthers with respect to the “Formation of carbon-carbon double bonds”. Spanish title: Síntesis de alquenos por descarboxilación de ácidos carboxílicos; vistas mecanísticas; De la serie: El cuaderno de notas de química orgánica, un enfoque didáctico, Nº6.
Enynones in organic synthesis. III. A novel synthesis of phenols
Tetrahedron Letters, 1988
Enynones are converted to phenols by an acid catalyzed process which can be controlled to give either of two regioisomeric series of products. During the course of efforts aimed at converting the acetylenic enone 1 to the acorone precursor 2,l.z we were surprised to find that collidine p-toluenesulfonate (CPTS) catalyzed a very efficient transformation of 1 to the dihydronaphthol derivative 3a at 250° C in mesitylene. None of the desired spirocycle 2 could be detected, and the 2 1 30 7. Phenol 15b has previously been prepared by Dreiding et al. in 33% GC yield by gas phase pyrolysis of lob at 7000 C:
Synthesis of the Tetracyclic Core of the Neomangicols Using a Late-Stage Indene Alkylation
Organic Letters, 2009
A general approach to the tetracyclic core of the neomangicol natural products via a late-stage indene alkylation reaction is presented. This strategy sets the stage for access to the neomangicol family and, in addition, provides a potential biogenetically inspired entry to the mangicol natural products. Historically, the carbon framework of terpenoid natural products has proven to be a synthetic challenge due to the lack of functional groups on these molecules that can direct CC bond formation. 1 As a result, synthetic chemists must design strategies for terpenoid syntheses that maximize carbon-carbon bond formation. Enolate methodology has been featured prominently in a wide range of CC bond forming cyclization tactics (e.g., intramolecular aldol and Dieckmann reactions) en route to terpene natural products, which often necessitate the removal of the enolate carbonyl oxygen at a late stage. In the context of [5-6] bicyclic ring-containing terpene natural products, we envisioned that indenes, which possess acidities comparable to carbonyl compounds (e.g., ketones), could serve as enolate equivalents in late-stage bondforming events. In this communication, we present the application of this tactic to the synthesis of the tetracyclic core of the natural product neomangicol C (2, Figure 1). Neomangicol C is a member of a group of rearranged sesterterpenoids isolated from a marine fungus of the genus Fusarium, which possess varied bioactivity. 2 For example, neomangicols A and B (1a and 1b, Figure 1) have shown in vitro cytotoxicity against human colon carcinoma. Furthermore, neomangicol B (1b) has shown potency against the Gram-positive bacterium Bacillus subtilis similar to that of the aminoglycoside gentamycin and may prove to be of general utility as an antibiotic. 2 Preliminary studies have not identified significant bioactivity for neomangicol C (2), and there is evidence that suggests it may be an isolation artifact arising from the net loss of HCl or HBr from 1a or 1b, respectively. 2 To date, there have been no reports of synthetic work toward the neomangicols. However, studies by Uemura 3 and Paquette 4 have recently begun to address the synthesis of the related
Synthesis of 3-alkylideneisoindolinones and isoindolones by a Horner–Wadsworth–Emmons reaction
Monatshefte für Chemie - Chemical Monthly, 2014
A series of 3-alkylideneisoindolinones was prepared by a Horner-Wadsworth-Emmons (HWE) reaction of aromatic aldehydes with N-(x-hydroxyalkyl)substituted 3-phosphoisoindolin-1-ones, obtained in onepot synthesis from 2-formylbenzoic acid. Additionally, the intramolecular HWE reaction of the N-(x-formylalkyl)substituted phosphoisoindolin-1-ones afforded the corresponding isoindolone derivatives. Keywords Phosphonates Á Three-component reaction Á Wittig reaction Á Heterocycles 180 W, 10 min) [28]. Remarkably, this process did not need any catalyst (Scheme 1). With the isoindolin-1-one-3-phosphonates 6a and 6b in hand, we focused our attention on the intermolecular HWE
Three component reaction of indane-1,2,3-trione, tosylmethyl isocyanide and benzoic acid derivatives
Arkivoc, 2008
The Passerini reactions of indane-1,2,3-trione, tosylmethyl isocyanide, and benzoic acid derivatives proceed at room temperature giving sterically congested 2,2-disubstituted indane-1,3dione derivatives in quantitative yield. The reactions are one-pot, and the products obtained did not require any purification.
Reaction of 2-amino-2-deoxyheptoses with cyclic β-dicarbonyl compounds
Carbohydrate Research, 1980
Thus, 6,6-dimethyl-2-(D-gala&-pen ti tol-l-yl)-4,5,6,7-tetrahydroindol4one (4a), 6,6-dimethyl-2-(D-gluco-pentitol-1 -y&4,5,6,7-tetrahydroindol4one (4b), and 6,6-dimethyl-2-(o-manno-pentitol-l-y1)4,5,6,7-tetra-hydroindol4one (4~) have been obtained from 5,5-dimethylcyclohexane-1,3-dione (2) and 2-amino-2-deoxyheptoses having D-glycero-L-glum (la), D-g~ycef-o-D-i& (lb), and D-glycero-D-?aZo (lc) configurations, respectively. 2-Amino-2-deoxy-D-g&ero-Lmanno-heptose (Id), the epimer of la, also reacts with 2, to yie1.d 4a. III a similar way, la, lb, and lc react with gyclohexane-1,3-dione (3), to give 2-(D-g&cto-pentitoll-yl)4,5,6,7-tetrahydroindol4one (5a), 2-(D-gluco-pentitol-1-yl)4,5,6,7_tetrahydro-indol4one (5h), and 2-(D-manna-pentitol-l-yl)4,5,6,7-tetrahydroindol4one (5c), respectively_ *Presented, in part, at -the 75th Anniversary Meeting of the Real Sociedad Espaiiola de Fisica y QuImica, Madrid, October 1978.
Domino synthesis of indenols and alkyl-indene ethers under modified Vilsmeier conditions
Tetrahedron Letters, 2006
Indenols are produced in high yields through domino reactions, when electron-rich trans-stilbenes and other trans arylalkyl olefins were subjected to Vilsmeier formylation in the presence of excess POCl 3 in a one-pot procedure. The method is even suitable for converting aryl-alkyl carbinols (precursors for olefins) directly into indenols. The corresponding indene ethers could be prepared in high yields directly when less reactive a,b-unsaturated aldehydes were subjected to cyclization in alcoholic HCl.