Rearrangement–cyclization of dialkyl(4-hydroxybut-2-ynyl)meth-allyl- and dialkylcrotyl(4-hydroxy-but-2-ynyl) ammonium halides

It was found that dialkyl(4-hydroxybut-2-ynyl)methallyl- and dialkylcrotyl(4-hydroxybut-2-ynyl)- ammonium halides undergo a Stevens rearrangement under the influence of aqueous alkali with transfer of the reaction center in the receiving group and inversion of the migrating group followed by cyclization to amino derivatives of furan.     

Synthesis of dialkyl(1-allyl-3-arylprop-2-yn-1-yl)-and dialkyl(1-allyl-3-alkenylprop-2-yn-1-yl)amines by the stevens rearrangement

The Stevens rearrangement of dialkyl(allyl)(3-arylprop-2-yn-1-yl)-and dialkyl(allyl)(3-alkenyl-prop-2-yn-1-yl)ammonium bromides gave dialkyl(1-allyl-3-arylprop-2-yn-1-yl)-and dialkyl(1-allyl-3-alkenyl-prop-2-yn-1-yl)amines. Here, the allyl group acts as migrating group, and 3-aryl-or 3-alkenylprop-2-yn-1-yl, as receiving one. The yields of the Stevens rearrangement products fall down as the alkyl chain becomes longer, as well as with introduction of a methyl group into the meta or para position of the aromatic ring.     

Transformations of dialkyl(4-hydroxy-2-butynyl)-(3-phenylallyl)ammonium bromides in an KOH aqueous solution or in the presence of powdered KOH

Under the action of a twofold excess of KOH and heating in aqueous solution, and also under the conditions of the Stevens rearrangement (with KOH powder and a small amount of methanol) dialkyl-(4-hydroxy-2-butynyl)(3-phenylallyl)ammonium bromides form dialkyl[4-(1-phenylallyl)-2,5-dihydro-2-furyl]amines. Rearrangement–cleavage reaction also occurs under the same conditions.     

Alkynyliodonium salts in organic synthesis. Dihydrofuran formation via a formal stevens shift of a carbon substituent within a disubstituted-carbon oxonium ylide

The addition of p-toluenesulfinate to the silyl, 1-furanyl, and 1-pyranyl ethers of 1-hydroxybut-3-ynyl(phenyl)iodonium triflate triggers a sequence of reactions that ultimately delivers 2-substituted 3-p-toluenesulfonyldihydrofuran products in variable yields. A putative 1,2-group shift within an unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of the ether substituent. Deuterium labeling studies clarify the mechanistic course of this shift by providing evidence consistent with intramolecular substituent transfer and by identifying the primary source of the proton that intercepts the ylide in the major yield-limiting process.     

A new intramolecular recyclization in water‐base cleavage reaction of 2,2‐dialkyl‐4‐hydroxymethylbenz[f]iso indolinium bromides and chlorides

The water‐base cleavage reaction of 2,2‐dialkyl‐4‐hydroxymethylbenz[f]isoindolinium bromides and chlorides (2b‐g) and (4a‐g) was investigated. It was established that the above‐mentioned salts in water‐base cleavage reaction undergo intramolecular recyclization. As a result 1,3‐dihydro‐4‐dialkylaminomethyl‐naphto[1,2‐c]furans (5a‐g) are obtained in 62‐72% yields. The same products in 65‐70% yields may be obtained by step cyclization cleavage reaction of dialkyl‐4‐hydroxybutyn‐2‐yl‐(3‐phenylpropargyl) ammonium salts (1b‐g) and (3a‐g) , as well. The structure of the resulting amines 5a‐g are determined and approved by X‐ray diffraction, nmr and ir spectroscopic methods.     

Study of the behavior of p-bis{3-[N,N-dialkyl-N-(4-hydroxybut-2-ynyl)ammonio]prop-2-ynyl}-benzene dichlorides in relation to aqueous alkali. Double intramolecular recyclization of benzo[5,6;5′,6′-a,c]di(2,2-dialkyl-4-hydroxymethyl)isoindolinium dichlorides

p-Bis{3-[N,N-dialkyl-N-(4-hydroxybut-2-ynyl)ammonio]prop-2-ynyl}benzene dichloride in the presence of catalytic amounts of aqueous alkali is subject to a double intramolecular cyclization forming benzo[5,6;5′,6′-a,c]di(2,2-dialkyl-4-hydroxymethyl)isoindolinium dichloride in 40–42% yield. Simultaneously an intramolecular recyclization takes place with the formation of dialkyl(6-dialkylaminomethyl-7,9,10,12-tetrahydro-8,11-dioxadicyclopenta[c,g]phenanthren-1-ylmethyl)amines in 7–9% yield. The same compounds are obtained in 70–72% yield by the recyclization of benzo[5,6;5′,6′-a,c]di(2,2-dialkyl-4-hydroxymethyl)isoindolinium dichlorides under conditions of aqueous alkaline degradation. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1329–1335, September, 2006.     

Tandem catalytic allylic amination and [2,3]-Stevens rearrangement of tertiary amines

We have developed a catalytic allylic amination involving tertiary aminoesters and allylcarbonates, which is the first example of the use of tertiary amines as intermolecular nucleophiles in metal-catalyzed allylic substitution chemistry. This process is employed in a tandem ammonium ylide generation/[2,3]-rearrangement reaction, which formally represents a palladium-catalyzed Stevens rearrangement. Low catalyst loadings and mild reaction conditions are compatible with an unprecedented substrate scope for the ammonium ylide functionality, and products are generated in high yields and diastereoselectivities. Mechanistic studies suggested the reversible formation of an ammonium intermediate.     

Synthesis of Potentially Bioactive 6-Bromobenzo[<Emphasis Type="Italic">f</Emphasis>]isoindolinium Bromides by Base-Catalyzed Intramolecular [4+2]-Cycloaddition

Intramolecular cyclization of bromides of diethyl-, dipropyl-, and penthamethylenepropargyl[3-(4-bromophenyl)prop-2-ynyl]ammonium into 6-bromobenzo[f]isoindolinium bromides catalyzed with bases occurs with moderate self-heating. The morpholine analog even in more diluted solutions reacts with vigorous self-heating. Cyclization of dimethyl analog takes place only at heating at 80–85°C during 1 h.     

Acid-catalyzed cyclization of alkoxyacryloylureas to 2,4(1H,3H)pyrimidinediones

1-Phenylthymine and the carbocyclic analog of thymidine were obtained in yields of 84-87% by cyclizing the appropriate 3-methoxy-2-methylacryloylureas in dilute sulfuric acid. High yields of 1-phenylthymine also resulted when the cyclization was carried out in trifluoroacetic acid, in acetic acid containing toluenesulfonic acid (TSA), or by fusion of the urea with a catalytic amount of TSA. In comparison, the typical aqueous-alkali catalyzed cyclizations gave lower yields of the two thymines, and cleavage of the acryloylureas was shown to occur. However, cyclization in concentrated aqueous ammonia produced high yields of both thymine derivatives.     

Ruthenium porphyrin catalyzed tandem sulfonium/ammonium ylide formation and [2,3]-sigmatropic rearrangement. A concise synthesis of (+/-)-platynecine

meso-Tetrakis(p-tolyl)porphyrinatoruthenium(II) carbonyl, [Ru(II)(TTP)(CO)], can effect intermolecular sulfonium and ammonium ylide formation by catalytic decomposition of diazo compounds such as ethyl diazoacetate (EDA) in the presence of allyl sulfides and amines. Exclusive formation of [2,3]-sigmatropic rearrangement products (70-80% yields) was observed without [1,2]-rearrangement products being detected. The Ru-catalyzed reaction of EDA with disubstituted allyl sulfides such as crotyl sulfide produced an equimolar mixture of anti- and syn-2-(ethylthio)-3-methyl-4-pentenoic acid ethyl ester. The analogous "EDA + N,N-dimethylcrotylamine" reaction afforded a mixture of anti- and syn-2-(N,N-dimethylamino)-3-methyl-4-pentenoic acid ethyl esters with a diastereoselectivity of 3:1. The observed catalytic activity of [Ru(II)(TTP)(CO)] for the ylide [2,3]-sigmatropic rearrangement is comparable to the reported examples involving [Rh(2)(CH(3)CO(2))(4)] and [Cu(acac)(2)] as catalyst. Similarly, cyclic sulfonium and ammonium ylides can be produced by intramolecular reaction of a diazo group tethered to allyl sulfides and amines under the [Ru(II)(TTP)(CO)]-catalyzed reaction conditions. The subsequent [2,3]-sigmatropic rearrangement of the cyclic ylides furnished 2-allyl-substituted sulfur and nitrogen heterocycles in good yields (>90%). By employing [Ru(II)(TTP)(CO)] as catalyst, the cyclic ammonium ylide [2,3]-sigmatropic rearrangement reaction was successfully applied for the total synthesis of (+/-)-platynecine starting from cis-2-butenediol.     

Microwave-assisted one-pot synthesis of benzo[b][1,4]thiazin-3(4H)-ones via Smiles rearrangement

The synthesis of benzo[b][1,4]thiazin-3(4H)-one derivatives in a simple and efficient method from the one-pot reaction of substituted 2-chlorobenzenthiols, chloroacetyl chloride, and primary amines via Smiles rearrangement under microwave irradiation gave high yields (65-92%) of the products with short reaction time (15-20 min).     

Transformations of 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones in the presence of amines

When heated in piperidine, 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones undergo cyclization into 2-(1-hydroxyalkyl)naphtho[2,3-g]indole-6,11-diones. In contrast, 1-amino-2-(3-hydroxy-3-phenylpropynyl)-9,10-anthraquinone reacts with primary and secondary amines to give the corresponding 1-amino-2-(1-amino-2-benzoylvinyl)-9,10-anthraquinones, which undergo cyclization into 4-dialkylamino- or 4-alkylamino-2-phenylnaphtho[2,3-h]quinoline-7,12-diones. Heating of the starting phenylpropynol with Et₃N causes its dehydrogenation and isomerization.     

New synthetic approach to substituted isoindolo[2,1-a]quinoline carboxylic acids via intramolecular Diels-Alder reaction of 4-(N-furyl-2)-4-arylaminobutenes-1 with maleic anhydride

Acylation of substituted 4-(furyl-2)-4-arylaminobut-1-enes with maleic anhydride provided 2-allyl-6-carboxy-4-oxo-3-aza-10-oxatricyclo[5.2.1.0^1,5]dec-8-enes in high yield under mild reaction conditions. The Diels-Alder adducts are formed via an initial amide formation followed by a stereoselective intramolecular [4+2] exo-cycloaddition reaction. Treatment of the tricyclic compounds with phosphoric acid at high temperatures (70-120 °C) promoted cyclic ether opening, intramolecular cyclization and aromatization to give the corresponding tetracyclic compounds, 5,6,6a,11-tetrahydro-10-carboxyisoindolo[2,1-a]quinolines, in moderate yields. The influence of the acid and the reaction temperature on the cyclization reactions are also discussed.     

Versatile and efficient solid-phase syntheses of pyrazoles and isoxazoles

[reaction: see text] Condensation of aromatic or aliphatic esters with resin-supported acetyl carboxylic acids 2, followed by cyclization with hydrazines or hydroxylamine, activation of the linker, and cleavage using amines provides highly substituted, isomeric pyrazoles or isoxazoles 5. This general method gives products in excellent yields and purities in which the ratio of the two isomers can be easily controlled. A variation of this scheme generates 1,4,5- and 1,3, 4-trisubstituted pyrazoles and related isoxazoles. Post-cleavage reduction with borane converts pyrazole amides to amines such as 11.     

Reaction of 2-(2-Cyanoethyl)-1,1-dimethylhydrazine with Prop-2-ynyl Bromide, 1,3-Dibromopropyne,and Allyl Bromide

The reactions of 2-(2-cyanoethyl)-1,1-dimethylhydrazine with prop-2-ynyl bromide, 1,3-dibromopropyne, and allyl bromide involve alkylation by a tertiary nitrogen atom to form 2-(2-cyanoethyl)-1,1-dimethyl-1-(prop-2-ynyl)-, 1-(3-bromoprop-1-ynyl)-2-(2-cyanoethyl)-1,1-dimethyl-, and 1-allyl-2-(2-cyanoethyl)-1,1-dimethylhydrazinium bromides.     

Synthesis and cyclization of 1-arylalk-1-ene-3,5-diynylamines

An investigation of the reaction of 1-lithio-1,3-diynes, generated in situ, with nitriles has been carried out. In the case of aromatic nitriles 1-arylalk-1-ene-3,5-diynylamines are formed, which undergo dimerization and cyclization on isolation, giving 3-(alka-1,3-diynyl)-4-(alk-2-ynyl)-2,6-diarylpyridines. The effect of the nature of the substituent in the benzonitrile molecule on the selectivity of the reaction and the yield of the products has been determined. A scheme is proposed for the conversions and the structures of the intermediates have been established. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 701–710, May, 2006.     

Stereoselective reductive tetraallylation of pyridinecarboxylic acids with triallylborane

Reductive tetraallylation of pyridine-3-and pyridine-4-carboxylic acids with triallylborane in the presence of propan-2-ol proceeded stereoselectively to yieldtrans-2,6-diallyl-3- andtrans-2,6-diallyl-4-(1-allyl-1-hydroxybut-3-en-1-yl)-1,2,5,6-tetrahydropyridines, respectively. Under the same conditions, the reaction with pyridine-2-carboxylic acid gave a mixture oftrans- andcis-2,6-diallyl-2-(1-allyl-1-hydroxybut-3-en-1-yl)-1,2,5,6-tetrahydropyridines in a ratio of 57:43. When 2,6-diphenylpyridine-4-carboxylic acid reacted with triallylborane, only the carboxylic group underwent reductive diallylation. When heated with triallylborane ino-xylene (130–133°C, 7 h),trans-2,6-diallyl-4-(1-allyl-1-hydroxybut-3-en-1-yl)-1,2,3,6-tetrahydropyridine was converted to the correspondingcis-isomer. The stereochemistry oftrans-2,6-diallyl-3-(1-allyl-1-hydroxybut-3-en-1-yl)-1,2,5,6,-tetrahydropyridine was confirmed by X-ray diffraction analysis. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2320–2326, November, 1998.     

Intramolecular 1,5-Hydride Transfer in Rearrangements of Ammonium Salts Containing Alkoxycarbonylmethyl and 4-Penten-2-ynyl Groups

The Stevens 3,2 rearrangement of dialkylammonium salts containing, along with 4-penten-2-ynyl, an alkoxycarbonylmethyl group, gives mostly hydrogenated products, with simultaneous dealkylation and aldehyde formation. On acid treatment enamine amino esters give keto esters or their further transformation product, 4-ethyl3-hydroxy-5-methyltetrahydrofuran-2-one.     

A simple and expedient method for the stepwise synthesis of 2-ethoxy-(4H)-3,1-benzoxazine-4-ones

A simple and practical route is described for the synthesis of 2-efhoxy-(4H)-3,1 -benzoxazine-4-ones using the coupling reaction of anthranilic acid derivatives with diethyl dicarbonate following with fast cyclization of the carbamate adduct with a dehydrocyclization agent such as cyanuric chloride and N,N′-dicyclohexylcarbodiimide in PEG at room temperature.High yields of the products obtained under mild reaction conditions with simple work-up of the reaction mixture.     

Alkynylhalocarbenes

(Alk-1-ynyl)chlorocarbenes (3), generated from 1,1-dihaloalk-2-ynes and 3-substituted 3-bromo-1,1,1-trichloropropanes under the action of Bu^tOK in THF at 20°C, react with excess alkali metal alkoxide4 to give 3-substituted 2-(alk-1-ynyl)oxiranes (6) in 26–78% yields, most likely as a result of insertion of carbene3 into the α-C−H bond of alkoxides4 and subsequent cyclization of the resulting 1-substituted 2-chloro-2-(alk-1-ynyl)etoxides. The yields of oxiranes6 depend on the nature of the alkali metal used to prepare alkoxides4 and on the method employed for the preparation of the latter. For Part 2, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1185–1192, June, 1998.