Silyl-enolization-asymmetric Claisen rearrangement of 2-allyloxyindolin-3-one: enantioselective total synthesis of 3a-hydroxypyrrolo[2,3-b]indoline alkaloid alline

Asymmetric Claisen rearrangement triggered by silyl-enolization of 2-(1′-nonel-3′-yloxy)indolin-3-ones was performed in order to prepare 3-(2′-nonenyl)-3-hydroxyindolin-2-ones. Total synthesis of 3-hydroxypyrrolo[2,3-b]indoline alkaloid, (+)-alline was achieved by transformation of the allylic moiety of 3-(2′-nonenyl)-3-hydroxyindolin-2-one to amine followed by reductive cyclization.     

Applications of NHC-mediated O- to C-carboxyl transfer: synthesis of (±)-N-benzyl-coerulescine and (±)-horsfiline

NHC-promoted O- to C-carboxyl transfer of 3-allyl indolyl phenyl carbonates generates 3-allyl-3-phenoxycarbonyl-oxindoles with good catalytic efficiency, which are readily converted into (±)-N-benzyl-coerulescine and (±)-horsfiline.     

Zinc-mediated synthesis of 3-alkynyl-3-hydroxyindolin-2-ones by addition of iodoalkynes to isatins

An efficient and economical method was developed for synthesis of 3 alkynyl-3-hydroxyindolin-2-ones by addition of iodoalkynes to isatins using zinc dust.     

4-Substituted 5-nitroisoquinolin-1-ones from intramolecular Pd-catalysed reaction of N-(2-alkenyl)-2-halo-3-nitrobenzamides

4-Methyl- and 4-benzyl-5-aminoisoquinolin-1-ones are close analogues of the water-soluble PARP-1 inhibitor 5-AIQ. Their synthesis was approached through Pd-catalysed cyclisations of N-(2-alkenyl)-2-iodo-3-nitrobenzamides. Reaction of N,N-diallyl-2-iodo-3-nitrobenzamide with Pd(PPh₃)₄ gave a mixture of 2-allyl-4-methyl-5-nitroisoquinolin-1-one and 2-allyl-4-methylene-5-nitro-3,4-dihydroisoquinolin-1-one. N-Benzhydryl-N-cinnamyl-2-iodo-3-nitrobenzamide similarly gave 2-benzhydryl-4-benzyl-5-nitroisoquinolin-1-one and 2-benzhydryl-4-benzylidene-5-nitro-3,4-dihydroisoquinolin-1-one. The isomeric products are not interconvertible. A deuterium-labelling study indicated that the isomers were formed by different pathways: a π-allyl-Pd route and the classical Heck route. The corresponding secondary amides N-allyl-2-iodo-3-nitrobenzamide and N-((substituted)-cinnamyl)-2-iodo-3-nitrobenzamide gave good yields of the required 4-methyl- and 4-((substituted)-benzyl)-5-nitroisoquinolin-1-ones, respectively, under optimised conditions (Pd(PPh₃)₄, Et₃N, Bu₄NCl, 150 °C, rapid heating). Hydrogenation of the nitro groups gave 4-methyl- and 4-benzyl-5-aminoisoquinolin-1-ones, which were potent inhibitors of PARP-1 activity.     

Organocatalytic asymmetric aldol reaction of ketones with isatins: straightforward stereoselective synthesis of 3-alkyl-3-hydroxyindolin-2-ones

An efficient asymmetric aldol condensation of ketones with isatins has been developed using an l-proline-derived bifunctional organocatalyst. This strategy allows the enantioselective synthesis of a variety of 3-alkyl-3-hydroxyindolin-2-ones with a stereogenic quaternary carbon center in excellent yields with good to excellent enantiomeric excess. The method has been applied to the enatioselective synthesis of (S)-convolutamydine A successfully.     

Synthesis and Halocyclization of 5-Allyl-2-benzyl(allyl)sulfanyl-6-methylpyrimidin-4(3H)-ones

Russian Journal of Organic Chemistry - Alkylation of 5-allyl-6-methyl-2-thiouracil with benzyl chloride and allyl bromide afforded 2-benzyl(allyl)sulfanyl-5-allyl-6-methylpyrimidin-4(3H)-ones....     

Synthetic studies towards furosesquiterpenoids: total synthesis of (±) desmethylpallescensin-A, (±) isopallescensin-A and (±) isopallescensin-1

A new approach for a short and efficient synthesis of common cyclohexenone intermediate towards the total synthesis of some furosesquiterpenes and their analogues are described. Regioselective alkylation of Hagemann's ester with 2/3-furyl-2-ethyl bromide followed by hydrolysis cum in situ decarboxylation and 1,4-addition with Gilman's reagent produced the cyclohexanone derivatives which have been utilized for total synthesis of (±) isopallescensin-A, (±) 10-desmethylpallescensin-A, (±) 5-desmethyl-4,5-dehydromicrocionin-1 and (±) isopallescensin-1.     

Synthesis of (±)-coerulescine and a formal synthesis of (±)-horsfiline

A straightforward synthesis of (±)-coerulescine and (±)-horsfiline has been established from 3-formyl-3-phenylpyrrolidine employing 4-hydroxypiperidine as the starting material. There are two remarkable steps for the synthesis of (±)-coerulescine and (±)-horsfiline. One is the rapid access to produce 3-formyl-3-phenylpyrrolidine by Lewis acid-catalyzed rearrangement of 3,4-dihydroxy-4-phenylpiperidine. The other key step is an intramolecular electrophilic cyclization from 3-benzylcarbamoyl-3-phenylpyrrolidine to the 3,3-spirocyclic 2-oxindole ring skeleton.     

Total synthesis of (±)-stemonamide, (±)-isostemonamide, (±)-stemonamine, and (±)-isostemonamine using a radical cascade

A total synthesis of (±)-stemonamide and (±)-isostemonamide has been achieved by using a radical cascade that involves two endo-selective cyclizations. (±)-Stemonamine and (±)-isostemonamine are synthesized by chemoselective reduction of (±)-stemonamide and (±)-isostemonamide, respectively.     

Investigation of the reactivities and tautomerism of azolidines. 53. Synthesis of 5-arylidene-2-allylamino-δ2-thiazolin-4-ones and 5-arylidene-2-imino-3-allylthiazolidin-4-ones

Depending on the reaction conditions, 2-allylamino-5-arylidene-²-thiazolin-4-ones, 2-imino-3-allyl-5-arylidenethiazolin-4-ones, and 3-allyl-5-arylidene-thiazolidine-2,4-diones are obtained by condensation of 2-allylamino-²-thiazolin-4-one and 2-imino-3-allylthiazolidin-4-one with aromatic aldehydes.See [1] for communication 52.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 494–497, April, 1985.     

Stereocontrolled total syntheses of (±)-clovan-3-one and (±)-epi-clovan-3-one and a facile total synthesis of (±)-pseudoclovene-A

Stereocontrolled total syntheses of the bridged tricyclic ketones (±)-clovan-3-one (5) and (±)-epi-clovan-3-one (6) and a facile total synthesis of the tricyclic sesquiterpene (±)-pseudoclovene-A (3) have been successfully accomplished involving participation of an aryl intramolecular cyclisation of the bromophenol 11 as a key step.     

Reverse aromatic cope rearrangement of 2-allyl-3-alkylideneindolines driven by olefination of 2-allylindolin-3-ones: synthesis of alpha-allyl-3-indole acetate derivatives

The reverse aromatic Cope rearrangement of 2-allyl-3-alkylideneindolines obtained by Horner-Wadsworth-Emmons olefination of 2-allylindolin-3-ones was performed. When 2-allylindolin-3-ones were treated with phosphonium ylides in refluxing toluene, domino Wittig reaction and reverse aromatic Cope rearrangement took place to give alpha-allyl-3-indole acetate derivatives in good yields. The aromatization as a new driving force in the Cope rearrangement is preferable to the conjugation with the carbonyl and cyano groups and also to the alkyl substitution pattern, which are well-known driving forces.     

Formal syntheses of (±)-Asterisca-3(15),6-diene and (±)-Pentalenene using Rh(I)-catalyzed [(5+2)+1] cycloaddition

Efficient formal syntheses of (±)-Asterisca-3(15),6-diene, a natural product with a bicyclo[6.3.0]undecane skeleton, and (±)-Pentalenene, a natural product with a tricyclo[6.3.0.0^4,8]undecane skeleton, have been achieved by using Rh(I)-catalyzed [(5+2)+1] cycloaddition. The [(5+2)+1] reaction provides an expeditious approach to reach the bicyclic cyclooctenone 4, which was quickly transformed (via hydroboration then oxidation) to diketone 14, a key advanced intermediate for the total synthesis of (±)-Asterisca-3(15),6-diene. Through further transformations, 14 was converted to diene 18, an advanced intermediate for the total synthesis of (±)-Pentalenene.     

A facile Lewis acid-promoted allylation of azetidin-2-ones

Exposure of 3α-chloro-3-phenylthioazetidin-2-ones and allyltrimethylsilane to a Lewis acid promotes a remarkably facile and stereoselective C-3 allylation to give 3α-allyl-3-phenylthioazetidin-2-ones 4 in excellent yield. These allylated azetidin-2-ones undergo smooth desulphurization with tri-n-butyltin hydride or Raney-nickel producing cis-3-allyl- and cis-3-propylazetidin-2-ones.     

Concise total syntheses of (±)isopaucifloral F, (±)quadrangularin A, and (±)pallidol

Concise total syntheses of (±)isopaucifloral F, (±)quadrangularin A, and (±)pallidol, starting from commercially available 3,5-dimethoxybenzoic acid, have been achieved by a sequential process. The overall synthetic strategy involves Nazarov cyclization, Ramberg-Backlund olefination, and Friedel-Crafts alkylation.     

A general approach to crinine-type Amaryllidaceae alkaloids: total syntheses of (±)-haemanthidine, (±)-pretazettine, (±)-tazettine, and (±)-crinamine

A general strategy for synthesizing the crinine-type Amaryllidaceae alkaloids was developed. And total syntheses of four representative crinine-type Amaryllidaceae alkaloids: (±)-haemanthidine, (±)-pretazettine, (±)-tazettine, and (±)-crinamine, were accomplished via a common intermediate 17. This crucial precursor was achieved on the basis of the NBS-promoted semipinacol rearrangement recently developed by our group and an intramolecular Michael addition, which efficiently constructed the sterically congested quaternary carbon center and the hydroindole skeleton of the crinine-type alkaloids, respectively.     

Enantio-complementary deracemization of (±)-2-hydroxy-4-phenylbutanoic acid and (±)-3-phenyllactic acid using lipase-catalyzed kinetic resolution combined with biocatalytic racemization

Deracemization of (±)-3-phenyllactic acid (1) and (±)-2-hydroxy-4-phenylbutanoic acid (2) was accomplished by lipase-catalysed kinetic resolution coupled to biocatalytic racemization of the non-reacting substrate enantiomers using Lactobacillus paracasei DSM 20008. Cyclic repetition of this sequence led to a single enantiomeric product from the racemate. Access to both enantiomers was achieved by switching between lipase-catalysed acyl-transfer and ester hydrolysis reactions. Both products constitute important building blocks for virus protease- and ACE-inhibitors, respectively.     

Synthesis of symmetrical and unsymmetrical 3,3-di(indolyl)indolin-2-ones under controlled catalysis of ionic liquids

Three ionic liquids, [BMIM][BF₄] doped with 60 mol % of LiCl ([BMIM][BF₄]-LiCl), N,N,N,N-tetramethylguanidinium trifluoroacetate (TMGT), and N,N,N,N-tetramethylguanidinium triflate (TMGT_f) were found useful as catalyst solvents for controlled 3-indolylation of isatins. Our investigation revealed that the reaction between isatin and indoles in [BMIM][BF₄]-LiCl or TMGT_f media stops at the step of addition of the two components providing 3-indolyl-3-hydroxyindolin-2-ones while the ionic liquid TMGT runs the reaction further through accompanying Friedel-Crafts substitution to afford symmetrical 3,3-di(indol-3-yl)indolin-2-ones. To take advantage of the difference between the effects of these ionic liquids on the reaction progress, we planned a two-step protocol for the efficient synthesis of unsymmetrical 3,3-di(indol-3-yl)indolin-2-ones.     

A new route to eremophilanes: synthesis of (±)-eremophilenolide, (±)-eremophiledinone, and (±)-deoxyeremopetasidione

A new and efficient route to the family of eremophilanes is reported. Key steps are the highly stereocontrolled Diels-Alder reaction and aldol condensation to furnish a cis-decalin system with the desired stereochemistry present in the eremophilane family of natural products. This approach is general and was utilized for the synthesis of (±)-eremophilenolide, (±)-eremophiledinone, and (±)-deoxyeremopetasidione.     

Unexpected Synthesis of Novel 3-Allyl-5-(arylidene)-2-thioxo-thiazolidin-4-ones in Reactions of 3-Allylrhodanine with 2-Arylidene-4-methyl-5-oxopyrazolidinium Ylides

Abstract

The reaction of 3-allylrhodanine with 2-arylidene-4-methyl-5-oxopyrazolidinium ylides proceeded unexpectedly to form novel 3-allyl-5-(arylidene)-2-thioxo-thiazolidin-4-ones 6a–k in good yields. All structures have been formulated on the basis of their spectral (IR, NMR, MS) data and elemental analyses. In addition, the structure of compound 6a was confirmed by means of x-ray crystallographic analysis.