固体酸Amberlyst 15催化合成3-吲哚取代的苯酞类化合物

室温下, 以吲哚和邻甲酰苯甲酸为原料, 通过Amberlyst 15 (15 wt%)催化的傅-克反应, 高产率合成得到一系列3-吲哚取代的苯酞类化合物. 并通过1H NMR, 13C NMR, 红外光谱, 高分辨质谱确证了产物的结构.     

Unprecedented Diastereoselective Arylogous Michael Addition of Unactivated Phthalides

The first highly enantioselective arylogous Michael reaction (AMR) of 3-unsubstituted phthalides has been described. This phase-transfer methodology, which uses catalytic amounts of KOH/18-crown-6 catalyst in mesitylene in the presence of N,O-bis(trimethylsilyl)acetamide (BSA), gives access to a broad range of 3-monosubstituted phthalides with high levels of syn diastereoselectivity and good yields, starting from 3-unsubstituted derivatives and diverse α,β-unsaturated carbonyl compounds. The reaction also applies to unactivated 3-alkyl phthalides to afford 3,3-dialkyl derivatives. A plausible mechanism has been suggested. DFT analysis of possible transition states gives a rationale of the high syn diastereoselectivity observed and its correlation with the solvent's dielectric constant.     

Quinine-derived thiourea promoted enantioselective Michael addition reactions of 3-substituted phthalides to maleimides

A highly diastereoselective and enantioselective Michael addition/desymmetrization reaction of maleimides with prochiral 3-substituted phthalides catalyzed by quinine-derived bifunctional thiourea was realized. A broad range of the 3,3′-disubstituted phthalides bearing vicinal quaternary-tertiary stereogenic centers were synthesized in moderate to good yields(up to 96%) with high diastereoselectivities(up to 19:1 dr) and enantioselectivities(up to 96:4 er).     

Expeditious synthesis of 3,4-dihydroisocoumarins and phthalides using the Heck-Matsuda reaction

Several 3,4-dihydroisocoumarins and phthalides were synthesized by an effective Heck-Matsuda reaction involving an ortho carboxybenzenediazonium salt with a series of styrenes bearing electron donating and electron withdrawing groups, methylvinyl ketone, and methyl acrylate. The reaction was carried out in an open-flask with 1% mol of palladium acetate in aqueous ethanol at ∼80 °C, giving the correspondent 3-aryl-3,4-dihydroisocoumarins and phthalides with good overall yields. The electronic nature of the group attached to the olefin is a key feature for the regioselectivity of the cyclization step.     

Ruthenium (II)-catalyzed synthesis of phthalides via the cascade addition and cyclization of aromatic acids with aldehydes

The ruthenium-catalyzed intermolecular cascade cyclization of aromatic acids with aromatic aldehydes, which involves the direct insertion of C–H bond into a polar C=O bond and the successive intramolecular nucleophilic substitution, was developed for the synthesis of 3-substituted phthalides in good to excellent yields. This one-pot procedure characterizes in a short reaction time, the cheaper Ru(II) as a catalyst, readily available acids and aldehydes as starting materials, and water as the only theoretical by-product.These merits make the protocol an efficient and cost-effective route for the synthesis of 3-substituted phthalides.     

Synthesis of phthalides and 3,4-dihydroisocoumarins using the palladium-catalyzed intramolecular benzannulation strategy

A novel method for the synthesis of phthalides and 3,4-dihydroisocoumarins via the palladium-catalyzed intramolecular benzannulation of bis-enyne and enyne-diyne systems is described. Various kinds of substituted phthalides 9 and 17 and 3,4-dihydroisocoumarins 19 were synthesized from 8, 16, and 18, respectively, in moderate to excellent yields. The benzannulation reaction proceeded chemoselectively to give the corresponding fused ring compounds A without the formation of the regioisomeric products B (eq 6). Furthermore, this methodology was applied to the synthesis of biologically active 3-n-butylphthalide 23.     

Rhodium(III)‐Catalyzed [4+1] Annulation of Aromatic and Vinylic Carboxylic Acids with Allenes: An Efficient Method Towards Vinyl‐Substituted Phthalides and 2‐Furanones

A highly regio‐ and stereoselective synthesis of 3,3‐disubstituted phthalides from aryl carboxylic acids and allenes using a rhodium(III) catalyst has been demonstrated. The reaction features broad functional group tolerance and provides a simple and straightforward route to the synthesis of various 3‐vinyl‐substituted phthalides. Furthermore, the catalytic reaction can also be applied to the synthesis of biologically active 5‐vinyl‐substituted 2‐furanones from α,β‐unsaturated carboxylic acids and allenes. The reactions proceed through a carboxylate‐assisted ortho‐C?H activation and [4+1] annulation. The preliminary mechanistic studies suggest that a C?H cleavage is the rate‐determining step.     

Highly Efficient Synthesis of Unsymmetrical 3,3′‐Bis(1H‐indol‐3‐yl)methanes in Water

A simple and practical approach for the preparation of unsymmetric bis(indolyl)methanes (BIMs) was realized by Lewis acid InBr₃‐catalyzed Friedel‐Crafts reaction of indoles with 3‐indolyl‐substituted phthalides in water.     

Ru-catalyzed synthesis of substituted phthalides through C–H bond activation and functionalization

Synthesis of substituted phthalides through a ruthenium-catalyzed reaction of phthalic anhydrides with acrylates is described. The reaction proceeds via CH bond activation and leads to the formation of vinylated phthalides through a successive double vinylation accompanied by decarboxylation and annulation reactions.     

Complexation of phthalides and substituted 3-benzylidene phthalides with Cr(CO)6

The acid-catalysed complexation of various substituted phthalides with Cr(CO)₆ has been studied. Complexation of substituted 3-benzylidene phthalides takes place at the phenyl ring in most cases, but with di-halogeno-substituted 3-benzylidene phthalides the complexation took place at the phthalide moiety. An explanation of this difference is based on molecular modelling quantum chemical calculations.     

Boron Trifluoride Promoted Reaction of Arenesulfinic Acids with Phthalaldehydic Acids: Enroute to 3-Arylsulfonyl Phthalides

The reaction of arenesulfinic acids 4 with phthalaldehydic acids 2 in the presence of boron trifluoride provides a practicable synthetic procedure for the preparation of 3-arylsulfonyl phthalides.     

Catalytic enantioselective synthesis of chiral phthalides by SmI2-mediated reductive cyclization of 2-acylarylcarboxylates

A significant new and efficient catalytic asymmetric approach for the highly enantioselective synthesis of chiral phthalides by SmI2-induced reductive cyclization of 2-acylarylcarbonylates was developed. The combination of (4S,5R)-4,5-diphenyloxazolidin-2-one and 2,2,6,6-tetramethylpiperidine was found to be a very effective catalyst system in the reaction. This method provides a ready access to a broad range of enantiomerically enriched phthalides (up to 99% ee).     

Stereochemistry of the halolactonisation reaction The reaction of cis- and trans- stilbene-2-carboxylic acids with halogens

The stereochemistry of the reaction of cis- and trans-stilbene-2-carboxylic acids with chlorine and bromine, yielding the two diastereoisomeric 3-phenyl-4-halo-3:4-dihydroisocoumarins (III) and (IV) has been investigated. The reactions are entirely stereospecific and involve intramolecular attack by the carboxyl group on an intermediate carbonium or halonium ion. The lactones (III) and (IV) yield the two 3-(-hydroxybenzyl) phthalides (V) and (VI), with retention of configuration. Thionyl chloride transforms (V) and (VI) into the 3-(-chlorobenzyl) phthalides (IX) and (X), with inversion. Steric effects are mainly responsible for the alternative formation of halolactones or normal dihalogenated derivatives in the reactions between unsaturated acids and halogens.     

The chemistry of phthalide-3-carboxylic acid - I decarboxylation in the presence of aldehydes

The decarboxylation of phthalide-3-carboxylic acid (3-oxo-l,3-dihydroisobenzofuran-1-carboxylic acid) has been studied in the melt, in dimethylsulfoxide, and in the presence of aromatic aldehydes. The latter are efficiently trapped to produce mixtures of 3-arylidene-phthalides and 3-(arylhydroxymethyl)phthalides. Kinetic and other evidence supports the proposal that this reaction occurs in a tight cyclic transition state.     

Unusual heterochiral crystallization tendency of 3-arylphthalide compounds in non-racemic solution: reinvestigation on asymmetric Ni-catalyzed tandem reaction of substituted o-halobenzaldehydes

The phenomenon of unusual heterochiral crystallization tendency of several 3-arylphthalide compounds in non-racemic solution was observed. With this finding, a range of highly enantiomerically enriched 3-arylphthalides were easily accessed through heterochiral crystallization. In addition, the previously reported nickel-catalyzed tandem reaction to asymmetric synthesis of chiral phthalides was reinvestigated and partial data were corrected.     

Synthesis of 3-arylphthalides with a quaternary carbon center via [4+1] cycloaddition of 2-carbonylcyclohexadienimines with isocyanides under metal-free conditions

Rapid synthesis of 3-arylphthalides with a quaternary carbon center has been achieved via a cascade [4+1] cycloaddition/nucleophilic 1,4-addition of 2-carbonylcyclohexadienimines with two molecules of isocyanides. The reaction proceeded smoothly under metal-free conditions leading to the formation of multi-functionalized phthalides in moderate to good yields.     

Synthesis of novel antifungal phthalides produced by a wheat rhizosphere fungus

Two antifungal phthalides produced by a wheat rhizosphere fungus have been synthesized using the Alder-Rickert reaction to construct their common isobenzofuranone core structure. The absolute configuration of one of the two phthalides has been determined to be S by synthesizing its (S)- and (R)-enantiomer and comparing their optical rotations with that of the natural product.     

New Synthesis of 3-(2-Furyl)phthalides

3-(2-Furyl)phthalides were synthesized for the first time by the reaction of 2-formylbenzoic acids with furan derivatives in the presence of an acidic catalyst. It was found that the reaction of 2-formylbenzoic acids and 2-alkylfurans in aqueous dioxane in the presence of perchloric acid leads to a mixture of 2-carboxyaryldifurylmethanes and 3-furylphthalides, which can be separated easily by preparative column chromatography. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1302–1304, September, 2005.     

Regio- and stereoselective (3 + 2)-cycloaddition of nitrile oxides and nitrones to <Emphasis Type="Italic">N</Emphasis>-vinylindole

1,3-Dipolar cycloaddition of nitrile oxides and nitrones to N-vinylindole proceeds regioselectively at the exocyclic multiple bond to form 5-indolyl-substituted isoxazolines and isoxazolidines in good yields.     

Nucleophile- or light-induced synthesis of 3-substituted phthalides from 2-formylarylketones

The surprisingly facile conversion (isomerization) of 2-formyl-arylketones into 3-substituted phthalides, as observed for the marine natural product pestalone and its per-O-methylated derivative, was investigated using a series of simple 2-acylbenzaldehydes as substrates. The transformation generally proceeds smoothly in DMSO, either in a Cannizarro-Tishchenko-type reaction under nucleophile catalysis (NaCN) or under photochemical conditions (DMSO, 350 nm).