Enantioselective cyanation/Brook rearrangement/C-acylation reactions of acylsilanes catalyzed by chiral metal alkoxides

New catalytic enantioselective cyanation/1,2-Brook rearrangement/C-acylation reactions of acylsilanes (4) with cyanoformate esters (7) are described. The products of the reaction are fully substituted malonic acid derivatives (8). Catalysts for this transformation were discovered via a directed candidate screen of 96 metal-ligand complexes. Optimization of a (salen)aluminum complex revealed significant remote electronic effects and concentration effects. The scope of the reaction was investigated by using a number of aryl acylsilanes and cyanoformate esters. Chemoselective reduction of the reaction products (8) afforded new enantioenriched alpha-hydroxy-alpha-aryl-beta-amino acid derivatives (32-34) and beta-lactams (35 and 36). This reaction provides a simple method for the construction of new nitrogen-containing enantioenriched chiral building blocks.     

Cyanide ion promoted addition of acyl phosphonates to ethyl cyanoformate: synthesis of tertiary carbinols via tandem carbon-carbon bond formations

New cyanation/phosphonate-phosphate rearrangement/C-acylation reactions of cyanophosphate anion with cyanoformate esters are described. Phase-transfer cocatalysts facilitate cyanide-catalyzed reactions between acyl phosphonates and cyanoformates to afford protected tertiary carbinol products in good to excellent yields (74-95%). Ethyl cyanoformate is used as a cyanide source and electrophile. The scope of the reaction was investigated by using a number of benzoyl and acyl phosphonates along with ethyl cyanoformate. Representative chemoselective reduction of the product 5a afforded ethyl 3-amino-2-hydroxy-2-phenylpropanoate (13) in good yield.     

Selective C-acylation of 2-aminoimidazo[1,2-a]pyridine: application to the synthesis of imidazopyridine-fused [1,3]diazepinones

A series of 20 optically pure 3,4-dihydro-5H-pyrido[1',2':1,2]imidazo[4,5-d][1,3]diazepin-5-ones which form a new family of azaheterocycle-fused [1,3]diazepines were synthesized in four steps with 17-66% overall yields. The key step consists of a selective C-acylation reaction of easily accessible 2-aminoimidazo[1,2-a]pyridine at C-3.     

A Facile Method for the Synthesis of 4- Acetylaminobenzo[15]crown-5

The 4-acetylaminobenzo[15]crown-5 is an important intermediate in the synthesis of crown ether cyanine dyes1, in addition, the acetylamino can easily be hydrolyzed to be amine2, to our knowledge which also is an usful intermediate3,4, The classical procedure for the synthesis of 4-acetylaminobenzo[15]crown-5 involves several steps2,5: typically nitration of the benzo[15]crown-5, followed by reduction of the introduced nitro group to form amine, and finally, acylation of the amine to give the am…     

Novel one-pot vicinal double C-acylation of styrenes and methacrylates by electroreduction

[reaction: see text] Electroreduction of styrenes or alkyl methacrylates in the presence of aliphatic acid anhydrides or N-acylimidazoles with an undivided cell equipped with zinc electrodes as the anode and the cathode brought about novel one-pot vicinal double C-acylation to afford the corresponding 1,4-diketones in satisfactory yields.     

The synthesis of [2,3,4-C3]glycitein

Glycitein is one of the soy isoflavones which have attracted considerable interest in recent years due to their possible beneficial effects on human health. However, glycitein has been much less studied than other members of this family due to the lack of good methods for its synthesis. Herein we report a short high yielding synthesis of a multiply ¹³C-labelled glycitein derivative, [2,3,4-¹³C₃]glycitein, which has been employed as an internal standard in LC–MS analysis. A key feature is a rapid and efficient synthesis of 2,4-dihydroxy-5-methoxy-[1′,2′-¹³C₂]acetophenone via acetylation of isovanillin with [¹³C₂]acetyl chloride followed by a Baeyer–Villiger reaction, selective hydrolysis and finally a BF₃ catalysed Fries rearrangement. An aldol reaction using 4-benzyloxy-[carbonyl-¹³C]benzaldehyde gave a chalcone and then thallium(III) mediated oxidative rearrangement, deprotection and cyclisation provided the [2,3,4-¹³C₃]glycitein. The overall yield for the 8 step reaction sequence, based on [¹³C₂]acetyl chloride, was 57%.     

Rapid construction of the unique BCD ring system of tricyclo[6.2.1.0] undecane in the C19-diterpenoid alkaloid aconitine

A model study leading to the preparation of the unique tricyclo [6.2.1.0] undecane BCD ring systems of aconitine is described. The synthesis features an unprecedented diastereoselective oxidative dearomatization/dimerization/retro-DA/IMDA cascade reaction and a highly efficient Wagner-Meerwein rearrangement.     

Yb(OTf)3-catalyzed reactions of 5-alkylidene Meldrum's acids with phenols: one-pot assembly of 3,4-dihydrocoumarins, 4-chromanones, coumarins, and chromones

[reaction: see text] The Yb(OTf)3-catalyzed annulation reactions of phenols with 5-alkylidene Meldrum's acids enabled the synthesis of structurally diverse heterocycles in high isolated yields. A series of 4-substituted 3,4-dihydrocoumarins, 2,2-disubstituted 4-chromanones, coumarins, and 2-substituted chromones were readily and efficiently assembled, including the naturally occurring coumarins citropten, scoparone, and ayapin. Addition of phenols to biselectrophilic 5-alkylidene Meldrum's acids proceeded through two distinct multibond-forming modes: Friedel-Crafts C-alkylation/O-acylation and Friedel-Crafts C-acylation/O-alkylation. The regioselectivity of the catalytic annulation reaction was controlled by the degree of substitution on the alkylidene moiety.     

Total synthesis of (+/-)-strychnine via a [4 + 2]-cycloaddition/rearrangement cascade

A new strategy for the synthesis of the Strychnos alkaloid (+/-)-strychnine has been developed and is based on an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium-catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. [reaction: see text].     

Condensed Isoquinolines. 16. Enamine Properties of Benzo[4,5]imidazo[1,2-b]isoquinolin-11(5H)-one in Terms of Its Acylation Reactions

A study has shown that the acylation of benzo[4,5]imidazol[1,2-b]isoquinolin-11(5H)-one occurs at N₍₅₎ or at C₍₆₎ depending on the nature of the acylating reagent and the reaction conditions. It was found that principally C-acylation takes place in the absence of base. The reaction with -halo-substituted carboxylic acid chlorides leads to the formation of C-acylated products which are converted to derivatives of the novel heterocyclic system 7H-2a,6b-diazabenzo[b]cyclopenta[l,m]fluorene-1,7(2H)-dione in the presence of base.     

Short and versatile route to a key intermediate for lactacystin synthesis

[reaction: see text] A key intermediate 14 for the synthesis of lactacystin 1 has been constructed in four steps and 33% overall yield. The key steps involve cyclization of a suitably functionalized glutamic acid derivative and concomitant alkylation of the resulting beta,beta-diketoester system, C-acylation of the cyclic alpha-amidoketone 9, and decarboxylbenzylation of 12. Alkylation of a related beta,beta-diketoester 5 was additionally achieved with several electrophiles.     

Novel trans-spanned palladium complexes as efficient catalysts in mild and amine-free cyanation of aryl bromides under air

[reaction: see text] The use of a novel trans-spanned palladium complex as an efficient and selective catalyst in the cyanation of aryl halides is described. The suggested reaction conditions are mild, exhibit good scope of substrates, and circumvent the need for an inert atmosphere and amine co-ligands.     

Biradicals/zwitterions from enallene-isonitriles. Formal [4 + 1] cycloadditions leading to 11H-indeno[1,2-b]quinoline and related compounds

[reaction: see text] 1,3-Prototropic rearrangement of the benzannulated enyne-isonitriles to the corresponding enallene-isonitriles followed by cycloaromatization generated the putative quinoline biradicals/zwitterions. A subsequent intramolecular radical-radical coupling or electrophilic aromatic substitution then gave the formal [4 + 1] cycloaddition adducts leading to 11H-indeno[1,2-b]quinoline and related compounds.     

Regio‐ and Stereospecific 1,3‐Allyl Group Transfer Triggered by a Copper‐Catalyzed Borylation/ortho‐Cyanation Cascade

A copper‐catalyzed borylation/ortho‐cyanation/allyl group transfer cascade was developed. Initiated by an unconventional copper‐catalyzed electrophilic dearomatization, this process features regio‐ and stereospecific 1,3‐transposition of the allyl fragment enabled by an aromatization‐driven Cope rearrangement. This method provides an effective means for the construction of adjacent tertiary and quaternary stereocenters with excellent diastereocontrol.     

First approach to the frondosin C ring system via a tandem cyclization/Claisen rearrangement sequence

[reaction: see text] A one-pot tandem 5-exo cyclization/Claisen rearrangement strategy is utilized as the key step in the straightforward construction of the tetracyclic ring system of frondosin C. This reaction is done under microwave irradiation in the presence of catalytic MeLi.     

Intramolecular iron-mediated diene/olefin cyclocoupling: formation of carbon spirocycles

[reaction: see text] A short and convenient diastereoselective synthesis of all-carbon spirocylic molecules was developed. A straightforward protocol that involves rearrangement of the diene-Fe(CO)(3) complex followed by cyclization delivers the desired product. The reaction substrates were easily prepared by reaction of an appropriate nucleophile and a cyclohexadienyl-Fe(CO)(3) cation.     

Sequential pericyclic reaction of ene-diallenes: an efficient approach to the steroid skeleton

[reaction: see text] The one-pot construction of polycyclic aromatic systems from acyclic ene-bis(propargyl alcohols) was achieved through a tandem dual [2,3]-sigmatropic rearrangement/6pi-electrocyclic reaction/intramolecular [4 + 2] cycloaddition sequence. A steroidal compound was conveniently synthesized using the present method.     

Zn-promoted regioselective and sequence-selective one-pot joining reaction of three components: alkyl iodides, alpha,beta-unsaturated esters (or nitriles), and acylating agents

One-pot treatment of alkyl iodides, alpha,beta-unsaturated esters (or nitriles), and acylating agents such as nitriles or acid anhydrides in the presence of Zn metal at room temperature in the same reaction system brought about a regioselective and sequence-selective three-component joining reaction involving first C-alkylation at the beta-position and second C-acylation at the alpha-position of alpha,beta-unsaturated esters (or nitriles) to afford the corresponding alpha,alpha-dialkylketoesters (or alpha,alpha-dialkylketonitriles) in moderate to good yields. [reaction: see text]     

An investigation into causes and effects of high cyanide levels in the palladium-catalyzed cyanation reaction

[reaction: see text] The palladium-catalyzed cyanation reaction is known to be sensitive to dissolved cyanide. Investigation into some causes of high levels of dissolved cyanide is presented here, along with a robust solution to this problem.     

Diastereoselective synthesis of substituted prolines via 5-endo-trig cyclisations of aza-[2,3]-Wittig sigmatropic rearrangement products

The major diastereoisomers of aza-[2,3]-Wittig sigmatropic rearrangement products from α-amino acid derivatives are susceptible to a rare nucleophilic 5-endo-trig cyclisations of an amine onto a non-conjugated vinylsilane in high yield and complete diastereocontrol. Five examples are presented, with cyclisation yields between 35 and 87%. A rationale for the stereoselectivity of the cyclisation is forwarded based upon the steric control factors that have been documented for the aza-[2,3]-Wittig sigmatropic rearrangement. A discussion of the mechanism in the context of the reaction conditions is also presented. Oxidation of the silyl group to a hydroxyl group and complete removal were demonstrated for synthetic utility.