Efficient electrocatalytic addition reactions of allyl phenyl sulfone to electron deficient alkenes

The use of tetraalkylammonium salts as electrolytes has been found to allow the formation of electrogenerated bases of especially high reactivity. Such conditions allow allyl phenyl sulfone to undergo addition to a variety of electron deficient vinyl and propenyl compounds (sulfone, ketone, nitrile, and ester). The additions are catalyzed by electrogenerated bases derived from the reactant itself, rather than via an added pro-base. The nature of the substrate molecule is seen to affect which type of product is formed, leading to an interplay between addition to 1 mol of substrate or to 2 mol of substrate. Yields of 1:1 adducts range from 6 to 81%, while yields of 1:2 adducts range from 57 to 96%.     

Direct synthesis of aliphatic vinyl aziridines

The synthesis of vinyl aziridines, by the reactions of a range of diphenylphosphinyl and p-toluenesulfonyl alkyl aldimines with the ylide derived from S-allyl tetrahydrothiophenium bromide, are reported.     

4-(Phenylsulfonyl)-4-lithiocyclopentene as a nucleophilic 2-pentene-1,5-dial synthetic equivalent. An aziridine-based synthetic approach to (−)-alstonerine

Reaction of 4-lithio-4-(phenylsulfonyl)cyclopentene with an l-tryptophan-derived N-tosylaziridine provides an adduct. Oxidative cleavage of the cyclopentene double bond provides a dialdehyde, which enters into acid-catalysed Pictet-Spengler-type bicyclisation to give a tetracyclic aldehyde. Completely regioselective silyl dienol ether formation followed by completely stereoselective hetero-Diels-Alder reaction with monomeric formaldehyde gives a late-stage intermediate in a planned total synthesis of the macroline-related alkaloid (−)-alstonerine.     

A highly regio- and chemoselective addition of carbon nucleophiles to pyrimidinones. A new route to C4 elaborated Biginelli compounds

Ethyl 6-methyl-pyrimidine-2-one-5-carboxylates react with C-nucleophiles in a diversity oriented synthetic sequence to afford C4 substituted congeners of medicinally potent Biginelli dihydropyrimidinones, in a highly regioselective manner.     

Diastereoselectivity in addition of nitrile-stabilized carbanions to Schiff bases and in subsequent alkylation reactions

The stereochemical course in the addition of lithiated benzylcyanide and propionitrile to aromatic Schiff bases, as well as of the subsequent alkylation reaction has been investigated. The stereochemical ratios in the condensation reaction are proved to result from the intermediacy of a prochiral carbanionic intermediate, produced by a fast proton shift in the initially formed azanion. Subsequent one-pot alkylation reaction with a variety of electrophiles leads in high to moderate yields to diastereoselective formation of a second carbon-carbon bond at the same carbon center. Diastereoselectivity in alkylation, which varies from outstanding to high and poor is rationalized in terms of open-chain, product-like or reactant-like transition state models.     

DABCO-mediated aza-Michael addition of 4-aryl-1H-1,2,3-triazoles to cycloalkenones. Regioselective synthesis of disubstituted 1,2,3-triazoles

Aza-Michael addition of 4-aryl-1H-1,2,3-triazoles to 2-cycloalken-1-ones has been studied in the presence of DABCO as organic base. The reactions were carried out in acetonitrile at room temperature to provide 2,4-disubstituted 2H-1,2,3-triazoles as major adducts and 1,4-disubstituted 1H-1,2,3-triazoles as minor adducts. Though the reaction times are longer (4–8 days), the two regioisomers were separated by using column chromatography and the adducts were obtained in very good to excellent combined chemical yields. The electron-rich and electron-poor substituents on aryl moiety of 4-aryl-triazoles could tolerate the reaction conditions to afford the title adducts.     

Regio- and stereoselective ring opening of aziridines with nitric oxide

Reaction of N-tosyl aziridines with nitric oxide affords the corresponding ring-opened products in regio-, stereoselectivities and excellent yields.     

Direct conversion of epoxides into aziridines with N-arylphosphoramidates

Treatment of terminal epoxides with N-arylphosphoramidate anions leads directly to N-aryl aziridines. Existing methods for this transformation employ either multi-step syntheses or an iminophosphorane in conjunction with a Lewis acid. The described method therefore presents an advantage in terms of brevity and atom economy.     

Mechanistic approaches to asymmetric synthesis of aziridines from guanidinium ylides and aryl aldehydes

To approach more realistic mechanisms for asymmetric aziridine synthesis from guanidinium ylides and aryl aldehydes, reactions were systematically carried out by using a variety of p-substituted benzaldehydes under modified conditions. Two kinds of reaction mechanisms controlled by the nature of the p-substituents of aryl aldehydes is proposed for the two-steps aziridine synthesis composed of a C-C bond formation by nucleophilic addition of guanidinium ylides to aryl aldehydes (step 1) and the fragmentation of intermediate adducts to aziridine products by intramolecular nucleophilic substitution (step 2). A S_Ni-like mechanism via cationic-like transition state is proposed for step 2 in the asymmetric synthesis using EDG-substituted benzaldehydes, whereas with EWG-substituted benzaldehydes, a S_N2-like mechanism is proposed. Hammett analysis, based on the diastereomeric ratio in the aziridine products, is consistent with the proposed rate-determining steps in these two mechanisms. A second Hammett analysis, based on the enantiomeric ratio of the aziridine products, clearly reveals the difference in the susceptibilities to the electronic substituents effect between step 1 and step 2.     

Carbocyanation of trisubstituted olefins via Cu-catalyzed atom transfer radical addition

A regioselective Cu(I)-catalyzed carbocyanation of non-polarized trisubstituted olefins 1 has been achieved by employing chlorinated cyanides 2 as starting materials. The present reaction gives the carbocyanated product 3 through radical-based 1,3-transfer of CN. Consequently, two different carbon units, cyano and chlorocyanomethyl groups, are introduced into the highly substituted olefins, generating consecutive quaternary and tertiary carbons. Since both of the attached carbon units can be used as handles for further synthetic elaborations, the present transformation offers a new synthetic methodology for rapid construction of architecturally complex carboskeletons.     

New approach to the synthesis of 4-phosphorylated 1,2,3-trisubstituted pyrroles

New synthetic method for preparation of previously unknown 1,2,3-trisubstituted pyrroles based on the reaction of the available phosphorus-containing 4-arylaminoacrylonitriles with chloroacetonitrile or ethyl chloroacetate is developed.     

Regioselective addition of chalcogenol to an η-propargyl/allenyl complex via formation of the carbon-chalcogen bond leading to new chalcogenoxyallyl species

Regioselective addition of chalcogenol to an ν³-propargyl complex Pt(PPh₃)₂(η³-C₃H₃)](BF₄) (2) via the formation of the C---O, C---S, or C---Se bond generates new cationic chalcogenoxyallyl species {Pt(PPh₃)₂[η³CH₂C(ER)CH₂]}(BF₄) (E = O, R = Me 4(a), Et (4b, ⁱPr (4c), ¹Bu (4d), Ph (4e); E=S, E=Et (5b), ^tBu (5d, Ph (5e); E=Se, R=Ph (6e )) respectively in good yields. Thiol and selenol react with complex 2 much faster than alcohol; and 2 reacts with p-(HO)C₆H₄(SH) to exclusively yield the thioxyallyl product {Pt(PPh₃)₂[η³-CH₂C(SC₆H₄OH)CH₂]}(BF₄) (5f). Among the alcoh and phenol, thereactivity follows the order MeOH > EtOH >, ⁱPrOH >, ^tBuOH > PhOH. A mechanism comprising a preceding coordination step is postulated. The X-ray structures of 4b, 4e, 5b, 5e and 6e are provided.     

A convenient and efficient ring-opening reaction of aziridines with acetylenes and synthesis of dihydropyrroles

In the presence of ^tBuOK, reaction of acetylenes with N-Ts substituted aziridines derived from both cyclic and acyclic alkenes at room temperature gave rise to homopropargylamines in good to high yields and in high regioselectivity. Not only Ph- and Me₃Si-substituted acetylenes but also acetylene itself was suitable reagents. Treatment of ring-opening products with I₂ and AgOAc in the presence of K₂CO₃ provided dihydropyrroles in high yields. One-pot synthesis of dihydropyrroles was also realized by the reaction of aziridines and phenylacetylene in the presence of NaH followed by the treatment with I₂ and AgOAc.     

Anti-Markovnikov addition to alkenes with a neighbouring thioacetal function

The acid-induced cyclisation of unsaturated thioacetals 6 gives anti-Markovnikov products 9, apparently involving sulfur elimination and readdition.     

Highly regioselective ring opening of epoxides and aziridines using (bromodimethyl)sulfonium bromide

Epoxides and aziridines undergo ring opening efficiently with (bromodimethyl)sulfonium bromide at room temperature to form the corresponding β-bromohydrins and β-bromoamines, respectively. The conversions are highly regioselective and afford the products in excellent yields within a short period of time.     

Ring opening of cyclic sulfamidates with bromophenyl metal reagents: complementarity of sulfamidates and aziridines

Bromophenyl magnesium reagents generated via a Knochel type magnesium-halogen exchange of aryl iodides undergo regioselective ring opening of cyclic primary and secondary N-Boc sulfamidates in good to excellent yields. With secondary sulfamidates the reaction proceeds with clean inversion of the stereochemistry. This protocol complements the ring opening of aziridines with bromophenyl metal reagents and extends its scope to secondary substrates.     

Phosphonyl radical addition to enol ethers. The stereoselective synthesis of cyclic ethers

Addition of diethyl phosphite or diethyl thiophosphite to enol ethers, in the presence of a radical initiator, results in the regioselective synthesis of organophosphonate or phosphonothioate derivatives, respectively, under mild conditions. This method can be applied to the stereoselective formation of substituted tetrahydrofurans and tetrahydropyrans, on cyclisation of vinyl ethers bearing unsaturated side chains.     

A synthetic approach to the functionalized hydroazulene core of guanacastepenes and heptemerenes

A functionalized hydroazulene derivative has been synthesized efficiently from 2-methylcyclopent-2-en-1-one as a part of a study oriented toward the total synthesis of diterpenoids of biological significance, guanacastepenes, and heptemerones.     

One-pot synthesis of aziridines from vinyl selenones and variously functionalized primary amines

Variously substituted aziridines were conveniently prepared by an aza-Michael Initiated Ring Closure (aza-MIRC) reaction starting from vinyl selenones and primary amines, aminoalcohols or diamines. The reactions proceed in very high yields at room temperature in toluene or water. A significant rate acceleration was observed under aqueous conditions.     

Scandium(III) triflate mediated intramolecular ring expansion of aziridines: a direct access to 4-aryltetrahydroisoquinolines

A novel, high yielding facile synthesis of 4-substituted tetrahydroisoquinolines has been developed by employing scandium(III) triflate mediated intramolecular ring expansion of aziridines. The meta-substituted electron-donating group on the benzene ring facilitates trapping of an in situ generated benzyl carbenium ion cation leading to the formation of tetrahydroisoquinolines.