Microwave-assisted 6π-electrocyclization in water

The recent development of microwave-assisted aqueous synthesis of polyheterocyclic-fused quinoline-2-thiones through 6π-electrocyclization was highlighted.     

Synthesis of 2,6-diaryl-1,2-dihydropyridines through a 6π-electrocyclization of N-sulfonylazatrienes

The development of an efficient synthetic method toward substituted 1,2-dihydropyridines from cinnamylideneacetophenones is reported. The key intermediates N-sulfonylazatrienes were synthesized through a TiCl₄-mediated direct condensation of primary sulfonamides with the substituted (E,E)-cinnamylideneacetophenones. The 6π-electrocyclization of these intermediates, catalyzed by a Lewis acid, selectively afforded the desired products in good yields.     

Synthesis of functionalized benzothiophenes by twofold Heck and subsequent 6π-electrocyclization reactions of 2,3-dibromothiophene

The Heck reaction of 2,3-dibromothiophene afforded 2,3-di(alkenyl)thiophenes which were transformed into benzothiophenes by domino ′6π-electrocyclization/dehydrogenation′ reactions.     

Copper-catalyzed tandem alkynylation, propargyl-allenyl isomerization, 6π-electrocyclization of Morita-Baylis-Hillman adducts to naphthalenes

An expedient synthetic approach of naphthalenes was developed by the reaction of Morita-Baylis-Hillman bromides and arylacetylenes. The synthesis was carried out via a tandem copper-catalyzed alkynylation, propargyl-allenyl isomerization, and 6π-electrocyclization protocol.     

6π/10π-Electrocyclization of ketene-iminium salts for the synthesis of substituted naphthylamines

An intramolecular 6π/10π-electrocyclization from ketene-iminium salts was developed for the preparation of naphthylamines. Various substituents on the nitrogen, on the aromatic ring, and on the olefin were studied. Tricyclic skeletons were obtained in few steps and good overall yields. The electrocyclization of ketene-iminium salts has been computationally explored by means of DFT calculations and their activation barriers were compared to the parent triene as well as the corresponding dienyl allenes and dienyl ketenes. Electrocyclizations for ketene-iminium salts were shown to be highly exergonic and have much smaller barriers to activation.     

Concise design and synthesis of pyridine-fused heterocycles via 6π-Azaelectrocyclization process of iminoalkyne derivatives

A concise and regioselective approach to the synthesis of pyridine-fused heterocycles and benzoxazepine derivatives was developed. Propargyl imines derived from aromatic aldehydes and propargyl amine underwent 6π-electrocyclization reactions at high temperatures in high yields to form pyridine-fused heterocycles. Application of the same methodology to aromatic imines having a hydroxyl group in the ortho position resulted in the formation of (benz)oxazepine derivatives. The formation mechanism of the products was discussed.     

Synthesis and anticancer activity of conformationally constrained Smac mimetics containing pseudo β turns

Herein, we report synthesis and in vitro anticancer activity of conformationally constrained Smac mimetics containing reverse turn inducing motifs “Ant-Pro” and “^sAnt-Pro”. The synthesis of Smac analogs with diverse hydrophobic groups at the C-terminus was carried out using solution phase peptide synthesis. The synthesis of Ant-Pro containing analogs 3a–j was carried out by ring opening of benzoxazinones 7a–c, whereas, their sulfonamide counterparts 4a–h were synthesized by using routine acid-amine coupling reaction. In vitro anticancer studies against breast cancer cell line MDA-MB-231 revealed that some of the new analogs had better anticancer activity than the standard AVPI Smac tetrapeptide.     

Novel enantioselective synthesis of trans-α-(2-carboxycycloprop-1-yl)glycines: conformationally constrained l-glutamate analogues

d- and l-α-(2-carboxycycloprop-1-yl)glycines were synthesized from trans-1,3-di(2-furyl)propenone. Conversion of the double bond to a cyclopropane is followed by the formation of an oxime ether. Enantioselective reduction of the oxime ether, separation of diastereomers and oxidation of the furane rings gave enantiomerically pure d- and l-CCG I and CCG II. The structure of oxime 7b was determined by X-ray crystal structure analysis. The key step is the oxazaborolidine catalyzed enantioselective conversion of oxime ethers to amines.     

Access to 3-aminobenzothiophenes and 3-aminothiophenes fused to 5-membered heteroaromatic rings through 6π-electrocyclization reaction of keteniminium salts

We described a general approach to 3-aminobenzothiophenes and 3-aminothiophenes fused to 5-membered heteroaromatic rings as thiophenes, furans and pyrroles through a 6π-elctrocyclization reaction of keteniminium salts. We investigated various substituents not only on the aromatic rings, but also at C-2 and on the nitrogen atom of the keteniminium salt. In particular, we have determined the electronic requirements of the nitrogen substitution to secure the efficient formation of the corresponding keteniminium salt. A clear relation between the pK_a of the amine leading to the formation of the keteniminium salt and the yield obtained for benzothiophene is established and should find broad application to other reactions involving these intermediates. Additional insight on the ease of this 6π-electrocyclization reaction was gained through competition reactions and DFT calculations.     

Sulfanyl-methylene-5(4H)-oxazolones and β-sulfanyl-α-nitroacrylates as appealing dienophiles for the synthesis of conformationally constrained cysteine analogues

A new class of masked constrained cysteine derivatives containing the norbornen/ane scaffold were prepared by the way of Diels–Alder cycloaddition reaction by exploitation of two different dienophiles, sulfanyl-methylene-5(4H)-oxazolones and β-sulfanyl-α-nitroacrylates. The new norbornen/ane amino acid derivatives can be considered versatile building blocks due to the presence of the α,α-disubstituted amino acid function, suitable for peptide synthesis, but also by the carbon–carbon norbornene double bond, which could be variously functionalized.     

Enantioselective synthetic approaches to cyclopropane and cyclobutane β-amino acids: synthesis and structural study of a conformationally constrained β-dipeptide

Synthetic approaches to carbocyclic compounds, namely cyclopropane and cyclobutane β-amino acids, are presented. One of them is based on enzymatic desymmetrization of meso diesters, leading to the enantioselective production of cis-hemiesters, which afforded β-amino acids through Curtius rearrangements. The enantiomeric excess for the cyclobutane derivatives was 91% whereas the cyclopropanes were obtained in 63% ee. According to another strategy, an enantiomerically pure cyclopropane trans-β-amino acid, bearing a quaternary center, has been synthesized from a homochiral precursor easily available from d-glyceraldehyde. The preparation and structural investigation of the first synthesized cyclobutane containing dipeptide is also described. A hairpin-like conformation of this molecule in the solid state has been demonstrated by X-ray structural analysis, showing crystal packing induced by the presence of the rigid cyclobutane moiety and the formation of intermolecular hydrogen bonds. NMR experiments confirmed that these molecules also tend to produce aggregates in solution. On the contrary, theoretical calculations suggest that intramolecular interactions are important in the gas phase, as expected.     

Synthesis of 1H-benzo[g]indazole derivatives: propargyl–allenyl isomerization and 6π-electrocyclization involving two aromatic π-bonds

An efficient synthesis of 1H-benzo[g]indazoles starting from Morita–Baylis–Hillman (MBH) adducts is disclosed. The synthesis was carried out from MBH bromide via a sequential copper-catalyzed alkynylation, one-pot synthesis of pyrazole, propargyl–allenyl isomerization, and a 6π-electrocyclization involving two aromatic π-bonds and an allenyl π-bond.     

Condensation reactions of 3-oxo-2-arylhydrazonopropanals with active methylene reagents: formation of 2-hydroxy- and 2-amino-6-substituted-5-arylazonicotinates and pyrido[3,2-c]cinnolines via 6π-electrocyclization reactions

3-Oxo-3-phenyl-2-(p-tolylhydrazono)propanal (1a) undergoes condensation with ethyl cyanoacetate in acetic acid in the presence of ammonium acetate to yield either 2-hydroxy-6-phenyl-5-p-tolylazonicotinic acid ethyl ester (6a) or 2-amino-6-phenyl-5-ptolyl-azonicotinic acid ethyl ester (8), depending on the reaction conditions. Similarly, other 3-oxo-3-aryl-2-arylhydrazonopropanals 1a,b condense with active methylene nitriles 2c,d to yield arylazonicotinates 6b,c. In contrast, 2-[(4-nitrophenyl)-hydrazono]-3-oxo-3-phenyl-propanal (1c) reacts with ethyl cyanoacetate to yield ethyl 6-(4-nitrophenyl)-2-oxo-2,6-dihydropyrido[3,2–c]cinnoline-3-carboxylate (11), via a novel 6π-electrocyclization pathway. Finally, 3-oxo-2-(phenylhydrazono)-3-p-tolylpropanal (1d) condenses with 2a-c to yield pyridazinones 13a-c.     

Efficient sulfonylation of ketones with sodium sulfinates for the synthesis of β-keto sulfones

The oxidative sulfonylation of ketones with sodium sulfinates as the sulfone source and DMSO as the oxidant is reported. A series of β-keto sulfones were obtained in good to excellent yields. The advantages of this efficient protocol include the low cost of DMSO and HBr, and a broad scope.     

An interesting competition between 6π-electro- and Garratt–Braverman cyclization in bis-diene-allene sulfones: synergy between experiment and theory

The reactivity of a series of bispropargyl sulfones with an ortho alkenyl moiety was studied. Under basic condition, these molecules isomerized to the bis-diene-allene system capable of undergoing 6π-electro-(EC) as well as Garratt–Braverman (GB) cyclization. The reaction generally favours the GB process but the balance can be tilted towards the 6π-EC pathway by suitable perturbation of structure and temperature. The findings are useful as the systems undergoing GB pathway can show DNA-damage activities.     

Reactivity Ratios for Microemulsion Copolymeriration of N-butyl Maleimide and Styrene

IntroductionReactivityratioscanofferthemessageofrelativereactivityofcomonomers.TWomonomerreactivityratioscanbeacquiredfromtheend-groupmodelproposedbyMayoandLewis,howevef,thereareonlyapparentreactivityratiosavailablefromthiskineticmodelwhencharge-transfercomplex(CTC)participatesinthecopolymerization.Therefore,thecopolymeriZationinwhichCTCexistsisworthyoffurtherresearch.Sofar,therearethreekineticmodelsofcopolymerizationwiththeparticipationofCTCinall,namely,SeinerandLittmodel',Shirotamodel…     

Reactivity Ratios for Microemulsion Copolymerization of N-butyl Maleimide and Styrene

The oil-in-water microemulsion containing N-butyl maleimide(NBMI, M1) and styrene(St, M2) was prepared. The complexation properties of NBMI and St in microemulsion were investigated by means of 1H-NMR. With the participation of charge-transfer complex(CTC), four reactivity ratios and the relative reactivity of free monomers and CTC were obtained. The result was compared with that measured by Mayo-Lewis method.     

α-Scission of sulfonyl radicals: a versatile process for organic synthesis

The reversible addition of aliphatic radicals to sulphur dioxide can be exploited to design a variety of tin-free chain reactions. This brief review summarises some of the possibilities, namely radical allylation, vinylation, alkynylation, and azidation of various substrates.     

Proposition for the acylation mechanism of serine proteases: A one-step process?

This work proposes a very detailed ab initio study of the hypothesis for a one-step serine protease acylation process with one water molecule acting as the main catalyst reactant. For the 11 increasing complexity models considered, the minimum and transition state conformations for the reaction are determined by full geometry optimizations at the ab initio self-consistent field (SCF ) levels within several basis sets, from MINI-1 to 6-31G, and, for the smallest complexes, at the post-SCF MP2 level within the 6-31G** basis set. The related thermodynamical quantities are calculated for all the conformations. The influence of the oxyanion hole stabilizer and of the dyad His57-Asp102 is quantified and a very good agreement is obtained with point mutagenesis. The activation barrier is found in the range 15–18 kcal/mol. © 1996 John Wiley & Sons, Inc.