Search

A novel one-pot organocatalytic selective process is described for the cascade synthesis of highly substituted o-hydroxydiarylamines and o-pyrrolidin-1-yldiarylamines. The direct combination of amine-catalyzed cascade Knoevenagel/Michael/aldol condensation/decarboxylation and cascade enamine amination/isoaromatization of alkyl acetoacetates, aldehydes and nitrosoarenes has provided the highly functionalized anilines with high yields.

An efficient copper-catalyzed double alkenylation of amides with (1Z,3Z)-1,4-diiodo-1,3-dienes is described. The reactions have produced di- or trisubstituted N-acylpyrroles in excellent yields by using Cul as the catalyst, [Cs.sub.2]C[O.sub.3] as the base and rac-trans-N,N'-dimethyl-cyclohexane-1,2-diamine as the ligand.

The effects of an ester group as an alkyne substituent on the reactivity of propargylic enynes, which inhibits the Rautenstrauch process, are analyzed. The steric interactions in the transition structure have provided different hyperconjugation interaction energies that have helped in determining the magnitude of the energy barrier for the rate-limiting H-abstraction step.

The [Me.sub.3]SiOTf-mediated condensation of 1-ethoxy-2-fluoro-1,3-bis(trimethylsilyloxy) 1,3-dienes with 3-cyanochromones to generate 3-cyano-2-(4-ethoxy-3-fluoro-2,4-dioxobutyl)chroman-4-ones is described. The product distribution in the reaction depends on the structure of the diene and the formation of the biaryls is demonstrated by an unprecedented domino 'retro-Michael/aldol/fragmentation' reaction.

The asymmetric C-H functionalization of norbornene and norbornadiene with five-, six-, and seven-membered cyclic enones mediated by the reactive intermediate [{[[eta].sup.5]-([super t]Bu[Me.sub.2]Si)[C.sub.5][H.sub.4]}Co[(NO).sub.2]] is described. A novel base mixture derived from enantiopure ammonium salts and NaHMDS is used as a source of chirality and the enantioselective desymmetrization of [C.sub.s] alkenes is applied to the asymmetric synthesis of [C.sub.2]- and [C.sub.1]-symmetric diene ligands.

The combination of Pd catalyst and Xantphos ligand in the presence of [Et.sub.3]B has promoted the allylation of aldehydes with conjugated dienes to provide dienyl homoallyl alcohols. The reaction has occurred selectively at the C-C double bond bearing higher electron density.

The development of a well-defined Fe catalyst and its application to the regio- and stereoselective 1,4-hydrosilylation of 1,3-dienes is reported. The study provides the first example of accessing a characterized low-valent Fe catalyst by controlled reductive elimination from a readily accessible Fe precatalyst.

A highly efficient asymmetric rhodium-catalyzed addition of sodium tetraarylborates to N-tosyl ketimines is described. The asymmetric catalysis is achieved by employing a chiral diene ligand and constructing chiral amine derivatives possessing [alpha]-tetrasubstituted carbon stereocenters with high enantioselectivity.

Variable-temperature NMR studies are conducted to demonstrate that the conformational restraints imposed by selected backbones increase the activation barrier for the helical isomerization in (Z,Z)-dienes that are generated in the cyclization of the diynes. The reaction chemistry could be applied to synthesize highly functionalized dibenzocyclooctadienes which adorn the carbon frames of several important cytotoxic natural products.

A highly stereoselective Au-catalyzed synthesis of 9-oxabicyclo[3.3.1]nona-4,7-dienes from diverse 1-oxo-4-oxy-5-ynes is reported. The findings revealed the feasibility of a formal [4 + 2] cycloaddition on an s-trans-heterodiene framework.

The dirhodium catalyzed tandem cyclopropanation/Cope rearrangement between bicyclic dienes and siloxyvinyldiazoacetate to achieve enantiodivergent [4 + 3] cycloadditions is reported. The reaction which proceeds by a cyclopropanation followed by a Cope rearrangement of the resulting divinylcyclopropane could be applied for the synthesis of (+)-barekoxide and (-)-barekol.

The article explains the mechanisms involved in the intramolecular two-step [1+4+1] process, which can be employed for bicyclic and polycyclic construction. The application of the reaction for the simultaneous construction of more than one carbocyclic ring is also analyzed.

Several analyses are conducted to explain the various mechanisms that are associated with the Cu(I)-catalyzed regioselective diamination of the conjugated dienes. The dienes are shown to undergo diamination at the internal double bonds in an extremely efficient manner.

1,2,3-Benzotriazin-4(3H)-ones have reacted with 1,3-dienes in the presence of a nickel(0)/phosphine complex to produce a variety of 3,4-dihydroisoquinolin-1(2H)-ones. Alkenes have undergone insertion into the five-membered ring azanickelacyclic intermediate and subsequent reductive elimination has given 3-substituted 3,4-dihydroisoquinolin-1(2H)-ones.

Enantioselective (formal) aza-Diels-Alder reactions are developed between acylhydrazones and non-Danishefsky-type dienes. The reactions are promoted by a chiral silicon Lewis acid and glyoxylate- and aliphatic aldehyde-derived hydrazones are used for preparing diverse arrays of tetrahydropyridines.

Silver(I) complex [[Ag[(diene).sub.2]].sup.+][Y.sup.-] (diene = cyclooctadiene, norbornadiene, and 1,3-cyclohexadiene, [Y.sup.-] = P[F.sub.6.sup.-], B[F.sub.4.sup.-]) has catalyzed the arylation of N-tosylaziridines with arenes and heteroarenes in order to provide the corresponding [beta]-aryl amine derivatives with excellent regioselectivity. In situ NMR ([super 1]H, [super 31]P, [super 109]Ag) and ESI-MS probe are used for understanding the nature of substrate activation and initial bond breaking/making steps.

Iridium-catalyzed asymmetric 1,6-addition of arylboroxines to [alpha],[beta],[gamma],[delta]-unsaturated carbonyl compounds is reported. The reaction gave [delta]-arylated carbonyl compounds in high yields with 90 to 99% enantioselectivity realized by use of an iridium/chiral diene complex.

Various studies are conducted to explain the mechanisms associated with the nickel catalyzed reaction taking place between carbonyls and dienes. The bis(pinacolato)diboron compound is shown to play an extremely significant role in the coupling reaction.

A practical synthetic route for the preparation of chiral bicycle[2.2.2]octane-2,5-dione, the precursor of chiral diene ligands, is realized by Diels-Alder reaction and resolution of an enol acetate derivative by immobilized lipases.

Density functional theory calculations are used for examining the mechanism of the oxidation of 1,5-dienes with osmium tetroxide. Enantioselectivity is induced by an enantioselective dihydroxylation followed by condensation of the 5,6-dihydroxyolefine with osmium tetraoxide, while the diastereoselectivity is achieved by the reaction of the 1,5-diene with osmium tetroxide and intermediate reoxidation of the osmium(VI) ester.

Naphthalenes have undergone Diels-Alder reactions when coencapsulated with a suitable dienophile within the cavity of a self-assembled host. The studies have shown that the localization of the reactant pair has reduced the entropic cost of the reaction and the tuning of substrate size and shape within molecular flasks has disclosed unusual reactivities of otherwise unreactive molecules.

The application of the ring-size-selective enyne metathesis approach for the desymmetrization of an enantiopure [C.sub.2]-symmetric building block is discussed. The presence of an unprotected hydroxy group is shown to act as the major factor that controls the ring-size selectivity in the reaction.

The synthesis of 1-alkoxy-2-methyl-3-acyloxy-(E,E)-penta-1,3-dienes is described. The process used modified DanishefskyEs general method and chiral, racemic, and achiral derivatives.

2-dimethylphenylsilyl-1,3-butadiene is prepared from chloroprene and Diels-Alder reactions of these dienes are described along with subsequent TBAF-assisted/Pd-catalyzed Hiyama cross-coupling reactions of those Diels-Alder adducts. Silicon-substituted cycloadducts and cross-coupled products are characterized by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy.

The mechanisms involved in the Au[X.sub.3]-mediated selective head-to-head dimerization of difluoropropargyl amides are discussed. The results show that the formation of these amides can be easily rationalized by the reductive elimination of the divinylgold species.

A modular total synthesis of the potent V-ATPase inhibitors archazolid A and B achieved by late-stage diversification of joint intermediates is reported. The key steps in the synthesis involve asymmetric boron-mediated aldol reactions, two consecutive, Still-Gennari olefinations to set the characteristic (Z,Z)-diene system, a Brown crotyboration, and a diastereoselective aldol condensation of highly elaborate intermediates.

A series of bicyclic 2'-deoxynucleosides that are locked in the N-type conformation because of three-carbon linkages between the 2'- and 4'-positions are prepared by ring-closing diene or enyne metathesis. A strong RNA-selective nucleic acid recognition is observed and it is shown that the 2'-oxygen atom is less vital for the formation of DNA:RNA duplexes than for the formation of DNA:RNA duplexes.

The influence of the substitution of novel cyclization/fluorination reaction of N-dienes in superacid on superelectrophilic character of dicationic intermediates was explored to determine their effect on the synthesis of fluoropiperidines. The newly obtained dicationic [alpha]-chloronium ammonium intermediates starting from halogen-substituted dienes were applied to synthesize high-valued fluorinated piperidines.

The development of an efficient acid-catalyzed method for the synthesis of vinylogous thioesters to produce 1-a lkylthio-3-silyloxybutadienes in high yields is reported. The application of highly reactive dienes in Diels-Alder reactions to afford the cycloadducts in high endo selectivity under mild conditions is also reported.

Asymmetric [4 + 3] cycloadditions between vinylcarbenoids and dienes to perform 18 step total synthesis of (-)-5-epi-vibsanin E is described. The quaternary stereogenic center generated in the process could be obtained with high asymmetric induction when the reaction is catalyzed by the chiral dirhodium complex, [Rh.sub.2][(S-PTAD).sub.4].

The ring-opening metathesis polymerization (ROMP) of dicarbomethoxynorbornadiene (DCMNBD) with 2% molybdenum-based monoaryloxide monopyrrolide (MAP) species, Mo(NAd)(CHC[Me.sub.2]Ph)([C.sub.4][H.sub.4]N)(HIPTO) in toluene is described. The Z-selective metathesis reactions could be applied to prepare cis and syndiotactic poly(DCMNBD), poly(cyclooctene) and poly(cyclooctadiene) as well as cis-3-heptene.

A ring-closing metathesis was used to prepare the diene 3-methylenecyclopentene from the naturally occurring monoterpene myrcene and Grubbs second generation catalyst. A detailed studies on radical, anionic, and cationic polymerizations of the diene 3-methylenecyclopentene and semicrystalline state of samples of 1,4-poly-diene 3-methylenecyclopentene is also described.

The synthesis of macrocycles 1-6 via ring closing metathesis of dienes 7-12 is described. The addition of chlorodicyclohexylborane to thermal and microwave assisted RCM of dienes has improved the yield and the geometric isomers of macrocyles are assigned by using X-ray crystallography and NMR.

A concerted process and a stepwise process involving a zwitterionic intermediate are used for decribing the mechanism of the addition of singlet carbenes to bicyclobutanes to produce 1,4-diene products. The calculated potential energy surface has shown that the reaction has proceeded through the zwitterionic intermediate both to the observed diene product and to one of the other isomers.

Free radical oxidation of many 1,4-dienes is carried out in the presence of variable concentrations of [alpha]-tocopherol to examine the effect of diene structure on product distribution. Groups at C-1 and C-5 of the diene has affected product distribution based upon steric demand in the oxygen-radical reaction and the effect of substituents on the rearrangement of the C-3 peroxyl radical to give conjugated diene products.

Mild and salt-free reduction of M[Cl.sub.5] (M = Nb, Ta) is achieved by using 3,6-bis(trimethylsilyl)-1,4-hexadiene derivatives as reducing agents. The salt-contact-free low-valent Ta[Cl.sub.3] has displayed high catalytic activity for the trimerization of ethylene to 1-hexene with excellent selectivity, thus providing new evidence for a metallacycle mechanism.

The total synthesis of (-)-bitungolide F is described. The major steps have involved a Myers asymmetric alkylation to introduce the C6 methyl with proper stereochemistry, a Claisen-like cyclization to construct the [alpha],[beta]-unsaturated [delta]-lactone and a Julia-Kocienski olefination to assemble the conjugated diene moiety.

The timing of the introduction of the unusually placed [[DELTA].sub.11,13] diene system in ansamitocin (AP) biosynthesis in Actinosynnema pretiosum is determined by preparing optically active potential tri- and tetraketide intermediates as their SNAC thioesters. The results have shown that the double bonds are installed in their final positions during processing of the nascent polyketide on module 3 of the asm PKS and that KS4 of the PKS has acted as a gatekeeper accepting only a tetraketide with shifted double bonds as substrate for further processing.

The structural analysis of bicyclo[3.3.1]nona-2,6-dienes based on 3,7-disubstituted bicyclo[3.3.1]nona-2,6-diene framework is used to design and synthesize new [C.sub.2]-symmetric chiral diene ligands. The obtained chiral ligands readily bind to rhodium(I) and the rhodium complexes and act as effective catalysts for 1,4-addition of alkenyl- and arylboronic acids to various [alpha],[beta]-unsaturated ketones.

The first systematic study of chemo-, peri-, and stereoselectivity of electron transfer catalyzed Diels-Alder reactions of a chiral diene as a function of the reaction conditions is reported.

The C-H bond dissociation enthalpies (BDEs) for the five- and six-membered ring alkanes, alkenes and dienes are examined and discussed in terms of conventional strain energies (SEs). The higher BDE in 1,3-cyclopentadiene is not attributed to the destabilizing strain effect in the radical but to the stabilizing effect in the parent molecule due to the conjugated double bond, thus mimicking the relation between the BDEs in the 1,3- and 1,4-pentadienes.

An efficient Pd(II)-catalyzed 1,2-carboamination of dienes that proceeds under mild conditions and facilitates the synthesis of indolines from N-aryl ureas via aryl C-H activation is reported. The results showed that the presence of urea moiety rather than a simple amide plays an important role in obtaining efficient C-H insertion.

A new method for the stereoselective synthesis of Z-[alpha],[beta],[gamma],[delta]-unsaturated amides is reported. The approach is based on a pericyclic cascade rearrangement of donor-acceptor dienes known as Zincke aldehydes.

The calculation results from density functional theory were used to explore the mechanism of the rearrangement of 7-azahepta-1,2,4,6-tetraene to methylidene-6-azacyclohexa-2,4-diene. The results provide insight into the significant role of nitrogen lone-pair's in the rearrangement as a secondary orbital effect.

A tandem Michael addition/ylide epoxidation is developed for the rapid creation of highly functionalized cyclohexadiene epoxide skeletons with three stereocenters. The readily accessible starting material, mild reaction conditions, high selectivities and recoverable chiral sulfide has made this reaction very useful in organic synthesis.

A step-economical synthesis of a new family of substituted [4.6.4.6]fenestradienes and [4.6.4.6]fenestrenes through a unique 8[pi]-6[pi]-[[O.sub.2]-oxi] cascade electrocyclization sequence is described. The high yields and the limited number of steps of the reaction sequence have made this process very attractive for preparing new fenestranes.

A four-step stereocontrolled synthesis of polyfunctionalized cis-decalins is described, which has involved oxidation of 2-methoxyphenol, intermolecular Diels-Alder reaction, olefination and Cope rearrangement. The application of this strategy to the total syntheses of (+-)eremopetasidione, (+-)-3[beta]-angeloyloxyfuranoeremophilane, and (+-)-3-[beta]-methacryloyloxyfuranoeremophilane is accomplished from creosol and ethyl vinyl ketone through a common intermediate.