Cross-conjugated Trienes Research Articles

Total Synthesis of Matrine Alkaloids.

The total synthesis of three diastereomeric matrine natural products is reported. The 8-step synthesis commences with simple acyclic precursors, forms all 4 rings of the tetracyclic natural product framework, and forges 10 of the 20 covalent bonds of the target structure. A cross-conjugated triene is positioned at the core of an acyclic branched structure. This precursor collapses to the tetracyclic natural product framework through an orchestrated sequence of two separate intramolecular cycloadditions. A subsequent, late-stage hydrogenation is accompanied by strain-release redox epimerizations to deliver the three natural products. An unprecedented carba-analogue is prepared in the same way. Semisynthetic manipulations of matrine provide access to 10 additional natural products.

Palladium-catalyzed oxidative acyloxylation/carbocyclization of allenynes.

Vinylallenes or cross-conjugated trienes are obtained selectively in the title reaction. Two possible mechanisms are suggested to rationalize the formation of the different types of products. Control experiments indicate that p-benzoquinone (BQ) plays an important role as a ligand in addition to its role as an oxidant. E=CO(2)Me.

Palladium‐Catalyzed Oxidative Arylating Carbocyclization of Allenynes

Vinylallenes or cross-conjugated trienes are obtained selectively in the title reaction. Two possible mechanisms are suggested to rationalize the formation of the different types of products. Control experiments indicate that p-benzoquinone (BQ) plays an important role as a ligand in addition to its role as an oxidant. E=CO(2)Me.

One-Pot Synthesis of Fused-Tetracyclic Scaffolds Employing a Lewis Acid Promoted Domino Reaction of Naphthoquinones

The facile synthesis of tetracyclic molecular frameworks employing a Lewis acid promoted domino reaction of naphthoquinones with hydroxy- and amino-functionalized cross-conjugated trienes is reported. The reaction cascade involves a heterocyclization via hemiacetal or imine formation, and an intramolecular Diels­-Alder cycloaddition.

Synthesis of cross-conjugated trienes by rhodium-catalyzed dimerization of monosubstituted allenes

A rhodium(I)/dppe catalyst promoted dimerization of monosubstituted allenes in a stereoselective manner to give cross-conjugated trienes, which are different from those obtained by a palladium catalyst.

Silver-Catalyzed Cycloisomerization of 1,n-Allenynamides

A variety of allenynamides can undergo cycloisomerization reactions in the presence of silver triflate thus leading to the formation of N-containing heterocycles incorporating cross-conjugated trienes. Access to new dienic 4-piperidinone and azepane motifs was achieved. An extension to one-pot tandem sequences involving silver-catalyzed cycloisomerization/Diels-Alder reaction was also examined.

Reprint of “Allene–alkyne cross-coupling for stereoselective synthesis of substituted 1,4-dienes and cross-conjugated trienes”

Titanium-mediated cross-coupling of allenic alcohols with alkynes has been investigated. Divergent reaction pathways were discovered that provide either stereodefined 1,4-dienes or substituted cross-conjugated trienes. In short, allene substitution plays a critical role in the determination of reaction pathway.

Gold-Catalyzed Cycloisomerization of 1,5-Allenynes via Dual Activation of an Ene Reaction

Tris(triphenylphosphinegold) oxonium tetrafluoroborate, [(Ph3PAu)3O]BF4, catalyzes the rearrangement of 1,5-allenynes to produce cross-conjugated trienes. Experimental and computational evidence shows that the ene reaction proceeds through a unique nucleophilic addition of an allene double bond to a cationic phosphinegold(I)-complexed phosphinegold(I) acetylide, followed by a 1,5-hydrogen shift.

Skeletal and appendage diversity as design elements in the synthesis of a discovery library of nonaromatic polycyclic 5-iminooxazolidin-2-ones, hydantoins, and acylureas

Amino-acid derived cross-conjugated trienes were used as a starting point for the synthesis of a discovery library of over 200 polycyclic 5-iminooxazolidin-2-ones, hydantoins, and acylureas. The main feature of this library synthesis is a triple branching strategy, which provides efficient access to five skeletally diverse scaffolds. In addition, four sets of building blocks were applied in both a front end and a back end diversification strategy. Multiple fused rings were obtained by cyclization of diamides with phosgene and stereoselective Diels–Alder reactions with maleimides. The 5-iminooxazolidin-2-one scaffold was rearranged into the isomeric hydantoin scaffold through a sequence of ring-opening and ring-closing reactions.

Allene–alkyne cross-coupling for stereoselective synthesis of substituted 1,4-dienes and cross-conjugated trienes

Titanium-mediated cross-coupling of allenic alcohols with alkynes has been investigated. Divergent reaction pathways were discovered that provide either stereodefined 1,4-dienes or substituted cross-conjugated trienes. In short, allene substitution plays a critical role in the determination of reaction pathway.

Cross-conjugated Z- and E-3-ferrocenylmethyl-idene-4-methyl-2-phenylpenta-1,4-dienes — Synthesis and some chemical properties

Dehydration of (Z)- and (E)-4-ferrocenyl-3-isopropenyl-2-phenylbut-3-en-2-ols and Z-3-ferrocenyl methyl idene-4-methyl-2-phenylpentane-2,4-diol affords (Z)- and (E)-3-ferrocenylethylidene-4-methyl-2-phenylpenta-1,4-dienes with a system of three cross-conjugated double bonds. One of the methylidene groups of the trienes obtained is smoothly protonated under the action of tetrafluoroboric acid etherate to yield (Z)- and (E)-3-ferrocenyl-2-isopropenyl-1-methyl-1-phenylallyl tetrafluoroborates. The cross-conjugated trienes undergo cationic cycloaddition to these allylic cations as well as proton-induced cyclodimerization resulting in 7-ferrocenyl-4-ferrocenylmethylidene-1,3-dimethyl-5-phenyl-8-(1-phenylethylidene)bicyclo[3.3.1]non-2-ene and isomeric 1,5-diferrocenyl-2,6-diisopropenyl-3,7-diphenylocta-1,3,6-trienes.Key words: cross-conjugated trienes, ferrocenylallylic cations, cyclodimerization, cycloaddition, ferrocene.

Observation of New Cycloisomerization Pattern of 1,5-Bisallenes. Catalyst and Substituent Effects

In this paper a new cycloisomerization pattern of 1,5-bisallenes based on the catalyst and substituent effects has been reported. A range of seven-membered cross-conjugated trienes 7 would be obtained efficiently via the beta-H elimination and reductive elimination of the intermediates formed via cycloisomerization.

The allenic Alder-ene reaction: constitutional group selectivity and its application to the synthesis of ovalicin

The scope of the novel allenic Alder-ene reaction using Rh(I) and Ir(I) catalysts has been extended to differentially substituted 1,1,3-trisubstituted allenes. This allenyl substitution pattern can give three possible cross-conjugated triene products. The selectivity of this transformation can be controlled by varying reaction temperature, solvent, and catalyst. Progress toward the synthesis of ovalicin using this triene forming protocol is described.

A consecutive Diels–Alder approach toward a Tet repressor directed combinatorial library

A combinatorial library of 180 tetracycline analogs was generated by solution phase parallel synthesis applying a consecutive Diels–Alder strategy. Chemical methodology suitable for three-dimensional solution phase parallel synthesis was developed that enabled us to generate a collection of potential TetR inducers. The synthesis was built on cross-conjugated trienes as central building blocks facilitating two consecutive cycloaddition processes with different dienophiles. Upon sequential exposure to naphthoquinone and maleimide derivatives, the generation of a carbocyclic skeleton of type 2 incorporating the diversity elements R1–R5 was envisaged.

Cycloaddition Reactions of Amino-Acid Derived Cross-Conjugated Trienes: Stereoselective Synthesis of Novel Heterocyclic Scaffolds

Cross-conjugated trienes obtained via a Rh(I)-catalyzed allenic Alder-ene reaction represent a new class of compounds. The synthesis of heterocyclic compounds containing multiple fused rings was accomplished via sequential Diels-Alder reactions of amino-acid derived cross-conjugated trienes. Newly synthesized imino-oxazolidinone fused trienes were used to control the stereoselectivity in an intermolecular cycloaddition sequence. Additionally, intramolecular cycloaddition of ester tethered tetraene stereoselectively afforded fused tricyclic pyridino-pyranone which was effectively utilized in subsequent cycloaddition reactions.

Consecutive Rh(I)‐Catalyzed Alder‐ene/Diels—Alder/Diels—Alder Reaction Sequence Affording Rapid Entry to Polycyclic Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Practical Synthesis and Diels−Alder Chemistry of [4]Dendralene

Spectacular new atom efficient domino cycloaddition sequences involving [4]dendralene, the simplest cross-conjugated tetraene, are reported. Up to eight stereocenters, three new rings, and six C-C bonds are generated in one synthetic operation. The site selectivity of dienophile addition to cross-conjugated trienes and tetraenes is controlled with a simple Lewis acid.

Consecutive Rh(I)-catalyzed Alder-ene/Diels–Alder/Diels–Alder reaction sequence affording rapid entry to polycyclic compounds

Conversion of acyclic allenynes to polycyclic compounds using consecutive transition metal catalyzed carbon–carbon bond forming reactions in a single chemical operation is described. Reaction of an allenyne with a Rh(I) catalyst affords a cross-conjugated triene via a formal Alder-ene reaction. The triene then participates in a Rh(I)-catalyzed intramolecular [4+2] cycloaddition reaction to generate a new conjugated diene. An external dienophile is added to this diene which then undergoes a second [4+2] cycloaddition reaction to afford a complex polycyclic ring system. This reaction sequence demonstrates the synthetic potential of allenynes and cross conjugated trienes and highlights the rapid increases in molecular complexity that are possible by one-pot sequential transition metal catalyzed carbon–carbon bond forming reactions.

Linear free energy relationships of the 1H and 13C NMR chemical shifts of 3-methylene-2-substituted-1,4-pentadienes

Linear free energy relationships (LFER) were applied to the 1H and 13C NMR chemical shifts ( δ N, N= 1H and 13C, respectively) in the unsaturated backbone of cross-conjugated trienes 3-methylene-2-substituted-1,4-pentadienes. The NMR data were correlated using five different LFER models, based on the mono, the dual and the triple substituent parameter (MSP, DSP and TSP, respectively) treatment. The simple and extended Hammett equations, and the three postulated unconventional LFER models obtained by adaptation of the later, were used. The geometry data, which are needed in Karplus-type and McConnell-type analysis, were obtained using semi-empirical MNDO-PM3 calculations. In correlating the data the TSP approach was more successful than the MSP and DSP approaches. The fact that the calculated molecular geometries allow accurate prediction of the NMR data confirms the validity of unconventional LFER models used. These results suggest the s- cis conformation of the cross-conjugated triene as the preferred one. Postulated unconventional DSP and TSP equations enable the assessment of electronic substituent effects in the presence of other interfering influences.

Allenes and Transition Metals: A Diverging Approach to Heterocycles

AbstractFor Abstract see ChemInform Abstract in Full Text.