(6Z,9Z,12Z)-6,9,12-Octadecatriene and (3Z,6Z,9Z,12Z)-3,6,9,12-icosatetraene, the novel sex pheromones produced by emerald moths

(6Z,9Z,12Z)-6,9,12-Octadecatriene and (3Z,6Z,9Z,12Z)-3,6,9,12-icosatetraene, hydrocarbons unsaturated more highly than usual lepidopteran Type II pheromones, were identified from geometrid females of Hemithea tritonaria and Thalassodes immissaria intaminata, respectively. The triene was synthesized by a double Wittig reaction between hexanal and an ylide derived from (Z)-1,6-diiodo-3-hexene, and the tetraene was synthesized by a coupling between (Z)-3-undecenal and an ylide derived from (3Z,6Z)-1-iodo-3,6-nonadiene. Each synthetic compound attracted males of the corresponding emerald moths in a field.     

Synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate

The first total synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate has been achieved in seven steps and in 16% overall yield. The synthesis confirmed the assigned structure of this polyunsaturated natural product.     

Efficient preparation of (Z)-alkenyl derivatives from (Z)-vinyl (N,N-diisopropyl)carbamate via Ni-catalysed coupling reactions

A (Z)-vinyl (N,N-diisopropyl)carbamate treated with Grignard reagents, under Wenkert Nickel-catalysed conditions, gave access to several substituted (Z)-alkenyl derivatives. These Nickel-catalysed reactions, carried out with vinyl-, phenyl-, p-methoxyphenyl-, trimethylsilylmethylmagnesium bromide and benzylmagnesium chloride, led to the corresponding (Z)-alkenyl derivatives in good yields and high stereoselectivities.     

A stereoselective synthesis for the (5Z,9Z)-14-methyl-5,9-pentadecadienoic acid and its monounsaturated analog (Z)-14-methyl-9-pentadecenoic acid

A stereoselective synthesis for the (5Z,9Z)-14-methyl-5,9-pentadecadienoic acid and the monounsaturated analog (Z)-14-methyl-9-pentadecenoic acid was accomplished in six to seven steps where double alkyne coupling was the key step. This synthesis will facilitate the study of the topoisomerase I inhibitory profile of this important class of fatty acids.     

Synthesis of deuterated 5(Z),11(Z)-eicosadienoic acid as a biomarker for trophic transfer

The poly-methylene interrupted fatty acid 5(Z),11(Z)-eicosadienoic acid and its tetradeuterated analogue were prepared via a convergent synthetic sequence.     

Stereospecific preparation of (2E, 4Z)-monofluorodienyl esters by the Heck reaction of high E/Z ratio 1-bromo-1-fluorostyrenes

High E/Z ratio (E/Z>75:25) 1-bromo-1-fluorostyrenes, which were prepared by isomerization of 1-bromo-1-fluorostyrenes (E/Z≈1:1), underwent the Heck reaction with methyl acrylate, and (2E, 4Z)-methyl 5-aryl-4-fluoropenta-2,4-dienoates were successfully isolated. Heck reactions of (Z)-1-bromo-1-fluorostyrenes also occur. However, the products are difficult to separate in a pure form, since they have an obvious tendency to isomerize on a silica gel column.     

Stereospecific preparation of symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes from 1-bromo-1-fluoroalkenes

A straightforward method to prepare symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes is described. High E/Z ratio 1-bromo-1-fluoroalkenes, prepared by isomerization from the E/Z ≈ 1:1 isomeric mixtures, reacted with Bu₃SnSnBu₃ and Pd(PPh₃)₄ to afford (1Z, 3Z)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes in good yield. (Z)-1-Bromo-1-fluoroalkenes, which were prepared by kinetic reduction from 1-bromo-1-fluoroalkenes (E/Z ≈ 1:1), can undergo similar reaction with Bu₃SnSnBu₃ and Pd(PPh₃)₄/CuI to prepare (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes.     

Cycloaddition reactions of ethyl (E)- and (Z)-3-fluoropropenoate

Ethyl (Z)-3-fluoropropenoate (Z-5) has been prepared in a pure state in 68% yield by a Wittig procedure developed by Burton. Ethyl (E)-3-fluoropropenoate (E-6) was prepared in 38% yield following the synthetic method of Purrington. The Z isomer gives cycloaddition with 1,3-diphenylisobenzofuran and cyclopentadiene to give a product with completely endo configurations. The E isomer also gives cycloadducts with same dienes to give mixtures of endo and exo products.     

Stereospecific synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes from 2-chloro-1-(n-N,N-dimethylaminophenyl)ethenes: fluorescence properties

The conjugated 1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes (n=o-, m-, p-) were efficiently synthesised by homocoupling of the appropriate 2-chloro-1-(n-N,N-dimethylaminophenyl)ethene (n=o-, m-, p-) with stoichiometric amounts of zerovalent nickel complexes. The 1,3-butadienes were obtained as a mixture of stereoisomers, with independence of the starting E or Z chlorovinyl isomer. Moreover, the stereospecific (Z,Z) stereoisomer was obtained by partial hydrogenation of the corresponding 1,3-butadiyne, while the stereospecific (E,E) stereoisomer was obtained by exposure to the sunlight radiation of the (Z,Z) or the (Z,E) compound in ethanol.     

The stereoselective synthesis of (Z)-HFCCFZnI and stereospecific preparation of (E)-1,2-difluorostyrenes from (Z)-HFCCFZnI via an unusual Pd(PPh3)4-Cu(I)Br co-catalysis approach or (Z)-HFCCFSnBu3

(Z)-HFCCFZnI was stereoselectively synthesized from activated zinc dust and (Z)-HFCCFI that was synthesized from chlorotrifluoroethene in a sequential manner. Compared to (E)-HFCCFZnI, (Z)-HFCCFZnI was more challenging to prepare in terms of sluggish metallation and formation of by-products, and underwent slower and incomplete Negishi coupling with aryl iodides. In a modification of Negishi coupling, (E)-α,β-difluorostyrenes were stereospecifically prepared in good to excellent yields under mild conditions from aryl iodides and (Z)-HFCCFZnI with the co-catalysis of Pd(PPh₃)₄/Cu(I)Br. Experimental investigation and mechanistic rationalization suggested that Cu(I)Br would be a scavenger of free ligands for the facilitation of Pd(PPh₃)₂ formation, and a supplier of ligand for the metathesis process. Alternatively, (Z)-HFCCFSnBu₃ and aryl iodides with an electron-withdrawing group underwent Stille-Liebiskind coupling to afford (E)-α,β-difluorostyrenes.     

Novel (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles from (E)- and (Z)-3-styrylchromones: the unexpected case of (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles

An efficient synthetic method for the preparation of (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles has been developed. The reaction of (E)- and (Z)-3-styrylchromones with hydrazine hydrate afforded the corresponding (E)- and (Z)-4-styrylpyrazoles, respectively, saved 4′-nitro-derivatives where both (E)- and (Z)-4′-nitro-3-styrylchromones afforded (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles. The reaction mechanism for these transformations was discussed and the stereochemistry of all products was assigned by NMR experiments.     

Regioselective synthesis of 5-alkylidene and 5-(iodoalkylidene)-pyrrol-2(5H)-ones by halolactamisation of (2Z,4E)-dienamides and (Z)-alk-2-en-4-ynamides

Stereo- and regioselective synthesis of 5-alkylidene (arylidene) and 5-(iodoalkylidene)-pyrrol-2(5H)-ones was achieved from (2Z,4E)-dienamides and (Z)-alk-2-en-4-ynamides by halocyclisation reaction. Selectivity was found to be highly dependent on the nature of the substituents and on the temperature.     

Approaches to the preparation of (Z)-1,2-difluorostilbenes

Methodology directed at the preparation of (Z)-1,2-difluorostilbenes has been evaluated. For symmetrical (Z)-1,2-difluorostilbenes, photochemical isomerization of the isomeric (E)-1,2-difluorostilbenes, and HPLC separation of the mixture of stilbene isomers is a reasonable route to a particular (Z)-stilbene. An alternative approach to both symmetrical and/or unsymmetrical (Z)-1,2-difluorostilbenes has been developed via stereospecific Pd(0) coupling of (E)-1,2-difluoro-aryl-ethenyltributylstannanes under Stille-Liebiskind conditions with aryl idodies. The requisite arylstannanes can be obtained via the reported route developed by Davis or via (E)-1,2-difluorovinyltributylstannane - a new route described in this work. The methodology tolerates almost any functionality in the aryl ring, is easily carried out, is stereospecific and provides the first general route to (Z)-1,2-difluorostilbenes.     

Novel diastereoselective synthesis of (E)- and (Z)-allylsilanes via organoboranes

A simple, novel diastereoselective synthesis of both (E)- and (Z)-allylsilanes via organoboranes is developed. (E)-1-Alkenylboronate esters easily prepared from the corresponding terminal alkynes via hydroboration with dibromoborane-methyl sulfide complex followed by treatment with 1,3-propane diol readily react with trimethylsilylmethyllithium at −78 °C in methanol followed by reaction with iodine in methanol to produce the corresponding (Z)-allylsilanes in high yields (72-80%) and in high stereochemical purities (98% as evidenced by CMR spectral data). Similarly, the (Z)-1-alkenylboronate esters react with trimethylsilylmethyllithium at −78 °C in methanol followed by treatment with iodine in methanol to produce the corresponding (E)-allylsilanes in moderate yields (57-65%) in high stereochemical purities (>98% as revealed by CMR spectral data).     

Stereoselective synthesis of (Z)-β-fluoro-α,β-unsaturated esters from (Z)-2-fluoro-1-alkenyliodonium salts

(Z)-β-Fluoro-α,β-unsaturated esters were stereoselectively synthesized from (Z)-2-fluoro-1-alkenyliodonium salts by the Pd-catalyzed methoxycarbonylation reaction. The reaction proceeded at room temperature and various functional groups on the substrate can tolerate the reaction conditions.     

Easy synthesis of (E)- or (Z)-perfluorinated β-enaminoesters

(E)- or (Z)-perfluorinated β-enaminoesters were prepared by direct addition of primary or secondary amines to ethyl perfluoroalkynoates without any catalyst.     

Siloxyallenes revisited. A useful functional intermediate for the synthesis of (Z)-β-branched Morita-Baylis-Hillman type adducts and (Z)-chalcones

Siloxyallenes proved to be a useful functional intermediate in the preparation of (Z)-β-branched Morita-Baylis-Hillman type adducts by the reaction of aldehydes with silylacetylenes or siloxypropynes. Various (Z)-chalcones were stereoselectively synthesized from siloxypropynes via siloxyallenes.     

Pd-catalyzed cross-coupling reaction of (Z)- and (E)-bromoenyne: unusual stereochemical outcome

Pd-catalyzed cross-coupling reaction of (E)-bromoenyne 1Z with 1-alkyne and tributylvinyl-stannane occurs with retention of the configuration in benzene but with an inversion of the configuration in DMF or CH₂Cl₂. On the other hand, that of (Z)-bromoenyne 1E occurs with retention of the configuration in these solvents.     

Concise total synthesis of (3Z,6Z,9S,10R)-9,10-epoxy-1,3,6-heneicosatriene, sex pheromone component of Hyphantria Cunea

The total synthesis of (3Z,6Z,9S,10R)-9,10-epoxy-1,3,6-heneicosatriene, sex pheromone component of Hyphantria cunea, using a convergent synthetic strategy, was achieved through the regioselective coupling of the two fragments, chiral epoxy tosylate and 1,4-diyne. The former fragment was synthesized in two efficient and convenient approaches starting from the same available material using Sharpless AE kinetic resolution as the key step.     

Domino pericyclic reactions of acyclic conjugated (E,Z,E,E)-tetraenes

Acyclic conjugated (E,Z,E,E)-tetraenes, upon thermolysis, undergo a domino pericyclic process involving 6π electrocyclisation of the (E,Z,E)-triene moiety to give the corresponding cis-disubstituted 5-vinyl-1,3-cyclohexadienes, followed by an intramolecular Diels-Alder reaction with the vinyl side chain to give tricyclo[3.2.1.0^2,7]oct-3-enes.