(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.     

A practical, stereospecific route to 18-, 19-, and 20-hydroxyeicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acids (18-, 19-, and 20-HETEs)

Suzuki-Miyaura cross-coupling of cis-vinylbromide 6, obtained in three steps from diol 4, with functionalized boranes provides a practical, stereospecific route to the title CYP P450 eicosanoids.     

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.     

Stereoselective synthesis of (Z)-axino- and (Z)-debromoaxinohydantoin

(Z)-Axinohydantoin and (Z)-debromoaxinohydantoin, two pyrrole-imidazole alkaloids isolated from different marine sponges, possess moderate activities in inhibiting the progress of the cell cycle at different phases. A stereoselective synthesis of both natural products was achieved. The key step in the synthetic pathway was the installation of the hydantoin northern ring by using 1-benzoyl-2-methylsulfanyl-1,5-dihydroimidazol-4-one.     

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.     

A convergent synthesis of (17R,5Z,8Z,11Z,14Z)-17-hydroxyeicosa-5,8,11,14-tetraenoic acid analogues and their tritiated derivatives

17(R)-OH-AA and 14,15-dehydro-17(R)-OH-AA were synthesized from a common tetraacetylenic precursor and their azide derivatives were obtained in moderate yields via the corresponding p-toluenesulfonates. Since the azido group remained stable during tritiation procedure on Lindlar's catalyst in benzene, both 14,15-dehydro-17(S)-N₃-AA and 14,15-dehydro-17(R)-OH-AA constitute useful intermediates in the synthesis of radio-labelled 17(S)-N₃-AA and 17(R)-OH-AA. In contrast, reduction of azide in methanol afforded 17(S)-NH₂-AA with 95% yield.     

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.     

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.     

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.     

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.     

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.     

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.     

Stereoselective synthesis of vinylic (Z)-vic-bis(arylchalcogenides)

Alkyne-titanium complexes 3, readily prepared in situ by the reaction of alkynes with Ti(O-i-Pr)₄/2 i-PrMgCl, react with electrophilic chalcogen species under mild conditions to provide the corresponding addition products in fair to good yields. The obtained vinylic vic-bis(arylchalcogenides) 4 are useful synthetic intermediates for introducing vinyl functions into organic molecules.     

E/Z Isomerization of 3,3-disubstituted allylic thioethers

Allylic thioethers of the general structure 1 underwent E/Z isomerization during both basic and acidic hydrolysis of the ester moiety at the remote end of the molecule. The isomerization was dependent on the substitution of the allylic moiety. The presence of a 5-membered heterocycle on the double bond supported the isomerization. However, analogous oxy-ethers were stable.     

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 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).     

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.     

Total synthesis of 1-(Z)-atractylodinol

The total synthesis of 1-(Z)-atractylodinol, a natural polyacetylenic alcohol with several biological activities, has been achieved using a newly developed telluride synthon and a novel use for the Negishi type coupling reaction employing vinyl tellurides.     

Synthesis of naturally occurring diene and trienes by Te/Li exchange on (1Z,3Z)-butyltelluro-4-methoxy-1,3-butadiene

(1Z,3Z)-Butyltelluro-4-methoxy-1,3-butadiene 2 was obtained by the hydrotelluration of (Z)-1-methoxy-but-1-en-3-ynes 1. The butadienyllithium 3 obtained by the Te/Li exchange reaction in the (1Z,3Z)-1-butyltelluro-4-methoxy-1,3-butadiene 2 reacted with aldehydes to form the corresponding alcohols 4a-d with total retention of configuration. The alcohols formed undergo hydrolysis, resulting in the α,β,γ,δ-unsaturated aldehydes of (E,E) configuration, which are precursors of trienes obtained from natural sources. The products of this reaction were employed in the synthesis of methyl-(2E,4E)-decadienoate 7, which is a component of the flavor principles of ripe Bartlett pears. Performing the Wittig reaction of the methyl triphenylphosphorane with the deca-(2E,4E)-dienal 5a, we were able to synthesize the undeca-(1,3E,5E)-triene 6a. This compound is a sex-pheromone component of the marine brown algae Fucus serratus, Dictyopteris plagiograma, and Dictyopteris australis. Performing the Wittig reaction of methyl triphenylphosphorane with the octa-(2E,4E)-dienal 5c, the nona-(1,3E,5E)-triene 6b was synthesized. The compound obtained is a sex-pheromone component of the marine brown alga Sargassum horneri. The octa-(1,3E,5E)-triene 6c was easily obtained from hepta-(2E,4E)-dienal 5d by the Wittig reaction with methyl triphenylphophorane. This compound is a sex-pheromone component of the marine brown alga Fucus serratus.