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.     

Transition-metal-free synthesis of (Z)-3-ylidenephthalides from 2-acyl-benzoic acids

We report a highly efficient method for the synthesis of (Z)-3-ylidenephthalides via intramolecular cyclization of readily available 2-acyl-benzoic acids mediated by TSTU at room temperature. Using this method, diversely substituted (Z)-3-ylidenephthalides have been generated in good to excellent yields. The application of the method is highlighted by gram-scale preparation of the antiplatelet drug n-butylphthalide.     

Trienylboronic acid, a versatile coupling tool for retinoid synthesis; stereospecific synthesis of 13-aryl substituted (11Z)-retinal

Trienylboronic acid 1a was prepared from iodotriene 3, which was coupled with (2Z,4Z)-3-aryl-5-iodo-2,4-pentadienol 9 by Suzuki coupling reaction to give geometrically pure 13-aryl substituted (11Z)-retinol 10. Oxidation of 10 gave 13-aryl substituted (11Z)-retinal 11.     

Z-Selective synthesis of o-bromoacetophenone N-tosylhydrazones and formation of 3-methylindazoles in aqueous ethanol

A practical and effective Z-selective synthesis of o-bromoacetophenone N-tosylhydrazones is developed. Subsequent cyclization of Z-tosylhydrazones to furnish 3-methylindazoles is accomplished with the aid of copper and DMEDA in aqueous ethanol. Cyclization reactions are complete at ambient temperature in 10 min to afford the desired compounds in excellent yields.     

The stereoselective synthesis of (E)-octafluoro-1,3,5-hexatriene and (3E,5E,7E)-dodecafluoro-1,3,5,7,9-decapentaene

(E)-(1,2-Difluoro-1,2-ethenediyl)bis[tributylstannane], 3, readily undergoes a Pd(PPh₃)₄/CuI-catalyzed cross-coupling reaction with iodotrifluoroethene to yield (E)-octafluoro-1,3,5-hexatriene, 4, in high isomeric purity. (1Z,3E,5Z)-(1,2,3,4,5,6-Hexafluoro-1,3,5-hexenetriyl)bis[tributylstannane], 7, was sequentially prepared from (1Z,3E,5Z)-(1,2,3,4,5,6-hexafluoro-1,3,5-hexenetriyl)bis[triethylsilane], 5, which was prepared via a Pd(PPh₃)₄/CuI-catalyzed cross-coupling reaction of 3 with (E)-1,2-difluoro-1-iodo-2-triethylsilylethene, 6. Pd(PPh₃)₄/CuI cross-coupling of 7 with iodotrifluoroethene gave (3E,5E,7E)-dodecafluoro-1,3,5,7,9-decapentaene, 8.     

Regio- and stereoselective synthesis of Z-vinylic tellurides from propargylic alcohols: a route to chiral Z-enynes

tert-Butyldimethylsilyl ethers of propargylic alcohols are hydrotellurated regioselectively to give 1,2-Z-vinylic tellurides. Enantiomerically pure propargylic alcohols give enantiomerically pure vinylic tellurides, which are coupled with alkynes under Pd catalysis to give enantiomerically pure allylic enynols.     

Z-Selective hydroamidation of terminal alkynes with secondary amides and imides catalyzed by a Ru/Yb-system

A catalyst system formed in situ from bis(2-methallyl)cycloocta-1,5-diene-ruthenium(II) [(cod)Ru(met)₂], 1,4-bis(dicyclohexylphosphino)butane (dcypb) and ytterbium(III) triflate hydrate (Yb(OTf)₃) was found to catalyze the addition of nitrogen nucleophiles to terminal alkynes under mild conditions to stereoselectively form the Z-enamide or Z-enimide products. Various secondary amides and imides could be added across the triple bond of a range of aliphatic and aromatic alkynes. The new bimetallic catalyst system sets new standards with regard to scope and selectivity for the synthesis of Z-configured anti-Markovnikov enamides.     

A novel method for (Z)-stereoselective preparation of CF3-substituted enediynes and their coupling reactions

Trifluoromethylated enynyl sulfones 3 were reacted with 2-4 equiv of phenyl, n-hexyl, trimethylsilyl, or triisopropylsilyl substituted ethynyllithium reagents in THF or ether at 0 °C to give trifluoromethylated enediynes 6 (Z)-stereoselectively in 41-96% yields. The reactions of β-fluoro-β-trifluoromethylvinyl sulfone 5 with same ethynyllithium reagents (4 equiv) afforded the corresponding enediynes 6 in 41-90% yields. The cross-coupling reactions of 6 bearing TMS group with aryl iodides in the presence of Pd(PPh₃)₂Cl₂, Ag₂CO₃, and n-Bu₄NBr provided the corresponding enediynes 6 in 20-71% yields. Dimerization of (Z)-6 bearing TMS group in the presence of CuBr₂ and K₂CO₃ yielded dimer (Z,Z)-7 in good yield.     

Mild and practical stereoselective synthesis of (Z)- and (E)-allyl bromides from Baylis-Hillman adducts using Appel agents (PPh3/CBr4): a facile synthesis of semiplenamides C and E

Appel agents (PPh₃/CBr₄) have been utilized for high-yielding stereoselective synthesis of (Z)- and (E)-allyl bromides from Baylis-Hillman adducts at room temperature. The method has been applied for the synthesis of naturally occurring bioactive fatty acid amides, semiplenamides C and E.     

Hydrothiolation of terminal alkynes with diaryl disulfides and diphenyl diselenide: selective synthesis of (Z)-1-alkenyl sulfides and selenides

A simple, stereoselective and efficient method for the hydrothiolation of terminal alkynes with diaryl disulfides and diphenyl diselenide has been developed. In the presence of CuI, rongalite, and Cs₂CO₃, a variety of disulfides underwent the reaction of terminal alkynes stereoselectively to afford the corresponding (Z)-1-alkenyl sulfides in moderate to excellent yields. It is noteworthy that hydroselenations of 1,2-diphenyldiselane with alkynes are also conducted smoothly to afford (Z)-1-alkenyl selenides in good yields under the standard conditions.     

Z/E Stereoselective synthesis of β-bromo Baylis-Hillman ketones using MgBr2 as promoter via a one-pot three-component reaction

The first time steroselective synthesis of (Z)-β-bromo Baylis-Hillman ketones has been achieved using a one-pot three-component reaction. The new system uses MgBr₂ as both the Lewis acidic promoter and the bromine source for the Michael-type addition with α,β-acetylenic ketones to form an active β-bromo allenolate intermediate, which in turn attacks various aldehydes to afford β-bromo Baylis-Hillman adducts in good yields and Z-selectivity.     

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.     

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.     

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.     

Identification of the sex pheromone of the lesser date moth, Batrachedra amydraula, using sequential SPME auto-sampling

The identification of the sex pheromone of the lesser date moth, Batrachedra amydraula (Meyrick) was based on GC-MS analysis of volatiles released by virgin females using sequential SPME auto-sampling of headspace and by synthesis of the key component, (4Z,7Z)-4,7-decadien-1-yl acetate. Substantial capture of males in a date palm plantation using a bait consisting of the key component and 5Z-decen-1-yl acetate in a ratio of 1:2 indicated that these are the essential components of the sex pheromone. Addition of 4Z-decen-1-yl acetate and decan-1-yl acetate, which were also identified, did not affect trap-capture. The lesser date moth is the first member of the Batrachedridae whose sex pheromone has been identified. (4Z,7Z)-4,7-Decadien-1-yl acetate is a novel compound among moth sex pheromones.     

A highly efficient stereoselective synthesis of (Z)- and (E)-allyl iodides from Baylis-Hillman adducts

A highly efficient synthesis of (Z)- and (E)-allyl iodides has been accomplished by treatment of Baylis-Hillman adducts with iodine and triphenylphosphine in methylene chloride at room temperature. The method is associated with mild reaction conditions, high yields and excellent stereoselectivity.     

Stereoselective synthesis of hex-2-(E)-en-4-yn-1,6-dioates and E,Z-muconic acid diesters via organo-catalyzed self-coupling of propiolates

Alkyl propiolate couples with itself in the presence of catalytic DABCO under very mild conditions to provide a quantitative yield of E-hex-2-en-4-yne dioates. Hydrogenation of these enyne dioates using Lindlar catalyst provides the corresponding E,Z-diene dioate, a common structural motif found in an array of natural products.     

Enantioselective synthesis of (2S,3′R,7′Z)-N-(3′-hydroxy-7′-tetradecenoyl)-homoserine lactone

A concise enantioselective total synthesis of (2S,3′R,7′Z)-N-(3′-hydroxy-7′-tetradecenoyl)-homoserine lactone is described. Key feature of this protocol is a catalytic asymmetric hydrogenation and a prophenol-zinc-catalyzed diazo addition to imine reaction as genesis of chirality. Moreover, flexibility is built in the synthesis to generate enantioenriched analogs using catalytic amount of enantioenriched C₂-symmetric ligands.     

One-pot hydrosilylation-protodesilylation of functionalized diarylalkynes: a highly selective access to Z-stilbenes. Application to the synthesis of combretastatin A-4

An efficient stereoselective synthesis of Z-stilbenes has been developed from diarylalkynes via a new hydrosilylation-protodesilylation process. The scope and limitation of this method is presented to stereoselectively prepare a wide range of (Z)-stilbenes in a one-pot way is presented. A concise application to the preparation of combretastatin A-4 (CA-4), a vascular targeting agent inhibitor of tubulin polymerisation is described.     

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.