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.     

An expedient stereoselective synthesis of (Z)- and (E)-allyl iodides from Baylis-Hillman adducts along with selective iodination of benzylic alcohols using the polymethylhydrosiloxane-iodine system

A stereoselective method has been developed for the synthesis of (Z)- and (E)-allyl iodides from Baylis-Hillman adducts using polymethylhydrosiloxane (PMHS) and iodine in chloroform at room temperature. In addition, the reagent system has been utilized for the iodination of benzylic alcohols selectively.     

Stereoselective synthesis of (E)-α-aryltellurenylvinylsilanes via hydromagnesiation reaction of alkynylsilanes

(E)-α-Aryltellurenylvinylsilanes have been synthesized stereoselectively via the hydromagnesiation of alkynylsilanes, followed by the reaction with aryltellurenyl iodides. (E)-α-Aryltellurenylvinylsilanes can undergo the cross coupling reaction with Grignard reagents in the presence of Ni(PPh₃)₂Cl₂ catalyst to afford (Z)-1,2-disubstituted vinylsilanes in good yields.     

Ultrasound-assisted convenient synthesis of hypolipidemic active natural methoxylated (E)-arylalkenes and arylalkanones

An ultrasound-assisted convenient method was developed for the conversion of toxic methoxylated cis-isomer of arylalkenes into its hypolipidemic active trans-isomer. Treatment of cis-isomer or mixture of all three isomers (1a-1j) with ammonium formate and 10% Pd/C gave arylalkanes (2a-2j), which upon oxidation with DDQ in anhydrous dioxane containing a little amount of silica gel, provided (E)-arylalkenes (3a-3g) in 42-72% yield depending upon the substituents attached at the aryl ring. The same method, upon addition of a few drops of water, provided hypolipidemic active arylalkanones (3h-3j) in 59-65% yield.     

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.     

Kinetic deconjugation: a gateway to the synthesis of Xxx-Gly (E)-alkene dipeptide isosteres

A new method for the preparation of Xxx-Gly (E)-alkene dipeptide isosteres (EADIs), using LDA deprotonation followed by 1 N HCl quench, was explored. The method, named kinetic deconjugation, enabled the synthesis of Tyr-Gly, Gly-Gly, Ser-Gly, Pro-Gly, and Phe-Gly EADIs, as well as one Tyr-Gly trisubstituted alkene dipeptide isostere (TADI). Overall, this method, based on commercially available materials, leads to high yields, requires few synthetic steps and works on the gram scale in the synthesis of a wide variety of EADIs.     

Preparation of enantiomerically pure (E)-β-sulfinylenones from β-ketoesters

Enantiomerically pure (E)-β-sulfinylenones are smoothly prepared from β-ketoesters in three steps with good overall yield. Since they can be the substrates of many diastereoselective reactions, they represent versatile precursors of a wide range of chiral building blocks. We propose a rationale to explain the formation of (E)-β-sulfinylenones from the corresponding δ-enol-methylethers.     

(E)-Selective Wittig reactions of Garner's aldehyde with nonstabilized ylides

In the Wittig olefination reactions of Garner's aldehyde with certain nonstabilized ylides, the (E)-alkenes could be produced as a major product by simply quenching the reactions with a large excess of MeOH at −78 °C. Even under the salt-free conditions, more than a 10:1 ratio of the (E)- to (Z)-alkene was resulted consistently from the ylides of a linear alkyl chain. Without addition of MeOH, usual selectivity for the (Z)-alkene was obtained in a ratio of 94:6.     

An improved synthesis of (2E,4Z)-6-(benzyloxy)-4-bromohexa-2,4-dien-1-ol

An improved synthesis of (2E,4Z)-6-(benzyloxy)-4-bromohexa-2,4-dien-1-ol has been devised. This new route increases the throughput and yield of the diene product by circumventing a low yielding preparation of boronic acid intermediate as well as removing the need to use multi-gram quantities of highly toxic thallium salts. In the process of developing this new route, a higher yielding preparation of (E)-3-hydroxyprop-1-enylboronic acid was also achieved.     

One-pot synthesis of 1-aryl-3-methyl-1,3-dienes using methallyl(trimethyl)silane and aldehydes and their low temperature (Z)→(E) isomerization induced by sulfur dioxide

2-Methylprop-2-ene-1-sulfonyl fluorides can be easily prepared via the ene reaction of methallylsilanes and SO₂. In the presence of a base, aldehydes and 2-methylprop-2-ene-1-sulfonyl fluorides give 1,3-(E) and (Z)-dienes. Their (Z)→(E) isomerization by classical means fails or leads to their polymerization. It is shown that SO₂ can isomerize 1-aryl-3-methyl-1,3-dienes at low temperature, without formation of sulfolenes (cheletropic addition/elimination). Preliminary mechanistic studies suggest that SO₂ adds to 1,3-dienes forming 1,4-diradical intermediates that are responsible for the (Z)→(E) isomerizations.     

One-pot sequential cross-metathesis/hydride reduction: highly stereoselective synthesis of primary (E)-allylic alcohols from terminal olefins

Several di- and trisubstituted primary (E)-allylic alcohols have been prepared from the corresponding terminal olefins in a highly stereoselective manner (>20:1 E/Z) by sequencing olefin cross-metathesis (CM) with hydride reduction (DIBAL-H) in good yields utilizing only commercially available reagents in a one-pot fashion. The method is a reliable alternative to the direct CM of terminal olefins with allyl alcohol, which is not always stereoselective but rather highly substrate dependent.     

Preparation of optically pure (3E,5E)-alkyl-2-hydroxy-6-arylhexa-3,5-dienoates by Candida parapsilosis ATCC 7330 mediated deracemisation of the racemates

Biocatalytic deracemisation of a range of racemic (3E,5E)-alkyl-2-hydroxy-6-arylhexa-3,5-dienoates using Candida parapsilosis ATCC 7330 resulted in pure (S)-enantiomers in yields of up to 80% and ee>99%.     

Synthesis of (E)-alkenes via hydroindation of CC in InCl3-NaBH4 system

In InCl₃-NaBH₄-MeCN system, terminal aryl alkynes could couple with aryl iodides and bromides to give disubstituted alkenes via hydroindation of CC. In the similar way, (E)-alkenylsilanes were synthesized via reduction of alkynylsilanes in tetrahydrofuran (THF) in high yields. The processes showed high regio- and stereoselectivity.     

Microwave-assisted solid phase synthesis of Imatinib, a blockbuster anticancer drug

An expeditious, high yield and convenient synthesis of Imatinib was carried out on an aldehydic, super acid-sensitive resin, through an efficient, microwave-assisted synthetic protocol. The high versatility of the reaction scheme may enable the straightforward preparation of libraries of potential protein kinase inhibitors endowed with large molecular diversity.     

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.     

Transformations of (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylates into pyridine and pyrrole derivatives

New, highly functionalised (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylates proved to be useful and versatile reagents in the formation of highly substituted pyridine, N-aminopyridine, pyrrole and pyrido[3,4-c]pyridazine derivatives. The formation of the particular type heterocyclic system is dependent on the starting (1E,3E)-1-(benzoylamino)-4-(dimethylamino)buta-1,3-diene-1,2,3-tricarboxylate. By an appropriate choice of different ester groups it is possible to drive the reactions towards the formation of either pyridine or pyrrole derivatives.     

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.     

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.     

Ti(III)-promoted cyclizations. Application to the synthesis of (E)-endo-bergamoten-12-oic acids. Moth oviposition stimulants isolated from Lycopersicon hirsutum

The Ti(III)-promoted radical cyclization of epoxyenone 8 is described as the key step to access the diol 10 as a convenient starting material of the target molecules. The synthesis of β-(E)-endo-bergamoten-12-oic acid 2a from (+)-8,9-epoxycarvone 8 was successfully achieved by Suzuki-Miyaura coupling of the terminal alkene 20 with β-iodomethacrylate 21c, followed by deprotection and dehydration processes. Moreover, synthesis of the α-(E)-endo-1-hydroxy-bergamoten-12-oic acid derivative 34 was achieved by iterative elongation processes of the diol 10 lateral chain.     

Asymmetric synthesis of (−)-(S,S)-homaline

The asymmetric synthesis of (−)-(S,S)-homaline was achieved in 8 steps from commercially available starting materials using the diastereoselective conjugate addition of the novel lithium amide reagent lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to methyl cinnamate to install the correct stereochemistry. Subsequent functional group manipulation of the resultant β-amino ester and Sb(OEt)₃-mediated macrolactamisation was followed by homodimerisation to give (−)-(S,S)-homaline in 18% overall yield, representing the first asymmetric, and by far the most efficient synthesis of this natural product reported to date.