New stereoselective methodology for the synthesis of dihydroxerulin and xerulin, potent inhibitors of the biosynthesis of cholesterol

A new stereoselective methodology for the synthesis of both dihydroxerulin and xerulin has been devised. The key step required cross-coupling reactions between the bromo trienyne, (1E,3E,5E)-1-bromo-8-trimethylsilyl-1,3,5-octatrien-7-yne and the appropriate conjugated diynes. The palladium-catalyzed tandem cross-coupling/cyclization reaction of the resulting polyenynes with (Z)-3-iodo-2-propenoic acid led directly to dihydroxerulin or xerulin with a high degree of stereoselectivity.     

Flexible access to 2,3,5,6-tetrasubstituted dehydropiperidines by Ni- or Co-catalyzed site-selective cross-coupling using Vilsmeier-Haack-derived α-chloro-β-formyltetrahydropyridines

A flexible and cost-effective method for the highly functional group-compatible and site-selective cross-coupling of readily affordable α-chloro-β-formyltetrahydropyridines has been developed, under nickel or cobalt catalysis, leading to the rapid synthesis of 2,3,5,6-tetrasubstituted dehydropiperidines bearing α-amino allylic stereocenters. Cobalt-catalyzed reductive cross-coupling of chloro enaminals with electronically-diverse bromostyrenes as coupling partners proceeds in good yields and with high E/Z selectivity to afford Diels-Alder-suitable cross-conjugated 1,3-dienes.     

Convergent stereocontrolled synthesis of substituted exo-glycals by Stille cross-coupling of halo-exo-glycals and stannanes

(Z)-exo-Glycals can be conveniently prepared in a convergent manner by Stille cross-coupling of (Z)-halo(Br,I)-exo-glycals and aryl or alkenyl stannanes, the latter are readily obtained by addition of tributylstannyl radicals to terminal alkynes.     

Synthesis of bis(alk-3-en-1-ynyl)benzene with either E- or Z-configuration via a one-pot three-component coupling reaction and its optical properties

A convenient, efficient and stereoselective synthesis of a range of bis(alk-3-en-1-ynyl)benzenes with E- and Z-configuration is described. The protocol involves Cu-mediated cross-coupling reaction of (E)- and (Z)-alk-1-enyldisiamylboranes with (trimethylsilyl)ethynyl bromide and Pd/Cu-catalyzed cross-coupling reaction with diiodobenzene. The sequential cross-coupling reaction proceeds readily under extremely mild conditions in a one-pot manner to afford bis(alk-3-en-1-ynyl)benzenes in good to excellent yields. The optical properties of the products are also described.     

Glycerol as a promoting medium for cross-coupling reactions of diaryl diselenides with vinyl bromides

We described herein the use of glycerol as a novel solvent in the cross-coupling reaction of diaryl diselenides with vinyl bromides catalyzed by CuI. This cross-coupling reaction was performed with diaryl diselenides and (Z)- or (E)-vinyl bromides bearing electron-withdrawing and electron-donating groups, affording the corresponding vinyl selenides in good to excellent yields. The mixture glycerol/catalyst can be directly reused for further cross-coupling reactions.     

Alternative approaches to (Z)-1,2-bis(2-bromopyridin-3-yl)ethenes, key intermediates in the synthesis of the 1,10-phenanthroline core

A study on the synthesis of (Z)-1,2-bis(2-bromopyridin-3-yl)ethenes, key intermediates in the preparation of 1,10-phenanthrolines, based on selective Sonogashira and Suzuki-Miyaura cross-coupling reactions has been carried out.     

Stereo- and regiospecific syntheses to provide conjugated (E,Z)- and (Z,Z)-alkadienes,and arylated (Z)-alkenes in excellent yields via the palladium-catalyzed cross-coupling reactions of (Z)-1-alkenylboronates with 1-bromoalkenes and aryl iodides

Titled alkadienes are obtained in excellent yields stereo- and regiospecifically by cross-coupling between (Z)-1-alkenylboronates and (E)- or (Z)-1-bromoalkenes in the presence of a catalytic amount of Pd(PPh₃)₄ and sodium ethoxide.     

Practical synthesis and applications of benzoboroxoles

A convenient one-pot synthesis of benzoboroxoles has been developed via the reaction of o-bromobenzyl alcohols with NaH, ⁿBuLi, and B(OⁱPr)₃ followed by acidic hydrolysis. Applications of these benzoboroxoles have been demonstrated in Pd-catalyzed cross-coupling reactions and the protocol has been extended for the synthesis of a chiral benzoboroxole. Exceptionally short synthesis of a potent antifungal agent AN2690 and several of its analogs has also been realized.     

Tellurium in organic synthesis: an approach to the synthesis of (Z,E)-dienic precursors of insect pheromones

A simple and straightforward route to (Z,E)-dienic precursors of insect pheromones was developed. The route features a cross-coupling of a (Z,E)-dienic telluride with an alkyl Lipshutz cuprate.     

Sequential ring-closing metathesis/Pd-catalyzed, Si-assisted cross-coupling reactions: general synthesis of highly substituted unsaturated alcohols and medium-sized rings containing a 1,3-cis-cis diene unit

A sequential ring-closing metathesis/silicon-assisted cross-coupling protocol has been developed. Alkenyldimethylsilyl ethers of allylic, homoallylic and bis(homoallylic) alcohols undergo facile ring closure with Schrock's catalyst to afford 5-, 6-, and 7-membered cycloalkenylsiloxanes, respectively, in some cases with substituents on both alkenyl carbons. These siloxanes are highly effective coupling partners that afford styrenes and dienes (with various aryl and alkenyl halides) in high yield and specificity as well as good functional group compatibility. The siloxanes bearing a Z-iodoalkenyl tether undergo an intramolecular coupling process in the presence of [allylPdCl]₂ which constitutes a powerful method for the construction of medium-sized rings with an internal 1,3-cis-cis diene unit. The formation of 9-, 10-, 11-, and 12-membered carbocyclic dienes is achieved in good yield. Extension to the synthesis of 9-membered ring unsaturated ethers has also been accomplished. Noteworthy features of this process include: (1) highly stereospecific intramolecular coupling, (2) flexible positioning of the revealed hydroxy group, and (3) potential extension to other medium-sized carbocycles and heterocycles.     

A general preparation of (Z)-1-fluorostilbene derivatives for the design of conformationally restricted peptidomimetics

The preparation of (Z)-1-fluoro-2-bromostyrenes provides a general route for the formation of (Z)-1-fluorostilbene derivatives as configurationally stable spacial linkers for the design of conformationally restricted peptidomimetics. Palladium-catalyzed aryl Suzuki and Stille cross-coupling reactions have been surveyed to proceed with complete retention of fluoroalkene geometry, and permit the direct incorporation of a variety of aryl and heteroaromatic substituents.     

Synthesis of carbohydrate-derived (Z)-vinyl halides and silanes: Samarium-promoted stereoselective 1,2-elimination on sugar-derived α-halomethylcarbinol acetates

A general and highly selective method for the synthesis of carbohydrate-derived (Z)-vinyl halides and silanes is described. This reaction takes place through a β-elimination process of sugar-derived α-halomethylcarbinol acetates promoted by samarium diiodide. Starting materials have been easily prepared in two steps consisting in an initial addition of halomethyllithium compounds to the corresponding galactose-derived aldehyde, followed by acetylation. A mechanism that explains both the formation of (Z)-vinyl derivatives and its selectivity is proposed. Finally, the synthetic usefulness of these compounds has been applied in cross-coupling reactions with ethynyl benzene towards the formation of selected enyne derivatives.     

Stereoselective synthesis of fluoroalkenes via (Z)-2-fluoroalkenyliodonium salts

Stereoselective synthesis of fluoroalkenes is described. (Z)-2-Fluoro-1-alkenyl(phenyl)iodonium tetrafluoroborates (1) were synthesized stereoselectively in good yields by Michael-type addition of HF to 1-alkynyl(phenyl)iodonium tetrafluoroborates (2) with a commercially available HF reagent, hydrofluoric acid or Et₃N-3HF. Pd-catalyzed cross-coupling reactions using 1 gave (Z)-2-fluoro-1-alkene derivatives in moderate yields. The treatment of 1 with KI in the presence of a catalytic amount of CuI gave (Z)-2-fluoro-1-iodo-1-alkenes (3). Pd-catalyzed cross-coupling reactions of 3 gave better results than that of 1, and a variety of (Z)-2-fluoro-1-alkene derivatives were synthesized in good yields.     

Dienic sex pheromones : Stereoselective syntheses of (7E,9Z)-7,9-dodecadien-1-yl acetate, (E)-9,11-dodecadien-1-yl acetate,and of (9Z), 11E)-9,11- tetradecadien-1-yl acetate by palladium-catalyzed reactions

Pure (7E,9Z-7, 9-dodecadien-1-yl acetate (1), the sex pheromone of Lobesiabotrana, has been prepared in 21.6% overall yield by a reaction scheme involving; (i) the cross-coupling of (E) - 8 - (2 - tetrahydropyranyloxy) -1 - octenyldisiamylborane with 1 - bromo - 1 - butyne, in the presence of a Pd (O) catalyst and base; (ii) the acetylation of the crude product of this reaction; (iii) the (Z)-stereoselective reduction of the obtained conjugated (E)-enyn-1-yl acetate. (E)-9,11-Dodecadien-1-yl acetate (2), a sex pheromone component of Diparopsiscastanea, has been analogously obtained (in 54.3% overall yield) by cross-coupling of (E) - 10 - (2 - tetrahydropyranyloxy) - 1 - decenyl borane with vinyl bromide, in the presence of a Pd (O) catalyst and base, followed by acetylation of the crude product. Compound 2, which was 87.7% chemically pure, was purified by column chromatography over SiO₂-AgNO₃. Chemically pure (9Z, 11E) - 9,11 - tetradecadien - 1 - yl acetate (3), a sex pheromone component of Spodopteralittoralis, has been prepared (in 30.2% overall yield) by reaction of 10 - (2 - tetrahydropyranyloxy) - 1 - decynylamagnesium bromide with (E)-1-iodo-1-butene, in the presence of a Pd (O) catalyst, followed by acetylation of the crude product and by (Z)-stereoselective reduction of the obtained (E)-enyn-1-yl acetate.The stereoisomeric purity of 1, 2 and 3 has been evaluated by glc analysis on glass capillary columns or by reverse phase hplc analysis.     

Gold-catalyzed rearrangement of propargylic tert-butyl carbonates

Diversely substituted 4-alkylidene-1,3-dioxolan-2-ones are efficiently synthesized by a gold(I)-catalyzed rearrangement of propargylic tert-butyl carbonates. The substrates are readily accessible and the transformation, which is performed under mild reaction conditions using a low loading of catalyst, allows the synthesis of cyclic carbonates, which would be less efficiently obtained using traditional methods. This procedure has also been applied to the stereoselective synthesis of (E)- or (Z)-4-halomethylene-1,3-dioxolan-2-ones, which proved to be suitable substrates for palladium-catalyzed cross-coupling reactions.     

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 insect sex pheromone analogs having a fluorine atom on their double bonds

Insect sex pheromone analogs having a fluorine atom on their double bonds, (9E,11E)-1-acetoxy-9-fluorotetradecadiene, (10E,12E)-13-fluorohexadecadien-1-ol, (9Z,11E)-1-acetoxy-9-fluorotetradecadiene, (10E,12Z)-13-fluorohexadecadien-1-ol were stereoselectively synthesized using cross-coupling reactions of alkenylboranes with (E)- or (Z)-2-fluoro-1-iodo-1-alkenes, stereoselectively prepared from 1-alkynes by our currently developed methods.     

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.     

Synthesis of trifluoromethylated γ- and β-lactones through the palladium-catalyzed cyclocarbonylation

3-Trifluoromethyl-2(5H)-furanones (γ-lactones) and 3-(2,2,2-trifluoroethylidene)-2-oxetanones (β-lactones) were obtained, respectively through the palladium-catalyzed cyclocarbonylation of (Z)-3-iodo-3-trifluoromethyl allylic alcohols and (Z)-2-iodo-3-trifluoromethyl allyl alcohols.     

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.