A novel approach to functionalized (E)-1,4-diaryl-1-butenes by Heck reaction and their applications for the construction of dibenzylbutyrolactone lignan skeletons by radical cyclization

A highly regio- and stereoselective [Pd(allyl)Cl]₂ catalyzed Heck reaction of aryl iodides and electronically neutral terminal olefins generated in situ by fluoride induced protiodesilylation of alkenylsilanol derivatives under mild conditions has been developed. The products, viz. terminally substituted styrenes and (E)-1,4-diaryl-1-butenes were obtained in very good yields. The dibenzylbutyrolactone lignan skeletons have been prepared employing two regio- and stereoselective Bu₃SnH-mediated radical cyclization routes.     

Stereoselective synthesis of substituted dienes by the double ortho ester Claisen rearrangement

This letter shows the highly stereoselective synthesis of substituted (E)-1,3-dienes from substituted propargylic diols via the double ortho ester Claisen rearrangement. The cyclohexyl-substituted diene undergoes thermal Diels-Alder cycloaddition with maleic anhydride to produce the corresponding bicyclic diester in highly stereoselective manner.     

Regio- and stereoselective synthesis of (E)-1-bromo-2-iodoalkenes through iodobromination of internal alkynes

One-step synthesis of (E)-1-bromo-2-iodoalkenes from internal alkynes through IBr addition is described. The IBr was generated in situ from commercially available TMSBr and NIS. This simple protocol enables highly efficient regio- and stereoselective iodobromination of the triple bond on a gram scale in anti-mode, and provides a potentially diverse scaffold for preparation of differentially all-carbon tetrasubstituted olefins.     

Facile stereoselective synthesis of (E)- and (Z)-α-substituted cinnamates: stereospecific dehydration reaction with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and copper(II) chloride

A highly stereoselective method for the synthesis of (E)- and (Z)-α-substituted cinnamates in good yield has been achieved by dehydration reaction of anti- and syn-α-substituted-β-hydroxyphenylpropiolate using EDC. This facile method has been used to synthesize various (E)- and (Z)-α-substituted cinnamates and (E)- and (Z)-α-alkylidene-γ-butyrolactones. The reaction mechanism of this highly stereospecific dehydration using EDC can be elucidated by the ω-dimethylamino group of EDC, which is believed to facilitate the deprotonation step.     

Cross-coupling of vinyldisilacyclobutane with olefins catalyzed by [RuH(Cl)(CO)(PCy3)2]

Cross-coupling of vinyldisilacyclobutane with a variety of olefins in the presence of [RuH(Cl)(CO)(PCy₃)₂] leads to stereoselective formation of functionalized vinyldisilacyclobutanes. Analogous homo-coupling of vinyldisilacyclobutane leads to the formation of E- and gem-bis(silyl)ethenes. The reaction offers a new route for synthesis of attractive monomers for ring opening polymerization (ROP).     

Palladium-catalyzed highly regioselective and stereoselective decarboxylative arylation of unactivated olefins with aryl carboxylic acids

Palladium(II)-catalyzed highly regioselective and stereoselective decarboxylative arylation of unactivated olefins with aryl carboxylic acids has been developed. This method is applicable to a variety of unactivated olefins, including allylamides, long chain functionalized olefins and purely aliphatic olefins, leads to the formation of linear E-configured products in high yields. Both electron-rich and electron-deficient aryl carboxylic acids are suitable arylation reagents. It was found that the choice of solvent, catalyst precursor and oxidant had an important influence on reaction efficiency. As a co-solvent and ligand, DMSO is critical to catalysis. This chemistry expands the scope of decarboxylative arylation of olefins with aryl carboxylic acids, and provides a rapid access to useful linear arylation products of unactivated olefins.     

An efficient stereoselective synthesis of difluoromethylated alkenes in a microreactor

Synthetic utility of microreactors and highly stereoselective isomerization (>99:<1) of terminal difluoromethylated alkenes to (E)-difluoromethylated alkenes with TBAF in DMF, are described.     

(E)-Cycloalkenes and (E,E)-cycloalkadienes by ring closing diyne- or enyne-yne metathesis/semi-reduction

A concise, practical and stereoselective entry into macrocyclic (E)-alkenes is outlined comprising a sequence of ring closing alkyne metathesis (RCAM), trans-selective hydrosilylation of the resulting cycloalkynes catalyzed by [Cp^∗Ru(MeCN)₃]PF₆, and a protodesilylation of the ensuing vinylsilanes with AgF in aq. THF/MeOH. Moreover, the first examples of intramolecular enyne-yne metathesis reactions catalyzed by the Schrock alkylidyne complex (tBuO)₃WCCMe₃ are reported; the resulting cyclic enynes can be converted along similar lines into the corresponding (E,E)-configured 1,3-dienes in good overall yields. Cycloalkyne 4 and the (E)-configured cyclic olefins 6 and 21 were characterized by X-ray crystallography.     

Cyclic 1,1-bis(silyl)alkenes—new building blocks for the stereoselective synthesis of unsymmetrical (E)-stilbenes and (E,E)-1,4-diarylbuta-1,3-dienes

A new efficient synthetic protocol for the highly stereoselective synthesis of unsymmetrical (or symmetrical) (E)-stilbenes and (E,E)-1,4-diarylbuta-1,3-dienes based on sequential palladium-catalyzed Heck arylation-Hiyama cross-coupling reactions using cyclic gem-bis(silyl)ethene as alkenyl building block is reported.     

A highly stereoselective transformation of carboxylic esters to trisubstituted olefins via cationic cyclopropyl-allyl rearrangement of sulfonates of cis-1,2-disubstituted cyclopropanols

Methanesulfonates of readily available cis-1,2-disubstituted cyclopropanols on reaction with magnesium bromide in diethyl ether undergo cyclopropyl-allyl rearrangement to afford allyl bromides, with an (E)-trisubstituted double bond, as main products. The amount of the corresponding (Z)-isomers did not exceed 5% when the reaction was performed at 0 °C, and the major concomitant products were the regioisomeric secondary bromides. The latter are sufficiently less reactive towards sulfur, phosphorus and hydrogen nucleophiles than the dominant (E)-disubstituted allyl bromides and these reactions are suitable for the stereoselective preparation of trisubstituted olefins.     

Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Cross-Coupling Reaction for the Stereoselective Synthesis of Multisubstituted Olefins

The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4-Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.     

Concise enantioselective synthesis of (−)-lasubine II

An enantioselective synthesis of the quinolizidine alkaloid (−)-lasubine II 1 is reported. Two different pathways to the key intermediate 2 are described. The first case involving a sequence of ring rearrangement metathesis (RRM), simple functional group interconversion operations, followed by a stereoselective cross metathesis (CM) and in the second case a domino ring opening-/ring closing-/cross metathesis step is involved. In both cases, following the metathesis reactions, exclusively the E-isomer was obtained. The final cyclisation towards the quinolizidine skeleton is achieved by an intramolecular Michael reaction. This concept represents the first example of a highly stereoselective RRM-CM combination in the synthesis of a natural product.     

Reactions of (Z)-3-aryl-3-chloropropenals with nucleophiles: stereoselective formation of (E)-vinylogous esters, (E)-vinylogous amides, and vinamidinium salts

The highly stereoselective conversions of (Z)-3-aryl-3-chloropropenals to (E)-3-alkoxy-3-arylpropenals, to (E)-3-aryl-3-morphorlinopropenals, and to vinamidinium salts are reported. The stereochemical assignments were based on 2D-NMR experiments.     

A new synthesis of alkyl (E)-(3-dimethylamino)acrylates

A highly stereoselective one-step method for the synthesis of alkyl (E)-(3-dimethylamino)acrylates from N,N-dimethylformamide and ketene acetals is reported.     

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 2-methylenepyrrolizidines by tandem cyclization of N-propargylaminyl radicals

Tandem cyclization of N-propargylaminyl radicals, generated by N-chlorination of (E)-alk-4-enylamines 2a-d and 2f followed by treatment with tributyltin radical, afforded 2-methylenepyrrolizidines 3a-d and 3f in a highly stereoselective manner. A similar radical cyclization of (Z)-N-propargyl-1-methyl-5-phenylpent-4-enylamine (2e) gave pyrrolizidine 3b having the same stereochemistry as that obtained from the E isomer 2b.     

Preparation of (E)-1-aryl-3,3,3-trifluoro-1,2-di(trimethylsilyl)-1-propenes via stereoselective bissilylation of trifluoromethyl aryl acetylenes and electrophilic substitution of its TMS groups

Preparations and reactions of (E)-1-aryl-3,3,3-trifluoro-1,2-di(trimethylsilyl)-1-propenes are described. (E)-1-Aryl-3,3,3-trifluoro-1,2-di(trimethylsilyl)-1-propene was prepared from aryl trifluoromethyl acetylenes via reductive bissilylation by TMSCl/Mg in good yields. The silyl groups of (E)-3,3,3-trifluoro-1,2-di(trimethylsilyl)-1-phenyl-1-propene were substituted by electrophiles in both a stepwise and stereoselective (and/or stereospecific) manner. This compound could be a building block for preparations of substituted trifluoropropenes.     

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.     

Highly regio- and stereoselective Michael addition of pseudouridine with propiolates: An efficient method for the synthesis of (E)-pseudouridine-N1-acrylate

The Michael addition of pseudouridine with various propiolates in the presence of DBU as a base and DMF as a solvent is described. It is noteworthy that the reaction is highly regio- and stereoselective and affords (E)-pseudouridine-N1-acrylate in good yields with high purities.     

Asymmetric aziridination with chiral allyl aminosulfoxonium ylides: synthesis of alkenyl aziridine carboxylates and palladium-catalyzed E,trans/E,cis-isomerization of an alkenyl aziridine

Chiral cyclic and acyclic allyl aminosulfoxonium ylides have been generated from aminosulfoxonium-substituted β,γ-unsaturated α-amino acids (method A) and 1-alkenyl aminosulfoxonium salts (method B) upon treatment with DBU. Their application to the asymmetric aziridination of N-tert-butyl-sulfonyl imino ester, generated either in situ (method A) or externally added (method B), gave the corresponding alkenyl aziridine carboxylates with medium to high diastereoselectivity and enantioselectivity. A highly stereoselective Pd(0)-catalyzed isomerization of an E,trans-configured alkenyl aziridine methanol derivative to its E-cis-isomer is described, which proceeded with retention of the double bond configuration.