A highly diastereoselective synthesis of (E)-B-2-(1-cyclopropyl-1-alkenyl)-1,3,2-dioxaborinanes. Isolation and oxidation to alkyl cyclopropyl ketones

A convenient, novel synthesis of alkyl cyclopropyl ketones based on Z-1-bromo-1-alkenylboronate esters is developed. α-Bromo-(Z)-1-alkenylboronate esters readily available from literature procedures smoothly undergo a reaction with cyclopropylmagnesium bromide in tetrahydrofuran to provide the corresponding ‘ate’ complexes. These ‘ate’ complexes undergo intramolecular nucleophilic substitution reactions to provide the corresponding (E)-1-alkenylboronate esters containing cylcopropyl moiety for the first time in good isolated yields (68-82%). The carbon skeleton present in these intermediates is confirmed by oxidation with hydrogen peroxide and sodium acetate to afford the corresponding alkyl cyclopropyl ketones in good yields (72-85%).     

A regio- and stereoselective synthesis of 1,2-disubstituted vinylsilanes

The alkylcopper reagents prepared from RMgBr and CuBr react with trimethylsilylacetylene to give regio- and stereo-selectivity 1-trimethylsilyl-1(Z)-alkenylcopper adducts. Hydrolysis affords 1-trimethylsilyl-1(E)-alkenes exclusively. Alkylation, acylation, halogenation, and stannylation proceed stereoselectively to afford synthetically useful intermediates. Homopropargylation of alkyl 1-trimethylsilyl-1(Z)-alkenylcuprates provided better yield than that of the original vinylcopper reagents.     

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).     

A facile stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones

Palladium-catalyzed hydrostannylation of acetylenic sulfones 1 in benzene at room temperature gives highly regio- and stereoselectively (E)-α-stannylvinyl sulfones 2 in high yields. (E)-α-Stannylvinyl sulfones 2 are new difunctional group reagents which undergo Stille coupling reactions with acyl chlorides 3 to afford stereoselectively (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 in good yields. A one-pot stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 has also been achieved by tandem hydrostannylation-Stille coupling reaction of acetylenic sulfones 1 under mild conditions.     

Stereoselective synthesis of vinylsilanes from alkynylsilanes by reductive alkylation via hydroboration,transmetallation and carbodemetallation

Hydroboration of 1-trimethylsilyl-1-alkynes with dicyclohexylborane gives 1-trimethylsilylvinylboranes regio- and stereoselectively whose successive treatment with methyllithium, cuprous iodide and alkyl halides affords (Z)-1,2-dialkylvinylsilanes in high yields. Functionalized 1-trimethylsilyl-1-alkynes give analogous results. Successive treatment of the intermediary 1-trimethylsilylvinylboranes with methyllithium and methyl iodide gives 2-trimethylsilyl-2(Z)-alkenes. Allyl halides give 4-trimethylsilyl-1,4(Z)-alkadienes analogously.     

Facile hydroboration of (Z)-1-trimethylsilyl-1-alkenes with dichloroborane-dioxane complex: An easy access to gem-dimetalloalkanes containing boron and silicon

(Z)-1-trimethylsilyl-1-alkenes easily prepared by the hydroboration of the corresponding 1-trimethylsilyl-1-alkynes followed by protonolysis with acetic acid, readily react with dichloroborane-dioxane complex in dichloromethane for 6 h. The resulting solution is then treated with 1,3-propane diol in dichloromethane at 0 °C for half an hour to provide the corresponding gem-dimetalloalkanes containing boron and silicon. These α-trimethylsilylalkylboronate esters are purified by vacuum distillation in high yields (72-84%) and the structures of these novel intermediates are further confirmed by selective oxidation with alkaline hydrogen peroxide to provide the corresponding alcohols containing α-trimethylsilyl group in 78-88% isolated yields.     

A simple synthesis of B-2-(1-trimethylsilyl-1-alkyl)-1,3,2-dioxaborinanes. Isolation and selective oxidation to 1-trimethylsilyl-1-alkanols

(Z)-1-Trimethylsilyl-1-alkenes easily prepared by the hydroboration of the corresponding 1-trimethylsilyl-1-alkynes followed by protonolysis with acetic acid, readily react with dibromoborane-methyl sulfide complex in dichloromethane for 6 h. The resulting solution is then treated with 1,3-propane diol in a 1:1 mixture of dichloromethane and n-pentane at 0°C for half an hour to provide the corresponding gem-dimetalloalkanes containing boron and silicon. These alpha-trimethylsilylalkylboronate esters are purified by vacuum distillation in high yields (72-84%) and the structures of these novel intermediates are further confirmed by selective oxidation with alkaline hydrogen peroxide to provide the corresponding alcohols containing trimethylsilyl group.     

A facile synthetic method of α-quaternary-β,γ-unsaturated aldehydes via the stereoselective 1,4-elimination and α-regioselective Ferrier reaction

The 1,4-elimination reaction of 2-substituted-(2Z)-4-methoxy-O-alkenyl acetals with n-butyllithium is shown to afford the 2-substituted-(1Z,3E)-O-1,3-dienyl acetals in high stereoselectivities. The Ferrier reaction of the O-1,3-dienyl acetals thus obtained provides the corresponding α-quaternary-β,γ-unsaturated aldehydes in excellent yields with high α-regioselectivities.     

Stereoselective synthesis of 1,3-dienylstannanes by palladium catalyzed cross-coupling reactions

(Z)-α-Bromovinylstannanes are new difunctional group reagents, which undergo palladium catalyzed cross-coupling reactions with (E)-alkenylzirconium complexes to give stereoselectively 1,3-dienylstannanes in good yields.     

Practical and robust method for stereoselective preparations of ketene silyl (thio)acetal derivatives and NaOH-catalyzed crossed-Claisen condensation between ketene silyl acetals and methyl esters

We developed an efficient, practical, and robust method for stereoselective preparations of (Z)-ketene trimethylsilyl (TMS) thioacetals from thioesters and alkyl (1Z)- or (1Z,3E)-1,3-bis(TMS)dienol ethers from alkyl β-ketoesters. The former preparation was performed by convenient procedure (LDA-TMSCl, 0-5 °C, 2.5 h), while the latter preparation involved convenient method A (2NaHMDS-2TMSCl) and cost-effective method B (NaH, NaHMDS-2TMSCl). The first catalytic NaOH-catalyzed crossed-Claisen condensation between ketene silyl acetals and methyl esters proceeded successfully to give a variety of α-monomethyl β-ketoesters and inaccessible α,α-disubstituted β-ketoesters. For further extension, a couple of Claisen-aldol tandem reactions of the obtained β-ketoester analogues utilizing TiCl₄ and TiCl₄-Bu₃N reagents smoothly proceeded with good to excellent stereoselectivity.     

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.     

Hydro-amination/-amidation of 1,3-diynes with indoles/azoles/amides under modified Ullmann conditions: stereo- and regio-selective synthesis of N-alkenynes via N-H bond activation

An efficient strategy for the stereo- and regio-selective synthesis of N-alkenynes has been described. The salient feature of the reaction involves hydro-amination/amidation of 1,3-diynes with indoles/azoles/amides via transition-metal catalyzed activation of N-H bond. The resulting N-alkenynes derived from N-heterocycles and cyclic amides were obtained as a mixture of Z/E isomers with Z-stereoselectivity ranging from 60% to 95%. In contrast, acyclic amides afforded N-alkenynes with exclusive E-stereoselectivity, albeit in reduced yield ranging from ∼10% to 41%.     

Stereoselective preparation of trisubstituted (Z)-alkenes; synthesis of the C17-C27 fragment of (−)-laulimalide

A Ni-catalyzed cross-coupling reaction of (Z)-5-(tert-butyldiphenylsilyl)oxy-3-bromo-1-trimethylsilyl-3-penten-1-yne (1) with alkyl Grignard reagent gives (Z)-3-alkyl-5-(tert-butyldiphenylsilyl)oxy-1-trimethylsilyl-3-penten-1-ynes (2) stereospecifically in good yields. The (Z)-enyne 2a is transformed in four steps to (Z)-3-methyl-5-silyloxy-3-pentenal (3), which is coupled with ketophosphonate 4 to give enone 13. The η-hydroxyallyl methanesulfonate derived from 13 is cyclized to 3,6-dihydro[2H]pyran by an intramolecular SN2′ reaction stereoselectively, furnishing a C17-C27 carbon unit of (−)-laulimalide.     

Novel stereoselective synthesis of 1,3-dienylsilanes via hydromagnesiation reaction of alkynylsilanes

Hydromagnesiation of alkynylsilanes gives (Z)-α-silylvinyl Grignard reagents, which undergo palladium-catalyzed cross-coupling reactions with alkenyl halides to afford stereoselectively 1,3-dienylsilanes in good yields.     

Hexafluorothioacetone based synthesis of fluorinated heterocycles

Cycloadducts of hexafluorothioacetone (HFTA) were prepared in high yield by a CsF catalyzed reaction between readily available 2,2,4,4-tetrakis-(trifluoromethyl)-1,3-dithietane (as a source of HFTA) with conjugated electron-rich hydrocarbon dienes, such as cyclopentadiene, 2,3-dimethylbuta-1,3-diene, cyclohexa-1,3-diene or (1Z,3Z)-cyclohepta-1,3-diene. Cyclohexa-1,4- and (1Z,5Z)-cycloocta-1,5-dienes, also undergo the reaction with in situ generated HFTA, but form the products of insertion of HFTA into the C-H bond of the diene as a result of ene-reaction. The highly selective reaction of HFTA with (1Z,3Z,5Z)-cyclohepta-1,3,5-triene and (1Z,3Z,5Z,7Z)-cycloocta-1,3,5,7-tetraene leads to the formation of cycloadducts derived from exclusive addition of thioacetone to the corresponding bicyclic isomers—bicyclo[4.1.0]hepta-2,4-diene or bicyclo[4.2.0]octa-2,4,7-triene, respectively. The corresponding cycloadducts of HFTA with 2,3-dimethylbutadiene-1,3-cyclohexa-1,3-cyclohexa-1,4-dienes and (1Z,3Z,5Z)-cyclohepta-1,3,5-triene were also prepared by direct reaction of sulfur/hexafluoropropene/KF and the corresponding hydrocarbon substrate at 35-45 °C in DMF.     

Gallium(III) halide promoted synthesis of 1,3,5-triaryl- 1,5-dihalo-1,4-pentadienes

Aryl substituted alkynes undergo smooth coupling with aldehydes in the presence of gallium(III) halides under extremely mild conditions to afford the corresponding 1,3,5-triaryl-1,5-dihalo-1,4-pentadienes in good yields with E,Z-selectivity. Similarly 1,3,5-triaryl-1,5-dichloro-1,4-pentadienes are also obtained with niobium(V) chloride.     

Novel stereoselective synthesis of 1-substituted 1,3-dien-2-yl sulfides via Stille coupling reactions of (E)-α-stannylvinyl sulfides with alkenyl iodides

(E)-α-stannylvinyl sulfides are new difunctional reagents which undergo Stille coupling reactions with alkenyl iodides to afford stereoselectively 1-substituted 1,3-dien-2-yl sulfides in good yields.     

Stereoselective synthesis of 4-fluoro-1,3-alkadienylboronates and their application in the stereoselective synthesis of fluoropolyenes

(1E,3E)- and (1E,3Z)-4-fluoro-1,3-alkadienylboronates were stereoselectively prepared by the Heck-reaction of a vinylboronate with (E)- or (Z)-2-fluoro-1-alkenyliodonium salts, and applied to the Suzuki-Miyaura coupling reaction for the synthesis of fluoropolyenes.     

Stereospecific synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes from 2-chloro-1-(n-N,N-dimethylaminophenyl)ethenes: fluorescence properties

The conjugated 1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes (n=o-, m-, p-) were efficiently synthesised by homocoupling of the appropriate 2-chloro-1-(n-N,N-dimethylaminophenyl)ethene (n=o-, m-, p-) with stoichiometric amounts of zerovalent nickel complexes. The 1,3-butadienes were obtained as a mixture of stereoisomers, with independence of the starting E or Z chlorovinyl isomer. Moreover, the stereospecific (Z,Z) stereoisomer was obtained by partial hydrogenation of the corresponding 1,3-butadiyne, while the stereospecific (E,E) stereoisomer was obtained by exposure to the sunlight radiation of the (Z,Z) or the (Z,E) compound in ethanol.     

A novel enzymatic tandem process: utilization of biocatalytic promiscuity for high stereoselective synthesis of 5-hydroxyimino-4,5-dihydrofurans

A lipase-catalyzed protocol for the synthesis of 5-hydroxyimino-4,5-dihydrofurans via tandem coupling between β-nitrostyrenes and 1,3-dicarbonyl compounds was developed in a ‘one-pot’ strategy. A series of β-nitrostyrenes were employed to expand the scope of this new biocatalytic promiscuity with high stereoselectivity (Z/E up to 99:1) and moderate to good yields. The reaction activity of 1,3-cyclohexanedione was found to be better than linear 2,4-pentanedione, while ethyl acetoacetate and diethylmalonate were not suitable for this reaction under the same conditions. Single-crystal X-ray diffraction analysis indicated that the reaction was stereoselective and Z-stereomer was found to be the major product. A reaction mechanism was supposed to elucidate the biocatalytic process.