A diastereoselective synthesis 1-trimethylsilyl-(E)-1,3-alkenynes and a simple synthesis of alkyl trimethylsilylethynyl ketones via organoboranes

A convenient, novel diastereoselective synthesis of 1-trimethylsilyl-(E)-1,3-alkenynes and a convenient synthesis of alkyl trimethylsilylethynyl ketones based on Z-1-bromo-1-alkenylboronate esters are developed. α-Bromo-(Z)-1-alkenylboronate esters readily available using literature procedures smoothly undergo a reaction with trimethylsilylethynyllithium (derived from the deprotonation of trimethylsilylethyne with n-butyllithium) in tetrahydrofuran to provide the corresponding ‘ate’ complexes. These ‘ate’ complexes undergo intramolecular nucleophilic substitution reactions to afford the corresponding (E)-1-alkenylboronate esters containing trimethylsilylethynyl moiety which upon protonolysis with acetic acid provide the corresponding 1-trimethylsilyl-(E)-1,3-alkenynes in good yields (70-82%) and in high stereochemical purities (>98%). These intermediates upon oxidation with hydrogen peroxide and sodium acetate afford the corresponding alkyl trimethylsilylethynyl ketones in good yields (66-78%).     

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

(Z)-1-Trimethylgermyl-1-alkenes easily prepared by the hydroboration of the corresponding 1-trimethylgermyl-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 germanium. These α-trimethylgermylalkylboronate esters are purified by vacuum distillation in high yields (72-82%) and the structures of these novel intermediates are further confirmed by selective oxidation with alkaline hydrogen peroxide to provide the corresponding alcohols containing α-trimethylgermyl group in very good yields (74-84%).     

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.     

Synthesis of 1,4-disubstituted (E,Z)-1,3-dienes from lithium dicyclohexyl(trans-1-alkenyl)(1-alkynyl)borates

Treatment of lithium dicyclohexyl(trans-1-alkenyl)(1-alkynyl)borates with either boron trifluoride etherate or tri-n-butyltin chloride results in the preferential migration of the alkenyl group from boron to the adjacent alkynyl carbon atom. Protonolysis of the resultant organoboron intermediates with acetic acid affords the corresponding 1,4-disubstituted (E,Z)-1,3-dienes in good yields, provided that the (Z)-alkenyl moiety of the diene does not contain a tertiary alkyl group. Demonstration that this novel procedure is applicable for the preparation of (E,Z)-1,3-dienes containing functional groups has been shown by the synthesis in 66% yield of methyl (10E, 12Z)-hexadecadienoate, a precursor via lithium aluminium hydride reduction of the sex pheromone of the female silk moth, Bombyx mori.     

Stereoselective acid-catalyzed homoallylic rearrangement of cyclopropylsilylmethanols: an efficient route to Z-homoallyl derivatives

Treatment of cyclopropylsilylmethanols derived from cyclopropyl silyl ketones with acid catalyst gives the corresponding silyl-substituted homoallyl derivatives in high yields with good stereoselectivity, independent of the substituents on the cyclopropyl ring. Cyclopropylsilylmethanols having a n-, s-butyl or phenyl group on the carbinyl carbon react to afford the E-homoallyl derivatives selectively. On the other hand, the reaction of cyclopropylsilylmethanols having a tert-butyl group gives Z-isomers exclusively. The following protiodesilylation of the resulting homoallyl derivatives proceeds with retention of configuration.     

A novel synthesis of (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxaborinanes and their conversion into carboxylic acids

A novel procedure for preparing heterocyclic compounds such as (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxaborinanes based on 1-trimethylgermyl-1-alkynes is described. 1-Trimethylgermyl-1-alkynes easily obtainable by deprotonation of 1-alkynes with n-butyllithium followed by treatment with trimethylgermanium chloride, are readily hydroborated in n-pentane in the presence of boron trichloride in hexane at 0 °C for 3 h. The resulting supernatant clear solution was separated from boron trichloride-methyl sulfide complex. It was then reacted with 1,3-propane diol at 0 °C for 0.5 h. The resulting representative (Z)-2-(1-trimethylgermyl-1-alkenyl)-1,3,2-dioxaborinanes were isolated in good yields (65-86%) and in high stereochemical purities (>98%) as evidenced by NMR spectral data. The carbon skeletons present in these intermediates were confirmed by alkaline hydrogen peroxide oxidation to the corresponding carboxylic acids.     

Synthesis of chiral ortho-(p-tolylsulfinyl) benzyl ketones

(S)-ortho-(p-Tolylsulfinyl)benzyl alkyl (and aryl) ketones 1a-e were prepared in good yields by reaction of esters or nitriles with the lithium benzyl carbanion derived from 2-(p-tolylsulfinyl) methylbenzene. α-Methylbenzyl ketones 2 were prepared as ca. 1:1 diastereoisomeric mixtures by methylation of the unsubstituted ketones 1 with NaH/MeI. The use of the ethylbenzene derivative as the starting material afforded complex mixtures. The obtention of pure (S,(S)S)-2 diastereoisomers could be attained in good yields by oxidation with PCC of the alcohols (epimeric mixtures at the hydroxylic carbon) obtained from reactions of aldehydes with the lithium carbanion derived from 2-(p-tolylsulfinyl)ethylbenzene.     

Lewis acid-catalyzed asymmetric radical additions of trialkylboranes to (1R,2S,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexyl-2H-azirine-3-carboxylate

The asymmetric addition of alkyl radicals to (1R,2S,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexyl-2H-azirine-3-carboxylate (1) yielding the corresponding 2-alkylaziridine-2-carboxylates has been investigated. High diastereoselectivities and good yields were obtained in the addition of primary alkyl radicals to azirine 1, while secondary radicals gave a lower dr. The influence of Lewis acids was also investigated; 10 mol% of CuCl were found to increase the dr.     

Asymmetric epoxidation of (Z)-enol esters catalyzed by titanium(salalen) complex with aqueous hydrogen peroxide

Titanium(salalen) complex 1 was an effective catalyst for asymmetric epoxidation of enol esters. Although (E)-enol esters were reluctant to proceed, (Z)-enol esters underwent asymmetric epoxidation to give the epoxides in high yields with high enantioselectivity ranging from 86 to >99% ee in the presence of aqueous hydrogen peroxide as the stoichiometric oxidant. Complete enantioselectivity was observed in the reaction of (Z)-3,3-dimethylbut-1-en-1-yl 4-methoxybenzoate. The obtained epoxide was readily transformed into the corresponding 1,2-diol by reduction with lithium borohydride without erosion of the high enantiomeric excess.     

Convenient Syntheses of Functionalized Dialkyl Ketones and Alkanoylsilanes: 1-(Benzotriazol-1-yl)-1-phenoxyalkanes as Alkanoyl Anion Equivalents

(Benzotriazol-1-yl)-1-phenoxyalkanes 10, prepared by two-step transformations of the corresponding aldehydes, are readily deprotonated at the methine group by BuLi. Subsequent reactions with alkyl halides, aldehydes, ketones, and imines yield the corresponding substituted derivatives that undergo hydrolysis under acidic conditions to afford the expected functionalized ketones 13, 15,17, 19, 21, 24, and25. Two successive lithiations of (benzotriazolyl)phenoxymethane, each followed by reaction with a trialkylsilyl chloride, alkyl halide, aldehyde, or ketone, generate similar intermediates 27, 29, 31,33, and 36. Subsequent hydrolyses of 27, 29, 31, 33, and 36 yield the functionalized ketones 28, 30, and 32 and the alkanoylsilanes 34 and 37 in good yields.     

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.     

Acylation of α-(N-carbamoyl)alkylcuprates and alkyl- or aryl(halo)cuprates

α-(N-Carbamoyl)alkylcuprates [R₂CuLi·LiX or RCuXLi (X=CN, Cl)] when prepared from THF soluble CuX·2LiCl (X=Cl, CN) undergo a reliable and generally high yield reaction with aroyl, alkanoyl, and alkenoyl chlorides to provide a rapid and efficient synthesis of α-carbamoyl ketones. Cuprates prepared from acyclic, cyclic, and a functionalized carbamate can be utilized. Although yields are a function of cuprate reagent and substrate structure, nearly quantitative yields can be obtained with reagents generated from 2RLi+CuCN·2LiCl. The use of reagents generated from CuCl·2LiCl are more efficient in the α-(N-carbamoyl)alkyl ligand, although yields are slightly lower. Acylation of alkyl(chloro)cuprates generated from one equivalent of CuCl·2LiCl and organolithium or Grignard reagents provides an efficient and high yield procedure for ketone synthesis.     

An efficient bakers’ yeast catalyzed synthesis of 3,4-dihydropyrimidin-2-(1H)-ones

Bakers’ yeast (Saccharomyces cerevisiae) efficiently catalyzes the three-component Biginelli reaction of aldehydes, β-keto esters, and urea/thiourea to form 3,4-dihydropyrimidin-2-(1H)-ones in good to excellent yields.     

Access to substituted trifluoromethyl ketones using the versatile synthetic intermediate (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine

The N,N-dimethylhydrazone of 1,1,1-trifluoroacetone, (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine, has been shown to undergo a diverse set of reactions following deprotonation with n-butyl-lithium; including alkylation, addition to ketones and aldehydes, as well as palladium-catalyzed cross-couplings with aryl bromides. Mild hydrolysis of the N,N-dimethylhydrazone products from these transformations affords the corresponding trifluoromethyl ketones in good to excellent yields.     

Synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-pyridyl) (or n-quinolyl)-1,3-butadienes from n-(2′-chloroethenyl)pyridine (or quinoline)

The homocoupling reaction between the conjugated n-(2-chloroethenyl)pyridine; n, 2-, 3- and 4- (or quinoline; n, 2- and 4-) mediated by zero-valent nickel complexes at room temperature affords to the corresponding 1,4-diaryl-1,3-butadiene, always as the 1E,3E stereoisomer. The yield in 1,4-diaryl-1,3-butadiene increases with the nickel catalyst and hence, the active zero-valent nickel catalyst is not regenerated during the homocoupling reaction.The stereospecific synthesis of (1Z,3Z)-1,4-di(4′-pyridyl)-1,3-butadiene stereoisomer was efficiently carried out by partial hydrogenation of the appropriate 1,4-di(4′-pyridyl)-1,3-butadiyne.     

First enantioselective catalyst based on a chiral terpyridine: synthesis of new C2-symmetric 2,2′:6′,2′′-terpyridine ligands and copper-catalyzed enantioselective cyclopropanation of alkenes

New C₂-symmetric chiral 2,2′:6′,2′′-terpyridines were prepared from readily available homochiral materials. Copper complexes of these ligands were prepared in situ and their catalytic activities in cyclopropanations of alkenes with alkyl diazoacetate to give cyclopropyl esters were studied. In all cases, the cyclopropyl ester yields were excellent and enantioselectivities up to 94% ee were observed. Competition experiments revealed that electron-donating substituents on styrene accelerate the reaction. Hammett plot exhibited a good linearity with negative ρ⁺ value (−0.79).     

Highly Z/E stereoselective approach to β-iodo aza Morita-Baylis-Hillman adducts

A multicomponent reaction between sulfonyl-protected imines, magnesium iodide, and acetylenic esters or ketones is described. The resulting β-iodo aza Morita-Baylis-Hillman adducts were obtained in good yields and excellent Z/E stereoselectivities. The reaction showed good tolerance for sulfonyl protecting groups, as well as for acetylenic ketones and esters. This work presents the first synthetic approach to β-iodo aza Morita-Baylis-Hillman adducts.     

4-alkyl(aryl)-1-germacyclohexa-2,5-diene

enThe 1(Z),4(Z)-1,5-dilithium-3R-3-methoxypenta-1,4-dienes react with diaryldichlorogermanes and dialkyldichlorogermanes to give the 1,1-diaryl- and 1,1-dialkyl-4R-4-methoxy-1-germacyclohexa-2,5-dienes, respectively.With phenyltrichlorogermane, methyl- and ethyl-trichlorogermanes the E/Z-isomeric 1-phenyl(methyl,ethyl)-1-chloro-4R-4-methoxy-1-germacyclohexa-1,3-dienes are obtained, reduction of these with LiAlH₄ makes the corresponding 1-aryl-(alkyl)-1H-4R-4-methoxy-1-germacyclohexa-2,5-dienes available.Reduction of 1-ethyl-1-chloro-4-phenyl-4-methoxy-1-germacyclohexa-2,5-diene with LiAlH₄ yields by additional ether cleavage 1-ethyl-1H-4-phenyl-1-germacyclohexa-2,4-diene.The ¹H NMR (60 MHz, 90 MHz), ¹³C NMR, IR and mass spectra are discussed, several ¹H NMR spectra are calculated according to the LAOCOONLAME program.