Stereoselective C(2)-vinylation of 1-substituted imidazoles with 3-phenyl-2-propynenitrile

First examples of direct vinylation of 1-substituted imidazoles at the 2-position of the imidazole nucleus are described. 1-Substituted imidazoles 1a-e are C(2)-vinylated with 3-phenyl-2-propynenitrile (2) at room temperature without catalyst and solvent to afford 3-(1-organyl-1H-imidazol-2-yl)-3-phenyl-2-propenenitriles 3a-e, mainly (c.a. 95%) as (Z)-isomers, in 56-88% yield. The reaction is likely to involve the zwitterionic intermediates, which prototropically isomerizes to imidazole carbene and eventually undergoes the selective 3,2-shift of the functionalized vinyl substituent.     

Biaryl formation from 5-(2-bromobenzyl)-substituted piperidin-2-ones via palladacycles

The reaction of piperdin-2-ones with a 2-bromobenzyl substituent in the 5-position in the presence of a palladium catalyst leads to biaryl compounds. Their formation can be explained via initial C-H insertion of the aryl palladium species into the allylic C-H bond of the piperidinone. This eventually leads to a metallacycle containing Pd(II) that inserts another aryl bromide, promoting the formation of the biaryl bond.     

Stereoselective rhodium-catalyzed amination of alkenes

The first stereoselective rhodium-catalyzed intermolecular aziridination and C-H amination of alkenes to produce chiral carbamate-protected aziridines and allylic amines is described. Good yields and diastereoselectivities were achieved using a readily available chiral N-tosyloxycarbamate and stoichiometric amount of the alkene substrate. Furthermore the protecting group is easy to cleave under mild reaction conditions.     

Stereoselective |2+2| photocycloaddition of chiral 2(5H)-furanones to alkenes

The steric and stereoelectronic dependence of the diastereoselectivity in the photochemical |2+2| cycloaddition of chiral 2(5H)-furanones to alkenes is investigated to prepare eventually cyclobutanic natural products. It is shown that the alkenes approach to different chiral 5-substituted 2(5H)-furanones mainly by the less hindered side.     

Novel uncatalysed Michael reactions of lithium trialkylalkynylborates with alkylidenemalonates and alkylideneacetoacetates.

Alkynylborates and alkylidenemalonates and alkylideneacetoacetates undergo unusual Michael reactions which involve migration of alkyl groups from boron to carbon, to yield products of synthetic value.     

Stereoselective synthesis of fluorobis(phenylsulfonyl)methyl-substituted alkenes using free radical fluoroalkylation

(PhSO₂)₂CFI was prepared in quantitative yield by the iodination of fluorobis(phenylsulfonyl)methane and utilized in facile radical bis(phenylsulfonyl)monofluoromethylation of various terminal alkenes. The synthetic methodology was further extended for the preparation of monofluoromethyl-substituted alkenes.     

Stereoselective cyclopropanation of chiral 5-substituted dihydro-2H-piperazines

The Simmon–Smith cyclopropanation of enantiomerically enriched dehydropiperazines is reported. The reaction is highly stereoselective and allowed us to prepare new, enantiomerically enriched 3-substituted 2,5-diazabicyclo[4.1.0]heptane cores with high diastereomeric purity and a relative anti-configuration, which was assigned by NMR analysis.     

Palladium(II) catalyzed allylic rearrangement: Stereoselective synthesis of 2-substituted (e)-β acetoxy (or benzoyloxy)ethylidenecyclohexanes

Diastereomeric mixtures of 2-substituted 1-vinyclyclohexyl acetates (or benzoates) are rearranged stereoselectively to 2-substituted (E)-β-acetoxy(or benzoyloxy)ethylidenecyclohexanes by the catalysis of bis(acetonitrile)palladium(II) chloride. A mechanism related to the stereoselectivity and reactivity is discussed in terms of the conformational requirements in a transition state.     

Stereoselective synthesis of 3-oxygenated-cis-dialkyl-2,5-substituted tetrahydrofurans from cyclohexadienediols

The 3-oxygenated-cis-dialkyl-2,5-substituted tetrahydrofuran system, present in several natural products, was prepared with good selectivity by acidic cyclization of 5-alkene-1,2,4-triol derivatives. The starting alkenol was obtained in few steps from a chiral cis-diol resulting from microbial oxidation of bromobenzene. The study of the cyclization allowed the rationalization of all experimental results by assuming a complete ionization at the allylic position and a model close to the one proposed by Labelle for homoallylic induction in five-membered ring closures.     

Stereoselective electrocatalytic transformation of malonate and alkylidenecyanoacetates into (E)-3-substituted 2-cyanocyclopropane-1,1,2-tricarboxylates

Electrolysis of malonate and alkylidenecyanoacetates in alcohols in an undivided cell in the presence of NaBr results in stereoselective formation of (E)-3-substituted 2-cyanocyclopropane-1,1,2-tricarboxylates in 75-90% yields.     

Stereoselective synthesis of CF(2)-substituted phosphothreonine mimetics and their incorporation into peptides using newly developed deprotection procedures

Stereoselective syntheses of all four stereoisomers of CF(2)-substituted nonhydrolyzable phosphothreonine derivatives (33, 39, and their enantiomers) and their incorporation into peptides are described herein. Key to the synthesis of these amino acids was construction of secondary phosphate-mimicking difluoromethylphosphonate units along with generation of two stereocenters. The former was achieved using a Cu(I)-mediated cross-coupling reaction of BrZnCF(2)P(O)(OEt)(2) (8) and beta-iodo-alpha,beta-unsaturated ester 12, with stereochemistry of both alpha- and beta-stereocenters being established using bornane-10,2-sultam as a chiral auxiliary. Diastereoselective hydrogenation of a chiral alpha,beta-unsaturated acylsultam (for the beta-center) (e.g., 16a) and subsequent stereoselective bromination (for the alpha-center of the threo derivative) or amination (for the alpha-center of erythro (allo) derivative) were utilized. Transesterification of the bromide to the benzyl ester followed by azide displacement of the halogen, then reduction of the resulting azide, followed by Boc-protection and finally removal of the benzyl group, afforded protected both L- and D-phosphothreonine mimetics (39 and its enantiomer). On the other hand, protected both L- and D-allo-phosphothreonine mimetics (33 and its enantiomer) were synthesized via transesterification of the above-mentioned amination product, followed by hydrogenolytic removal of the benzyl group. Key to utilization of these amino acid analogues in peptide synthesis was removal of ethyl protection from the difluoromethylphosphonate moiety. A two-step deprotection methodology, consisting of a combination of a first-step reagent [0.3 M BSTFA-TBAI in CH(2)Cl(2), BF(3).Et(2)O] followed by a second-step reagent [1 M TMSOTf-thioanisole in TFA, m-cresol, EDT] was developed for use in solid-phase protocols. A 12-residue Cdc (cell division cycle) 2-peptide 41, possessing two nonhydrolyzable phosphoamino acid mimetics (F(2)Pmab 6 and F(2)Pmp 4), was subjected to this deprotection procedure and was obtained in 25% yield based on the protected resin. The present synthetic method affords nonhydrolyzable phosphoamino acid mimetics-containing peptides in high yield without accompanying side reactions.     

Stereoselective halogenations of alkenes and alkynes in ionic liquids

[reaction: see text]. Room-temperature ionic liquids, 1-butyl-3-methylimidazolium hexafluorophosphate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium bromide, and 1-butyl-3-methylimidazolium chloride, are used as "green" recyclable alternative to chlorinated solvents for the stereoselective halogenation of alkenes and alkynes.     

Regioselective formation of alkylidenecyclopropanes from 2-substituted cyclobutylidenes generated from geminal dibromocyclobutanes and methyllithium

Four different 2-substituted geminal dibromocyclobutanes were reacted with methyllithium at -78 degrees C. In contrast to previous studies using diazocyclobutanes as carbene precursors at temperatures above 200 degrees C via reaction of the corresponding tosylhydrazone sodium salts, the organometallic route in each case produces only an alkylidenecyclopropane that could be isolated in good yields. B3LYP calculations were employed to rationalize the observed regioselective ring contraction of the generated cyclobutyliden(oid)s. [reaction: see text]     

Stereoselective intermolecular allylic C-H trifluoroacetoxylation of functionalized alkenes

Pd-catalyzed allylic C-H trifluoroacetoxylation of substituted alkenes was performed using PhI(OCOCF(3))(2) as the oxidant and acyloxy source. Trifluoroacetoxylation of monosubstituted cyclopentenes and cyclohexenes proceeds with excellent regio- and diastereoselectivity. Studies with one of the possible (η(3)-allyl)Pd(II) intermediates suggest that the reaction proceeds via stereoselective formation of Pd(IV) intermediates and subsequent stereo- and regioselective reductive elimination of the product.