Regioselective free radical phenylsulfenation of a non-activated δ-carbon atom by the photolysis of alkyl benzenesulfenate

A regioselective free radical introduction of a phenylthio group onto a non-activated δ-carbon atom was achieved by photolysis of alkyl benzenesulfenates in the presence of hexabutylditin, and δ-phenylthio alcohols were obtained in 35-91% yields. δ-Phenylsulfenylation of a non-activated carbon atom induced only by irradiation of alkyl benzenesulfenates (without initiation by hexabutylditin) also occurs, however, slower reaction rates were observed and lower yields of δ-phenylthio alcohols were obtained.     

Synthesis of novel chiral lipophilic pyridyl-containing β-amino alcohol ligands and enantioselective hydrolysis of α-amino acid esters by chiral metallomicelles

Seven novel chiral lipophilic pyridyl-containing β-amino alcohol ligands have been synthesized by coupling of 6-alkoxymethyl-2-chloromethylpyridine 3 with the corresponding chiral β-amino alcohols or l-cysteine. Their metal ion complexes have been investigated as catalysts for the enantioselective hydrolysis of N-protected α-amino acid esters in aqueous comicellar solution. The results indicate that the hydrophobic interactions between substrate and metallocatalyst, the rigidity of the ligand, the hydroxyl group of the ligand acting as a nucleophile for the transacylation process, and the micellar microenvironment are important factors for the activity and enantioselectivity. Large rate accelerations (up to three orders of magnitude) and moderate enantioselectivities (up to 7.81 (k_R/k_S)) employing 4a–Cu²⁺ have been observed.     

Synthese totale de la (±) negamycine

A total synthesis of (±) negamycine 1 has been achieved in 14 steps from the acrolein dimer 6, which possesses the same carbon skeleton as the key intermediate lactone 4. Treatment of 2-acetoxymethyl 3,4-dihydro[2H]pyran 8, obtained from 6, with lead tetracetate gave the allylic hemiketal 15, which was converted into the corresponding anomeric methyl ethers 23. Hydroxylation of the double bond of 23 with mercuric acetate, occurred selectively at the γ-position and the resulting isomeric alcohols 24 were isolated as their dimesylates 25a and 25b. Condensation of sodium azide with the (trans-derivative 25a resulted in the formation of the cis-diazide 26a by inversion of configuration at C₃. Hydrogenation of 26a followed by acetylation of the intermediate diamine gave the cis-diamide 28 having the required stereochemistry. Oxidation of the corresponding hemiketal 29 by means of silver silicate yielded the diacetamido-lactone 4, which was then hydrolysed into (±) δ-hydroxy β-lysine 2 by refluxing aqueous HCl. Under the conditions required to protect the amino-groups as benzylcarbamates, the lactone 30 was produced. However, 30 gave directly the hydrazine 36 by condensation with benzyl N-methyl-hydrazinoacetate in refluxing acetonitrile m the presence of SiO₂. Finally (±) negamycine was obtained by hydrogenolysis of the protecting groups of 36. The antibacterial activities of the racemic antibiotic have been compared, in vitro and in vivo, with those of the natural product and with gentamicine C.     

Synthesis of new chiral keto alcohols by baker’s yeast

Fourteen chiral α- and β-keto alcohols 2a–2r were synthesized by the asymmetric reduction of their corresponding diketones 1a–1r via baker’s yeast. In addition, ten corresponding racemic α-keto alcohols were synthesized by the benzoin condensation of their corresponding aldehydes, which were used for the determination of the ee values through their chiral resolution on chiral HPLC. Amongst the 15 diketones, 1j and chiral α-keto alcohols 2i, 2j and chiral β-keto alcohol 2r are novel compounds. Six keto alcohols 2b, 2c, 2d, 2f, 2h and 2p were synthesized by baker’s yeast for the first time. There are some studies in the literature where baker’s yeast was applied to the diketones 1a, 1g, 1e, 1k and 1n under various conditions different to those reported herein. The yields and the ee values of these studies were not as high as ours. All of the keto alcohols synthesized were characterized by IR, NMR (¹H and ¹³C), and MS. The relationship between the structure of the diketone and the yield, diastereoselectivity and enantiomeric excess is also discussed.     

Electrochemically Driven C−H Hydrogen Abstraction Processes with the Tetrachloro‐Phthalimido‐N‐Oxyl (Cl4PINO) Catalyst

The radical redox mediator tetrachloro‐phthalimido‐N‐oxyl (Cl₄PINO) is generated at a glassy carbon electrode and investigated for the model oxidation of primary and secondary alcohols with particular attention to reaction rates and mechanism. The two‐electron oxidation reactions of a range of primary, secondary, and cyclic alcohols are dissected into an initial step based on C−H hydrogen abstraction (rate constant k₁, confirmed by kinetic isotope effect) and a fast radical‐radical coupling of the resulting alcohol radical with Cl₄PINO to give a ketal that only slowly releases the aldehyde/ketone and redox mediator precursor back into solution (rate constant k₂). In situ electrochemical EPR reveals Cl₄PINO sensitivity towards moisture. DFT methods are applied to confirm and predict C−H hydrogen abstraction reactivity.     

Photodynamic cross-linking of proteins: IV. Nature of the His–His bond(s) formed in the rose bengal-photosensitized cross-linking of N-benzoyl-L-histidine

The photodynamic (photosensitized) cross-linking of N-benzoyl-L-histidine (Bz-His) as a model system was examined as part of a continuing study of the role of His–His intermolecular cross-links in the photosensitized cross-linking of proteins. The illumination of Bz-His in the presence of rose bengal (RB) bound to water insoluble plastic beads in 0.1 M sodium phosphate buffer of pH 7.4 resulted in the covalent cross-linking of the His derivative. The main dimeric cross-linked product (1) was isolated using a preparative silica gel 60 column and purified by preparative reverse phase HPLC. The chemical structure of the cross-link was determined using MS, 2D NMR spectral methods and other standard techniques. Product 1 was found to be a dimer of two His residues between the δ2-carbon of one residue (photo-oxidized to the carbonyl functionality at the ε1-carbon) and the ε2-nitrogen of the other residue. The formation of His–His cross-links was mediated by singlet oxygen, as would be expected with RB as the sensitizer. A mechanism for the formation of the cross-link was proposed in which the first step was the 1,4-cycloaddition of singlet oxygen to the Bz-His imidazole ring to give an unstable endoperoxide. This then underwent changes followed by nucleophilic addition and the elimination of one molecule of water to give 1.     

Asymmetric synthesis of new chiral long chain alcohols

Sixteen new chiral alcohols with alkyl (C₁₁–C₁₉) and aryl, substituted aryl, hetero aryl and biaryl groups 2a–2t were synthesized by three different asymmetric reduction methods from their corresponding ketones 1a–1t. Chiral NaBH₄ (method A), chiral BH₃ (method B) and chiral AIP (method C) were used as asymmetric reduction catalysts. Chiral NaBH₄ was modified by four different ligands 3a–3d, chiral BH₃ and chiral AIP by four different ligands 4a–4d. Ligand 4c was synthesized for the first time in this work. Chiral NaBH₄ generated chiral alcohols of (R)-configuration and chiral BH₃ and chiral AIP of (S)-configuration with high enantiomeric excesses, were analysed by chiral HPLC. In order to determine the ee values by chiral HPLC, sixteen corresponding racemic alcohols, synthesized by reducing their corresponding ketones via NaBH₄, were used for chiral resolution on a Daicel OD HPLC column. The sixteen starting ketones were synthesized in this study by Friedel–Craft acylation. The new chiral alcohols were characterized by IR, NMR, (¹H and ¹³C), MS, elemental analyses and specific rotation. The reduction methods A, B and C were applied to these ketones for the first time in this study and were compared with each other. The relationship between the structure of the ketone and the yield and the enantiomeric excess was discussed.     

Solvent-modulated chemoselective deprotections of trialkylsilyl esters and chemoselective esterifications

A series of trialkylsilyl esters were deprotected or transesterificated into their corresponding carboxylic acids or methyl esters under a catalytic amount of CBr₄ in alcohol reaction system. This method enables to desilylate secondary sp³-carbon, sp²-carbon, sp-carbon and aryl tethered trialkylsilyl esters to carboxylic acids, whereas primary sp³-carbon tethered trialkylsilyl esters were further converted into their methyl esters under CBr₄/MeOH reaction conditions. The highly chemoselective deprotections can be modulated and achieved by the introduced protecting trialkylsilyl groups and the used alcohols such as MeOH and EtOH under this photochemically-induced reaction conditions.     

The synthesis of barbaralyl systems via bicyclic[3.2.2] irontricarbonyl cations

Reaction of bicyclo[3.2.2] tertiary alcohols 7b,c and 23b with Fe₂(CO)⁹, resulted in the corresponding dienyl Fe(CO)₃ complexes, which upon HBF₄/Ac₂O treatment yielded the bicyclo [3.2.2] dienyl irontricarbonyl cations. Nucleophilic addition of CN^- to those cations, resulted in the formation of δ,μ-bonded complexes, which were degraded with Me₃NO to give substituted tricydic hydrocarbons (barbaralyl systems) in unusual positions. For purpose of comparison, the trifluoroacetolysis of 2-methyl-endo-6,7-benzobicyclo[3.2.2] nonatriene (22) has been studied.     

Efficient Swern oxidation and Corey–Kim oxidation with ion-supported methyl sulfoxides and methyl sulfides

The Swern oxidation of various benzylic and allylic alcohols, primary alcohols, and secondary alcohols with two ion-supported methyl sulfoxides A-1 (C₆) and B-1 (C₁₀), and oxalyl chloride in the presence of triethylamine in dichloromethane, followed by simple diethyl ether extraction of the reaction mixture, gave the corresponding aldehydes and ketones, respectively, in good yields with high purity. Similarly, the Corey–Kim oxidation of various benzylic and allylic alcohols, primary alcohols, and secondary alcohols with two ion-supported methyl sulfides A-2 (C₆) and B-2 (C₁₀), and N-chlorosuccinimide in the presence of triethylamine in dichloromethane, followed by simple diethyl ether extraction of the reaction mixture, furnished the corresponding aldehydes and ketones, respectively, in good yields with high purity. Both reactions did not produce any unpleasant odor at all. In the Swern oxidation, ion-supported methyl sulfides were recovered in high yields and could be re-oxidized to produce ion-supported methyl sulfoxides A-1 (C₆) and B-1 (C₁₀), for reuse in the same oxidation. In the Corey–Kim oxidation, ion-supported methyl sulfides A-2 (C₆) and B-2 (C₁₀) were recovered in high yields and could be also reused for the same oxidation.     

Chemistry of strained polycyclic compounds—VI : Stereospecific base induced homoketonization of cubane,homocubane and 1,3-bishomocubane bridgehead alcohols

The base induced homoketonization of bridgehead cubane alcohol 10, homocubane alcohol 1 and acetate 7, and 1,3-bishomocubane alcohols 13 and 17 has been studied. Under protic conditions, homocubane alcohol 1 and acetate 7 are converted quantitatively into half cage ketones 3 and 8, respectively, by exclusive cleavage of the C₄C₇ bond. Similarly, homoketonization of 1,3-bishomocubane alcohols 13 and 17 leads to half cage ketones 15 and 18, respectively, by exclusive cleavage of the C₂C₅ bond. As shown by deuterium labeling experiments homoketonization of 1, 7, 13 and 17 proceeds with high stereospecificity and with retention of configuration (96%) at the carbon of substitution. The cubane alcohol 10 gave, under similar conditions, complex mixtures of ring-opened products. Under aprotic conditions, base treatment of homocubane alcohol 1 leads to cleavage of the C₃C₄ and C₂C₅ bond giving the tricyclo[4.2.1.0.^2,5]nonene 21. The mechanism of homoketonization is discussed.     

Intramolecular addition of carbon radicals to aldehydes: synthesis of enantiopure tetrahydrofuran-3-ols

A simple and efficient substrate-controlled asymmetric synthesis of enantiopure tetrahydrofuran-3-ols by a 5-exo-trig radical cyclization is described. This cyclization occurs when a δ-carbon radical adds intramolecularly to the carbonyl group of an aldehyde. The δ-carbon radicals can be efficiently produced from the tin hydride mediated deselenenylation of 5-phenylseleno-3-oxapentanals, which were easily prepared starting from commercially available enantiopure epoxides or chlorohydrins.     

Vibrational spectrum of α- and δ-TiCl3

The vibrational spectrum of α-TiCl₃ is assigned on the basis of a normal coordinate analysis. The i.r. bands shift to higher frequency from α- to δ-TiCl₃. This is discussed in terms of a dispersion relation for k_c in α-TiCl₃ and force constants, where the former is carried out for examining effect on disorder to the c axis in δ-TiCl₃. The shift is explained in terms of a change in force constants rather than disorder.     

O−• chemical ionization of carbonyl compounds

The negative ion chemical ionization mass spectra of twentyeight C₄ to C₇ carbonyl compounds were recorded using the oxide radical anion O^?? as reagent ion. As noted earlier, the reactions occurring include H⁺ abstraction, H ₂ ^+? abstraction, H? atom displacement, and alkyl radical displacement. In addition, the [M?2H]^? ions fragment further by alkyl radical elimination. The relative importance of these reactions depends strongly on molecular structure, with the result that isomer distinction frequently is possible. Where this is not possible, as for isomeric aldehydes, the collisional charge inversion mass spectra of common product ions provides isomer distinction. The H ₂ ^+? abstraction reaction is shown to involve abstraction not only of two hydrogens from the same α-carbon but also, in part, abstraction of one hydrogen from each α-carbon.     

One-pot preparation of Julia-Kocienski sulfides and sulfones from alcohols

A method for one-pot preparation of Julia-Kocienski sulfides and sulfones from alcohols and thiols is reported. A variety of primary alcohols were converted to the corresponding mesylates by methansulfonyl chloride and triethylamine in THF. After the reaction is complete, thiol (1 or 10) and either NaH or t-BuOK were added. The Julia-Kocienski sulfides 3, 9 and 11 were prepared by one-pot two steps procedure from alcohols in 76–96% yields (16 examples). Furthermore, after the sulfide formation, the reaction mixture was neutralized by p-toluenesulfonic acid and treated with H₂O₂ and ammonium molybdate in EtOH to give the Julia-Kocienski sulfones 4 in good yields except for trans-2-hexen-1-ol.     

Vicinal phenyl group shift in the lead tetraacetate and related oxidations of 5,5,5-triphenyl-1-pentanol

In the lead tetraacetate and heavy metal-bromine oxidations of 5,5,5-triphenyl-1-pentanol 1d, the major cyclization product obtained was the rearranged 2,2,3-triphenyltetrahydro-2H-pyran 11d, resulting from homolytic and heterolytic 1,2-phenyl group shift (the latter only in the lead tetraacetate reaction) in the respective intermediate species with electron deficient δ-carbon 4d and 6d.     

Deshydrogenation d'alcools en composes carbonyles par le systeme CuCl/O2/Ligande

The dehydrogenation of alcohols to the corresponding carbonyl compounds by CuCl/O₂/ligand (L) shows relative rates of dehydrogenation according to the type of alcohol used; primary or secondary benzyl alcohols > allylic alcohols or aliphatic alcohols > cyclic alcohols. The rate of this reaction was found to be dependent upon the nature of the ligands used; e.g. phenanthroline 1–10 > bipyridyl 2,2' > TMEDA, etc. When L = phenanthroline 1–10 the catalytic effect, of the system ROH/CuCl/L (3:1:1), was found to be similar to the system ROH/CuCl/L (1:2:2). The pure oxygen was replaced by air without any noticeable change in the rate of the reaction. The primary aliphatic alcohols lead to the aldehydes containing 1, 2, etc. carbon atoms fewer than the starting alcohols.     

Enantioselective effects in the association behaviour of optically active alcohols

The association behaviour of four optically active secondary alcohols with chiral C atoms in the α-position was investigated by means of IR spectroscopy and calorimetry CCl₄ was used as a solvent. As compared to the racemic compounds, the corresponding optically active alcohols have slightly higher concentrations of free OH groups, i.e. lower degrees of association, but somewhat higher enthalpy of association. Consequently, the H-bonding of racemic alcohols is favoured by entropy. Differences have been found also in the absorption coefficients of the associated OH groups. Optically active solvents exert some influence on the association behaviour of optically active alcohols. No differences could be observed in the H-bonding of optically active monocarboxylic acids, as compared with the racemic ones     

Ferrous ion induced decomposition of alkyl hypochlorites

The decomposition of primary, secondary and tertiary alkyl hypochlorites induced by ferrous and other one-electron oxidizable metal ions leads to δ-chloro alcohols in yields of 34–76%. In decomposition of tertiary alkyl hypochlorites, β-fragmentation competes with intramolecular δ-chlorination. Tertiary cycloalkyl hypochlorites containing five- or six-membered rings undergo β-cleavage giving the corresponding ω-chloro ketones, while 1-methylcycloheptyl and 1-methylcyclooctyl hypochlorites by decomposition with ferrous ion proceed by transannular functionalization of δ-carbon atom and β-cleavage as a competing reaction.     

Enantioselective hydrolysis of long chain α-amino acid esters by chiral sulfur-containing macrocyclic metallomicelles

A novel chiral lipophilic sulfur-containing macrocyclic ligand 5 with bis-pendant alcohols in the proximity of the coordination center has been synthesized. Its metal ion complexes have been investigated as catalysts for the enantioselective hydrolysis of long chain α-amino acid esters in aqueous comicellar solution with Brij35. Large rate accelerations (up to 220 times) and moderate enantioselectivities (up to 4.85 (k_S/k_R)) employing the macrocyclic 5-Cu²⁺ have been observed, whereas the acyclic 3-Cu²⁺ exhibits less reactivity and stereoselectivity. Taking the analogous ligand 4, lacking the hydroxy groups leads to a dramatic rate decrease, and an inversion of enantioselectivity is observed. The pKa value of the hydroxyl bound to Cu²⁺ is determined to be pKa=7.2 under our micellar reaction conditions.