Alcohols 2a Research Articles

Copper mediated defluorinative allylic alkylation of difluorohomoallyl alcohol derivatives directed to an efficient synthetic method for ( Z)-fluoroalkene dipeptide isosteres

Difluoroallylation of optically pure O-silylated ( S)-2-methyl-3-hydroxypropanal 10a with bromodifluoropropene mediated by indium provided the corresponding difluorohomoallyl alcohol 11a with low diastereoselectivity, but without a decrease in optical purity. Defluorinative allylic alkylation of each diastereomer of the difluorohomoallyl alcohol efficiently proceeded by the reaction with trialkylaluminium and Cu(I) system or Grignard reagent and a catalytic amount of CuI system in THF to give the fluorine-substituted allylic alcohol 12 in an high yield and in an excellent Z selective manner. Subsequent imidate Claisen rearrangement of the allylic alcohol 12 proceeded with a complete 1,3-chirality transfer to give the fluoroalkene dipeptide isostere structure 14 after the final conversion of the primary alcohol 20 into the carboxylic acid form.

Enantioselective iridium-catalyzed vinylogous Reformatsky-aldol reaction from the alcohol oxidation level: linear regioselectivity by way of carbon-bound enolates.

Enantioselective iridium-catalyzed vinylogous Reformatsky-aldol reaction from the alcohol oxidation level: linear regioselectivity by way of carbon-bound enolates.

Synthesis and odour characteristics of racemic and optically active oxy-derivatives of gem-dimethylcyclohexene

Racemic and enantiomerically enriched oxy-derivatives of gem-dimethylcyclohexene as potential components of fragrance and flavoring compositions were synthesized. Ethyl esters (2a–d), alcohols (3a–d), acetates (4a–d), propionates (5a–d) and aldehydes (6a–d) were obtained from racemic and enantiomerically enriched gem-dimethylcyclohexenols (1a–d). In the first step allyl alcohols (1a–d) were transformed via the Claisen rearrangement into respective ethyl esters (2a–d), which were subjected to reduction (LiAlH4) affording the corresponding alcohols (3a–d). The acetates (4a–c) and propionates (5a–c) were synthesized in the standard manner in the reaction of alcohols 3a–d with the respective acetyl or propionyl chlorides. Alcohols (3a–d) were also oxidized with chromium(vi) oxide, a pyridine complex giving aldehydes (6a–d), respectively. All esters, alcohols 3c and 3d, and aldehydes 6b and 6c possess valuable odoriferous properties, which could be useful for the cosmetic and food industries. Copyright © 2011 John Wiley & Sons, Ltd.

One-Pot N-Alkylation of Amine with Alcohols Using Au/TiO2-VS

Titania-supported gold nanoparticles (Au/TiO2-VS, 1) were prepared and applied to the one-pot N-alkylation of amines with alcohols. Thus, nanocomposite 1 with an average size of 1.8 nm was obtained in three steps. The one-pot N-alkylation reaction of aniline 2a with benzyl alcohol 3a was carried out in the presence of Au/TiO2-SV 1 (0.5 mol% Au) to give 92% yield of N-benzyl­aniline (4a).

Concentration and Temperature Dependency of Regio- and Stereoselectivity in a Photochemical [2 + 2] Cycloaddition Reaction (the Paternò−Büchi Reaction): Origin of the Hydroxy-Group Directivity

A set of photochemical oxetane formation reactions, i.e., the Paternò-Büchi (PB) reactions, of tetrahydrobenzofuranol derivatives 1a-d with benzophenone (BP) was investigated to examine poorly understood hydroxy-group directivity on regio- and stereoselectivity. The selectivities of the PB reactions for allylic alcohols 1a,d were found to be largely dependent upon the concentration of the allylic alcohols and the reaction temperature. The temperature-dependent change of the regioselectivity at high concentrations of allylic alcohols was similar to that of the hydroxy-protected methyl ether 1b and tetrahydrobenzofuran (1c). The effect of concentration on regioselectivity can be explained by the hydrogen-bonded aggregates, which mimic the selectivities observed during the PB reaction of 1b,c. The hydroxy-directed cis-selectivity of the higher-substituted oxetane 3a,d formed at low concentration of 1a,d was found to be larger than that at the higher concentration of 1a,d. The cis-selectivity of 3a,d was found to be higher than that of the lower-substituted oxetane 2a,d. The regioselectivity of the cis-configured oxetanes was higher than that of the trans-configured oxetanes. These experimental results strongly suggest that hydroxy-group directivity, induced by hydrogen-bonding stabilization, plays a role in controlling the regio- and stereoselectivity of the PB reactions. The steric effect was also responsible for the diastereoselectivity, as shown by the fact that the cis selectivity in 3d was higher than that in 3a. Computational studies at the (U)MP2 and (U)DFT level of theory revealed that hydrogen-bonding stabilization becomes important only in the excited complex (exciplex) between the triplet excited state of carbonyls and alkenes, in which the charge transfer occurs from the alkene to the excited carbonyl to make the carbonyl oxygen nucleophilic. No significant stabilization energy was found in the intermediary triplet state of biradicals. The combined experimental and computational studies have clarified the origin of the poorly understood hydroxy-group effect on a high degree of regio- and stereoselectivity, i.e., the cooperative effect of hydrogen-bonding stabilization in exciplexes and the steric bulk of the substituents.

Asymmetric Reduction of Heteroaryl Methyl Ketones Using <i>Daucus carota</i>

Asymmetric reduction of the heteroaryl prochiral ketones to corresponding chiral alcohols by Daucus carota was studied. The study highlights selective bioreduction of different substituted heteroaryl ketones (1a - 1j) to their respective chiral alcohols (2a - 2j) using plant dehydrogenase enzymes present in Daucus carota in good yields (60% - 95%) and enantioselectivity (76% - 99%) with S-form configuration. The results obtained confirm that the membrane bound dehydrogenase enzyme has broad substrate specificity and selectivity in catalyzing both six and five membered heteroaryl methyl ketones. The present methodology demonstrates promising and alternative green route in the synthesis secondary chiral alcohols of biologically importance in a simple, inexpensive and eco-friendly process.

Amplification of Anti-Diastereoselectivity via Curtin−Hammett Effects in Ruthenium-Catalyzed Hydrohydroxyalkylation of 1,1-Disubstituted Allenes: Diastereoselective Formation of All-Carbon Quaternary Centers

Under the conditions of ruthenium-catalyzed transfer hydrogenation, 1,1-disubstituted allenes 1a-c and alcohols 2a-g engage in redox-triggered generation of allylruthenium-aldehyde pairs to form products of hydrohydroxyalkylation 3a-g, 4a-g, and 5a-g with complete branched regioselectivity. By exploiting Curtin-Hammett effects, good to excellent levels of anti-diastereoselectivity (4:1 to >20:1) are obtained. Thus, all carbon quaternary centers are formed in a diastereoselective fashion upon carbonyl addition from the alcohol oxidation level in the absence of premetalated nucleophiles or stoichiometric byproducts. Exposure of allene 1b to equimolar quantities of alcohol 2a and aldehyde 6b under standard reaction conditions delivers adducts 4a and 4b in a 1:1 ratio. Similarly, exposure of allene 1b to equimolar quantities of aldehyde 6a and alcohol 2b provides adducts 4a and 4b in an identical equimolar ratio. Exposure of allene 1b to d(2)-p-nitrobenzyl alcohol, deuterio-2a, under standard reaction conditions delivers the product of hydrohydroxyalkylation, deuterio-4a, which incorporates deuterium at the carbinol position (>95% (2)H) and the interior vinylic position (34% (2)H). Competition experiments involving exposure of allene 1b to equimolar quantities of benzylic alcohols 2a and deuterio-2a reveal no significant kinetic effect. The collective data corroborate rapid, reversible alcohol dehydrogenation, allene hydrometalation, and (E)-, (Z)-isomerization of the transient allylruthenium in advance of turnover-limiting carbonyl addition. Notably, analogous allene-aldehyde reductive C-C couplings employing 2-propanol as the terminal reductant display poor levels of anti-diastereoselectivity, suggesting that carbonyl addition is not turnover-limiting in reactions conducted from the aldehyde oxidation level.

Tunable Chiral Reaction Media Based on Two-Component Liquid Crystals: Regio-, Diastereo-, and Enantiocontrolled Photodimerization of Anthracenecarboxylic Acids

Three kinds of enantiopure amphiphilic amino alcohols (1a-c) were newly synthesized, of which the stereochemistry of the stereogenic carbons adjacent to the amino (C2) and hydroxy (C1) groups was systematically varied. By using these amino alcohols and four photoreactive carboxylic acids, 12 kinds of salts were prepared. The structure and thermal behavior of the salts were thoroughly investigated by various techniques, which revealed that the stereochemistry of the amino alcohol unit has significant effects on the properties of the salts; the salts of 1a with (1R,2S)-configuration did not exhibit any liquid crystal (LC) phase but showed high crystallinity, whereas 1b and 1c with (1S,2S)- and (1S)-configurations, respectively, generally afforded stable LC salts with smectic structure(s). Within the matrix of these amphiphilic salts, the in situ photodimerizations of 2-anthracenecarboxylic acid (2c) and 1-anthracenecarboxylic acid (2d) were conducted by the irradiation with UV/vis light (500 W, a high-pressure mercury arc lamp, >380 nm). Concerning reactivity and regio-/diastereo-/enantioselectivities, the LC phases were found to be superior to isotropic and crystalline phases. For the two substrates 2c and 2d, every LC phase promoted the photodimerization with unprecedentedly high head-to-head selectivity. Particularly in the case of 2c, diastereoselecitivity (syn(HH) vs anti(HH)) could be rationally controlled by the choice of the amino alcohol unit and mesophase (syn(HH):anti(HH) = 61:37 to 26:72). Moreover, one of the LC phases exhibited by 1b·2c afforded the anti(HH)-dimer of 2c with excellent enantioselectivity (up to 86% ee). On the basis of the hypothesis that the present photochemical outcome arises from the preorientation of the substrates, a preliminary structural model of these LCs was proposed.

Synthesis and characterization of 2-alkyl -5-{4-[(3-nitrophenyl-5-isoxazolyl)methoxy]phenyl}-2H-tetrazoles

Heteroaryl substituted analogs of antirhnoviral (A), was prepared by a convergent approach. 3-Nitrophenyl-5- bromooromethylisoxazoles 5a–b were synthesized by [3+2] cycloaddition of 3-(benzoyloxy)-propyne 2 to in situ generated arylnitrile oxides followed by deprotection of cycloadducts 3a–b and bromination of the resulting alcohols 4a–b. Coupling of 3- nitrophenyl-5-bromooromethylisoxazoles (5a–b) with 4-[5-(2-alkyl-2H-tetrazolyl)]phenols (6a–d) in N-methylpyrrolidinone under mild conditions afforded a new series of 2-alkyl-5-{4-[1-(3-nitrophenyl-5-isoxazolyl)methyloxy]phenylr}-2H-tetrazoles (7a–h) in high yields. The structures of the synthesized compounds were confirmed by their 1H NMR, Mass spectral, and Elemental Analysis data.

ChemInform Abstract: Synthesis, Structural and Conformational Study of 6-Hydroxy (or Acyloxy) Derivatives of the 1,3-Dimethyl-1,3-diazoniatricyclo(3.3.1.13- 7)decane System.

1,3-Dimethyl-1,3-diazoniatricyclo[3.3.1.13–7]decan-6-ol, and his p-chlorobenzoxy and diphenylacetoxy derivatives have been synthesized and studied by 1H and 13C nmr spectroscopy. The crystal structure of the alcohol 2a has been determined by X-ray diffraction. Each ring of the adamantane cage system is a nearly perfect chair. From the 1H and 13C nmr data, several stereoelectronic effects have been deduced.

ChemInform Abstract: The Reaction of β-(Trimethylsilyl)alkyl Phenyl Sulfones with Oxiranes. A Method for Stereocontrolled Synthesis of Homoallylic Alcohols.

Abstract The reaction of β-trimethylsilylalkyl sulfones ( 4a – 4b ) with oxirane derivatives ( 5a – 5d , 9 ) followed by treatment of the immediate adducts with sodium hydride, affords O-trimethylsilyl homoallylic alcohols ( 7a – 7e , 11 ), mainly (Z) isomers.

ChemInform Abstract: Iron-Peplomycin Catalyzed Oxygenation of Linoleic Acid.

Abstract Incubation of linoleic acid with Fe(III)-peplomycin under aerobic conditions produced a mixture of hydroperoxides 1a–d as primary products which then gave rise to the formation of the corresponding dienones ( 2a–d ), alcohols ( 3a–d ) and epoxyenones ( 4a, b ).

ChemInform Abstract: Enantioselective Synthesis of α-Amino Phosphonic Acids by an Application of Stereoselective Opening of Homochiral Dioxane Acetals with Triethyl Phosphite.

Abstract Stereoselective opening of homochiral acetals ( 2a–c ) with triethyl phosphite was applied to the enantioselective synthesis of phosphono alcohols ( 1a–c ), which were succssefully converted to the α-amino phosphonic acid diethyl esters ( 6a–c ).

ChemInform Abstract: Photooxygenation of α-Ionone and Oxygen Transfer Reactions of the Resulting Allylic Hydroperoxides.

The photooxygenation of α-ionone (4) in different solvents leads, with higher than 90% regioselectivity, to a mixture of two diastereomeric allylic hydroperoxides 5a and 5b (diastereomeric ratio 77:23). These compounds are transformed in the presence of Ti(OiPr)4 into the corresponding epoxy alcohols 8a and 8b (cis selectivity) and the allylic alcohols 7a and 7b with high diastereoselectivity. In these cases the substrate configuration exhibits a pronounced control of type selectivity: the cis allylic hydroperoxide 5a is preferentially reduced to the allylic alcohol 7a, whereas the diastereomeric trans compound 5b is preferentially (syn selectivity) converted to the epoxy alcohol 8b. Epoxidation of the allylic alcohol 7a with meta-chloroperbenzoic acid leads, in contrast to the Ti(IV)-catalyzed reaction, to a mixture of diastereomeric epoxy alcohols 8a and 8c, with the anti product 8c as major diastereomer (diastereomeric ratio 28:72). These reactions serve as a route to three of the four possible diastereomeric epoxides of 3-hydroxy-γ-ionone.

ChemInform Abstract: A Chemoenzymatic Synthesis of Enantiomerically Pure (R)- and (S)-2- Methyldecan-1-ol.

(R)- and (S)-2-methyldecan-1-ol 3a has been prepared in >98% enantiomeric excess (ee) by transesterification with vinyl acetate in chloroform in the presence of Pseudomonas fluorescens lipase. Oxidation of the alcohol 3a affords nearly optically pure 2-methyldecanoic acid 3b

ChemInform Abstract: Selective O-Methyloxime Formation from 6-Methoxy-2-((1′-methyl-2′,5′- dioxocyclopentyl)methyl)-3,4-dihydronaphthalen-1(2H)-one.

Reaction of 6-methoxy-2-[(1′-methyl-2′,5′-dioxocyclopentyl)methyl]-3,4-dihydronaphthalen-1(2H)-one (4a) with 1 or 2 moles of O- methylhydroxylamine hydrochloride in pyridine gave (1′SR,2RS)-6-methoxy-2-[(1′-methyl-2′,5′-dioxocyclopentyl)methyl]-3,4-dihydronaphthalen-1(2H)-one (E)-2′-O-methyloxime (5a), or the corresponding 2′,5′-bis(O-methyloxime ) (6), respectively. A minor product from the formation of the bis (O- methyloxime ) (6) was the (Z) isomer (5b) of the mono(O- methyloxime ) (5a); the structure and stereochemistry of (5a) and (5b) were established by X-ray crystallography. Reduction of the keto bis (O-methyloxime ) (6) with 0.25 mole of lithium aluminium hydride gave a diastereomeric mixture of the corresponding alcohols (7a), of which the major isomer was characterized by ester formation. The bis (O-methyloxime ) (6) could be hydrolysed to the parent triketone (4a), but it resisted deprotection with cetyltrimethylammonium permanganate. Reaction of the triketone (4a) with 1 mole of 4-anisidine in the presence of 4-toluenesulfonic acid resulted in retro Michael cleavage with formation of 3-(4′-methoxyphenyl)amino-2-methylcyclopent-2-en-1-one (1).

ChemInform Abstract: Synthesis of 2-Benzamidoisoquinolin-1(2H)-one from 2-Vinylbenzoic Acid.

Treatment of N 1 -(2-vinylbenzoyl)-N 2 -benzoylhydrazine (2a) with 3-chlo- ro peroxybenzoic acid led to a cyclization of the intermediate epoxy derivative (3a) to give the alcohol (4a). Conversion of (4a) to the thiocarbonate (5a) followed by a Chugaev type reaction gave the title compound (6)

ChemInform Abstract: Synthesis of 1,8,8-Trimethyl-6,10-dioxaspiro(4.5)dec-2-ene-1-ethanol; X-Ray Crystallography of (1RS,2SR)-1,8,8-Trimethyl-1-(prop-2′-enyl)-6, 10-dioxaspiro(4.5)dec-2-yl Benzoate.

Reaction of 2-methyl-2-(prop-2′-enyl)cyclopentane-1,3-dione (2) with 2,2-dimethylpropane-1,3-diol gave 1,8,8-trimethyl-1-(prop-2′-enyl)-6,10-dioxaspiro[4.5]decan-2-one (3), hydride reduction of which afforded a 1:1 epimeric mixture of the corresponding alcohols (4a) and (4b). They were separated, and the derived benzoates (5a) and (5b) were each subjected to a three-step sequence of oxidative cleavage, borohydride reduction and silylation to give the pure epimers (8a) and (8b) of 1,8,8-trimethyl-1-(2′-t-butyldimethylsilyloxyethyl)-6,10-dioxaspiro[4.5]dec-2-yl benzoate. Flash vacuum pyrolysis of a mixture of these epimeric benzoates (8a,b) gave an almost quantitative yield of 1,8,8-trimethyl-1-(2′-t-butyldimethylsilyloxyethyl)-6,10-dioxaspiro[4.5]dec-2-ene (9a), treatment of which with tetrabutylammonium fluoride afforded the corresponding alcohol (9b). The relative stereochemistry of (1RS,2SR)-1,8,8-trimethyl-1-(prop-2′-enyl)-6,10-dioxaspiro [4.5]dec-2-yl benzoate (5b) was established by X-ray crystallography.

ChemInform Abstract: Synthesis of 2S,5S- and 2R,5S-5-Hydroxypipecolic Acid via Amide- Methylenation of S-5-Hydroxy-2-piperidone with Dimethyltitanocene.

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ChemInform Abstract: A Short Access to Chiral Non‐Racemic Oxa‐ and Azaheterocycles by Cross‐Metathesis and Pd‐Catalyzed Cyclization Sequence.

A concise synthesis of chiral non-racemic 2-(3-benzoyloxyprop-1-enyl)tetrahydrofuran (5a), tetrahydropyran (5b), and piperidine (8) is described. Cross-metathesis of optically pure (S)-1-O-benzoyl-3-butene-1,2-diol (2) with protected 4-pentenol, 5-hexenol, and 5-hexenylamine gave the corresponding allyl alcohols (3a), (3b), and (7) in one step, respectively. PdCl 2 (MeCN) 2 catalyzed cyclization of 4a, 4b, and 7 afforded 5a, 5b, and 8 in excellent yields with high enantiomeric purity.