Markovnikov Orientation Research Articles

Nucleophilic Alkoxylations of Unactivated Alkyl Olefins and α‐Methyl Styrene by Photoredox Catalysis

AbstractN,N‐diisobutylaminophenyl‐phenothiazine is a strongly reducing catalyst that allows – for the first time – the photoredox catalytic addition of alcohols to alkyl olefins as non‐activated substrates to products with Markovnikov orientation. The irradiation at 365 nm does not require any additional reagent. Using α‐methyl styrene as activated substrate we additionally show that this photoredox catalytic method tolerates other functional groups, including allyl, alkynyl, cyanide, and even acid‐labile Boc groups within the substrate scope.

Analytical Methods: Electrochemical azido-selenenylation of some olefins by cyclic voltammetry and controlled-potential coulometry

Electrochemical azido-phenylselenenylation of some olefins was studied with the oxidation of diphenyl diselenide in the presence of some olefins and sodium azide in dimethyl formamide containing tetra butyl ammonium perchlorate as supporting electrolyte in an H-type cell. The electrochemical oxidation of the mixture of (PhSe)2, olefins, and NaN3 was studied by cyclic voltammetry and controlled-potential coulometry. Anti product can be obtained with Markovnikov orientation. This product was characterized .by 1H, 13C NMR, and IR spectroscopy.

Proline‐Rich Short Peptides with Photocatalytic Activity for the Nucleophilic Addition of Methanol to Phenylethylenes

Short proline‐rich peptides were synthesized and modified with 1‐(N,N‐dimethylamino)pyrene by copper(I)‐catalyzed cycloaddition. They perform photoredox catalysis of the nucleophilic addition of methanol to 1,1‐diphenylethylene derivatives into products with Markovnikov orientation. The common additive triethylamine is avoided because forward and backward electron transfer is controlled by substrate binding. A free carboxylic function in the substrate allows more precise substrate binding and defines the electron transfer path better than the unspecific exciplex formation with the substrate bearing a carboxylic ester. A proline‐type turn is an advantage for photoredox catalysis, but a proline‐induced helix is not required. This is the first successful example for introducing secondarily structured peptides to photoredox catalysis.

Ene Reactions of Nitrosocarbonyl Intermediates with Trisubstituted Cycloalkenes: "Cis Effect" and Steric and Conformational Factors Drive the Selectivity.

Nitrosocarbonyl intermediates, generated at room temperature by oxidation of nitrile oxides, undergo clean ene reactions with trisubstituted cycloalkenes. Nitrosocarbonyl benzene follows a Markovnikov orientation and abstracts preferentially the twix hydrogens over the lone ones. With the more sterically demanding nitrosocarbonyl mesitylene in the presence of 5- and 6-membered ring olefins, the Markovnikov directing effect is relieved, and twix and lone abstractions are observed. Endocyclic allylic hydrogens on the more congested side of the alkene are exclusively abstracted (the “cis effect”) resembling the singlet oxygen behavior. The balance between steric and conformational factors, as well as the acylnitroso generation conditions, dictates the regioselectivity in some cases. Larger ring olefins undergo selective twix allylic hydrogen abstraction. The photochemical generation of nitrosocarbonyl is totally selective according to the Markovnikov orientation. The synthetic utility of the ene compounds is also accounted.

MECHANISTIC STUDY OF A RUTHENIUM HYDRIDE COMPLEX OF TYPE [RuH(CO)(N-N)(PR3)2]+ AS CATALYST PRECURSOR FOR THE HYDROFORMYLATION REACTION OF 1-HEXENE

The catalytic activity of systems of type [RuH(CO)(N-N)(PR3)2]+ was evaluated in the hydroformylation reaction of 1-hexene. The observed activity is ex­plained through a reaction mechanism on the basis of the quantum theory. The mechanism included total energy calculations for each of the intermediaries of the elemental steps considered in the catalytic cycle. The deactivation of the catalyst precursors takes place via dissociation of the polypyridine ligand and the subse­quent formation of thermodynamically stable species, such as RuH(CO)3(PPh3)2 and RuH3(CO)(PPh3)2, which interrupt the catalytic cycle. In addition, the theoreti­cal study allows to explain the observed regioselectivity which is defined in two steps: (a) the hydride migration reaction with an anti-Markovnikov orientation to produce the alkyl-linear-complex ( 3.1a ), which is more stable by 19.4 kJ/mol than the Markovnikov orientation (alkyl-branched-complex) ( 3.1b ); (b) the carbon monoxide insertion step generates the carbonyl alkyl-linear specie ( 4.1a ) which is more stable by 9.5 kJ/mol than the alternative species ( 4.1b ), determining the preferred formation of heptanal in the hydroformylation of 1-hexene.

New Catalytic Method for the Synthesis of β‐Hydroxy Selenides

In the presence of NH4I as catalyst and m‐chloroperbenzoic acid as oxidant, the Se–Se bond cleavage of diselenides undergoes smoothly. The in situ generated reactive electrophilic Se species reacts with alkenes quickly, and a series of β‐hydroxy selenides are prepared in good yields. This new catalytic method for synthesis of β‐hydroxy selenides is a stereospecific anti addition, which occurs with a Markovnikov orientation.

N,O-Nucleosides from Ene Reactions of Nitrosocarbonyl Intermediates with the 3-Methyl-2-buten-1-ol

Nitrosocarbonyl intermediates undergo ene reactions with allylic alcohols, affording regioisomeric adducts in fair yields. Nitrosocarbonyl benzene reacts with 3-methyl-2-buten-1-ol and follows a Markovnikov orientation and abstracts preferentially the twix hydrogens over the lone ones. With the more sterically demanding nitrosocarbonyl mesitylene and anthracene, the Markovnikov directing effect is relieved and lone abstraction is observed, affording the 5-hydroxy-isoxazolidines that serve as synthons for the preparation of N,O-nucleoside analogues according to the Vorbrüggen protocol.

New Bridges in [2.2]Paracyclophanes: The Interaction of Chalcogenide Halides with Pseudo-Geminal Triple Bonds

Novel heteroatom containing bridges have been introduced in [2.2]paracyclophanes by the interaction of chalcogenide halides with pseudo-geminal triple bonds. The anti-addition with Markovnikov orientation of selenium halides to 4,15-bisethynyl[2.2]paracyclophane leads to the corresponding E-adducts. The interaction of pseudo-geminally substituted bispropargylic alcohols with disulfur dichloride and sulfur dichloride leads to a mixture of cyclic ethers. These compounds are formed under mild acidic conditions provided by the organic ammonium chlorides or silica gel. The corresponding dipropargyloxy sulfides have been identified as reaction intermediates. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Nitrosonium Salts, NO+X− (X = B(3,5-diCF3Ph)4− or PW12O403−), as Electrophilic Catalysts for Alkene Activation in Arene Alkylation and Dimerization Reactions

It has been found that in apolar reaction media the nitrosonium cation (NO+) activated alkenes under mild conditions toward electrophilic substitution of arene substrates to yield the alkylated arene with Markovnikov orientation. In the absence of arenes the alkenes react with themselves to yield a mixture of dimeric alkenes. The nitrosonium cation can be dissolved in the reaction medium by using the tetrakis-(bis-(3,5-trifluromethyl)phenyl) borate anion, where upon the reactions occur effectively at 30 degrees C. Alternatively an insoluble, heterogeneous catalyst was prepared so as to yield a NO+ cation with a polyoxometalate (PW12O403-) anion. This catalyst was generally more effective and selective toward a broader range of substrates at 70 degrees C.

Synthesis of enantiomerically pure β-azidoselenides starting from natural terpenes

Several unsaturated natural terpenes have been easily converted, in good yields, into the corresponding enantiomerically pure β-azidoselenides by addition of the electrophilic selenium reagent PhSeOTf in the presence of sodium azide. These reactions are stereospecific anti additions, which occur with a Markovnikov orientation. Examples of the synthetic importance of these β-azidoselenides are also reported.

Variable Markovnikov Orientation and “cis Effect” in Ene Reactions of Nitrosocarbonyl Intermediates

Nitrosocarbonyl intermediates, generated at room temperature by the mild oxidation of nitrile oxides, undergo clean ene reactions with trisubstituted olefins. Allylic hydrogens on the more congested side of the alkene are exclusively abstracted (the "cis effect"), thus resembling singlet oxygen behavior. Nitrosocarbonyl benzene follows a Markovnikov orientation and abstracts preferentially the twix hydrogens over the lone ones. With the more sterically demanding nitrosocarbonyl mesitylene, the Markovnikov directing effect is relieved, and comparable twix and lone abstraction are observed.

Regio- and stereoselectivity of diethylaluminum azide opening of trisubstituted epoxides and conversion of the 3 degrees azidohydrin adducts to isoprenoid aziridines.

The regioisomer ratios (3 degrees,2 degrees /2 degrees,3 degrees ), and in some cases the stereochemistry, of vicinal azidohydrins formed in reactions of 11 trisubstituted terpene epoxides with Et(2)AlN(3) in toluene are reported. The more highly substituted azide usually predominated (3 degrees,2 degrees /2 degrees,3 degrees ratios >or= 40:1 to 2.5-1) in accord with a Markovnikov orientation and an S(N)1-like transition state. Reversed regioisomer ratios were observed with 6,7-epoxygeranyl acetate (1:2.5) and cis-1,2-epoxylimonene (1:3.3 to 1:10). The tertiary azido diols from 2,3-epoxygeraniol, 2,3-epoxyfarnesol, and 2,3-epoxynerol were formed as single isomers with inversion of configuration at C3 (>or= 35-40:1 for the C(10) azido diols). The regioselectivity was affected by the presence and proximity of oxy functional groups on the epoxide substrate (OH, OAc, and OSi-tBuMe(2)), the equivalents of Et(2)AlN(3), and additives (EtOAc or EtOH). The results and trends are rationalized by consideration of the structural and stereoelectronic characteristics of proposed diethylaluminum epoxonium ion intermediates and transition states, together with the nucleophilicity of the azide donor. Six of the 3 degrees,2 degrees azidohydrins were converted to the corresponding aziridines by primary-selective silylations of four azido diols, mesylations, and reductive cyclizations with LiAlH(4).

Reactions of Gaseous Vinyl Halide Radical Cations with Ammonia. A Study of Mechanism by Fourier-Transform Ion Cyclotron Resonance Spectrometry and ab Initio Molecular Orbital Calculation

The reactions of the radical cations of vinyl chloride (1) and vinyl bromide (2) with ammonia in the gas phase have been studied by FT-ICR spectrometry and ab initio molecular orbital calculations. The FT-ICR experiments show that vinyl halide radical cations react mainly by substitution of the halogen atom, yielding C2H6N+ product ions and moderately by formation of NH4+ with a total reaction efficiency of 57% (1•+) and 35% (2•+), respectively. The initial formation of NH3D+ from 1-d3•+ and 2-d3•+ establishes a direct deprotonation of the radical cations by NH3. Ab initio calculations confirm an exothermic deprotonation for all possible halovinyl radicals as the neutral product. The structure of the substitution product ions C2H6N+ was investigated by CA mass spectrometry and gas-phase titration experiments. The results show the presence of vinylammonium ions 5+ and acetaldiminium ions (6+) in the product ion mixture, but additional experiments reveal that 6+ is generated by a base catalyzed isomerization of initially formed 5+ (“shuttle mechanism”). The reaction energy profiles of the reactions of the vinyl halide radical cations 1•+ and 2•+ with ammonia were calculated by ab initio methods. The addition of NH3 is very exothermic for both radical cations generating chemically activated distonic ammonium ions in the first reaction step. The addition proceeds regioselectively (Markovnikov and anti-Markovnikov), yielding preferentially an unreactive distonic ion by the Markovnikov orientation. This intermediate has to rearrange by a 1,2-NH3 shift before eventually decomposing into vinylammonium ions 5+ by loss of the halogen atom. It is suggested that this rearrangement corresponds to the “bottle neck” of the substitution process. The activation energy of the 1,2-NH3 shift in the chloro- and bromo-substituted distonic ion is not significantly different, but the increased chemical activation of the chloro derivative results in an increased reaction efficiency for the total substitution process for the vinyl chloride radical cation. The ab initio calculations reveal further that the generation of the more stable substitution product acetaldiminium ion 6+ is inhibited by a large activation barrier for the hydrogen rearrangements necessary within the intermediate distonic ion.

Synthesis of monofluorinated C 4-building blocks based on methallyl chloride

Halofluorination of methallyl chloride using N-halosuccinimides in combination with triethylamine trishydrofluoride (Et 3N·3HF) gave in each case more than 98% of the Markovnikov products and <2% of the regioisomers in good yield. The formal addition of methanesulfenyl fluoride with the combination of dimethyl(methylthio)sulfonium fluoroborate (DMTSF) and Et 3N·3HF gave a 94:6 mixture of both regioisomers. Only small phenylsulfenyl fluorination of methallyl chloride has been observed when treated with N-phenylthiophthalimide (NPTP) and Olah's reagent. With benzenesulfenyl chloride, 1,3-dichloro-2-methyl-2-(phenylthio)propane is formed which on treatment with Olah's reagent at 0 °C or with Et 3N·3HF at 60 °C rearranges to 1,2-dichloro-2-methyl-2-(phenylthio)propane. Treatment of 1,3-dichloro-2-methyl-2-(phenylthio)propane with silver fluoride in methylene chloride at −30 °C gave 1-chloro-2-fluoro-2-methyl-3-(phenylthio)propane which was also obtained by reaction of 1-bromo-3-chloro-2-fluoro-2-methylpropane with thiophenolate. Chlorofluorination of methallylphenylthio ether using NCS/Et 3N·3HF failed, while corresponding reactions with NBS or NIS and Et 3N·3HF gave mainly the bromo- or iodo-fluorides with Markovnikov orientation in 61% or 35% yields. Related halofluorinations of methallylphenyl ether gave the halofluorides in good yield. All attempts to obtain chromanes or thiochromanes bearing a 3-fluorine substituent by cyclization of these halofluorinated ethers or thio ethers failed using different Lewis acids. However, the benzyl protected o-allylphenol which was bromofluorinated with NBS/Et 3N·3HF in good yield gave on catalytic hydrogenation over Pd/C the 3-fluoro-2 H-chromane in nearly quantitative yield.

Telechelics via addition of dithiols onto alkadienes, 2. Base and acid catalysis

AbstractThe base‐catalyzed Michael‐type addition of dithiols onto activated diacrylates and dimethacrylates proceeds quantitatively and leads to products with anti‐Markovnikov orientation of the addition. This reaction was used to prepare telechelics using non‐stoichiometric ratios of monomers. The acid‐catalyzed addition of dithiols onto divinyl ethers also yields polymers and telechelics, however, these products show Markovnikov orientation of the addition.

Acetamidinosulphenylation of alkynes via electrophilic addition of 4′-substituted benzenesulphenanilides in acetonitrile

A number of 4′-substituted benzenesulphenanilides and N-methyl-4′-nitrobenzenesulphenanilide are shown to add to simple alkynes in acetonitrile in the presence of boron trifluoride–diethyl ether to give acetamidinovinyl sulphides in varying yields. Addition is largely favoured by dialkyl substitution on the alkyne and by electron-attracting anilide substituents. Moreover, the azasulphenylation adducts are produced with trans-stereospecificity and high regioselectivity (Markovnikov orientation). A likely mechanism involves nucleophilic displacement by the alkyne at the activated sulphur of the anilide complexed with boron trifluoride leading to the initial formation of a thiirenium ion intermediate. Subsequent back-side attack of acetonitrile on the thiirenium ion gives a nitrilium ion which is ultimately trapped by the liberated arylamine.

Electrophilic addition of 4′-nitrobenzenesulphenanilide to alkynes in acetic acid. A synthesis of β-acetoxyvinyl sulphides

4′-Nitrobenzenesulphenanilide reacts at room temperature with simple alkyl- and aryl-alkynes in acetic acid in the presence of boron trifluoride–diethyl ether to afford products of acetoxysulphenylation in moderate to good yields. The addition products are generally produced with trans-stereospecificity and in a regioselective fashion (Markovnikov orientation). The findings are consistent with a mechanism involving intermediary of thiirenium ions which would result from alkyne attack at the sulphur atom of the anilide complexed with boron trifluoride.

Gas-Solid Reactions in Organic Synthesis

Abstract Various new branches in the field of preparative scale organic gas-solid reactions (additions, substitutions, eliminations, condensations) are elaborated following a historical review. Polar gases (HBr, HCl, HI, HSCH3) react at 1 bar and temperatures from 40 to -80°C with gram quantities of crystalline N-vinylimides, -amides, -amines, and S-vinylthioethers usually in the Markovnikov orientation, but there is also an exception. The polar gases H2O and NH3 transform some of the crystalline addition products and H2O may be added catalytically to N-vinylphthalimide. All reactions run to high conversion rapidly and several of the highly sensitive products cannot be synthesized in solution. Liquid compounds like N-vinylpyrrolidinone which polymerize in solution crystallize and add polar gases smoothly upon freezing. Polar gases are applied to crystalline chalcone, cinnamic acid, and stilbenes with variable success. Pd-doped crystals are hydrogenated. Contrary to literature reports chlorine and bromine ...

Dreikomponentenreaktionen. XVI Zur Halogenierung von Alk‐1‐enen in Gegenwart von Ethylenoxid und Propylenoxid

Three Component Reactions. XVI. Halogenation of Alk‐1‐enes in the Presence of Ethylene Oxide und Propylene OxideThe products of the chlorination of alk‐1‐enes in the presence of ethylene oxide and propylene oxide were investigated in relation to products of the chlorination in the presence of corresponding chloroalcohols4and5. Isomers dominating in the Markovnikov orientation were found in all cases. Two of the three pairs of diastereomeric bischloropropylethers expected for the chlorination of propene in the presence of propylene oxide were identified by capillar GLC and13C n.m.r. spectroscopy.