The first example of magnesium carbenoid 1,3-CH insertion reaction: a novel method for synthesis of cyclopropanes from 1-chloroalkyl phenyl sulfoxides in high yields

Treatment of 1-chloroalkyl phenyl sulfoxides having a geminal methyl group or a geminal benzyl group at the 2-position in THF at −78 °C with isopropylmagnesium chloride gave magnesium carbenoids. Carbenoid 1,3-CH insertion reaction of the magnesium carbenoids took place instantaneously to afford cyclopropanes in high to quantitative yields.     

Asymmetric synthesis of cyclic α-amino acid derivatives by the intramolecular reaction of magnesium carbenoid with an N-magnesio arylamine

The synthesis of pipecolic acid and homopipecolic acid derivatives was developed from ω-(2-aminophenyl)-1-chloroalkyl p-tolyl sulfoxides by treatment with i-PrMgCl. An intramolecular nucleophilic substitution reaction of a magnesium carbenoid with an N-magnesio arylamine is the key step of this reaction. Proline and pipecolic acid derivatives were also synthesized from ω-(arylamino)-1-chloroalkyl p-tolyl sulfoxides by the same chemistry. Starting from enantiomerically pure (1S,R_S)-1-chloro-3-[2-(N-methylamino)phenyl]propyl p-tolyl sulfoxide, enantiomerically pure (R)-pipecolic acid derivative was obtained. The intramolecular nucleophilic substitution reaction of the magnesium carbenoid with N-magnesio arylamine was proven to take place with inversion of the carbenoid carbon. The stereochemistry of these reactions is also discussed.     

Formation and reactivity of the addition products of alkoxides and thiolate anions to vinyl selenones

Vinyl selenones react with sodium methanethiolate in methanol to give the product of conjugate addition and subsequent displacement of the selenonyl group. On the contrary, the same reaction carried out with alkoxide anions affords the conjugate addition products in excellent yields. These β-alkoxy alkyl phenyl selenones are stable compounds which can react in several ways with loss of the selenonyl group. Their reactions with MeONa or MeSNa have been investigated both in MeOH and in DMF. The products observed derive from substitution and elimination processes as well as from retro Michael reactions followed by nucleophilic substitution of the vinyl selenone thus generated. These results indicate that the ArSeO₂ is a strong electron attracting group with peculiar properties. Beside making acidic the α-hydrogen atoms it activates the carbon-carbon double bond towards the addition of anionic reagents and it acts as a good leaving group in nucleophilic substitution, both aliphatic and vinylic, and in elimination reactions. The appropriate choice of the reagent and of the solvent allows to direct the reaction towards the desired products. Useful synthetic applications of these reactions are presented.     

Chalcogenation of 1,3-dichloropropene with elemental chalcogens in the system hydrazine hydrate–base

Sulfur reacts with 1,3-dichloropropene in the system hydrazine hydrate–KOH to form bis(1-chloroprop-1-en-3-yl) sulfide, and in the system hydrazine hydrate–monoethanolamine, bis(1-chloroprop-1-en- 3-yl) disulfide. The reaction of tellurium in the system hydrazine hydrate–KOH leads to diallyl telluride, the product of nucleophilic substitution of the allylic chlorine atom and reductive cleavage of the С_sp2–Cl bond. The reaction of selenium with 1,3-dichloropropene gives a complex mixture of products. At excess KOH (Se: KOH = 1: 5) bis(1-chloroprop-1-en-3-yl) selenide was isolated.     

Complexation of selenium to (R)‐Rh2(MTPA)4: thermodynamics and stoichiometry

Variable‐temperature ¹H and ⁷⁷Se NMR data for 3‐phenylselenenyl‐1‐phenyl‐1‐propene (1) in the presence of Rh₂(MTPA)₄ (Rh*) prove that the equilibria are strongly shifted towards the adduct Rh*···1; free selenide molecules cannot be detected as long as uncomplexed rhodium atoms are available. In the case of excess Rh*, both 1 : 2 and 1 : 1 adducts (Rh* vs 1) are formed, and the latter is slightly favoured. With excess selenide, the system strongly favours the complexation of two selenide molecules (1 : 2 adduct), i.e. one at each rhodium atom. In this situation, intermolecular selenide exchange can be monitored by variable‐temperature ¹H NMR spectroscopy and the energy barrier is estimated to be 54–55 kJ mol^?1. Copyright © 2001 John Wiley & Sons, Ltd.     

Selective One-Pot Synthesis of Allenyl Phenyl Selenide and 1-(Phenylseleno)Propyne. Role of Sodium Benzeneselenolate as a Base in Dmf

The reaction of excess sodium benzeneselenolate with propargyl bromide in DMR-THF at room temperature produced allenyl phenyl selenide or l-(phenylseleno)propyne selectively, depending only on the reaction time.     

Cyclic and stripping voltammetry of Se(+4) and Se(−2) at the HMDE in acidic media

Electroreduction of Se(+4) and electrooxidation of Se(?2) were studied at mercury electrodes in acidic media and an improved mechanism of the reduction process was proposed. This mechanism takes into account the fact that the reduction path is concentration-dependent. At lower concentrations of Se(+4), mercury selenide and hydrogen selenide are formed at various potentials. At higher Se(+4) concentrations the electrode quickly becomes covered by a rigid deposit of mercury selenide and then the reduction starts to proceed to elemental selenium. Another form of selenium was formed in the vicinity of the mercury surface due to a chemical reaction between H₂SeO₃ and H₂Se. Oxidation of hydrogen selenide proceeds similarly, in the sense that after coverage of the electrode surface by a deposit of mercury selenide the oxidation starts to proceed to elemental selenium. The cathodic stripping peak of mercury selenide can be obtained down to 2 × 10^?8M of Se(+4), but this peak is often split and therefore the determination of traces of Se(+4) by the cathodic stripping technique is cumbersome.     

Metal π-allyl chemistry III. The preparation of π-allylpalladium complexes from palladium(II) salts

A number of routes for the preparation of π-allylpalladium complexes from palladium(II) salts were investigated with a view to obtaining a quantitative yield. Quantitative yields were obtained rapidly when a stream of ethylene was passed through an aqueous solution of Na₂PdCl₄ and the allylic chloride, and more slowly on vigorously shaking an aqueous solution of Na₂PdCl₄ with a 3-fold excess of allyl chloride.Spectroscopic evidence is presented to confirm that the first stage of the reaction of allylic compounds with palladium(II) salts involves the formation of an olefinic complex. It is found that such palladium(II)olefin complexes of CH₂CHCH₂X are very much less susceptible to nucleophilic attack when X = Cl than when X = C₅H₁₁, OH or OAc, which are all attacked rapidly by nucleophilic solvents, such as methanol, with deposition of palladium metal.     

Conformation et reactivite de derives (4.n.0) bicycliques a jonction trans—XXIV: Trifluoroéthanolyse du phényl-4a et du méthyl-4a tosyloxy-3a bicyclo (4.2.0) octane trans. mise en évidence d'une réaction d'élimination à partir d'union phénonium

Rate constants and reaction products for trifluoroethanolysis of transfused 4a-phenyl 3a-tosyloxy bicyclo (4.2.0) octane 1 and 4a-methyl 3a-tosyloxy bicyclo(4.2.0) octane 1' are reported. As for methanolysis, this reaction occurs through the E₁(ip) process. Nevertheless, first-formed secondary cations are rearranged before reacting, by hydride migration for 1 and 1', and phenyl migration for 1. Reaction products result from solvent or leaving group basic and nucleophilic attack on tertiary ions, and phenonium ion for 1. Elimination via phenonium ion has been established by the characterisation of a rearranged olefin (with equatorial phenyl). A mechanism for this elimination reaction is proposed.     

Chloromethyl chlorosulfate: a new, catalytic method of preparation and reactions with some nucleophiles

The reaction of liquid (gamma-) SO3 with CH2Cl2 at room temperature leads to SO3 insertion into the C-Cl bonds, giving the useful chloromethylating agent chloromethyl chlorosulfate (CMCS). The process is very slow but becomes rapid on addition of catalytic quantities of trimethyl borate. The product mixture consists almost entirely of CMCS and the product of further sulfation, methylene bis(chlorosulfate)(MBCS), in a ratio of ca. 2 : 1, but typical yields of CMCS, isolated by distillation, are only 30-35%. The catalysed reaction in the homogeneous liquid phase at -45 degrees C has been followed as a function of time and of reactant concentration by 1H nmr spectroscopy. It is observed that, besides CMCS and MBCS, three additional, transient products (designated A, B and C) are formed. Products A, B and C decompose slowly at -45 degrees C but much more rapidly if the reaction mixture is raised to room temperature, giving additional CMCS and MBCS. From an analysis of the SO3 balance, it is inferred that products A, B and C arise from the reaction of one molecule of CH2Cl2 with respectively two, three and four molecules of SO3; they are suggested to be chloromethyl chloropolysulfates. By measuring initial rates of CMCS formation or total CH2Cl2 consumption, it is shown that the reaction is first order in the catalyst and roughly third order in SO3. A mechanistic scheme is proposed in which SO3 forms equilibrating zwitterionic molecular complexes with CH2Cl2. of 1 : 1, 2 : 1 and higher stoichiometries. The boron-containing catalyst can activate these complexes towards nucleophilic attack at carbon by the negatively charged oxygen of another zwitterion. An analogous mechanism can be written for the conversion of CMCS into MBCS by SO3 in the presence of trimethyl borate. CMCS reacts rapidly with anionic nucleophiles, such as halide or acetate ions (X-), in homogeneous solution of their tetrabutylammonium salts in CD3CN, or in a two-phase system (CDCl3/H2O) using alkali-metal salts in conjunction with a phase-transfer catalyst. In both situations the products (ClCH2X) arise by rapid nucleophilic displacement of the chlorosulfate moiety; this then more slowly liberates chloride ion, which converts further CMCS into CH2Cl2. The reactivity of CMCS has been compared with that of MBCS and methyl chlorosulfate (MCS) in competitive experiments; the reactivity order is MCS > MBCS > CMCS > CH2Cl2. Evidence is also presented suggesting that, in contrast to the halide nucleophiles, reaction of CMCS with sodium phenoxide in tetrahydrofuran solution leads to nucleophilic displacement of the sulfur-bound chloride.     

Degradation of poly(vinyl chloride) by u.v. radiation—II: Mechanism

The mechanism of the light-induced degradation of solid poly(vinyl chloride) (PVC) has been investigated, and an overall reaction scheme has been developed, based on values of the quantum yields for the primary photoproducts. Only a very small fraction (0.2%) of the excited polyenes induces the degradation of PVC, primarily by photocleavage of the allylic CCl bond. The high instability of β-chloroalkyl radicals is responsible for the chain dehydrochlorination that leads to formation of polyenes. In the absence of O₂, chain scissions and crosslinking are postulated to originate mainly from α-chloroalkyl radicals through β-cleavage of CC bonds and radical coupling, respectively. In the presence of O₂, the chain dehydrochlorination still proceeds, together with an oxidative chain process which yields, via peroxy and alkoxy radicals, hydroperoxides, ketones and peroxide crosslinks. Cleavage of the polymer backbone results most probably from the decomposition of tertiary alkoxy radicals by a carbon-carbon β-scission process.     

相转移催化合成羧酸醚酯类化合物

将[N(Bu)~4]Br或FeCl~3-PEG-400作为相转移催化剂,应用于α-氯代烷基烷基醚与无水乙酸钠(或无水甲酸钠)之间的亲核取代反应, 以合成具有RCOOCHR'OR'型结构的羧酸醚酯类香料化合物, 产物产率可提高10%. 中间化合物与产物的结构均经IR, NMR 与元素分析证实.     

Oxidation and halogenation of divinyl selenide. first synthesis of divinyl selenoxide

Efficient procedure was developed for the preparation of divinyl selenoxide in 92% yield by oxidation of divinyl selenide with sodium periodate. At the action of S-nucleophiles on the divinyl selenoxide it is reduced to divinyl selenide. The reaction of divinyl selenide with an equimolar amount of sulfuryl chloride or bromine led to halogenation products at the selenium atom: divinylselenium dichloride and divinylselenium dibromide. A rearrangement was discovered of divinylselenium dibromide into vinyl(1,2-dibromoethyl)-selenide. The hydrolysis of divinylselenium dichloride results in divinyl selenide.     

Highly enantioselective reaction of alpha-selenoorganolithium compounds with chiral bis(oxazoline)s and preparation of enantioenriched benzylidencyclohexanes

The enantioselective reaction of alpha-seleno carbanions derived from bis(phenylseleno)acetal and bis(2-pyridylseleno)acetal in the presence of bis(oxazoline)s with various electrophiles gave products with high enantioselectivity. The enantioselective reaction of alpha-lithio benzyl 2-pyridyl selenide gave the products with stereochemistry reverse to that obtained in the reaction of alpha-lithio benzyl phenyl selenide. Mechanistic investigation suggests the enantiodetermination of these reactions at -78 degrees C depends on dynamic thermodynamic resolution. The enantioselective reaction was applied to the preparation of enantioenriched olefins and epoxide.     

Conformation et réactivité de dérivés [4.n.0] bicycliques à jonction trans—XXVI: Méthanolyse du tosylate de phényl-4a bicyclo(4.2.0]-octyle-3a trans et du tosylate de phényl-4e bicyclo[4.2.0]octyle-3e trans en l'absence et en présence de MeONa. mise en évidence d'un intérmediaire ion phénonium

The structure of the reaction products and the rate constants for methanolysis of 4a-phenyl 3a-tosyloxy bicyclo[4.2.0]octane trans 1 and 4e-phenyl 3e-tosyloxy bicyclo(4.2.0]octane trans 2 in different MeO?/MeOH systems, suggest that these reactions do not involve a phenyl-assisted, but an ion-pairing process. The secondary cation formed in a first slow step leads to the phenyl-bridged ion by a phenyl shift. Owing to steric hindrance, solvent attack is not observed on the covalent compound 1, and a solvent change causes the mechanism to change: phenyl participation which has been previously established in CF₃CH₂OH, a convenient solvent for this assisted process, is not observed in MeOH. So in a more nucleophilic medium when solvent assistance is inhibited, unlike β phenylalkyl primary derivatives, a secondary β phenyl substrate may not react by phenyl participation but may present a nearly limiting behavior.     

Generation of magnesium carbenoids from 1-chloroalkyl phenyl sulfoxides with a Grignard reagent and applications to alkylation and olefin synthesis

Treatment of 1-chloroalkyl phenyl sulfoxides with a Grignard reagent at low temperature gave magnesium carbenoids in quantitative yields. The generated magnesium carbenoids were found to be stable at lower than −60 °C for long periods of time and are reactive with Grignard reagents to give alkylated products. The reaction of the generated magnesium carbenoids with various kinds of lithium α-sulfonyl carbanions gave olefins with carbon-carbon bond-formation in good to high yields. This method offers a good way for the preparation of olefins. The scope and limitations of the above-mentioned reactions are described.     

The Synthesis of 2-Amino-4-(4-imidazolyl)pyridines

A general synthetic scheme for the preparation of 2-amino-4,(4-imidazolyl)pyridines, potential histamine H₂ antagonists, is described. The synthesis is based on the Neber rearrangement of l,(4-pyridyl)l-alkanone oxime 0-tosylates to the appropriate α-aminoketones or α-aminoketals, which are then converted to the corresponding imidazoles. The reaction of Grignard reagents with 2-chloroisonicotinonitrile, as well as nucleophilic displacement of chloride by amines on 2-chloroisonicotinonitrile and derivatives, are discussed in relation to the preparation of the ketone intermediates.     

Nucleophilic vinylic substitutions on unactivated substrates. : The behaviour of styryl alkyl sulphides and selenides towards sulphur and selenium nucleophiles.

Sodium alkanethiolates or lithium methyl selenide react with styryl alkyl sulphides and selenides, in DMF at 100°C, to give the products of vinylic or aliphatic substitution. The two nucleophilic reagents are extremely selective. In the case of RSNa the attack at the vinylic carbon atom is much faster than that at the aliphatic carbon atom and the (Z)- or (E)- styryl alkyl sulphides are obtained as the result of a stereospecific vinylic substitution which occurs with retention of configuration. On the contrary, in the case of MeSeLi, under the same experimental conditions, the only reaction occurring is the aliphatic substitution which affords the vinyl thiolate anions, as an equilibrium mixture of the (E)- and (Z)- isomers, or the vinyl selenide anions which retain the configuration of the starting styryl alkyl selenides.     

An unexpected course of the Meisenheimer reaction : aryl phosphates in the reaction of phosphoryl chloride with 2, 3-diphenylquinoxaline-N1-oxide.

Contrary to what is observed with other π-deficient heteroaromatic N-oxides, the reaction of 2, 3-diphenylquinoxaline-N₁-oxide with OPCl₃ gives only very poor yields of chlorinated quinoxalines. It is shown that the major product arises from an unprecedented attack by the nucleophilic oxygen atom of the reagent at a carbon atom of the homocycle of the O-phosphorylated N-oxide, leading ultimately to the corresponding mono- (or di-) aryl ester of phosphoric acid. Using a much smaller excess of OPCl₃ and dilution of the medium with an inert solvent strongly increase the yield of chlorination products.     

Gas phase anionic ipso substitution reactions of some alkyl phenyl ethers

It is shown by ¹⁸O labelling that phenoxide anions are formed both by an S_N2 and a nucleophilic aromatic substitution mechanism in the reaction of OH^? with methyl phenyl ether. These mechanisms are of minor importance in the ethyl phenyl ether system where phenoxide anions are generated almost exclusively by an E₂ mechanism.