Cleavage of an aromatic carbon-heteroatom bond in a single step or successive steps?--A mechanistic distinction in the reduction of 5-bromo-1,3-dichloro-2-iodobenzene

The electrochemical reductive cleavage of the carbon-iodine bond in 5-bromo-1,3-dichloro-2-iodobenzene has been analyzed from the mechanistic point of view employing the Marcus theory of heterogeneous outer sphere electron transfer. The variation of the electrochemical transfer coefficient with potential has been estimated from the cyclic and convolution voltammetric studies. The comparison of the experimental reorganization energy with the theoretical predictions has revealed the existence of the radical anion of 5-bromo-1,3-dichloro-2-iodobenzene as a transient species.     

Electrochemical reductive cleavage of carbon-halogen bonds in 5-bromo-1,3-dichloro-2-iodobenzene

The electrochemical reduction of carbon-halogen bonds in 5-bromo-1,3-dichloro-2-iodobenzene follows quadratic activation-driving force relationship except in one of the carbon-chlorine bonds. The variation of the transfer coefficient with the electrode potential has been estimated using the voltammetric data coupled with the convolution analysis. The standard potentials pertaining to the reduction of carbon-halogen bonds are evaluated using the Marcus theory of outer sphere electron transfer.     

A stereoselective method for the synthesis of enantiopure 3-substituted 4-hydroxyproline derivatives via 1,3-dipolar cycloadditions

The stereoselective 1,3-dipolar cycloaddition between (Z)-1,4-dichloro-2-butene and a menthone-derived nitrone led to the corresponding isoxazolidine. Regioselective azidation of a single chlorine atom followed by another Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) induced enantiopure 1,2,3-triazolyl-functionalized isoxazolidines. The subsequent acidic cleavage of the menthone chiral auxiliary and reductive cleavage of the isoxazolidine N–O bond triggered an intramolecular cyclization through the displacement of the second chlorine. This rapid and stereoselective synthetic strategy provided reliable access to a series of enantiopure 3-substituted 4-hydroxyproline derivatives.     

Efficient cleavage of the N-O bond of 3,6-dihydro-1,2-oxazines mediated by some alpha-hetero substituted carbonyl compounds in mild conditions

The efficient cleavage of the N-O bond of some nitroso Diels-Alder cycloadducts has been achieved in mild conditions, mediated either by 2,2-dimethyl-1,3-dioxan-5-one or 1,3-dithiolane-2-carboxaldehyde. These new and purely organic conditions allow an excellent tolerance with respect to many functional groups that would have been affected by previous reductive cleavage conditions.     

Unexpected formation of benzaldehydes by the reactions of dithioacetals derived from cinnamaldehydes with 2,3-dichloro-5,6-dicyano-p-benzoquinone in aqueous solvents

1,3-Dithianes 1 , 1,3-dithiolanes 2 , and diphenyl dithioacetals 3 derived from cinnamaldehydes reacted with 2,3-dichloro-5,6-dicyano-p-benzoquinone in aqueous solvents to give benzaldehydes 4 . Hydride transfer from 1–3 to 2,3-dichloro-5,6-dicyano-p-benzoquinone followed by hydrolysis and oxidative carbon-carbon bond cleavage would produce benzaldehydes 4 .     

A new nitrile oxide based synthesis of the antitumor agent geiparvarin

Geiparvarin 1 has been synthesized utilizing the 3,5-disubstituted isoxazole 8 as protected synthon for the 3(2h)furanone system, the desired α′-hydroxy-1,3-diketone precursor being eventually revealed by Mo(CO)₆ promoted reductive cleavage.     

Palladium/nickel-cocatalyzed cycloaddition of 1,3-dehydro-o-carborane with alkynes. Facile synthesis of C,B-substituted carboranes

o-Carboryne (1,2-dehydro-o-carborane) has been reported as a very reactive intermediate and regarded as a three-dimensional relative of benzyne, whereas the 1,3-dehydro-o-carborane has remained elusive. In this article, we present the preparation of 1,3-dehydro-o-carborane from 3-iodo-1-lithio-o-carborane mediated by palladium(0). This reactive intermediate can be trapped by alkynes via Pd/Ni-cocatalyzed [2 + 2 + 2] cycloaddition reaction, leading to the formation of C,B-substituted-o-carborane derivatives. The possible reaction mechanism involving the formation of metal-1,3-dehydro-o-carborane followed by stepwise insertions of 2 equiv of alkyne and reductive elimination is proposed, and the relative reactivity of M-C versus M-B bond in metal-1,3-dehydro-o-carborane complexes is also discussed. This work offers a new methodology for B-functionalization of carboranes and demonstrates that metal-1,3-dehydro-o-carborane can be viewed as a new kind of boron nucleophile.     

The reaction of selenium dichloride with divinyl sulfide

A synthesis of novel selenium heterocycles based on the reaction of selenium dichloride with divinyl sulfide has been described. At −50 °C the reaction affords 2,6-dichloro-1,4-thiaselenane in quantitative yield. At room temperature the reaction gives 2,6-dichloro-1,4-thiaselenane and 5-chloro-2-chloromethyl-1,3-thiaselenolane. Upon standing in chloroform solution, 2,6-dichloro-1,4-thiaselenane undergoes spontaneous rearrangement to 5-chloro-2-chloromethyl-1,3-thiaselenolane. Under the action of pyridine, 2,6-dichloro-1,4-thiaselenane is converted to 2-chloromethyl-1,3-thiaselenole in 95% yield.     

Synthesis and Biological Activity of a Novel Pentacyclic Heterocycle

A novel pentacyclic heterocycle has been synthesized starting from D ‐glucose involving two crucial conversions: the intramolecular cycloaddition of O‐allyloxy furanaldoxime derived from D ‐glucose to furanopyran‐2‐isoxazoline and its diastereoselective reductive cleavage to the corresponding cis‐1,3‐amino alcohol. The antibacterial and antifungal activities of the synthesized heterocycle have been examined.     

A sort synthesis of polyhydroxylated pyrrolizidines via sequential 1,3-dipolar cycloaddition and reductive amination

Polyhydroxylated pyrrolizidines bearing a methyl group at C-5 have been synthesized by 1,3-dipolar cycloaddition of five membered cyclic nitrones with methyl vinyl ketone followed by a N–O reductive cleavage and in situ intramolecular reductive amination. The stereochemistry of the obtained compounds is examined in relation to the reactions mechanism.     

First direct reductive amination of mucochloric acid: a simple and efficient method for preparing highly functionalized alpha,beta-unsaturated gamma-butyrolactams

[reaction: see text] The first direct reductive amination of mucochloric acid (1) has been accomplished. Reaction of 1 with various alkyl, aryl, and benzylamines, followed by reduction in the same pot, provides an efficient method of obtaining N-benzyl-3,4-dichloro-1,5-dihydro-pyrrol-2-one and N-aryl (or alkyl)-3,4-dichloro-1,5-dihydro-pyrrol-2-ones.     

Intermolecular cycloaddition of N-boranonitrone with alkenes

Ethyl glyoxylate O-tert-butyldimethylsilyloxime (8), on treatment with 2.2 equiv of BF3 x OEt2, generated N-boranonitrone E, which underwent intermolecular cycloaddition with alkenes 18 to afford isoxazolidines 19 in moderate to high yields. The cycloaddition of N-boranonitrone E with most of the alkenes gave 3,5-trans isoxazolidines as the major isomers via a concerted mechanism. However, in the case of 1-methylated cyclic alkenes (18j and 18l), the cycloaddition surprisingly furnished the 3,3a-cis-cycloadducts (19j and 19l) as major isomers. A possible explanation is that the reaction of 1-methylated cyclic alkenes proceeds mainly via a stepwise mechanism. This reaction of terminal alkenes is very useful for synthesis of 1,3-anti aminoalcohol derivatives by reductive cleavage of an N-O bond.     

Pentaerythrityltetramine scaffolds for solid-phase combinatorial chemistry

Straightforward synthesis for two pentaerythrityltetramine precursors, 2,2-bis(azidomethyl)propane-1,3-diamine (1) and 2-[N-(allyloxycarbonyl)aminomethyl]-2-azidomethylpropane-1,3-diamine (2), has been described. Both propane-1,3-diamines have been attached by reductive amination to a solid-supported backbone amide linker derived from 4-(4-formyl-3,5-dimethoxyphenoxy)butyric acid. The presence of the two methoxy substituents on the linker is essential to avoid cross-linking between two linkers. The remaining free primary amino group of the propane-1,3-diamine moiety may then be selectively acylated with an appropriately protected amino acid using conventional N,N-dicyclohexylcarbodiimide/1-hydroxybenzotriazole (DCC/HOBt) activation without any interference by the secondary amino function. The latter group may be subsequently acylated by an anhydride method. Sequential reduction of the azido group and removal of the allyloxycarbonyl protection from 2 allow further coupling of two different amino acids, and hence, this handle may be utilized in construction of branched structures containing four different amino acids or peptides. Solid-supported 1 may, in turn, be used for the synthesis of similar constructs containing two identical branches. It is worth noting that no acid-labile protecting groups are required in this approach, and hence, this dimension may be saved for the cleavage of the linker. The applicability of the scaffolds to library synthesis has been demonstrated by preparation of 11 pentaerythrityl-branched tetra- and octapeptides.     

Mechanism of carbon-halogen bond reductive cleavage in activated alkyl halide initiators relevant to living radical polymerization: theoretical and experimental study

The mechanism of reductive cleavage of model alkyl halides (methyl 2-bromoisobutyrate, methyl 2-bromopropionate, and 1-bromo-1-chloroethane), used as initiators in living radical polymerization (LRP), has been investigated in acetonitrile using both experimental and computational methods. Both theoretical and experimental investigations have revealed that dissociative electron transfer to these alkyl halides proceeds exclusively via a concerted rather than stepwise manner. The reductive cleavage of all three alkyl halides requires a substantial activation barrier stemming mainly from the breaking C-X bond. The activation step during single electron transfer LRP (SET-LRP) was originally proposed to proceed via formation and decomposition of RX(?-) through an outer sphere electron transfer (OSET) process (Guliashvili, T.; Percec, V. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 1607). These radical anion intermediates were proposed to decompose via heterolytic rather than homolytic C-X bond dissociation. Here it is presented that injection of one electron into RX produces only a weakly associated charge-induced donor-acceptor type radical anion complex without any significant covalent σ type bond character between carbon-centered radical and associated anion leaving group. Therefore, neither homolytic nor heterolytic bond dissociation applies to the reductive cleavage of C-X in these alkyl halides inasmuch as a true radical anion does not form in the process. In addition, the whole mechanism of SET-LRP has to be revisited since it is based on presumed OSET involving intermediate RX(?-), which is shown here to be nonexistent.     

Synthesis and Characterization of O-Nitrosubstituted Polyimides

Poly(o-nitro)imides have been synthesized by one-stage polycondensation in DMAc at 130°C of 1,3-dichloro-4,6-dinitrobenzene with the di-potassium salt of pyromellitic or 3,3′,4,4′-benzophenonetetracarboxylic acid diimide. The structure was confirmed by elemental analysis, IR, and UV-Vis spectroscopy, and the influence of the o-nitrosubstituents on the solubility and the thermal stability of the prepared polymers was studied. These polymers could be used as pyrrone precursors. The model compound for these polymers has been also prepared by condensation of 1,3-dichloro-4,6-dinitrobenzene with potassium phthalimide.     

Reductive cleavage of C-OH bonds in allyl position-formation of gaseous products in the course of the cathodic reduction of some simple unsaturated alcohols

The problem of the reductive cleavage of C?OH bonds in allyl position has been considered starting from the literature data concerning the behaviour of allyl alcohol. The formation of hydrocarbons has been shown in the case of the electroreduction of crotyl alcohol, 2-butene-1,4-diol, propargyl alcohol, 2-butyne-1,4-diol and 1-butyne-3-ol. The composition of the gaseous products was analyzed, current efficiency values with respect to the hydrocarbon formation were calculated. Schemes for the reduction path were given.     

Enantioselective total synthesis of (+)-leucascandrolide A macrolactone

[reaction: see text] The enantioselective synthesis of the (+)-leucascandrolide A macrolactone has been achieved in 20 linear steps from 1,3-propanediol. The key steps in the synthesis are a reductive cleavage of bicyclic ketal 5 to establish the C15 stereogenic center and a diastereoselective aldol of the boron enolate of methyl ketone 3 to aldehyde 4 in preparation for a heteroconjugate addition for the introduction of the C3 stereocenter.     

A novel thermal rearrangement of the 2-thiabicyclo[3,1,0]hex-3-ene system. The crystal and molecular structure of ethyl-2,4-dichloro-5-hydroxy-6-methylbenzoate

Thermal rearrangement of 1,3-dichloro-6-ethoxycarbonyl-2-thiabicyclo[3, 1, 0]hex-3-ene does not follow the anticipated course, but leads instead to ethyl-2,4-dichloro-5-hydroxy-6-methylbenzoate, whose structure has been confirmed by an X-ray crystal structure determination.     

1,3:4,6-Di-O-benzylidene-d-mannitol as a source for novel chiral intermediates through regioselective reductive cleavage

Synthetically useful chiral intermediates have been synthesized starting from 1,3:4,6-di-O-benzylidene-d-mannitol by regioselective reductive cleavage using BF₃·Et₂O and Et₃SiH in high yields.     

Comments on some chemical properties of diphenyl disulfide and its derivatives: II.Correlating the studies of reductive cleavage of disulfide bonds with the studies of anti-human immunodeficiency virus activity with lowest unoccupied molecular orbital properties

The higher anti-human immunodeficiency virus activity of a symmetrical 2,2′-disubstitued derivative of diphenyl disulfide (DPDS) has been explained by the lower energy of the lowest unoccupied molecular orbital (LUMO), resulted from a better hydrogen bond stabilization of the σ*_SS bond orbital (BO). This conclusion entails the participation of σ*_SS BO in constructing the LUMO. The higher content of σ*_SS BO, compared to π*_CC BOs of phenyl groups, in LUMO of DPDS has been found through analysis of the LUMO of DPDS expanded in the BO space. The high content of σ*_SS BO (%σ*_SS) in the LUMO of DPDS has laid the foundation for the formation of σ-type radical anion intermediate in the stepwise reductive cleavage of disulfide bond in the symmetrical 4,4′-disubstitued DPDS derivatives. For the nine 4,4′-disubstituted DPDS-derivatives under reductive cleavage studies, the increasing %σ*_SS in the LUMOs is parallel to the increasing value of inner reorganization energy.