Stereospecific palladium-catalyzed 1,4-acetoxychlorination of 1,3-dienes

Palladium-catalyzed oxidation of 1,3-dienes in acetic acid in the presence of LiCl and LiOAc produces 1-acetoxy-4-chloro-2-alkenes in high selectivity. The 1,4-adducts were stereo- and regioselectively functionalized.     

Stereospecific synthesis of 2,3-disubstituted 1,4-benzodioxans

The synthesis of cis- and trans-2-methyl-3-phenyl-1,4-benzodioxans 4 and 5 , from 1-phenyl-2-[2-(hydroxy)-phenoxy]propanols threo 2 and erythro 3 are described.     

Gas-phase carbene radical anions: new mechanistic insights

The gas-phase reactivity of the CHCl*- anion has been investigated with a series of halomethanes (CCl4, CHCl3, CH2Cl2, and CH3Cl) using a FA-SIFT instrument. Results show that this anion primarily reacts via substitution and by proton transfer. In addition, the reactions of CHCl*- with CHCl3 and CH2Cl2 form minor amounts of Cl2*- and Cl-. The isotopic distribution of these two products is consistent with an insertion-elimination mechanism, where the anion inserts into a C-Cl bond to form an unstable intermediate, which eliminates either Cl2*- or Cl- and Cl*. Neutral and cationic carbenes are known to insert into single bonds; however, this is the first observation of such reactivity for carbene anions.     

Ammonium-directed olefinic epoxidation: kinetic and mechanistic insights

The ammonium-directed olefinic epoxidations of a range of differentially N-substituted cyclic allylic and homoallylic amines (derived from cyclopentene, cyclohexene, and cycloheptene) have been investigated, and the reaction kinetics have been analyzed. The results of these studies suggest that both the ring size and the identity of the substituents on nitrogen are important in determining both the overall rate and the stereochemical outcome of the epoxidation reaction. In general, secondary amines or tertiary amines with nonsterically demanding substituents on nitrogen are superior to tertiary amines with sterically demanding substituents on nitrogen in their ability to promote the oxidation reaction. Furthermore, in all cases examined, the ability of the (in situ formed) ammonium substituent to direct the stereochemical course of the epoxidation reaction is either comparable or superior to that of the analogous hydroxyl substituent. Much slower rates of ring-opening of the intermediate epoxides are observed in cyclopentene-derived and cycloheptene-derived allylic amines as compared with their cyclohexene-derived allylic and homoallylic amine counterparts, allowing for isolation of these intermediates in both of the former cases.     

Stereospecific construction of a trans-1,4-diphosphacyclohexane skeleton

trans-1,4-Diphosphacyclohexanes were successfully synthesized by the stereospecific intramolecular coupling reaction of the optically active bisphosphine. This is a new route for the construction of the trans-1,4-diphosphacyclohexane skeleton. A cis isomer was also prepared along with the trans isomer from a mixture of rac- and meso-bisphosphines. The coordinated boranes were easily removed to afford the corresponding 1,4-diphosphacyclohexanes.     

A New Stereospecific Synthesis of 1,2,4-Trideoxy-1,4-Imino-D-Erythro-Pentitol

ABSTRACT

1,2,4-Trideoxy-1,4-imino-D-erythro-pentitol [(2R,3S)-3-hydroxy-2-hydroxyme-thylpyrrolidine] (4) was synthesised from 2,5-di-O-tosyl-D-ribono-1,4-lactone in 42% overall yield. The key steps were deoxygenation at C-2 and a stereospecific inversion of the configuration at C-4. Compound 4 inhibited α-D-glucosidase (K_i = 25 μM) and β-D-glucosidase (K_i = 80 μM).     

Chiral N-acyloxazolidines: synthesis, structure, and mechanistic insights

A series of chiral imines derived from 1-amino-1-deoxyalditols such as d-glucamine, a rather unexplored raw material from the chiral pool, have been serendipitiously transformed into a novel family of N-acetyl-1,3-oxazolidines by means of an unexpected acetylation. The structure of these substances is supported by spectroscopic and crystallographic data. The acetylates also trigger a complex dynamic transformation, in which an initially configured trans oxazolidine converts into a more stable cis-configured derivative. Both isomers can also exist as rotational conformers (E,Z) as a consequence of the restricted rotation around the N-acetyl bond. The barriers to rotation have been determined by variable-temperature experiments. Overall, this transformation most likely involves the intermediacy of a chiral iminium ion, which has been documented in the synthesis of nitrogen heterocycles, thus explaining the experimental facts.     

Copper-catalyzed aerobic oxidative C-H functionalizations: trends and mechanistic insights

The selective oxidation of C-H bonds and the use of O(2) as a stoichiometric oxidant represent two prominent challenges in organic chemistry. Copper(II) is a versatile oxidant, capable of promoting a wide range of oxidative coupling reactions initiated by single-electron transfer (SET) from electron-rich organic molecules. Many of these reactions can be rendered catalytic in Cu by employing molecular oxygen as a stoichiometric oxidant to regenerate the active copper(II) catalyst. Meanwhile, numerous other recently reported Cu-catalyzed C-H oxidation reactions feature substrates that are electron-deficient or appear unlikely to undergo single-electron transfer to copper(II). In some of these cases, evidence has been obtained for the involvement of organocopper(III) intermediates in the reaction mechanism. Organometallic C-H oxidation reactions of this type represent important new opportunities for the field of Cu-catalyzed aerobic oxidations.     

Stereospecific synthesis and carbon-13 nmr spectra of 1,4-epoxydecahydronaphthalenes

The stereoselective synthesis of cis-fused 1,4-epoxydecahydronaphthalenes from transannular reactions of medium-ring compounds is described. The carbon-13 nmr spectra of both are reported, and assignments of the various resonances have been made based on model compounds and off-resonance decoupling experiments.     

Cobalt(I)-mediated cycloisomerization of enynes: mechanistic insights

[CpCo(CO)2] catalyzes the cycloisomerization of 1,n-enynes to afford selectively five- and six-membered ring systems in high yields. The factors governing the cyclization have been explored and we have discovered that the reaction associates two different, but complementary, reactivities of the cobalt(I) complexes. By a judicious choice of the substitution of the enyne, it was also possible to isolate a cyclobutene that arises from a cobaltcyclopentene     

Supramolecular catalysis of unimolecular rearrangements: substrate scope and mechanistic insights

A cavity-containing metal-ligand assembly is employed as a catalytic host for the 3-aza Cope rearrangement of allyl enammonium cations. Upon binding, the rates of rearrangement are accelerated for all substrates studied, up to 850-fold. Activation parameters were measured for three enammonium cations in order to understand the origins of acceleration. Those parameters reveal that the supramolecular structure is able to reduce both the entropic and enthalpic barriers for rearrangement and is highly sensitive to small structural changes of the substrate. The space-restrictive cavity preferentially binds closely packed, preorganized substrate conformations, which resemble the conformations of the transition states. This hypothesis is also supported by quantitative NOE studies of two encapsulated substrates, which place the two reacting carbon atoms in close proximity. The capsule can act as a true catalyst, since release and hydrolysis facilitate catalytic turnover. The question of product hydrolysis was addressed through detailed kinetic studies. We conclude that the iminium product must dissociate from the cavity interior and the assembly exterior before hydroxide-mediated hydrolysis, and propose the intermediacy of a tight ion pair of the polyanionic host with the exiting product.     

Palladium-NHC complexes do catalyse the diboration of alkenes: mechanistic insights

Novel catalytic activation of the B-B bond by palladium(II)-NHC complexes in presence of a mild base (NaOAc) and an excess of diboron reagent enables chemoselective 1,2-diboration of alkenes, suggesting the heterolytic cleavage of diboron rather than oxidative addition of a B-B bond to the metal.     

Ozonolysis of bicyclic 1,2-dioxines: initial scope and mechanistic insights

The ozonolysis of bicyclic 1,2-dioxines was investigated using a variety of 1,4-disubstituted 1,2-dioxines along with a 1,3-dialkyl and steroidal example, with yields ranging from moderate to excellent. Two different pathways were observed upon reaction of the 1,4-disubstituted 1,2-dioxines with ozone; one pathway saw the "expected" results, that is, cleavage of the olefinic moiety with generation of 1,4-dicarbonyl 1,2-dioxines, while the other pathway revealed a previously unobserved rearrangement involving cleavage of the peroxide linkage along with loss of either CO or CO(2). Several unsymmetrical ozonolyses were also performed to further investigate the origins of this rearrangement, and initial mechanistic insights into the fragmentation pathways are discussed.     

Quantum chemical investigation by the AM1 method of the catalytic cyclodehydration of 1,4-butanediol

1,4-Butanediol is converted into tetrahydrofuran in the presence of silica gel at temperatures of 245–340°C. The mechanism of the conversion of 1,4-butanediol has been studied by the quantum chemical AM1 method with full optimization of the geometry. It was established that two parallel reactions are possible depending on the conformation of the molecule. The cyclodehydration reaction is effected by conversion of a semicyclic conformer of the protonated diol molecule at a basic center of the catalyst by a concerted mechanism. The heat of the reaction forming tetrahydrofuran is —161.768 kcal/mole.Latvian Institute of Organic Synthesis, Riga LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 608–613, May, 1998.     

Exhaustive oxidation of a nickel dithiolate complex: some mechanistic insights en route to sulfate formation

A study of the step-wise oxidation of a Ni(II) diaminodithiolate complex through the formation of sulfate, the ultimate sulfur oxygenate, is reported. Controlled oxygenations or peroxidations of a neutral, planar, tetracoordinate, low-spin Ni(II) complex of a N(2)S(2)-donor ligand, (N,N'-dimethyl-N-N'-bis(2-mecaptoethyl)-1,3-propanediaminato) nickel(ii) (1), led to a series of sulfur oxygenates that have been isolated and characterized by ESI-MS and single-crystal X-ray diffraction. A monosulfenate complex (2) was detected by ESI-MS as a product of oxidation with one equivalent of H(2)O(2). However, this complex proved too unstable to isolate. Reaction of the dithiolate (1) with two equivalents of H(2)O(2) or one O(2) molecule leads to the formation of a monosulfinate complex (3), which was isolated and fully characterized by crystallography. The oxidation product of the monosulfinate (3) produced with either O(2) or H(2)O(2) is an interesting dimeric complex containing both sulfonate and thiolate ligands (4), this complex was fully characterized by crystallography, details of which were reported earlier by us. A disulfonate complex (7) is produced by reaction of 1 in the presence of O(2) or by reaction with exactly six equivalents of H(2)O(2). This complex was isolated and also fully characterized by crystallography. Possible intermediates in the conversion of the monosulfinate complex (3) to the disulfonate complex (7) include complexes with mixed sulfonate/sulfenate (5) or sulfonate/sulfinate (6) ligands. Complex 5, a four-oxygen adduct of 1, was not detected, but the sulfonate/sulfinate complex (6) was isolated and characterized. The oxidation chemistry of 1 is very different from that reported for other planar cis-N(2)S(2) Ni(ii) complexes including N,N'-dimethyl-N-N'-bis(2-mecaptoethyl)-1,3-ethylenediaminato) nickel(II), (8), and N,N'-bis(mercaptoethyl)-1,5-diazacyclooctane nickel(II). To address the structural aspects of the reactivity differences, the crystal structure of 8 was also determined. A comparison of the structures of planar Ni(II) complexes containing cis-dithiolate ligands, strongly suggests that the differences in reactivity are determined in part by the degree of flexibility that is allowed by the NN' chelate ring.     

Oxidative transformation of azides to aryl nitriles using DIB/TBHP: scope and mechanistic insights

Bis(tert-butylperoxy)iodobenzene, generated in situ by the reaction between diacetoxyl iodobenzene (DIB) and tert-butyl hydroperoxide (TBHP), was used in the oxidative transformation of primary azides to nitriles, and secondary azides to ketones.     

Cycloisomerization of 1,n-enynes: challenging metal-catalyzed rearrangements and mechanistic insights

Metal-catalyzed cycloisomerization reactions of 1,n-enynes have appeared as conceptually and chemically highly attractive processes as they contribute to the highly demanded search for atom economy and allow the discovery of new reactions. Since the pioneering studies with palladium by the research group of Barry Trost in the mid-1980s, several other metals have been identified as excellent catalysts for the rearrangement of enyne skeletons. Moreover, the behavior of 1,n-enynes may be influenced by other functional groups such as alcohols, aldehydes, ethers, alkenes, or alkynes, thus enhancing the molecular complexity of the synthesized products. Apart from the intrinsic rearrangements of 1,n-enynes, several tandem reactions incorporating intramolecular trapping agents or intermolecular partners have been discovered. This Review aims to highlight the main contributions in this field of catalysis and to propose and comment on the mechanistic insights of the recent discoveries.     

Stereocontrolled intramolecular aziridination of glycals: ready access to aminoglycosides and mechanistic insights from DFT studies

Stereocontrolled intramolecular aziridination of the glycal-derived sulfamates offers a highly efficient strategy to divergently prepare aminoglycosides. Rhodium-catalyzed nitrogen-atom transfer to C==C bonds formed semistable aziridines, which were subjected to various nucleophiles (C, O, S, and N) to give cyclic sulfamate-containing aminosugar derivatives selectively. The second nucleophilic displacement of sulfonyloxy moieties of [1,2,3]-oxathiazepane-2,2- dioxides allows straightforward access to aminoglycosides with selective alpha- or beta-linkages. This approach is operationally simple, complements existing methods, and is a versatile protocol for the synthesis of polyfunctionalized amino sugars. In addition, the mechanism of the rhodium-catalyzed intramolecular aziridination of glycals and its ring-opening reaction was extensively studied by using DFT calculations.