Regiodivergent epoxide opening: a concept in stereoselective catalysis beyond classical kinetic resolutions and desymmetrizations

An approach to highly regiodivergent epoxide openings (REOs) is presented. The very popular kinetic resolutions of epoxides and openings of meso-epoxides constitute subclasses of such REOs. REOs are attractive for parallel resolutions, double asymmetric reactions of enantiomerically enriched epoxides, and for semisynthetic applications in the functionalization of natural products. They have been notoriously difficult to realize by means of SN2 mechanisms. Our titanocene-catalyzed radical REO addresses this issue by decoupling epoxide opening and radical trapping and is firmly based on a mechanistic study of the reductive epoxide opening.     

Cyclocarbopalladation of alkynes: a stereoselective method for preparing dibenzoxapine containing tetrasubstituted exocyclic alkenes

[reaction: see text] A palladium-catalyzed cascade carbometalation-cross coupling of alkyne route was developed for the preparation of tetrasubstituted exocyclic alkenes with high stereo- and regiocontrol. The effectiveness of this novel methodology was demonstrated by the synthesis of a number of dibenzoxapines in sufficient quantities to support their further development.     

Highly stereoselective method to prepare bis-phenylchalcogen alkenes via addition of chalcogenolate to phenylseleno alkynes

The preparation of bis-phenylchalcogen alkenes starting from phenylseleno alkynes is described. The nucleophilic species of selenium, tellurium and sulfur were generated in situ from the reaction of the respective diphenyl dichalcogenide with NaBH₄ in PEG-400 as solvent. The chalcogenolate anions were efficiently and selectively added to a variety of phenylselenoalkynes at mild conditions, furnishing the respective (Z)-1,2-bis-phenylchalcogen alkenes in good yields.     

Synthesis and photochemical investigations of tetrasubstituted alkenes as molecular switches--the effect of substituents

Molecular switches based on helical tetrasubstituted alkenes, substituted with either electron-withdrawing (CF(3), F, CN; 2a-c, 3a,c) or -donating substituents (Me, OMe; 2d,e), have been synthesized from acyclic precursors 4 and 5 in a domino carbopalladation/Stille reaction. This palladium-catalyzed process allowed the rapid assembly of two C-C bonds, two six-membered rings, and the tetrasubstituted double bond in a completely diastereoselective fashion. The electronic effects of the substituents on the overall switching process were investigated by alternating irradiation of two different wavelength regions. Although the substituents had only a small influence on the absorption maxima, drastic differences in the switching behavior were observed.     

On the regioselectivity for the Michael addition of thiols to unsymmetrical fumaric derivatives

The regiochemistry of the Michael addition of thiols to unsymmetrical fumaric derivatives was investigated. Conjugate addition of thiols to unsymmetrical fumaric diester was well controlled by the presence of lithium cation and one of the two possible regioisomers was prepared in a highly selective manner. Fumaric ester amides underwent the regioselective Michael addition that was controlled by the presence or absence of the base; either of the regioisomers was prepared as an almost diastereomerically pure form. The present control of the regiochemistry can be explained by the factors of change of active site for the addition by the coordination or non-coordination of proton or lithium cation to the carbonyls. To clarify the origin of the regioselectivity, the relative rates of the conjugate addition of thiol to acrylate derivatives were measured under competitive conditions. Ethyl acrylate reacted with thiol faster than tert-butyl acrylate and the rate difference was enhanced by the presence of lithium cation. In the presence of base, ethyl acrylate gave the adducts much faster than acrylamide, while under non-basic conditions acrylamide showed higher reactivity than the ester. This regioselectivity was also observed in the Michael/aldol reaction and multi-substituted γ-butyrolactones were prepared in a stereoselective manner. The thio groups introduced here served as a leaving group and a convenient stereoselective synthesis of β-, γ- and δ-lactams was developed.     

Regioselectivity and reactivity in the addition of trichloromethyl radicals to amides of unsaturated carboxylic acids

The AM1 method was used to analyze the factors that correlate with regioselectivity in the addition of radicals to 1,2-disubstituted unsaturated compounds. The rate constants of the addition of^.CCl₃ radicals to RCH=CHC(O)X (R = Ph, Me; X = N-pyrrolidyl) were determined by ESR. The analysis of the spin density distribution in mono- and 1,2-disubstituted alkenes and the experimental values for the rate constants of the addition of^.CCl₃ radicals to these alkenes allowed the authors to conclude that the efficiency of the addition of^.CC1₃ to unsaturated compounds depends only on steric effects.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 452–455, March, 1995.     

The MARDi cascade: a Michael-initiated domino-multicomponent approach for the stereoselective synthesis of seven-membered rings

The MARDi cascade is a recently invented three-component Michael-initiated condensation involving 1,3-dicarbonyl derivatives. It allows regio- and stereocontrolled access to a variety of functionalised and substituted seven-membered rings. The substitution array can be diastereoselectively modulated by appropriate choice of the reaction partners, and the reaction allows the control of up to five newly created stereocentres and a complete chiral induction in the case of an optically active ketone precursor. The high level of diastereoselectivity observed has been attributed to total thermodynamic control of the reaction. The attractiveness of the present domino three-component approach to seven-membered rings resides in the diversity of carbo- and heterocyclic structures that can be accessed with total regiocontrol and high stereocontrol by starting from simple substrates, under user and environmentally friendly conditions, as now required in modern organic chemistry.     

Phosphonyl radical addition to enol ethers. The stereoselective synthesis of cyclic ethers

Addition of diethyl phosphite or diethyl thiophosphite to enol ethers, in the presence of a radical initiator, results in the regioselective synthesis of organophosphonate or phosphonothioate derivatives, respectively, under mild conditions. This method can be applied to the stereoselective formation of substituted tetrahydrofurans and tetrahydropyrans, on cyclisation of vinyl ethers bearing unsaturated side chains.     

Oxidative Catalysis Using the Stoichiometric Oxidant as a Reagent: An Efficient Strategy for Single‐Electron‐Transfer‐Induced Tandem Anion–Radical Reactions

Oxidative single‐electron transfer‐catalyzed tandem reactions consisting of a conjugate addition and a radical cyclization are reported, which incorporate the mandatory terminal oxidant as a functionality into the product.     

A general and stereoselective method for synthesis of tri- and tetrasubstituted alkenes

A convenient, general and stereoselective synthesis of trisubstituted alkenes and tetrasubstituted alkenes containing a cyanide function as well as trisubstituted episulphides have been elaborated. Methodology described for the preparation of these compounds is based on the corresponding readily available selenophosphates 1 and thiophosphates 2.     

Synthetic applications of the nickel-catalyzed cyclization of alkynes combined with addition reactions in a domino process

Carbonickelations of alkynes and functionalization of the resulting vinylnickel moiety have been performed efficiently in a nickel-catalyzed domino cyclization-condensation process. This reaction, which does not require the preparation of any other organometallic reagent, proceeds only by exo-dig cyclization. This convenient and mild method constitutes a one-pot synthesis of substituted dihydrobenzofurans, chromans, isochromans, indoles, or indanes. Theses valuable products are generally obtained in good yields and high stereoselectivity. They are shown to be useful synthons for rapid access to functionalized polycyclic skeletons.     

N-Phenyltriazolinedione as an initiator in the radical addition of thiophenol to alkenes

N-Phenyltriazolinedione is found to be an efficient initiator in the radical (anti-Markovnikov) addition of thiophenol to 2-methyl-2-butene. A second, minor, product (an alcohol, from oxygen addition) was also obtained, and a possible mechanistic scheme is proposed.     

Highly stereoselective one-pot procedure to prepare bis- and tris-chalcogenide alkenes via addition of disulfides and diselenides to terminal alkynes

We present here the reaction of diorganoyl dichalcogenides with terminal alkynes under catalyst-free conditions, by a one-pot procedure, to prepare bis- and tris-chalcogenide alkenes selectively, avoiding the previous preparation of chalcogen alkynes. The reaction proceeded cleanly under mild reaction conditions, and the addition of dichalcogenides to alkynes occurred stereoselectively to give exclusively the corresponding Z isomers. We observed that the selectivity control was governed by the effective participation of the hydroxyl group from propargyl alcohols. In addition, the bis-chalcogenide alkenes were exclusively obtained with propargyl alcohol having the acidic hydroxyl group proton. Conversely, the alkynes with no potentially acidic hydroxyl group proton, at propargyl positions, gave exclusively the tris-chalcogenide alkenes.