Cobalt(diamine)-catalyzed cross-coupling reaction of alkyl halides with arylmagnesium reagents: stereoselective constructions of arylated asymmetric carbons and application to total synthesis of AH13205

A cobalt-diamine complex catalyzes the cross-coupling reactions of primary and secondary alkyl halides with aryl Grignard reagents. It is confirmed that oxidative addition of alkyl halide to cobalt proceeds via a radical process. Optically pure Ueno-Stork halo acetals undergo diastereoselective cross-coupling reactions, the products of which are transformed into optically active THF derivatives. A sequential radical cyclization/arylation reaction under cobalt catalysis provides extremely short access to a synthetic prostaglandin AH13205.     

Catalytic C=N bond metathesis of carbodiimides by group 4 and 5 imido complexes supported by guanidinate ligands

A family of guanidinate-supported imido metal complexes are novel, effective catalysts for C=N metathesis of alkyl and aryl carbodiimides and evidence suggests that this reaction proceeds via a sequential addition/elimination pathway.     

Cobalt-catalyzed cross-coupling reactions of alkyl halides with aryl Grignard reagents and their application to sequential radical cyclization/cross-coupling reactions

Reactions of alkyl halides with arylmagnesium bromides in the presence of cobalt(II)(diphosphine) complexes are discussed. Treatment of 1-bromooctane with phenylmagnesium bromide with the aid of a catalytic amount of CoCl₂(dppp) [DPPP=1,3-bis(diphenylphosphino)propane] yielded octylbenzene in good yield. The reaction mechanism would include single electron transfer from an electron-rich cobalt complex to alkyl halide to generate the corresponding alkyl radical. The mechanism was justified by CoCl₂(dppe)-catalyzed [DPPE=1,2-bis(diphenylphosphino)ethane] sequential radical cyclization/cross-coupling reactions of 6-halo-1-hexene derivatives that yielded benzyl-substituted cyclopentane skeletons.     

Cobalt-mediated cross-coupling reactions of primary and secondary alkyl halides with 1-(trimethylsilyl)ethenyl- and 2-trimethylsilylethynylmagnesium reagents

[reaction: see text] This paper describes cobalt-mediated cross-coupling reactions of alkyl halides with 1-(trimethylsilyl)ethenylmagnesium bromide and 2-(trimethylsilyl)ethynylmagnesium bromide, respectively. The cobalt system allows for employing secondary as well as primary alkyl halides as the substrates. The reactions offer facile formations of alkyl-alkenyl and alkyl-alkynyl bonds. The reaction mechanism would include single-electron transfer from a cobalt complex to alkyl halide to generate the corresponding alkyl radical. The cobalt system thus enables sequential radical cyclization/alkenylation and cyclization/alkynylation reactions of 6-halo-1-hexene derivatives.     

A New Route to Dithiocarbamates from Tertiary N-Methyl and N-Benzylamines

The sequential treatment of various tertiary N-methyl and N-benzylamines with carbon disulfide, and then with an alkyl halide in tetrahydrofuran gave the corresponding dithiocarbamates in good to excellent yields.     

Sequential one-pot ruthenium-catalyzed azide-alkyne cycloaddition from primary alkyl halides and sodium azide

An experimentally simple sequential one-pot RuAAC reaction, affording 1,5-disubstituted 1H-1,2,3-triazoles in good to excellent yields starting from an alkyl halide, sodium azide, and an alkyne, is reported. The organic azide is formed in situ by treating the primary alkyl halide with sodium azide in DMA under microwave heating. Subsequent addition of [RuClCp*(PPh(3))(2)] and the alkyne yielded the desired cycloaddition product after further microwave irradiation.     

Synthesis of functionalised cyclohexadienes through addition of lithiated phosphine borane complexes to benzonitriles

Functionalised 1,3- and 1,4-cyclohexadienes have been prepared through dearomatisation of benzonitriles by sequential conjugate addition of -lithium alkyl(diphenyl)phosphine borane in the presence of HMPA and capture of the intermediate anion with protonating and alkylating reagents.     

Observation of neighboring ortho-hydroxyl group participation in organocatalytic asymmetric sequential Michael-lactonization reactions: synthesis of highly substituted chiral spirodihydrocoumarins

A general approach to asymmetric synthesis of highly substituted spirodihydrocoumarins with a quaternary stereocenter was achieved through neighboring ortho-hydroxyl group induced sequential Michael-lactonization reactions on 2-(2-nitrovinyl)phenols with alkyl cyclopentanone-2-carboxylates in the presence of a catalytic amount of quinine-NH-thiourea followed by p-TSA.     

A straightforward method for the synthesis of unsymmetrically substituted 1,3-diynes

An efficient synthetic approach to a variety of unsymmetrically substituted conjugated diynes has been developed, starting from the readily available 1,4-bis(trimethylsilyl)-1,3-butadiyne, based upon the selective and sequential substitution of the trimethylsilyl groups with alkyl, aryl and vinyl groups.     

A direct functionalization of tertiary alkyl bromides with O-, N-, and C-nucleophiles

Silver oxide used in stoichiometric amounts promoted the direct functionalization of tert-alkyl bromides and provided the desired adducts in 39-96% isolated yield. Reaction of tert-bromides with carboxylic acids yielded esters, with alcohols and phenols yielded alkyl and aryl ethers, with amines and anilines yielded selectively mono-alkylated amines and anilines, and with a C-nucleophile yielded an all-carbon quaternary hydrocarbon. The method was applied to a sequential alkylation of a primary amine with two different alkyl bromides yielding selectively a tertiary amine with three different substituents in one-pot.     

Rhodium(I)‐Catalyzed Sequential C(sp)C(sp3) and C(sp3)C(sp3) Bond Formation through Migratory Carbene Insertion

A Rh^I‐catalyzed three‐component reaction of tert‐propargyl alcohol, diazoester, and alkyl halide has been developed. This reaction can be considered as a carbene‐involving sequential alkyl and alkynyl coupling, in which C(sp)? C(sp³) and C(sp³)? C(sp³) bonds are built successively on the carbenic carbon atom. The Rh^I‐carbene migratory insertion of an alkynyl moiety and subsequent alkylation are proposed to account for the two separate C? C bond formations. This reaction provides an efficient and tunable method for the construction of all‐carbon quaternary center.     

Rhodium(I)‐Catalyzed Sequential C(sp)?C(sp3) and C(sp3)?C(sp3) Bond Formation through Migratory Carbene Insertion

A Rh^I‐catalyzed three‐component reaction of tert‐propargyl alcohol, diazoester, and alkyl halide has been developed. This reaction can be considered as a carbene‐involving sequential alkyl and alkynyl coupling, in which C(sp) C(sp³) and C(sp³) C(sp³) bonds are built successively on the carbenic carbon atom. The Rh^I‐carbene migratory insertion of an alkynyl moiety and subsequent alkylation are proposed to account for the two separate C C bond formations. This reaction provides an efficient and tunable method for the construction of all‐carbon quaternary center.     

Synthesis of 2,4,6-tri-substituted-1,3,5-triazines

Several specific synthetic protocols were developed for the preparation from cyanuric chloride of a range of symmetric and non-symmetric di- and tri-substituted 1,3,5-triazines containing alkyl, aromatic, hindered, chiral and achiral hydroxyalkyl, ester and imidazole groups via sequential nucleophilic substitution of the C-Cl bond by C-O, C-N and C-S bonds.     

A mathematical relationship between the number of isomers of alkenes and alkynes: a result established from the enumeration of isomers of alkenes from alkyl biradicals

A simple and fast algorithm for enumerating alkene isomers is described. This algorithm is based on a 2-step hypothetical chemical reaction. In the first step, an alkane molecule loses two protons becoming an alkyl biradical. In the second step, two alkyl biradicals react to form an alkene molecule. By using two sequential recursive algorithms, the number of computational terms in the enumeration process is much less than when using the Henze–Blair algorithm. By using this simple algorithm, the numbers of constitutional isomers of alkenes and alkynes for carbon content greater than 30 are easily enumerated. In addition, through this algorithm, a mathematical relationship between the number of constitutional isomers of alkenes and alkynes has been established for the first time. This revised version was published online in July 2006 with corrections to the Cover Date.     

One-pot synthesis of tertiary alkyl fluorides from methyl oxalates by radical deoxyfluorination under photoredox catalysis

Tertiary alkyl fluorides have been prepared from methyl oxalates derived from tertiary alcohols by a sequential one-pot hydrolysis/photoredox catalyzed radical deoxyfluorination sequence. The reaction operates under mild conditions and tolerates a wide range of functional groups. This method provides an alternative approach to ionic deoxyfluorination transformations for the incorporation of Carbone–Fluorine quaternary centers into organic molecules.     

A highly selective tandem cross-coupling of gem-dihaloolefins for a modular, efficient synthesis of highly functionalized indoles

A highly efficient method of indole synthesis using gem-dihalovinylaniline substrates and an organoboron reagent was developed via a Pd-catalyzed tandem intramolecular amination and an intermolecular Suzuki coupling. Aryl, alkenyl, and alkyl boron reagents are all successfully employed, making for a versatile modular approach. The reaction tolerates a variety of substitution patterns on the aniline leading to indoles with group at C2-C7. The orthogonal approach of the sequential copper- and palladium-mediated synthesis of 1,2-diarylindoles exploited the wide availability of diverse organoboron reagents.     

Palladium and gold-palladium catalysts for the direct synthesis of hydrogen peroxide

Today hydrogen peroxide is produced by an indirect process in which an alkyl anthraquinone is sequentially hydrogenated and oxidized. In this way hydrogen and oxygen are kept separate during the manufacturing process. A process where molecular oxygen is directly hydrogenated could be preferred if control of the sequential hydrogenation can be achieved, particularly if high rates can be attained under intrinsically safe, non-explosive conditions. Herein we describe recent progress in the direct synthesis of hydrogen peroxide using supported palladium and gold-palladium alloy catalysts and consider some of the problems that have to be overcome.     

Polymerization of Polar Monomers Using Cyclopentadienyl Complexes of the Alkaline Earth Metals

Tetramethylcyclopentadienyl complexes of magnesium, calcium and strontium are efficient catalysts at −78 °C for the solution polymerization of polar monomers such as alkyl methacrylates in the presence of only small amounts of triethylaluminium as cocatalyst. The molecular mass of the resulting polymers is predictable on the monomer/catalyst ratio. The polymerization reaction follows a first order kinetics with respect to the initial catalyst concentration. Block-copolymers are easily available by sequential dosage of the monomer. A living polymerization mechanism is proposed involving activation of the catalyst by alkylation and subsequent insertion of coordinated monomers.     

Mechanistic studies on the alkyltransferase activity of serotonin N-acetyltransferase

BACKGROUND: Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) catalyzes the first, rate-limiting step in the biosynthesis of the circadian hormone melatonin (5-methoxy-N-acetyltryptamine) from serotonin. Our recent discovery that, in addition to catalyzing the acetyl transfer from acetyl-coenzyme A (acetyl-CoASH) to serotonin, AANAT is also a robust catalyst for the alkyl transfer reaction between CoASH and N-bromoacetyltryptamine has not only opened up a new way to develop cell-permeable AANAT acetyltransferase inhibitors that are valuable in vivo tools in helping elucidate melatonin's (patho)physiological roles, but has also raised a question - how does AANAT accelerate the alkyl transfer reaction? In this study, mechanistic aspects of the AANAT-catalyzed alkyl transfer reaction were explored by employing CoASH and a series of N-haloacetyltryptamines that were also evaluated for their AANAT acetyltransferase inhibitory activities. RESULTS: Investigation of various N-haloacetyltryptamine analogs showed a similar leaving group effect on the enzymatic and non-enzymatic reaction rates. Steady-state kinetic analyses demonstrated that AANAT alkyltransferase obeys a sequential, ternary complex mechanism, with random substrate binding. Rate versus pH profiles revealed the catalytic importance of an ionizable group with pK(a) of approximately 7. All those N-haloacetyltryptamines that serve as substrates of AANAT alkyltransferase are also potent (low micromolar) in vitro inhibitors against AANAT acetyltransferase activity. In particular, N-chloroacetyltryptamine was also shown to be a potent inhibitor of intracellular melatonin production in a pineal cell culture assay. CONCLUSIONS: This is the first detailed investigation of the alkyltransferase activity associated with an acetyltransferase. Our results indicate that AANAT does not accelerate the alkyl transfer reaction by simple approximation effect as previously proposed for the similar alkyl transfer reaction catalyzed by other acyltransferases. This study has general implications for developing novel inhibitors by taking advantage of the promiscuous alkyltransferase activity associated with several acyltransferases.     

Synthesis of saponins using partially protected glycosyl donors

[reaction: see text] A new class of glycosyl donors having unprotected 2- and 2,4-hydroxyl groups were investigated under the standard glycosylation conditions. This approach was shown to be generally effective for the synthesis of alkyl and steroidal glycosides. A natural saponin, containing 2,4-branched oligosaccharide, was prepared in 35% overall yield in four straightforward sequential reactions by taking advantage of these partially protected donors.