C-C bond-forming desulfurizations of sulfoximines

Highly substituted, enantiomerically pure azaheterocyclic ring systems play an important role in medicinal chemistry as potential peptide mimetics. Metalated 2-alkenyl sulfoximines offer an efficient entry to this class of compounds. In this paper, we describe a new means to remove the sulfonimidoyl auxiliary with concomitant formation of a C-C double bond.     

Ti-catalyzed homolytic opening of ozonides: a sustainable C-C bond-forming reaction

The unprecedented homolytic opening of ozonides promoted and catalyzed by titanocene(III) is reported. This novel reaction proceeds at room temperature under neutral, mild conditions compatible with many functional groups and provides carbon radicals suitable to form C-C bonds via both homocoupling and cross-coupling processes. The procedure has been advantageously exploited for the straightforward synthesis of the natural product brittonin A.     

Microwave-assisted C-C coupling reaction using polymer-supported electron-rich oxime palladacycles in aqueous condition

Previously reported polymer-supported oxime palladacycle catalyst has shown effective catalytic activity in the Suzuki coupling reaction. In this work, the effect of microwave on reaction rate and induction period was examined by comparing them with the conventional heating. Undoubtedly, microwave heating effectively enhanced the catalytic performance in the Suzuki reaction. In-depth observation of the kinetic profiles revealed that the microwave irradiation not only reduced the overall reaction time but also significantly decreased the induction period to less than 3 min. Finally, the performance of the catalyst in water, coupling of potassium phenyltrifluoroborate and aryl bromides, and recyclability were also examined.     

Tandem carbon-carbon bond-forming radical addition-cyclization reaction of oxime ether and hydrazone

The novel tandem radical addition-cyclization of oxime ethers and hydrazones intramolecularly connected with the alpha,beta-unsaturated carbonyl group is described. The radical reaction of oxime ethers 1, 2, and 4 connected with acryloyl and methacryloyl moieties proceeded smoothly to give the heterocycles via a tandem C-C bond-forming process. The tandem reaction of hydrazone 5 took place in the presence of Zn(OTf)(2) as a Lewis acid to give the trans-cyclic product 17 without the formation of the cis-isomer. The diastereoselective radical addition-cyclization reaction of chiral oxime ether 19 was also studied. The tandem reaction of 19 proceeded smoothly even in aqueous media, providing the novel method for asymmetric synthesis of gamma-butyrolactones and beta-amino acid derivatives.     

Pd-catalyzed C-C bond-forming reactions of thymidine mesitylene sulfonate

Facile synthesis of C-4 aryl pyrimidinone nucleoside analogues from an easily prepared O4-arylsulfonate derivative of thymidine is reported. Two O4-arylsulfonylthymidine precursors, (4-methylphenyl)sulfonyl and (2,4,6-trimethylphenyl)sulfonyl, were prepared and analyzed for their stabilities. Of the two, the latter possessed suitable stability as well as reactivity for Pd-catalyzed C-C bond-forming reactions with a variety of arylboronic acids. These reactions at the C-4 position are nontrivial in comparison with similar reactions at the C-5 position of pyrimidine nucleosides, with hydrolysis of the arylsulfonate precursor being a competing reaction in some cases. There are pronounced solvent influences in these reactions, but successful reactions can be attained by careful control of conditions. Many reactions proceeded efficiently at room temperature, and electron-deficient arylboronic acids can also be cross-coupled under suitable conditions. Desilylation of these products was also nontrivial, and various conditions were tested. Finally, antiviral screening was performed with the C-4 aryl pyrimidinone nucleoside analogues, but none possessed any interesting activity. The study represents the first successful synthesis of C-4 aryl pyrimidinone nucleoside analogues by cross-coupling of arylboronic acids with an arylsulfonate derived from a pyrimidine nucleoside, as well as antiviral testing of this new class of compounds.     

Palladacyclic catalysts in C-C and C-heteroatom bond-forming reactions

Palladacycles are amongst the most active catalysts in Heck-type carbon-carbon bond formation and related carbon-heteroatom bond forming reactions. For instance they have recently emerged as showing the highest activity in the Suzuki coupling of electronically challenging aryl chloride substrates. In addition to the high activity they display, their ease of synthesis, facile modification and comparative stability all act to enhance their appeal.     

Aerobic, Cu-catalyzed desulfitative C-C bond-forming reaction of ketene dithioacetals/vinylogous thioesters and arylboronic acids

A new Cu-catalyzed thioorganic-boronic acid desulfitative C-C bond-forming reaction involving ketene dithioacetals/ vinylogous thioesters is reported to proceed without the assistance of ligating S-pendant. Vinylogous thiolesters and tetrasubstituted olefins were prepared by this reaction in which Cu catalyst plays a dual role under aerobic conditions.     

Total synthesis of bryostatin 7 via C-C bond-forming hydrogenation

The marine macrolide bryostatin 7 is prepared in 20 steps (longest linear sequence) and 36 total steps with five C-C bonds formed using hydrogenative methods. This approach represents the most concise synthesis of any bryostatin reported, to date.     

C-C bond-forming reactions via Pd-mediated decarboxylative alpha-imino anion generation

Alpha-imino anions are generated under neutral reaction conditions via a Pd-mediated decarboxylation of allyl diphenylglycinate imines with concomitant formation of a pi-allylpalladium species. The resulting delocalized anion can attack the pi-allyl-Pd(II) species or be intercepted by aldehydes to afford homoallylic amines or protected 1,2-amino alcohols, respectively.     

Hydrocarbon oxidation vs C-C bond-forming approaches for efficient syntheses of oxygenated molecules

[Reaction: see text] A hydrocarbon oxidation approach has been applied to the construction of several linear (E)-allylic alcohols that have served as intermediates in the synthesis of natural products and natural product-like molecules. In the original syntheses, these intermediates were constructed using a standard Wittig-type olefination approach. We report here that routes to these same intermediates designed around a hydrocarbon oxidation approach are more efficient both in the total number of functional group manipulations (FGMs) and overall steps, as well as in the overall yield.     

Modification of ligand properties of phosphine ligands for C-C and C-N bond-forming reactions

A series of ligands have been prepared for use in Pd-catalysed coupling reactions to form C-C and C-N bonds; significant differences are exhibited by similar ligands containing different phosphorus substituents.     

A Giese reaction for electron-rich alkenes

A general method for the hydroalkylation of electron-rich terminal and non-terminal alkenes such as enol esters, alkenyl sulfides, enol ethers, silyl enol ethers, enamides and enecarbamates has been developed. The reactions are carried out at room temperature under air initiation in the presence of triethylborane acting as a chain transfer reagent and 4-tert-butylcatechol (TBC) as a source of hydrogen atom. The efficacy of the reaction is best explained by very favorable polar effects supporting the chain process and minimizing undesired polar reactions. The stereoselective hydroalkylation of chiral N-(alk-1-en-1-yl)oxazolidin-2-ones takes place with good to excellent diastereocontrol.

Giese reaction not anymore limited to electron poor alkenes! A general method for the radical mediated hydroalkylation of electron rich alkenes including enol ethers, silylenolethers, enamides, and enecarbamates has been developed.     

Catalytic addition of metallo-aldehyde enolates to ketones: a new C-C bond-forming hydrogenation

The first catalytic cross-aldolization of metallo-aldehyde enolates with ketone acceptors is enabled via hydrogenation of keto-enals with cationic rhodium catalysts. These results, in conjunction with prior studies involving the catalytic hydrogen-mediated reductive coupling of enones, dienes, and diynes with carbonyl acceptors, support the feasibility of developing a broad new class of catalytic C-C bond formations based on the electrophilic trapping of hydrogenation intermediates. [reaction: see text]     

C-C bond-forming reductive elimination from a zirconium(IV) redox-active ligand complex

Carbon-carbon bond-forming reductive elimination of biphenyl is observed upon two-electron oxidation of the [ZrIVPh2(ap)2]2- dianion. Crossover experiments confirm that the C-C bond-forming step occurs at a single zirconium metal center. The reactivity is enabled by the participation of a redox-active amidophenolate ligand set.     

Synthesis of aminocyclohexitol via carbon-carbon bond-forming radical cyclization of oxime ether

The stannyl radical mediated-cyclization of oxime ether, derived from D-glucose, gave the aminocyclohexitol derivative. Stereoselective C-C bond forming cyclization proceeded via favorable conformers minimizing A(1,3)-strain between the oxime ether group and alpha-substituents.     

Mechanistic variety in zirconium-catalyzed bond-forming reaction of arsines

Triamidoamine-supported zirconium complexes have been demonstrated to catalyze a range of bond-forming events utilizing arsines. Three different mechanisms have been observed in these reactions. In the first mechanism, triamidoamine-supported zirconium complexes of the general type (N(3)N)ZrX (N(3)N = N(CH(2)CH(2)NSiMe(3))(3)(3-); X = monoanionic ligand) catalyzed the dehydrogenative dimerization of diphenylarsine. Mechanistic analysis revealed that As-As bond formation proceeds via sigma-bond metathesis steps similar to the previously reported dehydrocoupling of phosphines by the same catalysts. In the second mechanism, sterically encumbered primary arsines appear to be dehydrocoupled via alpha elimination of an arsinidene fragment. Dehydrocoupling of dmpAsH(2) (dmp = 2,6-dimesitylphenyl) to form (dmp)As = As(dmp) by (N(3)N)Zr-complexes appeared to proceed via elimination of dmpAs: from the arsenido intermediate, (N(3)N)ZrAsH(dmp). Further support for alpha-arsinidene elimination came from the thermal decomposition of (N(3)N)ZrAsHMes () to (MesAs)(4) (), which obeyed first-order kinetics. In the third mechanism, the observation of stoichiometric insertion reactivity of the Zr-As bond with polar substrates, PhCH(2)NC, PhCN, (1-napthyl)NCS, and CS(2), led to the development of intermolecular hydroarsination catalysis of terminal alkynes. Here, (N(3)N)ZrAsPh(2) () catalyzed the addition of diphenylarsine to phenylacetylene and 1-hexyne to give the respective vinylarsine products. Arsenido complexes and and tetraarsine have been structurally characterized.     

Palladium-catalyzed highly regioselective Heck reaction of aryl nonaflates with electron-rich olefins

Highly efficient palladium-catalyzed Heck coupling of aryl nonaflates with electron-rich vinyl ethers, and enamides is described. These reactions afforded exclusively the branched products in good yields. The results indicated that aryl nonaflates are effective alternative to the frequently employed aryl triflates.     

New titanium complexes with symmetric or asymmetric cis-9,10-dihydrophenanthrenediamide ligands formed through sequential intramolecular C-C bond-forming reactions

A series of new titanium(IV) complexes with symmetric or asymmetric cis-9,10-dihydrophenanthrenediamide ligands, cis-9,10-PhenH(2)(NR)(2)Ti(O(i)Pr)(2) [PhenH(2) = 9,10-dihydrophenanthrene, R = 2,6-(i)Pr(2)C(6)H(3) (2a), 2,6-Et(2)C(6)H(3) (2b), 2,6-Me(2)C(6)H(3) (2c)], cis-9,10-PhenH(2)(NR(1))(NR(2))Ti(O(i)Pr)(2) [R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Et(2)C(6)H(3) (2d); R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Me(2)C(6)H(3) (2e)], and [cis-9,10-PhenH(2)(NR(1))(2)][o-C(6)H(4)(CH=NR(2))]TiO(i)Pr [R(1) = 2,6-(i)Pr(2)C(6)H(3), R(2) = 2,6-Et(2)C(6)H(3) (3a); R(1) = 2,6-(i)Pr(2)C(6)H(3), 2,6-Me(2)C(6)H(3) (3b)], have been synthesized from the reactions of TiCl(2)(O(i)Pr)(2) with o-C(6)H(4)(CH=NR)Li [R = 2,6-(i)Pr(2)C(6)H(3), 2,6-Et(2)C(6)H(3), 2,6-Me(2)C(6)H(3)]. The symmetric complexes 2a-2c were obtained from the reactions of TiCl(2)(O(i)Pr)(2) with 2 equiv of the corresponding o-C(6)H(4)(CH=NR)Li followed by intramolecular C-C bond-forming reductive elimination and oxidative coupling processes, while the asymmetric complexes 2d-2e were formed from the reaction of TiCl(2)(O(i)Pr)(2) with two different types of o-C(6)H(4)(CH=NR)Li sequentially. The complexes 3a and 3b were also isolated from the reactions for complexes 2d and 2e. All complexes were characterized by (1)H and (13)C NMR spectroscopy, and the molecular structures of 2a, 2b, 2e, and 3a were determined by X-ray crystallography.