Photochemical and Single Electron Transfer Generation of 2'-Deoxycytidin-4-yl Radical from Oxime Esters.

A 2'-deoxycytidin-4-yl radical (dC·), a strong oxidant that also abstracts hydrogen atoms from carbon-hydrogen bonds, is produced in a variety of DNA damaging processes. We describe here the independent generation of dC· from oxime esters under UV-irradiation or single electron transfer conditions. Support for this σ-type iminyl radical generation is provided by product studies carried out under aerobic and anaerobic conditions, as well as electron spin resonance (ESR) characterization of dC· in a homogeneous glassy solution at low temperature.

Reactivity and DNA Damage by Independently Generated 2'-Deoxycytidin-4-yl Radical.

Oxidative stress produces a variety of radicals in DNA, including pyrimidine nucleobase radicals. The nitrogen-centered DNA radical 2'-deoxycytidin-4-yl radical (dC·) plays a role in DNA damage mediated by one electron oxidants, such as HOCl and ionizing radiation. However, the reactivity of dC· is not well understood.

Access to a Key Building Block for the Prostaglandin Family via Stereocontrolled Organocatalytic Baeyer-Villiger Oxidation.

A new protocol for the construction of a crucial bicyclic lactone of prostaglandins using a stereocontrolled organocatalytic Baeyer-Villiger (B-V) oxidation was developed. The key B-V oxidation of a racemic cyclobutanone derivative with aqueous hydrogen peroxide has enabled an early-stage construction of a bicyclic lactone skeleton in high enantiomeric excess (up to 95 %). The generated bicyclic lactone is fully primed with two desired stereocenters and enabled the synthesis of the entire family of prostaglandins according to Corey's route.

Gold-Catalyzed Oxidative Coupling of Alkynes toward the Synthesis of Cyclic Conjugated Diynes.

A gold-catalyzed oxidative coupling of alkynes was developed as an efficient approach for the synthesis of challenging cyclic conjugated diynes (CCD). Compared to the classical copper-promoted oxidative coupling reaction of alkynes, this gold-catalyzed process exhibits a faster reaction rate due to the rapid reductive elimination from the Au(III) intermediate. This unique reactivity thus allowed a challenging diyne macrocyclization to take place in high efficiency.

Chiral Syn-1,3-diol Derivatives via a One-Pot Diastereoselective Carboxylation/ Bromocyclization of Homoallylic Alcohols.

Chiral syn-1,3-diols are fundamental structural motifs in many natural products and drugs. The traditional Narasaka-Prasad diastereoselective reduction from chiral β-hydroxyketones is an important process for the synthesis of these functionalized syn-1,3-diols, but it is of limited applicability for large-scale synthesis because (1) highly diastereoselective control requires extra explosive and flammable EtBOMe as a chelating agent under cryogenic conditions and (2) only a few functional syn-1,3-diol scaffolds are available. Those involving halogen-functionalized syn-1,3-diols are much less common.

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of -cyclic anhydrides.

A family of novel chloramphenicol base-amide organocatalysts possessing a NH functionality at C-1 position as monodentate hydrogen bond donor were developed and evaluated for enantioselective organocatalytic alcoholysis of -cyclic anhydrides. These structural diversified organocatalysts were found to induce high enantioselectivity in alcoholysis of anhydrides and was successfully applied to the asymmetric synthesis of ()-GABOB.

Recent advances in asymmetric total synthesis of prostaglandins.

Prostaglandins (PGs) are a series of hormone-like chemical messengers and play a critical role in regulating physiological activity. The diversified therapeutic activities and complex molecular architectures of PGs have attracted special attention, and huge progress has been made in asymmetric total synthesis and discovery of pharmaceutically useful drug candidates. In the last 10 years, several powerful syntheses have emerged as new solutions to the problem of building PGs and represent major breakthroughs in this area.

Gold Redox Catalysis through Base-Initiated Diazonium Decomposition toward Alkene, Alkyne, and Allene Activation.

The discovery of photoassisted diazonium activation toward gold(I) oxidation greatly extended the scope of gold redox catalysis by avoiding the use of a strong oxidant. Some practical issues that limit the application of this new type of chemistry are the relative low efficiency (long reaction time and low conversion) and the strict reaction condition control that is necessary (degassing and inert reaction environment). Herein, an alternative photofree condition has been developed through Lewis base induced diazonium activation.

Nucleophile promoted gold redox catalysis with diazonium salts: C-Br, C-S and C-P bond formation through catalytic Sandmeyer coupling.

Gold-catalyzed C-heteroatom (C-X) coupling reactions are evaluated without using sacrificial oxidants. Vital to the success of this methodology is the nucleophile-assisted activation of aryldiazonium salts, which could be an effective oxidant for converting Au(i) to Au(iii) even without the addition of an assisting ligand or photocatalyst. By accelerating the reaction kinetics to outcompete C-C homo-coupling or diazonium dediazoniation, gold-catalyzed Sandmeyer reactions were achieved with different nucleophiles, forming C-Br, C-S and C-P bonds in high yields and selectivities.

Synergistic Gold and Iron Dual Catalysis: Preferred Radical Addition toward Vinyl-Gold Intermediate over Alkene.

A dual catalytic approach enlisting gold and iron synergy is described. This method offers readily access to substituted heterocycle aldehydes via oxygen radical addition to vinyl-gold intermediates under Fe catalyst assistance. This system shows good functional group compatibility for the generation of substituted oxazole, indole, and benzofuran aldehydes.

Gold-catalyzed oxidative cross-coupling of terminal alkynes: selective synthesis of unsymmetrical 1,3-diynes.

Gold-catalyzed oxidative cross-coupling of alkynes to unsymmetrical diynes has been achieved for the first time. A N,N-ligand (1,10-Phen) and PhI(OAc)2 were identified as crucial factors to promote this transformation, giving the desired cross-coupled conjugated diynes in excellent heteroselectivity (>10:1), in good to excellent yields, and with large substrate tolerability.

Silver-catalyzed intramolecular aminofluorination of activated allenes.

A nice combination: the intramolecular oxidative aminofluorination of allenes using silver catalysis and FN(SO(2)Ph)(2) as the fluorinating reagent has been developed. This reaction represents an efficient method for the synthesis of various 4-fluoro-2,5-dihydropyrrole compounds. Further transformation provided the corresponding fluorinated pyrrole derivatives in good yields.

Palladium-catalyzed tandem fluorination and cyclization of enynes.

A novel palladium-catalyzed tandem fluorination and cyclization of enynes has been developed. A favorable cis-fluoropalladation is proposed as a key step to construct a vinyl-F bond, and the final C(sp3)-Pd bond is reduced by alcohol. This transformation represents an efficient road to synthesize fluorinated lactams.