Oxidative Cleavage of Ketoximes with Iodosobenzene Diacetate

Hypervalent iodine oxidation of ketoximes (1) using iodosobenzene diacetate leads to cleavage of 1 with the formation of corresponding ketones (2) under neutral conditions in good yields. The scope and limitations of the reaction are discussed as well as the mechanism.     

Selective Cleavage of the HIV-1 TAR-RNA with a Peptide–Cyclen Conjugate

Covalent linkage of the arginine-rich fragment of the Tat protein to 1,4,7,10-tetraazacyclododecane (cyclen) results in the selective cleavage of the TAR-RNA of HIV-1 (see picture; the biotin at the 5′ end acts as a label for the subsequent analysis of the cleavage fragments). The cleavage occurs at room temperature and is diminished when Eu^III ions are present—at a concentration of about 1/10 of the concentration of the peptide–cyclen conjugate. The pH dependence indicates that two ammonium ions are responsible for the cleavage reaction. The white arrows in the schematic diagram mark the cleavage sites in RNase T1, and the black arrows the sites in the peptide–cyclen conjugate.     

Regioselective Cleavage of Thioether Linkages in Microcystin Conjugates

Microcystins are cyanobacterial toxins that can be found in fresh and coastal waters during algal blooms. Microcystin contamination of water can cause severe poisoning of animals and humans. Quantification of these toxins in biological samples is complicated because a major proportion of microcystins is covalently linked to proteins through thioether bonds formed through a Michael‐type addition of cysteine residues of proteins to an N‐methyldehydroalanine residue in the microcystins. We investigated chemical methods that can be used to cleave such thioether bonds by means of an elimination reaction that leaves the microcystin backbone intact for subsequent analysis. The known reagent O‐mesitylenesulfonylhydroxylamine (MSH) led to regioselective thioether cleavage, but a large excess of reagent was needed, thus making purification challenging. An unexpected side reaction observed during the investigation of the base‐induced elimination inspired us to develop a new thioether‐cleavage methodology based on the addition of propargylamine as a nucleophile that can trap the elimination product. This methodology could be successfully applied to the quantitative cleavage of a microcystin‐LF–glutathione conjugate. The alkyne moiety introduced by this procedure offers the possibility for further reactions with azides by using click chemistry, which might be useful for the derivatization or isolation of microcystins.     

Enantioselective conjugate addition of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones catalyzed by chiral bifunctional organocatalysts

The catalytic enantioselective conjugate addition reaction of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones promoted by chiral bifunctional organocatalysts is described. The treatment of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones under mild reaction conditions afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are useful for the synthesis of chiral monofluoromethylated compounds.     

Highly enantioselective conjugate additions to alpha,beta-unsaturated ketones catalyzed by a (salen)Al complex

Chiral (salen)Al complex 1a catalyzes the highly enantioselective conjugate addition of carbon- and nitrogen-based nucleophiles to acyclic alpha,beta-unsaturated ketones. This methodology is tolerant of substantial variation of the ketone structure, providing access to a wide range of useful chiral building blocks in high yield and enantiomeric excess. Synthetic manipulations of the conjugate addition products are demonstrated, including the straightforward preparation of beta-amino ketones and highly enantioenriched carbo- and heterocyclic compounds.     

Bismuth trichloride-catalyzed oxy-Michael addition of water and alcohol to α,β-unsaturated ketones

An efficient method was developed for the conjugate addition of water to various α,β-unsaturated ketones by using bismuth(III) chloride as a catalyst. The reactions proceeded smoothly in the presence of a catalytic amount of BiCl₃ (20 mol%) in aqueous media to furnish a variety of synthetically useful β-hydroxyl ketones in moderate to good yields. Apart from water molecule, various alcohols could also be employed as nucleophiles to react with α,β-unsaturated ketones, leading to β-alkoxyl ketones in modest to high yields. In addition, the mild reaction conditions also entailed the conjugate addition reactions to proceed with the tolerance to a range of functional groups.     

A convenient approach to β-heteroarylated (C-N bond) ketones from Cs2CO3 promoted reaction between propargyl alcohols and nitrogen-heterocycles

An efficient and direct approach to β-heteroarylated (C-N bond) ketones is demonstrated. Base promoted redox isomerization of propargyl alcohol to α,β-unsaturated ketone followed by conjugate addition to NH-heteroarenes affords a wide range of β-heteroarylated ketones in good to excellent yields. Aryl, heteroaryl, alkyl C(sp), and terminal alkynes containing unactivated propargyl alcohols effectively undergo redox-isomerization conjugate addition (RICA) with NH-heteroarenes. Reaction of 3-substituted pyrazoles or indazole with propargyl alcohols enables highly regioselective products. A diverse range of NH-bearing nucleophiles such as: pyrazoles, imidazole, triazoles, pyrrole, indoles and aniline participate in this reaction and deliver the corresponding β-heteroarylated ketones.     

Ceric ammonium nitrate (CAN) as a green and highly efficient promoter for the 1,4-addition of thiols and benzeneselenol to α,β-unsaturated ketones

A mild and efficient process for the 1,4-addition of thiols and benzeneselenols to various α,β-unsaturated ketones using a catalytic amount of CAN with excellent product yields is described. This inexpensive, nontoxic, and readily available catalytic ceric(IV) ammonium nitrate system efficiently catalyzes conjugate addition reactions between thiol derivatives and various α,β-unsaturated ketones under solvent-free conditions. A plausible mechanism for the role of CAN, both as a promoter in free radical chain addition reactions as well as a catalyst for the conjugate addition process is proposed.     

Cobalt-Catalyzed Aerobic Oxidative Cleavage of Alkyl Aldehydes: Synthesis of Ketones,Esters, Amides,and α-Ketoamides

A widely applicable approach was developed to synthesize ketones, esters, amides via the oxidative C−C bond cleavage of readily available alkyl aldehydes. Green and abundant molecular oxygen (O₂) was used as the oxidant, and base metals (cobalt and copper) were used as the catalysts. This strategy can be extended to the one-pot synthesis of ketones from primary alcohols and α-ketoamides from aldehydes.     

Organocatalytic C3-selective Friedel-Crafts alkylations of indoles with alpha,beta-unsaturated ketones

The use of an equimolar amount of pyrrolidine and HClO4 (30 mol%) was found to be effective in promoting the conjugate addition of indoles to (E)-alpha,beta-unsaturated ketones, affording the corresponding beta-indolyl ketones in excellent yields.     

Enantioselective conjugate radical addition to alpha'-hydroxy enones

Enantioselective conjugate radical addition to alpha'-hydroxy alpha,beta-unsaturated ketones, compounds containing bidentate donors, has been investigated. It has been found that radical additions to alpha'-hydroxy alpha,beta-unsaturated ketones in the presence of Mg(NTf2)2 and bisoxazoline ligand 5a proceeded cleanly, yielding the addition products in high chemical yields and good enantiomeric excesses.     

Copper/Palladium‐Cocatalyzed Aerobic Synthesis of Bisaryl Ketones from Olefins via C‐C Double Bonds Cleavage

A novel palladium/copper‐catalyzed aerobic synthesis of bisaryl ketones from 1,2‐diarylalkenes via C‐C double bonds cleavage has been described. This reaction constitutes a new transformation from 1,2‐diarylalkenes into bisaryl ketones, providing a unifying, simple and environmentally friendly complement to the available methods.     

Enantioselective organocatalytic conjugate addition of α-nitroacetate to α,β-unsaturated ketones in water

The catalytic enantioselective conjugate addition reaction of α-nitroacetate to α,β-unsaturated ketones promoted by chiral bifunctional organocatalysts is described. The treatment of α-nitroacetate to α,β-unsaturated ketones under aqueous-phase reaction conditions afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are easily converted to chiral δ-keto nitroalkanes and δ-keto esters.     

Copper-catalyzed enantioselective 1,4-conjugate addition of dialkylzinc reagents to α,β- and α,β,γ,δ-unsaturated ketones

An enantioselective Cu(II)-catalyzed conjugate addition of dialkylzinc reagents to α,β- or α,β,γ,δ-unsaturated ketones with chiral cyclohexane-based amidophosphine ligands was developed. With 2 mol% of Cu(OAc)₂·H₂O/L5, the conjugate addition of diethylzinc to α,β-unsaturated ketones was achieved in good-to-excellent yields (up to 98%) and high enantioselectivities (up to 92% ee). This catalytic system was shown to be efficient for the 1,4-conjugate addition of Et₂Zn to (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one with 85% yield and 90% ee. Moreover, with 1 mol% of Cu(OTf)₂/L11, the conjugate addition of α,β,γ,δ-unsaturated ketones was accomplished with 1,4-regioselectivity, good yields (79–86%) and excellent enantioselectivities (up to 97% ee).     

Copper‐Catalyzed Aerobic Oxidative CC Bond Cleavage for CN Bond Formation: From Ketones to Amides

A novel copper‐catalyzed aerobic oxidative C(CO)? C(alkyl) bond cleavage reaction of aryl alkyl ketones for C? N bond formation is described. A series of acetophenone derivatives as well as more challenging aryl ketones with long‐chain alkyl substituents could be selectively cleaved and converted into the corresponding amides, which are frequently found in biologically active compounds and pharmaceuticals.     

Low-Valent Titanium Mediated Reductive Deoxygenation of Carbonyls to Methylenes Via Carbon-Nitrogen Bond Cleavage in N-(Arylmethyl) Anilines

The reduction of aryl aldehydes and ketones in neutral medium, to the corresponding hydrocarbons via carbon-nitrogen bond cleavage of the intermediate N-(arylmethyl)anilines with low-valent titanium reagents is described. It provides a mild, convenient and selective pathway for deoxygenation of carbonyls without the production of any side product.     

Enantioselective conjugate addition of both aromatic ketones and acetone to nitroolefins catalyzed by chiral primary amines bearing multiple hydrogen-bonding donors

A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition of aromatic ketones to nitroolefins in good yields (up to 87%) with excellent enantioselectivities (97→99% ee) but also enantioselective conjugate addition of acetone to nitroolefins in excellent yields (90-96%) with high enantioselectivities (up to 97% ee).     

The Cleavage Effect of Histidyl-Lysine on RNA

Recentlytherehasbeenconsiderableinterestindevel0pingcatalyststhathydrolyticallycleavethePhosPhodiesterbackbone0fRNAsite-specificallyforthepotentialaPplicati0nstomolecularbi0l0gyandgenetheraPy"2SmallmoleculeswithRNAcleavageactivityareusedasresearchtoolsfortheinVestigationofnucleicacidstrUctUres.3'4SeveralexamPlesofoxidativecleavagecatalystshavebeenrePortCd.'MuchefforthasbeendevotedtoRNAhydIolysiscatalystSduet0theadvatgesover0xidativecleavageones.'MetaLbasedhydrolysisofRNAhasbeenreport…     

Water-Promoted Carbon-Carbon Bond Cleavage Employing a Reusable Fe Single-Atom Catalyst

The development of methods for selective cleavage reactions of thermodynamically stable C−C/C=C bonds in a green manner is a challenging research field which is largely unexplored. Herein, we present a heterogeneous Fe−N−C catalyst with highly dispersed iron centers that allows for the oxidative C−C/C=C bond cleavage of amines, secondary alcohols, ketones, and olefins in the presence of air (O₂) and water (H₂O). Mechanistic studies reveal the presence of water to be essential for the performance of the Fe−N−C system, boosting the product yield from <1 % to >90 %. Combined spectroscopic characterizations and control experiments suggest the singlet ¹O₂ and hydroxide species generated from O₂ and H₂O, respectively, take selectively part in the C−C bond cleavage. The broad applicability (>40 examples) even for complex drugs as well as high activity, selectivity, and durability under comparably mild conditions highlight this unique catalytic system.     

A facile synthesis of polysubstituted pyrroles

alpha-Aminoalkylcuprates prepared from CuX.2LiCl (X = Cl, CN) and 1 equiv of an alpha-lithiocarbamate undergo conjugate addition reactions to alpha,beta-alkynyl ketones in moderate to good yields, affording E:Z mixtures of alpha,beta-enones. Treatment of the conjugate adducts with PhOH/TMSCl in CH(2)Cl(2) effected carbamate deprotection and cyclization to afford a flexible two-step synthesis of substituted pyrroles.