Direct, facile aldehyde and ketone alpha-selenenylation reactions promoted by L-prolinamide and pyrrolidine sulfonamide organocatalysts

[reaction: see text] A new catalytic method for direct alpha-selenenylation reactions of aldehydes and ketones has been developed. The results of exploratory studies have demonstrated that L-prolinamide is an effective catalyst for alpha-selenenylation reactions of aldehydes, whereas pyrrolidine trifluoromethanesulfonamide efficiently promotes reactions of ketones. Under optimized reaction conditions, using N-(phenylseleno)phthalimide as the selenenylation reagent in CH2Cl2 in the presence of L-prolinamide (2 mol %) or pyrrolidine trifluoromethanesulfonamide (10 mol %), a variety of aldehydes and ketones undergo this process to generate alpha-selenenylation products in high yields. Mechanistic insight into the L-proline and L-prolinamide catalyzed alpha-selenenylation reactions of aldehydes with N-(phenylseleno)phthalimide has come from theoretical studies employing ab initio methods and density functional theory. The results reveal that (1) the rate-limiting step of the process involves attack of the enamine intermediate at selenium in N-(phenylseleno)phthalimide and (2) the energy of the transition state for the reaction catalyzed by prolinamide is lower than that promoted by proline. This result is consistent with experimental observations. The role of hydrogen bond interactions in stabilizing the transition states for this process is also discussed.     

Reactions of substituted (1,3-butadiene-1,4-diyl)magnesium, 1,4-bis(bromomagnesio)butadienes and 1,4-dilithiobutadienes with ketones, aldehydes and PhNO to yield cyclopentadiene derivatives and N-Ph pyrroles by cyclodialkenylation

1,4-Dilithiobutadiene derivatives 1, 1,4-bis(bromomagnesio)butadiene derivatives 2 and metallacyclic (1,3-butadiene-1,4-diyl)magnesium reagents 3 were prepared and their reactions with ketones, aldehydes, and PhNO were investigated. Multiply substituted cyclopentadienes and N-Ph pyrroles were formed by unprecedented reaction conditions. The carbonyl group of aldehydes and ketones was deoxygenated during the reaction and behaved formally as a one-carbon unit; the N==O moiety of PhNO was cleaved to afford N-Ph pyrrole derivatives. Furthermore, different reactivities among these three types of reagents 1, 2 and 3 were revealed. The 1,4-dilithium reagents 1 readily reacted with both aldehydes and ketones; the 1,4-dimagnesium reagents 2 reacted with aldehydes, but not ketones; the metallacyclopentadiene reagents of magnesium 3 showed higher reactivity and did react with ketones.     

Triflic acid catalyzed reductive coupling reactions of carbonyl compounds with O-, S-, and N-nucleophiles

Highly efficient metal-free reductive coupling reactions of aldehydes and ketones with a range of nucleophiles in the presence of triflic acid (1-5 mol%) as the catalyst are presented. The reactions can be performed at ambient temperature without exclusion of moisture or air. A range of symmetrical and unsymmetrical ethers were obtained by this method in high yields and short reaction times. For the first time, the influence of additional functionalization has been studied. Furthermore, the formation of thioethers from ketones (by addition of unmodified thiols) and of sulfonamides from either aldehydes or ketones has been achieved under catalytic conditions.     

Sequential aldol condensation-transition metal-catalyzed addition reactions of aldehydes, methyl ketones, and arylboronic acids

Sequential aldol condensation of aldehydes with methyl ketones followed by transition metal-catalyzed addition reactions of arylboronic acids to form β-substituted ketones is described. By using the 1,1'-spirobiindane-7,7'-diol (SPINOL)-based phosphite, an asymmetric version of this type of sequential reaction, with up to 92% ee, was also realized. Our study provided an efficient method to access β-substituted ketones and might lead to the development of other sequential/tandem reactions with transition metal-catalyzed addition reactions as the key step.     

Direct catalytic aldol-type reactions using RCH2CN

[reaction: see text] A copper fluoride-catalyzed cyanomethylation that can be applied to a wide range of ketones and aldehydes was developed using TMSCH(2)CN as a nucleophile. The reaction was extended to a conceptually more advanced copper alkoxide-catalyzed direct addition of alkylnitriles to aldehydes, which can act as a surrogate direct catalytic aldol reaction of esters. These reactions can be applied to the first catalytic enantioselective cyanomethylation of ketones and direct catalytic enantioselective cyanomethylation of aldehydes.     

House bulb light-induced photochemical acetalization of carbonyl compounds catalyzed by Eosin Y

We have systematically studied the reactions of acetalization and found that high reaction efficiency can be achieved using cheap and readily available organic Eosin Y as catalyst. The reaction proceeds smoothly under house bulbs and shows excellent functional group tolerance. The substrates of the reaction system are compatible with aromatic aldehydes, aliphatic aldehydes, aromatic ketones, and cyclic ketones with high yields.     

Transition metal salt-catalyzed direct three-component mannich reactions of aldehydes, ketones, and carbamates: efficient synthesis of N-protected beta-aryl-beta-amino ketone compounds

The transition metal salt-catalyzed direct three-component Mannich reactions of aryl aldehydes, aryl ketones, and carbamates are described. The RuCl(3).xH(2)O-, AuCl(3)-PPh(3)-, and AuCl(3)-catalyzed direct Mannich reactions led to the synthesis of N-protected beta-aryl-beta-amino ketones, and the results create new possibilities for exploiting the transition metal salt-catalyzed direct Mannich reaction and facile synthesis of beta-amino ketone libraries.     

Atom-Efficient,Solvent-Free,Green Synthesis of Chalcones by Grinding

An improved Claisen–Schmidt condensation reaction of methyl ketones and aromatic aldehydes can be achieved by grinding at room temperature in the absence of solvents. This process is simple, efficient, economical, and environmentally benign compared to classical reactions.     

Inorganic ammonium salts as catalysts for direct aldol reactions in the presence of water

Inorganic ammonium salts catalyze the direct aldol reaction between unmodified ketones and aldehydes to furnish the corresponding β-hydroxy ketones in aqueous media. The reactions are highly chemoselective and operationally simple.     

Aromatic bromination of aldehydes and ketones using 1,3-di-n-butylimidazolium tribromide [BBIm]Br3 ionic liquids under solvent-free conditions

An environmentally benign and efficient process for the preparation of monobromo derivatives of aryl aldehydes and ketones was developed by simple and practical reactions of aryl aldehydes or ketones with 1,3-di-n-butylimidazolium tribromide ([BBIm]Br₃), as a brominating reagent under solvent-free conditions in very high yields. The process has several advantages: high conversions, short reaction time, mild reaction conditions, simple workup with good to quantitative yields and re-usable ionic liquid.     

Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures(1)

Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH(3)CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH(4).     

Nickel-catalyzed cycloadditions of unsaturated hydrocarbons, aldehydes, and ketones

The nickel-catalyzed cycloaddition of unsaturated hydrocarbons and carbonyls is reported. Diynes and enynes were used as coupling partners. Carbonyl substrates include both aldehdyes and ketones. Reactions of diynes and aldehydes afforded the [3,3] electrocyclic ring-opened tautomers, rather than pyrans, in high yields. The cycloaddition reaction of enynes and aldehydes afforded two distinct products. A new carbon-carbon bond is formed, prior to a competitive beta-hydrogen elimination of a nickel alkoxide, between the carbonyl carbon and either one of the carbons of the olefin or the alkyne. The steric hindrance of the enyne greatly affected the chemoselectivity of the cycloaddition of enynes and aldehydes. In some cases, dihydropyran was also formed. The scope of the cycloaddition reaction was expanded to include the coupling of enynes and ketones. No beta-hydrogen elimination was observed in cycloaddition reaction of enynes and ketones. Instead, C-O bond-forming reductive elimination occurred exclusively to afford dihydropyrans in excellent yields. In all cases, complete chemoselectivity was observed; only dihydropyrans where the carbonyl carbon forms a carbon-carbon bond with a carbon of the olefin, rather than of the alkyne, were observed. All cycloaddition reactions occur at room temperature and employ nickel catalysts bearing the hindered 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) or its saturated analogue, 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene (SIPr).     

Mannich-type reactions of aromatic aldehydes, anilines, and methyl ketones in fluorous biphase systems created by rare earth (III) perfluorooctane sulfonates catalysts in fluorous media

Rare earth (III) perfluorooctane sulfonates (RE(OPf)₃) catalyze the three-component Mannich-type reactions of different ketones with various aromatic aldehydes and aromatic amines in fluorous media to give various β-arylamino ketones in good yields. By simple separation of the fluorous phase containing only catalyst, reaction can be repeated several times.     

Highly efficient aza-Baylis-Hillman reaction of N-tosylated imines with MVK, acrolein, and phenyl acrylate or alpha-naphthyl acrylate: Lewis base effects and a convenient method to synthesize alpha,beta-unsaturated beta-amino carbonyl compounds

This paper describes several highly efficient aza-Baylis-Hillman reactions of N-tosylated imines with MVK, acrolein, and phenyl acrylate or alpha-naphthyl acrylate in the presence of a Lewis base. In most cases, the reaction can be completed within 1 h using the appropriate Lewis base catalyst. An efficient method to synthesize beta-amino ketones, aldehydes and esters in high yields and short reaction time has been developed.     

Titanocene(III)‐Catalyzed Three‐Component Reaction of Secondary Amides,Aldehydes, and Electrophilic Alkenes

An umpolung Mannich‐type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one‐pot formation of C? N and C? C bonds by a titanocene‐catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N‐substituted γ‐amido‐acid derivatives and γ‐amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α‐amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A.     

The breakdown of vinyl ethers as a two-center synchronous reaction

The experimental data on the molecular decomposition of vinyl ethers of various structures to alkanes and the corresponding aldehydes or ketones in the gas phase were analyzed using the method of intersecting parabolas. The enthalpies and kinetic parameters of decomposition were calculated for 17 reactions. The breakdown of ethers is a two-center concerted reaction characterized by a very high classical potential barrier to the thermally neutral reaction (180–190 kJ/mol). The kinetic parameters (activation energies and rate constants) of back reactions of the formation of vinyl ethers in the addition of aldehydes or ketones to alkanes were calculated using the method of intersecting parabolas. The factors that influenced the activation energy of the decomposition and formation of ethers were discussed. Quantum-chemical calculations of several vinyl ether decomposition reactions were performed. Ether formation reactions were compared with the formation of unsaturated alcohols as competitive reactions, which can occur in the interaction of carbonyl compounds with alkenes.     

Titanocene(III)‐Catalyzed Three‐Component Reaction of Secondary Amides,Aldehydes, and Electrophilic Alkenes

An umpolung Mannich‐type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one‐pot formation of C N and C C bonds by a titanocene‐catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N‐substituted γ‐amido‐acid derivatives and γ‐amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α‐amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A.     

Anionic four-electron donor-based palladacycles as catalysts for addition reactions of arylboronic acids with alpha,beta-unsaturated ketones, aldehydes, and alpha-ketoesters

Anionic four-electron donor-based palladacycle-catalyzed 1,4-additions of arylboronic acids with alpha,beta-unsaturated ketones and 1,2-additions of arylboronic acids with aldehydes and alpha-ketoesters are described. Our study demonstrated that palladacycles were highly efficient, practical catalysts for these addition reactions. The work described here not only opened a new paradigm for the application of palladacycles, but may also pave the road for other metalacycles as practically useful catalysts for such addition reactions including asymmetric ones. [reaction: see text].     

Bu4NI-catalyzed α-acyloxylation reaction of ethers and ketones with aldehydes and tert-butyl hydroperoxide

The reaction of (hetero)aromatic aldehydes or cinnamaldehyde with di-/multi-ethers in the presence of Bu₄NI and tert-butyl hydroperoxide generated corresponding α-acyloxy ethers. Reactions between (hetero)aromatic aldehydes or cyclohexanecarbaldehyde with arylalkyl ketones under similar conditions resulted in α-acyloxy ketones. Collectively, Bu₄NI-catalyzed α-acyloxylation reactions exhibit a broad scope of substrates and a high compatibility with functional groups.     

Cyclization into perhydronaphthalenones using samarium diiodide

Samarium(II) diiodide has been employed to promote the intramolecular cyclization reactions of aldehydes or ketones onto α,β-unsaturated ketones. The cyclization reactions described herein provide a general approach to the syntheses of perhydronaphthalenones with a cis-relationship between the OH at C-5 and the proton or methyl group at C-4a with good diastereoselectivity under mild reaction conditions.