Carbon-carbon Bond-forming Reactions Research Articles

Lewis Acid-Assisted Photoinduced Intermolecular Coupling between Acylsilanes and Aldehydes: A Formal Cross Benzoin-Type Condensation.

Intermolecular carbon-carbon bond-forming reaction between readily available acylsilanes and aldehydes was achieved under photoirradiation conditions with assistance of a catalytic amount of Lewis acid. Nucleophilic addition of photochemically generated siloxycarbenes to aldehydes followed by 1,4-silyl migration afforded synthetically useful α-siloxyketones. Electrophilic activation of aldehydes by Lewis acid is highly important to realize this reaction efficiently, otherwise the yield of the desired coupling products were significantly decreased. Noteworthy is that a formal cross benzoin-type reaction using acylsilanes was achieved under Lewis acidic conditions. This is the first example of Lewis acid-catalyzed reaction of photochemically generated siloxycarbenes with electrophiles.

Catalytic Carbon-Carbon Bond-Forming Reactions of Weakly Acidic Carbon Pronucleophiles Using Strong Brønsted Bases as Catalysts.

Catalytic carbon-carbon bond-forming reactions of weakly acidic carbon pronucleophiles with N-aryl imines, α,β-unsaturated amides, and others under proton-transfer conditions were developed by designing strongly basic reaction intermediates known as product bases. The reactions proceed smoothly in the presence of a catalytic amount of strong base such as KH or alkaline metal amides. Modification of the metal cations by using chiral macrocyclic crown ethers allowed catalytic asymmetric 1,4-addition reactions to proceed with high enantioselectivities. This concept can be applied to Brønsted-base-catalyzed reactions of a wide range of weakly acidic carbon pronucleophiles.

Iron-Catalyzed Asymmetric Nitro-Mannich Reaction.

The first enantioselective addition of nitroalkanes to imines (nitro-Mannich reaction), mediated by an iron(II) catalyst assembled by a hindered hydroxyethyl-pybox ligand, is described. This valuable carbon-carbon bond-forming reaction proceeds smoothly at room temperature to afford enantioenriched β-nitro amines in good yields and high enantioselectivity, up to 98% with unprecedentedly low iron catalyst loading (5 mol %).

Journey Heading towards Enantioselective Synthesis Assisted by Organocatalysis.

This personal account summarizes the design of various organocatalysts derived from amino acids and Cinchona alkaloids and their applications in enantioselective carbon-carbon and carbon-nitrogen bond formation reactions. This account begins with the short description of the background of asymmetric organocatalysis. Various types of reactions like aldol reaction, Michael reaction, aza-Henry reaction, Morita-Baylis-Hillman reaction are described in this account.

S-5 触媒的不斉炭素-炭素結合を機軸とする天然物の全合成(記念講演要旨)

S-5 触媒的不斉炭素-炭素結合を機軸とする天然物の全合成(記念講演要旨)

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions.

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. Detailed and generalized protocols are also presented for testing the catalytic activity of such complexes in arylation and Suzuki-Miyaura cross-coupling reactions. Representative results are shown for the catalytic activity of the four complexes in arylation and Suzuki-Miyaura type reactions. For each of the reactions investigated, at least one of the four complexes successfully catalyzed the reaction, qualifying them as promising candidates for catalysis of many carbon-carbon bond-forming reactions. The protocols presented are general enough to be adapted for the synthesis, purification and catalytic activity testing of new palladium N-heterocyclic carbene complexes.

Access to Tetronic Acids via Silver-Catalyzed CO2 Incorporation into Conjugated Ynones.

Facile and versatile access to highly functionalized tetronic acids has been successfully achieved through the reaction of conjugated ynones with carbon dioxide. In the presence of a base, the enolates generated from the ynones capture CO2 via a carbon-carbon bond-forming reaction, accompanied by a 5-exo-dig cyclization reaction of the resulting carboxylate to the alkyne, activated by a silver catalyst. The present method should be applicable to the synthesis of a wide variety of tetronic acids.

Carbon–Carbon Bond Formation in a Weak Ligand Field: Leveraging Open‐Shell First‐Row Transition‐Metal Catalysts

Unique features of earth-abundant transition-metal catalysts are reviewed in the context of catalytic carbon-carbon bond-forming reactions. Aryl-substituted bis(imino)pyridine iron and cobalt dihalide compounds, when activated with alkyl aluminum reagents, form highly active catalysts for the polymerization of ethylene. Open-shell iron and cobalt alkyl complexes have been synthesized that serve as single-component olefin polymerization catalysts. Reduced bis(imino)pyridine iron and cobalt dinitrogen compounds have also been discovered that promote the unique [2+2] cycloaddition of unactivated terminal alkenes. Studies of the electronic structure support open-shell intermediates, a deviation from traditional strong-field organometallic compounds that promote catalytic C-C bond formation.

Benzyltriboronates: Building Blocks for Diastereoselective Carbon-Carbon Bond Formation.

A highly diastereoselective carbon-carbon bond-forming reaction involving the tandem coupling of benzyltriboronates, enoates, and alkyl halides is described. This method was enabled by the discovery of α-diimine nickel catalysts that promote the chemoselective triborylation of benzylic C(sp3)-H bonds using B2Pin2 (Pin = pinacolate). The C-H functionalization method is effective with methylarenes and for the diborylation of secondary benzylic C-H bonds, providing direct access to polyboron building blocks from readily available hydrocarbons. Combination of the benzylic perborylation with a new deborylative conjugate addition-alkylation method enables a one-pot procedure in which multiple simple precursors are combined to generate diastereopure products containing quaternary stereocenters.

Grinding assisted, column chromatography free decarboxylative carbon-carbon bond formation: Greener synthesis of 3, 3-disubstituted oxindoles

The decarboxylative carbon-carbon bond formation reaction of β-ketoacid derivatives with isatylidene malononitrile derivatives catalyzed by DBU afford adducts in excellent yield. The desired product can be easily isolated using simple filtration method without performing any column chromatography. The decarboxylative adduct was further subjected to reductive-cyclization to obtain biologically important spirooxindoles in 89% yield.

A radical approach to posttranslational mutagenesis.

Introducing diverse protein side chains via carbon-carbon bond-forming reactions

ChemInform Abstract: Nucleophilic and Electrophilic Activation of Non‐Heteroaromatic Amides in Atom‐Economical Asymmetric Catalysis

AbstractReview: [35 refs.

Extremely Active Organocatalysts Enable a Highly Enantioselective Addition of Allyltrimethylsilane to Aldehydes.

The enantioselective allylation of aldehydes to form homoallylic alcohols is one of the most frequently used carbon-carbon bond-forming reaction in chemical synthesis and, for several decades, has been a testing ground for new asymmetric methodology. However, a general and highly enantioselective catalytic addition of the inexpensive, nontoxic, air- and moisture-stable allyltrimethylsilane to aldehydes, the Hosomi-Sakurai reaction, has remained elusive. Reported herein is the design and synthesis of a highly acidic imidodiphosphorimidate motif (IDPi), which enables this transformation, thus converting various aldehydes with aromatic and aliphatic groups at catalyst loadings ranging from 0.05 to 2.0 mol % with excellent enantioselectivities. Our rationally constructed catalysts feature a highly tunable active site, and selectively process small substrates, thus promising utility in various other challenging chemical reactions.

ChemInform Abstract: Asymmetric Aldol Reaction with Formaldehyde: A Challenging Process

AbstractReview: [66 refs.

Sequential Addition Reaction of Sulfanylmethyllithiums and Grignard Reagents to Thioformamides Leading to the Formation of 2-Phenyl-2-sulfanylethyl Tertiary Amines.

The reaction of sulfanylmethyllithiums generated from benzylsulfanes and n-BuLi with N,N-dimethylthioformamide followed by the addition of Grignard reagents gave 2-phenyl-2-sulfanyl tertiary amines in moderate to good yields. A range of Grignard reagents involving primary alkyl, aryl, vinyl, and alkynyl Grignard reagents were used. Two carbon-carbon bond-forming reactions were achieved through a one-pot reaction. The reaction showed good to high diastereoselectivity, particularly with alkynyl Grignard reagents.

Aqueous-Medium Carbon-Carbon Bond-Forming Radical Reactions Catalyzed by Excited Rhodamine B as a Metal-Free Organic Dye under Visible Light Irradiation.

The utility of rhodamine B as a water-soluble organic photocatalyst was studied in the cascade radical addition-cyclization-trapping reactions under visible light irradiation. In the presence of (i-Pr)2NEt, the electron transfer from the excited rhodamine B to perfluoroalkyl iodides proceeded smoothly to promote the carbon-carbon bond-forming radical reactions in aqueous media. When i-C3F7I was employed as a radical precursor, the aqueous-medium radical reactions proceeded even in the absence of (i-Pr)2NEt. In these reactions, the direct electron transfer from the excited singlet state of rhodamine B would take place. Furthermore, the cleavage of the C-I bond in less reactive i-PrI could be achieved by the reductive electron transfer from the excited rhodamine B, which was confirmed by the fluorescence quenching of rhodamine B with the addition of i-PrI.

Asymmetric Aldol Reaction with Formaldehyde: a Challenging Process.

The asymmetric aldol reaction with formaldehyde is a fundamental carbon-carbon bond-forming reaction in organic synthesis, as well as in the quest of the origin of life, as it is thought to have been the first "molecular brick" involved in the synthetic path to complex sugars. Products of aldol reactions, i.e., the β-hydroxy carbonyl compounds, are versatile building blocks used to access a great variety of functionalised molecules. The employment of formaldehyde, as a C1 symmetric electrophile, in aldol reactions can be likely considered the most challenging, yet simplest, process to introduce a hydroxymethyl group in an asymmetric fashion. In this account, an overview of the progress achieved in the asymmetric metal- and organocatalysed aldol reaction, using readily available formalin or paraformaldehyde sources, is illustrated. Our recent contribution to this area, with the application of asymmetric hydroxymethylation in cascade processes for the synthesis of γ-butyrolactones, is also shown.

Corrigendum: Mutations Closer to the Active Site Improve the Promiscuous Aldolase Activity of 4-Oxalocrotonate Tautomerase More Effectively than Distant Mutations.

The enzyme 4-oxalocrotonate tautomerase (4-OT), which catalyzes enol-keto tautomerization as part of a degradative pathway for aromatic hydrocarbons, promiscuously catalyzes various carbon-carbon bond-forming reactions. These include the aldol condensation of acetaldehyde with benzaldehyde to yield cinnamaldehyde. Here, we demonstrate that 4-OT can be engineered into a more efficient aldolase for this condensation reaction, with a >5000-fold improvement in catalytic efficiency (kcat /Km ) and a >10(7) -fold change in reaction specificity, by exploring small libraries in which only "hotspots" are varied. The hotspots were identified by systematic mutagenesis (covering each residue), followed by a screen for single mutations that give a strong improvement in the desired aldolase activity. All beneficial mutations were near the active site of 4-OT, thus underpinning the notion that new catalytic activities of a promiscuous enzyme are more effectively enhanced by mutations close to the active site.

Lewis Acid Catalyzed Regiospecific Cross-Dehydrative Coupling Reaction of 2-Furylcarbinols with β-Keto Amides or 4-Hydroxycoumarins: A Route to Furyl Enols

Lewis acid catalyzed directly dehydrative carbon-carbon bond formation reaction of 2-furylcarbinols with β-keto amides provides a straightforward method for regioselective synthesis of (Z)-furyl enols. Moreover, this Lewis acid catalyzed cross-coupling reaction can be extended to an interesting heterocyclic version featuring a functionalized 3-furyl-4-hydroxycoumarin synthesis.

Mutations Closer to the Active Site Improve the Promiscuous Aldolase Activity of 4-Oxalocrotonate Tautomerase More Effectively than Distant Mutations.

The enzyme 4-oxalocrotonate tautomerase (4-OT), which catalyzes enol-keto tautomerization as part of a degradative pathway for aromatic hydrocarbons, promiscuously catalyzes various carbon-carbon bond-forming reactions. These include the aldol condensation of acetaldehyde with benzaldehyde to yield cinnamaldehyde. Here, we demonstrate that 4-OT can be engineered into a more efficient aldolase for this condensation reaction, with a >5000-fold improvement in catalytic efficiency (kcat /Km ) and a >10(7) -fold change in reaction specificity, by exploring small libraries in which only "hotspots" are varied. The hotspots were identified by systematic mutagenesis (covering each residue), followed by a screen for single mutations that give a strong improvement in the desired aldolase activity. All beneficial mutations were near the active site of 4-OT, thus underpinning the notion that new catalytic activities of a promiscuous enzyme are more effectively enhanced by mutations close to the active site.