Reaction Of Aliphatic Aldehydes Research Articles

(Invited) Catalytic Allylation of Aldehydes Using Feedstock Alkenes

The efficient production of fine chemicals from simple and readily available bulk materials such as simple alkenes is an important research area in synthetic organic chemistry. Lower alkenes are produced by one of the most common chemical processes (i.e. hydrocarbon cracking) on over 500 million metric tons scale. Development of catalytic methods which enable the direct use of these abundant organic molecules as carbon sources is highly demanded for practical and selective chemical reactions. However, despite several previous examples, the use of feedstock alkenes in synthetically useful transformations remains a challenging task.Catalytic aldehyde allylation plays an important role in synthetic organic chemistry. Traditionally, nucleophilic allylmetal species as stoichiometric starting materials have contributed to the development of this catalytic process. Despite usefulness of this approach, however, there is room for improvement in the overall efficiency, redox/atom/step economy, and environmental sustainability. The catalytic generation of nucleophilic allylmetal species in situ from simple and feedstock alkenes via allylic sp3 C-H bond activation would be a straightforward approach. We envisioned that radical sp3 C-H bond activation followed by oxidative interception of the resulting carbon-centered radical by a metal complex is a promising strategy for the catalytic generation of organometallic species from inert substrates. We supposed the ternary hybrid catalysis comprising a photoredox catalyst, a hydrogen-atom-transfer (HAT) catalyst, and a metal catalyst would realize catalytic allylation of aldehydes with simple alkenes.We planned to use a combination of an acridinium photoredox catalyst (Mes-Acr+) and a thiophosphoric imide (TPI) HAT catalyst to activate an allylic C-H bond of the alkenes through the HAT process. Under visible light irradiation, single-electron oxidation of TPI by a photo-excited acridinium catalyst (*Mes-Acr+) generates a sulfur-centered radical (RS•). The RS• radical abstracts the allylic C-H bond of alkenes, affording allyl radicals. Based on the mechanism of Nozaki-Hiyama allylation, we expected that a chromium(II) complex catalyst oxidatively intercepted allyl radicals, giving allylchromium(III) species. This species reacts with aldehydes via a Zimmerman-Traxler transition state to produce chromium alkoxides in an anti-selective fashion. Protonolysis by the proton generated in the HAT catalysis should afford the target homoallylic alcohols and chromium(III) species. Single-electron reduction by the photoredox catalyst (Mes-Acr•) would close the catalytic cycle with regenerating a chromium(II) complex catalyst and the oxidized form of the photoredox catalyst (Mes-Acr+).Based on this mechanism, we studied the substrate scope with a combination of 5 mol% CrCl2, 10 mol% TPI catalyst (HAT) and 5 mol% acridinium photoredox catalyst (PC). First, the scope of alkenes was investigated. In all cases, the branched constitutional isomer was produced exclusively (>20/1). The reactions of C4 feedstocks, 1-butene and 2-butenes which are annually produced on a 105 metric ton scale, with benzaldehyde afforded the product in 94% and 100% yield, respectively, with high diastereoselectivity (14-16/1). This crotylation reaction using butenes as a starting material will significantly streamline polyketide synthesis. 3-Methyl-1-butene selectively afforded the product containing a quaternary carbon. Branched C6 alkenes were also competent substrates. Other alkenes, including cyclic, halide-containing, and ether-containing, all afforded the product in high yield. The aldehyde scope was then investigated by fixing the alkene substrate to 2-butene. A series of aromatic aldehydes bearing halogens, electron-withdrawing groups, and a boronate ester afforded the corresponding products with high diastereoselectivity. A methyl substituent at the ortho-, meta-, and para positions of the aromatic ring did not affect the results. The reactions of aliphatic aldehydes, including those containing potentially sensitive functional groups (e.g. amine, alkyl halide, sulfide and benzyl oxy moiety), also proceeded efficiently. Next, we investigated the application to highly functionalized substrates. Propranolol derivative bearing free hydroxy group were competent substrate. A dipeptide and a nucleic acid derivative containing coordinating polar functional groups such as amides and an adenine heterocycle did not affect the reaction progress. Therefore, the allylation of aldehydes mediated by the ternary hybrid catalysis realized high functional group compatibility and chemoselectivity using easily available feedstock alkenes.In conclusion, we developed a ternary hybrid catalysis, enabling catalytic allylation of aldehydes using simple alkenes, under visible light irradiation at room temperature. This hybrid catalysis is applicable to various types of unactivated alkenes including feedstock lower alkenes. Due to the high chemoselectivity and mild conditions, the reaction was applicable to highly functionalized bioactive molecules. The asymmetric variant enabled facile access to enantiomerically and diastereomerically enriched homoallylic alcohols by introducing a chiral ligand to the chromium catalyst. Further studies to expand the scope are ongoing. Figure 1

2,4-dinitrophenyl hydrazone derivatives as potent of alpha amylase inhibitors

Our current attempt was made to synthesize a new 2,4-dinitrophenyl hydrazone derivatives (1–13) compounds and explored their alpha amylase inhibitory potential. The thirteen new derivatives of 2,4-dinitrophenyl hydrazone (1–13) were achieved from the reaction of aliphatic aldehydes and aromatic aldehydes with dinitrophenyl hydrazine in methanol under reflux in the presence of catalyst used acetic acid. The molecular docking study was examined through standard software MOE (Molecular Operating Environment). The result of docking shown that compounds in the catalytic site of enzyme is more potentially active for binding and arrangement. Our results predict compound 12 IC50 =16.42 µg/mL, 5 IC50 =12.16µg/mL, and 6 IC50 =15.03µg/mL more potent and excellent inhibitor than a standard acarbose IC50 = 42.47µg/mL for alpha amylase. It’s concluded that compounds (1–13) can provide us a pathway for new antidiabetic drugs in the market the further analysis and exploration of these compound is important and valuable.

Stereoselective synthesis of chromane derivatives via a domino reaction catalyzed by modularly designed organocatalysts.

A highly enantio- and diastereoselective method for the synthesis of functionalized chroman-2-ones and chromanes was achieved by using an organocatalytic domino Michael/hemiacetalization reaction of aliphatic aldehydes and (E)-2-(2-nitrovinyl)phenols followed by a PCC oxidation and dehydroxylation, respectively. Using the modularly designed organocatalysts (MDOs) self-assembled from cinchona alkaloid derivatives and amino acids in the reaction media, the title products were obtained in good to high yields (up to 97%) and excellent diastereoselectivities (up to 99 : 1 dr) and enantioselectivities (up to 99% ee).

An Ionic Liquid-Based Green Synthesis Strategy: Synthesis of Dihydropyrimidinones by Three-Component Biginelli-Type Reaction of Aliphatic Aldehydes, Aromatic Aldehydes and Urea

An Ionic Liquid-Based Green Synthesis Strategy: Synthesis of Dihydropyrimidinones by Three-Component Biginelli-Type Reaction of Aliphatic Aldehydes, Aromatic Aldehydes and Urea

Synthesis of secondary amines by reductive amination of aldehydes with nitroarenes over supported copper catalysts in a flow reactor

Supported copper catalysts were investigated for the one-pot reductive amination of aldehydes with nitroarenes in a continuous flow reactor. This process is considered advantageous compared to current traditional methods, which present several drawbacks, such as toxicity of reducing or alkylation agent, lack of monoalkylation selectivity and large amounts of waste produced. Various secondary amines were synthesized in good to excellent yields in the reactions of aliphatic aldehydes with nitroarenes using molecular hydrogen as a reducing agent. It was found that the yield of secondary amine depends on the rate of formation of intermediate imine.

Front Cover Picture: Auto‐Tandem Catalysis‐Induced Synthesis of Trisubstituted Furans through Domino Acid‐Acid‐Catalyzed Reaction of Aliphatic Aldehydes and 1,3‐Dicarbonyl Compounds by using N‐Bromosuccinimide as Oxidant (Adv. Synth. Catal. 11/2017)

Front Cover Picture: Auto‐Tandem Catalysis‐Induced Synthesis of Trisubstituted Furans through Domino Acid‐Acid‐Catalyzed Reaction of Aliphatic Aldehydes and 1,3‐Dicarbonyl Compounds by using <i>N</i>‐Bromosuccinimide as Oxidant (Adv. Synth. Catal. 11/2017)

Auto‐Tandem Catalysis‐Induced Synthesis of Trisubstituted Furans through Domino Acid‐Acid‐Catalyzed Reaction of Aliphatic Aldehydes and 1,3‐Dicarbonyl Compounds by using N‐Bromosuccinimide as Oxidant

AbstractA simple aluminium(III) chloride‐catalyzed synthesis of tri‐substituted furans from aliphatic aldehydes and 1,3‐dicarbonyl compounds was developed by using N‐bromosuccinimide (NBS) as an oxidant. This method was effective for the synthesis of various furan derivatives. Some of the products were not accessible with the previously reported methods. Mechanically, this reaction involved an auto‐tandem catalysis based on a newly reported acid‐acid‐catalyzed tandem reaction to ensure that furans were successfully synthesized.magnified image

Reactions of P(III) chlorides with aldehydes: I. Synthesis of primary intermediates of the reactions of aliphatic aldehydes with P(III) chlorides possessing electrophilic properties

An approach to investigation of reactions of electrophilic P(III) chlorides with aliphatic aldehydes is developed. Its essence is the removal of HCl impurity from chloride and catalytic blocking of electrophilic center of the carbonyl group. For these purposes nitrogen-containing organic bases and alkyl vinyl ethers are used. Three types of primary intermediates with the nearest P(III) environment POCl2, O2PCl, and O3P are synthesized. It is established that the stability of intermediates increases with the growing acceptor properties of substituents at P(III) and donor properties of the aldehyde fragment.

ALIPHATIC ALDEHYDES IN THE SYNTHESIS OF CONDENSED 4-ALKYL(CYCLOALKYL)-2-AMINO-3-CYANO-4H-PYRANS

Substituted 4-alkyl(cycloalkyl)-2-amino-3-cyano-4H-pyrans have been obtained from the reaction of aliphatic aldehydes with malononitrile and some other CH acids in the presence of N-methylmorpholine. Authors: G. V. Klokol, S. G. Krivokolysko, V. D. Dyachenko, and V. P. Litvinov. English Translation in Chemistry of Heterocyclic Compounds , 1999, 35 (10), pp 1183-1186 http://link.springer.com/article/10.1007/BF02323376

ChemInform Abstract: Highly Chemo‐ and Enantioselective Cross‐Benzoin Reaction of Aliphatic Aldehydes and α‐Ketoesters.

AbstractDensely oxygenated syn‐diols are available by diastereoselective reduction of the primary products.

One-pot three-component synthesis of pyrano[3,2-d]isoxazoles catalyzed by N,N,N,N-tetramethylguanidinium formate [TMG][HCO2] as mild basic ionic liquid under mild conditions

The mildly basic ionic liquid N,N,N,N-tetramethylguanidinium formate [TMG][HCO2] was found to be a very effective solvent and basic catalyst for the condensation between 3-phenylisoxazolone, Meldrum's acid, and aldehydes to afford some novel pyrano[3,2-d]isoxazoles in high yields. The stages, through which these reactions might proceed, depend largely on the nature of the aldehyde substrates. The reaction of aliphatic aldehydes has given access to some novel carboxylated products. The ionic liquid could be recycled several times without loss of efficiency with regards to the reaction times and yields.

Enantioselective Aldol Reactions of Aliphatic Aldehydes with Singh’s Catalyst

Aldols from aliphatic aldehydes had been synthesized enantioselectively using Singh’s catalyst. Self and crossed aldol reactions with several linear aldehydes were performed.

ChemInform Abstract: Catalytic Asymmetric Cross‐Aza‐Benzoin Reactions of Aliphatic Aldehydes with N‐Boc‐Protected Imines.

AbstractThis reaction provides access to useful 1,2‐amino alcohol synthons in a single step.

Cross-Aza-Benzoin Reactions of Aliphatic Aldehydes with Imines

Cross-Aza-Benzoin Reactions of Aliphatic Aldehydes with Imines

Synthesis of 4-substituted pyrano[4,3-b]pyran-2,5-diones in an ionic liquid

The mildly basic ionic liquid N,N,N,N-tetramethylguanidinium triflate (TMGTf) was found to be a very effective solvent for the reaction between 4-hydroxy-6-methyl-2H-pyran-2-one, Meldrum's acid, and aldehydes to afford some novel pyrano[4,3-b]pyran-2,5-diones in high yields at room temperature. The stages, through which these reactions might proceed, depend largely on the nature of the aldehyde substrates. The reaction of aliphatic aldehydes has given access to some novel carboxylated products.

Catalytic Asymmetric Cross‐Aza‐Benzoin Reactions of Aliphatic Aldehydes with N‐Boc‐Protected Imines

Über Kreuz: Ein Katalysatorsystem wurde entwickelt, das die direkte asymmetrische Kupplung aliphatischer Aldehyde mit N-Boc-geschützten Iminen in einer gekreuzten Aza-Benzoin-Reaktion ermöglicht (siehe Schema, Boc=tert-Butoxycarbonyl). Der aktive Katalysator reagiert schnell mit dem Imin, die Anwesenheit einer Säure als Cokatalysator erhält jedoch die Reversibilität der Reaktion und führt zur Regeneration des Katalysators. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ChemInform Abstract: Aliphatic Aldehydes in the Synthesis of Condensed 4-Alkyl(cycloalkyl)-2-amino-3-cyano-4H-pyrans.

Substituted 4-alkyl(cycloalkyl)-2-amino-3-cyano-4H-pyrans have been obtained from the reaction of aliphatic aldehydes with malononitrile and some other CH acids in the presence of N-methylmorpholine.

Catalytic Asymmetric Allylation of Aliphatic Aldehydes by Chiral Bipyridine N,N′-Dioxides

A new class of axially chiral bipyridine N,N¢-oxides with bis(tetrahydroisoquinoline) framework were tested as catalysts in the reaction of aliphatic aldehydes with allyl(trichloro)silane to af- ford homoallylic alcohols. The course of the reaction, that is, the catalytic activity as well as enantioselectivity, is strongly dependent on the solvent used. The products were obtained in good yields and up to 68% ee in chloroform.

L‐Proline‐Catalyzed One‐Pot Three‐Component Reaction for the Synthesis of β‐Alkoxy Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Organozinc Alkoxide‐Promoted Aldol‐Tishchenko Reaction of Aliphatic Aldehydes: An Expedient Entry to Prepare α‐Methylene Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.