De Mayo Reaction Research Articles

Asymmetric photoredox catalytic formal de Mayo reaction enabled by sensitization-initiated electron transfer.

Visible-light-driven photoredox catalysis is known to be a powerful tool for organic synthesis. Its occurrence critically depends on the twice exothermic single-electron transfer processes of photosensitizers, which are governed by the redox properties of the species involved. Hence, the inherently narrow range of redox potentials of photosensitizers inevitably constrains their further availability. Sensitization-initiated electron transfer has recently been found to effectively overcome this substantial challenge. However, feasible and practical strategies for designing such complicated catalytic systems are rather scarce. Herein we report an elaborate dual-catalyst platform, with dicyanopyrazine as a visible light photosensitizer and a pyrenyl-incorporated chiral phosphoric acid as a co-sensitizer, and we demonstrate the applicability of this sensitization-initiated electron transfer strategy in an asymmetric formal de Mayo-type reaction. The catalysis platform enables otherwise thermodynamically unfavourable electron transfer processes to close the redox cycle and allows for precise access to valuable enantioenriched 1,5-diketones with a wide substrate range.

Front Cover Picture: Harnessing the Power of the De Mayo Reaction: Unveiling a Photochemical and Photocatalytic Masked [2+2] Methodology for Organic Synthesis (Adv. Synth. Catal. 2/2024)

Front Cover Picture: Harnessing the Power of the De Mayo Reaction: Unveiling a Photochemical and Photocatalytic Masked [2+2] Methodology for Organic Synthesis (Adv. Synth. Catal. 2/2024)

Harnessing the Power of the De Mayo Reaction: Unveiling a Photochemical and Photocatalytic Masked [2+2] Methodology for Organic Synthesis

AbstractIn 1962, Paul J. de Mayo initially described the photochemical reaction involving 1,3‐diketones and double bonds, resulting in the formation of 1,5‐diketones. Since then, this reaction has been extensively utilized for the synthesis of a wide range of fascinating natural products. Over time, this synthetic methodology has been applied to various carbonyl systems, including locked enol‐tautomers of diketones, β‐keto esters, and β‐enaminones. Additionally, it has found application in other unsaturated systems such as allenes and alkynes. In this review article, we provide a comprehensive overview of the classical de Mayo reaction, highlighting its scope and potential. Furthermore, we focus on recent advances achieved through photocatalytic conditions. Special emphasis is placed on the regioselectivity of the process and the underlying reaction mechanism, particularly within the context of photocatalysis.

Catalytic Asymmetric Visible-Light de Mayo Reaction by ZrCl4-Chiral Phosphoric Acid Complex.

Catalytic asymmetric de Mayo reaction was achieved for the first time under visible light using asymmetric binary acid catalysis (ABC) involving zirconium chloride and chiral phosphoric acid (CPA). The chiral zirconium catalysis enables effective reactions over a broad range of 1,3-diketones and alkenes with up to >99% yield and 98% ee. The key chiral zirconium enolate was isolated and characterized to account for the observed catalysis and stereoselectivity.

Investigating the Effect of Lewis Acid Co-catalysts on Photosensitized Visible-Light De Mayo Reactions.

Herein, we describe studies showing that Lewis acid co-catalysts can significantly broaden the scope of alkenes that can be incorporated into the photosensitized visible-light De Mayo reaction. Mechanistic studies suggest that the primary benefit of the Lewis acid is not on substrate sensitization but rather on bond-forming steps downstream of energy transfer, highlighting the diverse effects that Lewis acids can have on sensitized photoreactions.

Synthesis of (±)-Ingenol

Key words (±)-ingenol - De Mayo reaction - Corey–Posner–Whitesides–House reaction - Upjohn Dihydroxylation - Dess–Martin oxidation - Luche reduction

Visible-light promoted de Mayo reaction by zirconium catalysis.

Zirconium catalysis with ZrCl4 was developed to facilitate a de Mayo reaction under visible light conditions without any external photosensitizer and additive.

Dynamic Kinetic Sensitization of β-Dicarbonyl Compounds-Access to Medium-Sized Rings by De Mayo-Type Ring Expansion.

Herein, we present a photocatalyzed two-carbon ring expansion of β-dicarbonyl compounds with unactivated olefins that provides facile access to medium-sized rings. Selective sensitization of the substoichiometric enol tautomer enables reactivity of substrates incompatible with the classical De Mayo reaction conditions. Key to success is the identification of the metal-based sensitizer fac-[Ir(CF3 -pmb)3 ], which can be excited using common near-visible LEDs, and possesses a high triplet excited state energy of 73.3 kcal mol-1 . This exactly falls in the range between the triplet energies of the enol and keto tautomer, thereby enabling a dynamic kinetic sensitization. Demonstrating the applicability of fac-[Ir(CF3 -pmb)3 ] as a photocatalyst in organic synthesis for the first time, we describe a two-step photocycloaddition-ring-opening cascade with β-ketoesters, -diketones, and -ketoamides. The mechanism has been corroborated by time-resolved spectroscopy, as well as further experimental and computational studies.

Uncovering New Excited State Photochemical Reactivity by Altering the Course of the De Mayo Reaction.

An unprecedented and previously unknown photochemical reactivity of 1,3-dicarbonyl compounds is observed with amino-alkenes leading to dihydropyrans. This novel photochemical reactivity changes the established paradigm related to the De Mayo reaction between 1,3-dicarbonyl compounds and alkenes. This new reaction allows convenient access to the Marmycin core in a single step from commercially available reactants. The origin and scope of this new photoreaction is detailed with preliminary photophysical and mechanistic investigations.

Divergent Total Synthesis of Euphoranginol C, Euphoranginone D, ent-Trachyloban-3β-ol, ent-Trachyloban-3-one, Excoecarin E, and ent-16α-Hydroxy-atisane-3-one.

A divergent synthetic approach to biogenetically related diterpenoids such as ent-kauranes, ent-trachylobanes, ent-beyerane, and ent-atisane has been developed. The unified synthetic route involves the De Mayo reaction to rapidly generate the bicyclo[3.2.1]-octane moiety of ent-kaurane. The key reactions also include bioinspired nucleophilic cyclopropanation generating the [3.2.1.02,7 ]-tricyclic core of ent-trachylobane and regioselective cyclopropane fragmentation furnishing ent-beyerane and ent-atisane through the nucleophilic attack and protonation of the cyclopropane ring. This strategy enables the asymmetric total syntheses of six diterpenoids from the commercially available geraniol.

Divergent Total Synthesis of Euphoranginol C, Euphoranginone D, ent‐Trachyloban‐3β‐ol, ent‐Trachyloban‐3‐one, Excoecarin E, and ent‐16α‐Hydroxy‐atisane‐3‐one

AbstractA divergent synthetic approach to biogenetically related diterpenoids such as ent‐kauranes, ent‐trachylobanes, ent‐beyerane, and ent‐atisane has been developed. The unified synthetic route involves the De Mayo reaction to rapidly generate the bicyclo[3.2.1]‐octane moiety of ent‐kaurane. The key reactions also include bioinspired nucleophilic cyclopropanation generating the [3.2.1.02,7]‐tricyclic core of ent‐trachylobane and regioselective cyclopropane fragmentation furnishing ent‐beyerane and ent‐atisane through the nucleophilic attack and protonation of the cyclopropane ring. This strategy enables the asymmetric total syntheses of six diterpenoids from the commercially available geraniol.

Leptosperols A and B, Two Cinnamoylphloroglucinol-Sesquiterpenoid Hybrids from Leptospermum scoparium: Structural Elucidation and Biomimetic Synthesis.

Leptosperols A and B (1 and 2), two cinnamoylphloroglucinol-sesquiterpenoid hybrids featuring unprecedented 1-benzyl-2-(2-phenylethyl) cyclodecane and 2-benzyl-3-phenylethyl decahydronaphthalene backbones, along with their biosynthetic precursor (3), were isolated from Leptospermum scoparium. Compounds 1 and 2 represent the first example of phloroglucinol derivatives biogenetically constructed by a De Mayo reaction. The biomimetic synthesis of leptosperol B (2) was achieved using the proposed biosynthetic pathway. In addition, compounds 1 and 2 showed significant anti-inflammatory effects in zebrafish acute inflammatory models.

Construction of 4-substituted 2-(pyrrolidine-3-yl)acetic acid derivatives as cyclic γ-aminobutyric acid analogues employing intermolecular [2+2]-photocycloaddition as key steps

The synthesis of new 2-(pyrrolidine-3-yl)acetic acid derivatives as cyclic γ-aminobutyric acid analogues, which are additionally substituted at the 4-position, is reported. A de Mayo reaction, i.e. a combination of an intermolecular [2+2]-photocycloaddition of 1,3-dioxinones with N-protected 3-pyrroline and a fragmentation reaction of the resulting cyclobutane moiety, represent the key steps.

Development of an Alkyne Analogue of the de Mayo Reaction: Synthesis of Medium-Sized Carbacycles and Cyclohepta[b]indoles.

Embedded medium-sized carbacycles and cyclohepta[b]indoles occur frequently as scaffold elements in natural products and bioactive compounds. Described herein is a conceptionally novel photochemically triggered cascade process to these scaffolds. Key to the cascading ring-expansion process is an unprecedented intramolecular alkyne analogue of the de Mayo reaction.

Development of an Alkyne Analogue of the de Mayo Reaction: Synthesis of Medium‐Sized Carbacycles and Cyclohepta[b]indoles

AbstractEmbedded medium‐sized carbacycles and cyclohepta[b]indoles occur frequently as scaffold elements in natural products and bioactive compounds. Described herein is a conceptionally novel photochemically triggered cascade process to these scaffolds. Key to the cascading ring‐expansion process is an unprecedented intramolecular alkyne analogue of the de Mayo reaction.

Reinventing the De Mayo reaction: synthesis of 1,5-diketones or 1,5-ketoesters via visible light [2+2] cycloaddition of β-diketones or β-ketoesters with styrenes

A visible light mediated De Mayo reaction between 1,3-diketones and styrenes following a [2+2] cycloaddition pathway via a photosensitization mechanism gives access to 1,5-diketones. The reaction has been applied to substituted styrenes and aryl- and alkyl-substituted ketones. Moreover, the method converts β-ketoesters, β-amido esters, and β-cyano ketones. Seven membered rings, a frequent structural motif of natural products, are also accessible using this methodology.

ChemInform Abstract: 3,3-Dimethyl-7-methylenecycloocta-1,5-dione, a Versatile Building Block for the Preparation of Substituted Cyclooctadienones and δ- Valerolactones.

Abstract De Mayo reaction of dimedone with allene results in the formation of 3,3-dimethyl-7-methylenecycloocta-1,5-dione 6 together with the corresponding head-to-tail adduct 5 which spontaneously dimerizes to the hetero Diels-Alder adduct 7 . Reduction of 6 together with sodium borohydride or Grignard reagents affords the transannular hemiketals 9 which can easily be isomerized (DBU) to their conjugated analogues 10 . Depending on the substrate chosen ( 9 or 10 , the substituent R and the applied reaction conditions, an acid-catalyzed rearrangement of these hemiketals leads to the cyclooctadienones 12 in either pure form or in admixture with δ-valerolactones 11 or substituted cyclohexenones.

Card (Computer-Aided Reaction Design) program as a heuristic tool to propose new reactions. Application to the de Mayo reaction

We present the card program which is a new approach in the field of Computer-Aided Reaction Design. The objective of card is to generate new reactions from the combination of two other reactions.

A silyl-mediated [3+2] photochemical cycloaddition

The generation of larger rings from intermediate cyclobutanes via a two-step [2+2] photocycloaddition – ring expansion, known as the de Mayo reaction, has been widely applied in synthesis. Herein a one-step synthesis of cyclopentanoids has been developed based on the photochemical irradiation of an enone in the presence of an allylsilane. The ability of the silyl moiety to stabilize the intermediate biradical is believed to be responsible for this unique transformation where one normally expects to see the [2+2] cyclobutane adduct.Key words: [2+2] photocycloaddition - ring expansion, allylsilanes, cyclopentanoids, photochemical.

A photochemical approach to the Galanthan ring system.

A five-step, atom-efficient synthesis of the Galanthan tetracyclic skeleton has been developed. The key step is an unusual intramolecular de Mayo reaction using an isocarbostyril substrate with a functionalized tether on nitrogen. The target molecule is produced in 35% overall yield from isocarbostyril.