Organocatalytic Asymmetric Allylic Benzylborylation via Fluoride-Assisted Catalytic Generation of α-Boryl Carbanionic Intermediates.

Herein we describe the organocatalytic asymmetric allylic benzylborylation of allyl fluorides with α-silyl benzylboronic esters. The catalytic protocol leverages the singular features of fluoride as an unconventional leaving group, enabling the catalytic generation of reactive α-boryl carbanion species through desilylative activation. It allows the construction of a wide set of homoallylic benzylated organoboronates bearing two contiguous stereocenters.

Catalytic asymmetric defluorinative allylation of silyl enol ethers.

The stereocontrolled installation of alkyl fragments at the alpha position of ketones is a fundamental yet unresolved transformation in organic chemistry. Herein we report a new catalytic methodology able to construct α-allyl ketones defluorinative allylation of silyl enol ethers in a regio-, diastereo- and enantioselective manner. The protocol leverages the unique features of the fluorine atom to simultaneously act as a leaving group and to activate the fluorophilic nucleophile a Si-F interaction.

Understanding the Diastereopreference of Intermediates in Aminocatalysis: Application to the Chiral Resolution of Lactols.

Downstream intermediates are crucial for the reactivity and selectivity of aminocatalytic reactions. We present an analysis of the stereopreference in aminocatalytic downstream intermediates, which reveals an inconspicuous mechanism of chiral recognition between the catalyst and the rest of the molecule. We delineate a stereoelectronic model to rationalize the mode of chiral transmission.

A Rational Approach to Organo-Photocatalysis: Novel Designs and Structure-Property Relationships.

Organic photocatalysts are emerging as viable and more sustainable tools than metal complexes. Recently, the field of organo-photocatalysis has experienced an explosion in terms of applications, redesign of well-established systems, and identification of novel scaffolds. A rational approach to the structural modification of the different photocatalysts is key to accessing unprecedented reactivity, while improving their catalytic performances.

A visible-light Paternò-Büchi dearomatisation process towards the construction of oxeto-indolinic polycycles.

A variety of highly functionalised -containing polycycles (35 examples) are synthesised from simple indoles and aromatic ketones through a mild visible-light Paternò-Büchi process. Tetrahydrooxeto[2,3-]indole scaffolds, with up to three contiguous stereocenters, are generated in high yield (up to >98%) and excellent site- regio- and diastereocontrol (>20 : 1). The use of visible light (405 or 465 nm) ensures enhanced performances by switching off undesired photodimerisation side reactions.

Light-Triggered Catalytic Asymmetric Allylic Benzylation with Photogenerated -Nucleophiles.

Herein is reported the asymmetric allylic benzylation of Morita-Baylis-Hillman (MBH) carbonates with 2-methylbenzophenone (MBP) derivatives as nonstabilized photogenerated -nucleophiles. The dual activation of both reaction partners, chiral Lewis-base activation of the electrophile and light activation of the nucleophile, enables the stereoselective installation of benzyl groups at the allylic position to forge tertiary and quaternary carbon centers.

Microfluidic light-driven synthesis of tetracyclic molecular architectures.

Herein we report an effective synthetic method for the direct assembly of highly functionalized tetracyclic pharmacophoric cores. Coumarins and chromones undergo diastereoselective [4 + 2] cycloaddition reactions with light-generated photoenol intermediates. The reactions occur by aid of a microfluidic photoreactor (MFP) in high yield (up to >98%) and virtually complete diastereocontrol (>20:1 dr).

Transition Metal-Free CO Fixation into New Carbon-Carbon Bonds.

CO is the ultimate renewable carbon source on Earth and the essential C building block for carbohydrate biosynthesis in photosynthetic organisms. Modern synthetic chemistry is facing the key challenge of developing fundamental transformations, such as C-C bond formation, in a sustainable and efficient manner from renewable sources. In this Minireview, the most significant methods recently reported for CO fixation under transition metal-free conditions are summarized, organized into three different chapters according to the nature of the chemical transformation that forges the new C-C bond.

A microfluidic photoreactor enables 2-methylbenzophenone light-driven reactions with superior performance.

Light-driven reactions of 2-methylbenzophenones (2-MBPs) occur with improved yields (up to >98%) and reaction rates (up to 0.240 mmol h-1) by using a tailored microfluidic photoreactor (MFP). For the first time, coumarins were converted into 4-benzylated chromanones in high yields (50-93%) and diastereoselectivity (up to >20 : 1 dr), thus by-passing their photo-dimerisation end-reaction.

Distribution of Catalytic Species as an Indicator To Overcome Reproducibility Problems.

Irreproducibility is a common issue in catalysis. The ordinary way to minimize it is by ensuring enhanced control over the factors that affect the reaction. When control is insufficient, some parameters can be used as indicators of the reaction performance.

Deciphering the roles of multiple additives in organocatalyzed Michael additions.

The synergistic effects of multiple additives (water and acetic acid) on the asymmetric Michael addition of acetone to nitrostyrene catalyzed by primary amine-thioureas (PAT) were precisely determined. Acetic acid facilitates hydrolysis of the imine intermediates, thus leading to catalytic behavior, and minimizes the formation of the double addition side product. In contrast, water slows down the reaction but minimizes catalyst deactivation, eventually leading to higher final yields.

First one-pot organocatalytic synthesis of α-methylene-γ-lactones.

All in one pot: an organocatalytic highly enantioselective synthesis of α-methylene-γ-lactones has been reported. The reaction between protected 2-hydroxymalonates and MBH carbonates is simply catalysed by chiral Lewis bases affording after acid treatment the corresponding lactones in excellent yields and enantioselectivities.

Enantioselective organocatalytic oxyamination of unprotected 3-substituted oxindoles.

An enantioselective α-oxyamination of unprotected 3-substituted oxindoles with nitrosobenzene catalyzed by tertiary amine-thiourea bifunctional organocatalysts has been developed and affords the corresponding 3-amino-2-oxindole derivatives in good yields and with moderate to excellent enantioselectivities (up to > 99.9 : 0.1 er when the product is isolated by direct filtration from the reaction mixture).

Enantioselective organocatalytic asymmetric allylic alkylation. Bis(phenylsulfonyl)methane addition to MBH carbonates.

The highly enantioselective asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates with bis(phenylsulfonyl)methane is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and enantioselectivities.

Enantioselective organocatalytic synthesis of fluorinated molecules.

The enantioselective synthesis of fluorinated molecules has drawn much attention within the chemical community due to its unique stereoelectronic properties. The main aim of this review is to cover the most important organocatalytic enantioselective methodologies to obtain them. The review is divided into three parts: first, the direct introduction of a fluorine atom studied in the early 2000s.

Organocatalytic synthesis of spiro compounds via a cascade Michael-Michael-aldol reaction.

The synthesis of spiro compounds via a Michael-Michael-aldol reaction is reported. The reaction affords spirooxindole derivatives in good yields and in almost diastereo- and enantiopure form. Moreover, the reaction works with several heterocycles such as oxindoles, benzofuranones, pyrazolones or azlactones rendering the final spiro compounds in good yields and excellent stereoselectivities.

Sulfones: new reagents in organocatalysis.

The development of new asymmetric methodologies that afford different structures in an enantioselective fashion is one of the most exciting goals for chemists nowadays. In this subject, lately, the use of sulfones has become a fast growing field. From the works of Tan and Shibata until the last works of Palomo, sulfones have demonstrated their versatility and power in organocatalytic asymmetric reactions.

Enantioselective organocatalytic addition of oxazolones to 1,1-bis(phenylsulfonyl)ethylene: a convenient asymmetric synthesis of quaternary alpha-amino acids.

A new, easy, and highly enantioselective method for the synthesis of quaternary alpha-alkyl-alpha-amino acids based on organocatalysis is reported. The addition of oxazolones to 1,1-bis(phenylsulfonyl)ethylene is efficiently catalyzed by simple chiral bases or thioureas. The reaction affords alpha,alpha-disubstituted alpha-amino acid derivatives with complete C4 regioselectivity and with excellent yields and enantioselectivities.