Asymmetric Ion-Pairing Photoredox Catalysis for Stereoselective Cationic Polymerization under Light Control.

By virtue of noninvasive regulations by light, photocontrolled polymerizations have attracted considerable attention for the precision synthesis of macromolecules. However, a cationic polymerization with simultaneous photocontrol and tacticity-regulation remains elusive so far. Herein, we introduce an asymmetric ion-pairing photoredox catalysis strategy that allows for the development of a stereoselective cationic polymerization with concurrent light regulation for the first time. By employing an ion pair catalyst (PC+/*A-) consisting of a photoredox active cation (PC+) and a sterically confined chiral anion (*A-) to deliver the stereochemical control, the cationic polymerization of vinyl ethers can be achieved with photocontrol and high isotactic selectivity (up to 91% m) at a remarkable low catalyst loading (50 ppm).

Visible Light-Regulated Ring-Opening Polymerization of Lactones by Employing Indigo as a Photoacid Catalyst.

The development of visible light-regulated polymerizations for precision synthesis of polymers has drawn considerable attention in the past years. In this study, an ancient dye, indigo, is successfully identified as a new and efficient photoacid catalyst, which can readily promote the ring-opening polymerization of lactones under visible light irradiation in a well-controlled manner, affording the desired polyester products with predictable molecular weights and narrow dispersity. The enhanced acidity of indigos by excitation is crucial to the H-bonding activation of the lactone monomers. Chain extension and block copolymer synthesis are also demonstrated with this method.

The Development of Visible-Light Organic Photocatalysts for Atom Transfer Radical Polymerization via Conjugation Extension.

This work aimed to develop organic photocatalysts (PCs) that could mediate organocatalytic atom transfer radical polymerization (O-ATRP) under visible light. Through the core-modification of known chromophoric structures and ring-locking to reach a conjugation extension, annulated N-aryl benzo[kl]acridines were identified as effective visible light-responsive photocatalysts. The corresponding selenium-doped structure showed excellent performance in the O-ATRP of methacrylates, which could afford polymer products with controlled molecular weights and low dispersities under the irradiation of visible light at a 100 ppm catalyst loading.

Radical Fluorosulfonamidation: A Facile Access to Sulfamoyl Fluorides.

Recently, the introduction of fluorosulfonyl (-SO2F) groups have attracted considerable research interests, as this moiety could often afford enhanced activities and new functions in the context of chemical biology and drug discovery. Herein, we report the design and synthesis of 1-fluorosulfamoyl-pyridinium (FSAP) salts, which could serve as an effective photoredox-active precursor to fluorosulfamoyl radicals and enable the direct radical C-H fluorosulfonamidation of a variety of (hetero)arenes. This method features mild conditions, visible light, broad substrate scope, good group tolerance, etc., and a metal-free protocol is also viable by using organic photocatalysts. Further, FSAP can also be applied to the radical functionalization of alkenes via 1,2-difunctionalization, radical distal migration, tandem radical-polar crossover reactions, etc. In addition, a formal C-H methylamination of (hetero)arenes by combining this radical C-H fluorosulfonamidation with subsequent hydrolysis as well as product derivatization are also demonstrated.

Organocatalytic [2 + 2] Photopolymerization under Visible Light: Accessing Sustainable Polymers from Cinnamic Acids.

Herein, the successful development of a metal-free, solution [2 + 2] photopolymerization of natural cinnamic acid-derived bisolefinic monomers is reported, which is enabled by a strategy based on direct triplet state access via energy transfer catalysis. 2,2'-Methoxythioxanthone has been identified as an effective organic photocatalyst for the [2 + 2] photopolymerization in solution, which can be excited by visible light and activate the biscinnamate monomers via triplet energy transfer. This method features its metal-free conditions, visible light utilization, solution polymerization, and abundant biomass-based feedstock, as well as processable polymer products, which is different from the rigid, insoluble products obtained from solid-state photopolymerization. This solution polymerization method also shows a good compatibility to monomer structures; cinnamic acid-derived bisolefinic monomers with different linkers, including diamine, natural diol, and bisphenol, can all readily undergo [2 + 2] photopolymerization, and be transformed into colorless, sustainable polymers.

Organocatalytic, Stereoselective, Cationic Reversible Addition-Fragmentation Chain-Transfer Polymerization of Vinyl Ethers.

Tacticity is a crucial factor affecting the properties of synthetic polymer materials. Here, we introduce a type of chiral organic Brønsted acid catalyst, 1,1'-bi-2-naphthol-derived N,N'-bis(triflyl)phosphoramidimidates (PADIs), for the cationic polymerization of vinyl ethers, which enables the development of the first organocatalytic, highly stereoselective, cationic reversible addition-fragmentation chain-transfer (RAFT) polymerization of vinyl ethers with a trithiocarbonate chain-transfer agent. This metal-free RAFT process could afford isotactic poly(vinyl ethers) with high stereoselectivity, controllable molecular mass, and narrow dispersity at low catalyst loadings (as low as 200 ppm). Moreover, the trithiocarbonate chain-end allows for chain extension to synthesize diblock copolymers comprising an isotactic poly(vinyl ether) block, by a mechanistic switching from stereoselective cationic RAFT polymerization to visible-light-regulated cationic and radical RAFT polymerization.

Radical Hydro-Fluorosulfonylation of Unactivated Alkenes and Alkynes.

Recently, radical fluorosulfonylation is emerging as an appealing approach for the synthesis of sulfonyl fluorides, which are highly in demand in various disciplines, particularly in chemical biology and drug discovery. Here, we report the first establishment of radical hydro-fluorosulfonylation of alkenes, which is enabled by using 1-fluorosulfonyl 2-aryl benzoimidazolium (FABI) as an effective redox-active radical precursor. This method provides a new and facile approach for the synthesis of aliphatic sulfonyl fluorides from unactivated alkenes, and can be further applied to the late-stage modifications of natural products and peptides, as well as ligation of drugs in combination with click chemistry. Remarkably, this system could enable the radical hydro-fluorosulfonylation of alkynes, affording valuable alkenylsulfonyl fluoride products with a rare, high Z-selectivity, which are normally less stable and more challenging to synthesize in comparison with the E-configured products.

Metal-Free Cationic Polymerization of Vinyl Ethers with Strict Temporal Control by Employing an Organophotocatalyst.

By virtue of spatiotemporal control over the chain propagating, visible-light-regulated organocatalytic photoredox cationic polymerization provides an appealing approach for the construction of metal-free, well-defined polymers and materials. However, so far, organic photocatalysts capable of mediated cationic polymerization of vinyl ethers are quite limited, and the photocontrol or efficiency is often eroded due to the difficulty in achieving a good activation-deactivation balance, which is greatly dependent on the redox property of the catalyst. Here, we introduce a new type of organic photocatalysts, bisphosphonium salts, which show high performance in the photoregulated reversible addition-fragmentation chain transfer cationic polymerization of vinyl ethers and allow the synthesis of poly(vinyl ethers) with predictable molecular weights and narrow dispersities at low ppm catalyst loadings under visible light. In particular, the tunable redox potential and excellent stability endow the bisphosphonium salts strict temporal control, thus enabling the metal-free polymerization with a halt in a long dark period.

Introducing A New Class of Sulfonyl Fluoride Hubs via Radical Chloro-Fluorosulfonylation of Alkynes.

Sulfonyl fluorides have widespread applications in many important fields, including ligation chemistry, chemical biology, and drug discovery. Therefore, new methods to increase the synthetic efficiency and expand the available structures of sulfonyl fluorides are highly in demand. Here, we introduce a new and powerful class of sulfonyl fluoride hubs, ß-chloro alkenylsulfonyl fluorides (BCASF), which can be constructed via radical chloro-fluorosulfonyl difunctionalization of alkynes under photoredox conditions. BCASF molecules exhibit versatile reactivities and well undergo a series of transformations at the chloride site while keeping the sulfonyl fluoride group intact, including reduction, Suzuki coupling, Sonogashira coupling, as well as nucleophilic substitution with various nitrogen, oxygen, and sulfur nucleophiles. By using BCASF as a synthetic hub, a wide range of sulfonyl fluorides becomes readily accessible, such as cis alkenylsulfonyl fluorides, dienylsulfonyl fluorides, and ynenylsulfonyl fluorides, which are challenging or even not possible to synthesize before with the known methods. Moreover, further application of BCASF to the late-stage modification of peptides and drugs is also demonstrated.

Radical Fluorosulfonylation: Accessing Alkenyl Sulfonyl Fluorides from Alkenes.

Sulfonyl fluorides have widespread applications in many fields. In particular, their unique biological activity has drawn considerable research interest in the context of chemical biology and drug discovery in the past years. Therefore, new and efficient methods for the synthesis of sulfonyl fluorides are highly in demand. In contrast to extensive studies on FSO2+ -type reagents, a radical fluorosulfonylation reaction with a fluorosulfonyl radical (FSO2. ) remains elusive so far, probably owing to its instability and difficulty in generation. Herein, the development of the first radical fluorosulfonylation of alkenes based on FSO2 radicals generated under photoredox conditions is reported. This radical approach provides a new and general access to alkenyl sulfonyl fluorides, including structures that would otherwise be challenging to synthesize with previously established cross-coupling methods. Moreover, extension to the late-stage fluorosulfonylation of natural products is also demonstrated.

Electrochemical Oxo-Fluorosulfonylation of Alkynes under Air: Facile Access to ß-Keto Sulfonyl Fluorides.

Radical fluorosulfonylation is emerging as an appealing approach for the synthesis of sulfonyl fluorides, which have widespread applications in many fields, in particular in the context of chemical biology and drug development. Here, we report the first investigation of FSO2 radical generation under electrochemical conditions, and the establishment of a new and facile approach for the synthesis of ß-keto sulfonyl fluorides via oxo-fluorosulfonylation of alkynes with sulfuryl chlorofluoride as the radical precursor and air as the oxidant. This electrochemical protocol is amenable to access two different products (ß-keto sulfonyl fluorides or α-chloro-ß-keto sulfonyl fluorides) with the same reactants. The ß-keto sulfonyl fluoride products can be utilized as useful building blocks in the synthesis of various derivatives and heterocycles, including the first synthesis of an oxathiazole dioxide compound. Furthermore, some ß-keto sulfonyl fluorides and derivatives exhibited notably potent activities against Bursaphelenchus xylophilus and Colletotrichum gloeosporioides.

Catalytic Enantioselective Conversion of Epoxides to Thiiranes.

A highly efficient and enantioselective Brønsted acid catalyzed conversion of epoxides to thiiranes has been developed. The reaction proceeds in a kinetic resolution, furnishing both epoxide and thiirane in high yields and enantiomeric purity. Heterodimer formation between the catalyst and sulfur donor affords an effective way to prevent catalyst decomposition and enables catalyst loadings as low as 0.01 mol %.

The Activation of Carboxylic Acids via Self-Assembly Asymmetric Organocatalysis: A Combined Experimental and Computational Investigation.

The heterodimerizing self-assembly between a phosphoric acid catalyst and a carboxylic acid has recently been established as a new activation mode in Brønsted acid catalysis. In this article, we present a comprehensive mechanistic investigation on this activation principle, which eventually led to its elucidation. Detailed studies are reported, including computational investigations on the supramolecular heterodimer, kinetic studies on the catalytic cycle, and a thorough analysis of transition states by DFT calculations for the rationalization of the catalyst structure-selectivity relationship. On the basis of these investigations, we developed a kinetic resolution of racemic epoxides, which proceeds with high selectivity (up to s = 93), giving the unreacted epoxides and the corresponding protected 1,2-diols in high enantiopurity. Moreover, this approach could be advanced to an unprecedented stereodivergent resolution of racemic α-chiral carboxylic acids, thus providing access to a variety of enantiopure nonsteroidal anti-inflammatory drugs and to α-amino acid derivatives.

Asymmetric Annulation of Donor-Acceptor Cyclopropanes with Dienes.

An efficient [4 + 3] cycloaddition reaction of D-A cyclopropanes with dienes has been successfully developed. The reaction proceeds well with various dienolsilyl ethers in the presence of Lewis acid, delivering a variety of cycloheptenes and [n,5,0]carbobicycles with excellent stereoselectivity. The asymmetric version of this reaction is also realized using a newly designed chiral Cy-TOX ligand, providing a new approach to access optically active cycloheptenes and [n,5,0]carbobicycles. Mechanisic study reveals that the reaction involves a stepwise pathway, which undergoes an unusual ring opening of five-membered [3 + 2] intermediate and sequential intramolecular cyclization to afford the thermodynamically stable [4 + 3] annulation product.

Asymmetric 1,2-perfluoroalkyl migration: easy access to enantioenriched α-hydroxy-α-perfluoroalkyl esters.

This study has led to the development of a novel, highly efficient, 1,2-perfluoro-alkyl/-aryl migration process in reactions of hydrate of 1-perfluoro-alkyl/-aryl-1,2-diketones with alcohols, which are promoted by a Zn(II)/bisoxazoline and form α-perfluoro-alkyl/-aryl-substituted α-hydroxy esters. With (-)-8-phenylmenthol as the alcohol, the corresponding menthol esters are generated in high yields with excellent levels of diastereoselectivity. The mechanistic studies show that the benzilic ester-type rearrangement reaction takes place via an unusual 1,2-migration of electron-deficient trifluoromethyl group rather than the phenyl group. The overall process serves as a novel, efficient, and simple approach for the synthesis of highly enantioenriched, biologically relevant α-hydroxy-α-perfluoroalkyl carboxylic acid derivatives.

Side arm strategy for catalyst design: modifying bisoxazolines for remote control of enantioselection and related.

In asymmetric catalysis, the remote control of enantioselection is usually difficult due to the long distance communication between the chiral center of the catalyst and the reactive site of the substrate. The development of efficient and highly enantioselective catalysts for such reactions is of great importance and highly desirable. The stereocontrol over an asymmetric reaction is a delicate process (ca. 3.0 kcal/mol difference in transition states can lead to >99/1 enantiomeric selectivity at room temperature), it therefore requires fine-tuning on the electronic nature of the central metal together with a precisely created cavity to accommodate the substrates and reagents. We envision that a solution is the design of new catalysts by finding an easy and efficient way to tune the electronic properties, the chiral space, and the shape of the catalytic site. Since an extra coordination group in the organometallic complex could not only alter the microenvironment around the metal center in a three-dimensional manner but also tune the electronic properties of the metal center, about 10 years ago, we introduced a side arm strategy for ligand/catalyst design. This Account describes our efforts toward this goal. Based on this side arm strategy, we have developed two series of ligands based on the bisoxazoline framework; namely, trisoxazoline (TOX) ligands and side armed bisoxazoline (SaBOX). The "side arms" are shown to play multiple roles in different cases, for example, as a ligating group, a steric group, or a directing group, which are dependent on the metal and the functionality at the side arm. Metal catalysts based on these ligands have proven to be highly efficient for a number of asymmetric transformations, including Friedel-Crafts reaction, Kinugasa reaction, Nazarov reaction, 1,2-Stevens rearrangement, Cannizzaro reaction, and cyclopropanation. In comparison with the parent BOX ligands, the metal catalysts based on these TOX and SaBOX ligands usually exhibit higher efficiency and diastereo- and enantioselectivity with better impurity tolerance and stability. Moreover, in several TOX-metal complex catalyzed reactions such as Friedel-Crafts reaction and [3 + 2] cycloaddition, stereoselectivity could be switched based on reaction conditions. These ligands were particularly prominent in the remote controls of enantioselection such as the conjugate additions to alkylidene malonates and ring-opening/cyclization cascades of cyclopropanes, for which high stereoselectivity is usually difficult to achieve due to the poor chiral communication. The works by us and other groups have demonstrated that the side arm strategy can be employed as a general principle for ligand and catalyst design and should not be limited to the BOX scaffolds and the reactions described in this Account. Wide application of the new strategy in organometallic homogeneous catalysis can be anticipated.

Stereochemical Communication within a Chiral Ion Pair Catalyst.

Ionic interactions are increasingly appreciated as a key, asymmetry-inducing factor in enantioselective catalytic transformations, including those involving Brønsted acid or base catalysis, phase-transfer catalysis, and related processes. However, a detailed understanding of these interactions is often lacking. Herein, we show how an enantiopure anion enforces a chiral conformation onto a catalytically relevant achiral cation. Specifically, we use vibrational circular dichroism (VCD) spectroscopy to monitor the transmission of stereochemical information from a chiral phosphate anion to a flexible manganese(III)-salen cation. We show that VCD can be used to study solvent effects and that the obtained chiroptical data directly and quantitatively correlate with the experimentally observed enantioselectivity in an asymmetric olefin epoxidation reaction.

Radical Ring-Opening Fluorosulfonylation of Methylenecyclobutanols via Electron Donor-Acceptor Photoactivation.

A visible-light-mediated catalyst- and additive-free method for radical ring-opening fluorosulfonylation of methylenecyclobutanols is reported. Sulfuryl chlorofluoride acts as a FSO2 radical precursor as well as an electron acceptor to form electron donor-acceptor complexes with various methylenecyclobutanol substrates. This method shows fully regioselective and (E)-stereoselective ring-opening processes, providing a variety of FSO2-functionalized γ,δ-unsaturated carbonyls in 38-77% yields. A selection of product diversifications has been studied to demonstrate the versatility of these sulfonyl fluoride products.

Radical Hydro-Fluorosulfonylation of Propargylic Alcohols via Electron Donor-Acceptor Photoactivation.

A radical hydro-fluorosulfonylation of propargyl alcohols with FSO2Cl is presented based on the photoactivation of the electron donor-acceptor (EDA) complex. The reaction avoids the requirement for photocatalysts, bases, hydrogen donor reagents, any other additives, and harsh conditions, enabling the facile synthesis of various functionalized γ-hydroxy (E)-alkenylsulfonyl fluorides. These multifunctional sulfonyl fluorides can be further diversified, providing access to various privileged molecules of biological relevance.

Fluorosulfonyl Arylation of Alkynes via Electron Donor-Acceptor Photoactivation.

A radical fluorosulfonyl arylation of alkynes with sulfuryl chlorofluoride as the FSO2 radical precursor via electron donor-acceptor photoactivation driven by daylight or a blue light-emitting diode is disclosed. A series of valuable benzo-fused carbocycles and heterocycles have been produced with simple operation under mild conditions in the absence of any external catalysts or additives. The synthetic potential of this protocol has further demonstrated excellent scalability, as well as diverse postderivatizations, including SuFEx reactions and other useful cascade reactions.