Search

Herein, we report the novel strategy for the synthesis of 4-enamino-5-phenyl-2,3-dihydroisothiazole 1-oxides (in other words α-phenyl β-enamino γ-sultims) based on the CSIC reaction. Particularly, readily available α-amino nitriles (the Strecker products) reacted with benzyl sulfinyl chloride to give the corresponding sulfinamides, which upon treatment with excess of LiHMDS converted into the target α-phenyl β-enamino γ-sultims. The method works well and tolerates strained 3- and 4-membered spirocyclic substituents. A preliminary in silico study indicated that the γ-sultim scaffold can be considered a promising pharmacophore template. [ABSTRACT FROM AUTHOR]

Sulfur-containing units are fundamental components widely found in bioactive compounds, prompting notable efforts toward developing synthetic methodologies for incorporating sulfur functionality into organic precursors. The synthesis of sulfinate esters and sulfinamides has garnered significant interest owing to their immense potential for applications, especially in drug development. However, most existing synthetic protocols suffer from some limitations. To address these challenges, we herein present a practical and efficient approach for the reductive sulfinylation of diverse nucleophiles with sulfonylpyridinium salts (SulPy) through the nucleophilic chain substitution, namely SNC reaction, which involves S(VI) to S(IV) nucleophilic chain isomerization process. These versatile sulfinylation reagents can be readily accessed from diverse commercially available resourses. The late-stage modification of complex molecules and the ability to rapidly synthesize numerous sulfinyl bioisosteres of various drugs highlights the utility of this protocol. The synthesis of sulfinate esters and sulfinamides has garnered significant interest owing to their potential for applications. Here, the authors report the reductive sulfinylation of diverse nucleophiles with sulfonylpyridinium salts through nucleophilic chain substitution, which involves S(VI) to S(IV) nucleophilic chain isomerization process. [ABSTRACT FROM AUTHOR]

A straightforward "one-column" continuous flow method of Grignard generation and reaction was successfully developed. The diverse mixtures of aryl- or alkyl- halides and electrophiles were flowed through an activited magnesium packed-bed column, delivering a series of ketones, secondary alcohols, tertiary alcohols, esters, amides, and sulfinamides immediately in moderate to good yields. By combining Grignard generation and reaction into one step and avoiding the separate preparation and storage of Grignard reagents, this practical and efficient protocol dramatically enhanced the safety of operation and provided a convenient access for Grignard reactions, compared with traditional batch process. The continuous flow synthesis of Grignard generation and reaction is carried out in a magnesium packed-bed column successfully.The target product is provided in moderate to good yields within 6.0 min. This protocol with preferable controllability, good selectivity, and safety extremely simplified operational procedure. [ABSTRACT FROM AUTHOR]

Combining simple amines with the bench‐stable sulfinylamine Tr‐NSO allows in situ preparation of reactive alkyl sulfinylamines, which when combined with alkyl radicals generated by photocatalytic decarboxylation, provides N‐alkyl sulfinamides. The reactions are broad in scope and tolerate a wide variety of functional groups on both the acid and amine components. The sulfinamide products are used to prepare a selection of challenging S(VI) products. The method provides a convenient way to use reactive and unstable alkyl sulfinylamines. [ABSTRACT FROM AUTHOR]

Herein, we demonstrate a method for the syntheses of sulfinamides and sulfinate esters using a novel sulfur(IV) fluoride exchange reaction with organometallic reagents. Our strategy involves the addition of an amine or alcohol nucleophile to thionyl fluoride, acting as a S(IV) SuFEx hub, followed by an organometallic reagent. This approach allows efficient access to sulfinamides (45–91% yields) and sulfinate esters (44–82% yields) in only 30 minutes. The sulfinamide and sulfinate esters also can be readily derivatized to the corresponding S(VI) sulfonamides, sulfonate esters, sulfonimidamides, and sulfonimidates without isolation of the intermediates. [ABSTRACT FROM AUTHOR]

The sulfinyl group, as one of the bioisosteres of carbonyl groups, attracts considerable attention in the field of synthetic chemistry. In particular, the asymmetric construction of chiral sulfinyl compounds and their derivatives remains in the early stages of development. Sulfinyl compounds mainly include sulfoxides, sulfinate esters and sulfinamides, according to the different functional groups connected to the sulfur atom. This Review summarizes the fascinating recent progress made over the past decade on the asymmetric synthesis of enantiopure sulfinyl derivatives. 1 Introduction 2 Asymmetric Synthesis of Chiral Sulfoxides 3 Asymmetric Synthesis of Chiral Sulfinate Esters 4 Asymmetric Synthesis of Chiral Sulfinamides 5 Conclusion and Outlook [ABSTRACT FROM AUTHOR]

Sulfinamidines are promising aza‐SIV chiral building blocks in asymmetric synthesis and drug discovery. However, no report has documented their enantioselective synthesis. Here we present an enantioselective synthesis of sulfinamidines via electrophilic amination of sulfenamides using an enantiopure N−H oxaziridine. The resulting enantiomerically enriched primary sulfinamidines are configurationally stable at 90 °C in solution and show remarkable stability against organic acids and bases under non‐aqueous conditions. We also demonstrate a one‐pot, three‐component, enantioselective synthesis of sulfinamides using N−H oxaziridine reagents. [ABSTRACT FROM AUTHOR]

An Artificial Metalloenzyme (ArM) built employing the streptavidin‐biotin technology has been used for the enantioselective synthesis of binaphthyls by means of asymmetric Suzuki‐Miyaura cross‐coupling reactions. Despite its success, it remains a challenge to understand how the length of the biotin cofactors or the introduction of mutations to streptavidin leads the preferential synthesis of one atropisomer over the other. In this study, we apply an integrated computational modeling approach, including DFT calculations, protein‐ligand dockings and molecular dynamics to rationalize the impact of mutations and length of the biotion cofactor on the enantioselectivities of the biaryl product. The results unravel that the enantiomeric differences found experimentally can be rationalized by the disposition of the first intermediate, coming from the oxidative addition step, and the entrance of the second substrate. The work also showcases the difficulties facing to control the enantioselection when engineering ArM to catalyze enantioselective Suzuki‐Miyaura couplings and how the combination of DFT calculations, molecular dockings and MD simulations can be used to rationalize artificial metalloenzymes. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of S-stereogenic sulfinamides has garnered considerable attention due to their structural and physicochemical properties. However, catalytic asymmetric synthesis of sulfinamides still remains daunting challenges, impeding their broad application in drug discovery and development. Here, we present an approach for the synthesis of S-stereogenic sulfinamides through peptide-mimic phosphonium salt-catalyzed asymmetric skeletal reorganization of simple prochiral and/or racemic sulfoximines. This methodology allows for the facile access to a diverse array of substituted sulfinamides with excellent enantioselectivities, accommodating various substituent patterns through desymmetrization or parallel kinetic resolution process. Mechanistic experiments, coupled with density functional theory calculations, clarify a stepwise pathway involving ring-opening and ring-closing processes, with the ring-opening step identified as crucial for achieving stereoselective control. Given the prevalence of S-stereogenic centers in pharmaceuticals, we anticipate that this protocol will enhance the efficient and precise synthesis of relevant chiral molecules and their analogs, thereby contributing to advancements in drug discovery. The enantioselective synthesis of S-stereogenic sulfinamides has garnered considerable attention due to their unique structural and physicochemical properties but catalytic asymmetric synthesis of sulfinamides still remains challenging. Here, the authors present the synthesis of S-stereogenic sulfinamides through the peptide-mimic phosphonium salt-catalyzed asymmetric skeletal reorganization of simple prochiral and racemic sulfoximines. [ABSTRACT FROM AUTHOR]

Isofagomine (IFG) and its analogues possess promising glycosidase inhibitory activities. However, a flexible synthetic strategy toward both C5a-functionalized IFGs remains to be explored. Here we show a practical synthesis of C5a-S and R aminomethyl IFG-based derivatives via the diastereoselective addition of cyanide to cyclic nitrone 1. Nitrone 1 was conveniently prepared on a gram scale and in high yield from inexpensive (−)-diethyl d-tartrate via a straightforward method, with a stereoselective Michael addition of a nitroolefin and a Nef reaction as key steps. A 268-membered library (134 × 2) of the C5a-functionalized derivatives was submitted to enzyme- or cell-based bio-evaluations, which resulted in the identification of a promising β-glucocerebrosidase (GCase) stabilizer demonstrating a 2.7-fold enhancement at 25 nM in p.Asn370Ser GCase activity and a 13-fold increase at 1 μM in recombinant human GCase activity in Gaucher cell lines. Isofagomine (IFG) and its analogs have promising glycosidase inhibitory activities, however, a flexible synthetic strategy toward C5a-functionalized IFGs remains to be achieved. Here, the authors show a practical synthesis of C5a-S and R-aminomethyl IFG derivatives via diastereoselective addition of cyanide to cyclic nitrone, and the synthesized derivatives are subsequently assessed for their efficacy as GCase stabilizers. [ABSTRACT FROM AUTHOR]

The conversion of commercially available chiral sulfinamides into pharmaceutically useful chiral sulfoximines via direct SIV-functionalization is synthetically attractive but challenging due to the competitive reaction of N-functionalization. Herein, we disclose a novel strain-release strategy to access stereospecific and chemoselective SIV-arylation and alkenylation of sulfinamides using arynes and strained cyclic alkynes. This method tolerates an unprecedented chemical diversity of functional groups attached to the nitrogen center (N–R). The origin of the high SIV-selectivity is elucidated by density functional theory calculations, suggesting a stepwise mechanism for the aryne substrates and a concerted mechanism for the cyclic alkynes. [ABSTRACT FROM AUTHOR]

The literature on cyclic sulfinamides (put simply, sultims) published from 1989 to 2022 has been summarized and reviewed. The information is divided into two sections: the analysis of synthetic methods on the preparation of cyclic sulfinamides and the discussion of the chemical properties of cyclic sulfinamides focusing on their reactions and applications. The survey of the reaction conditions, provided in the most detailed way, and a critical view of the reaction mechanisms add an extra dimension to the text. The data presented will be useful to specialists in different areas, especially those who work in the field of synthetic organic and pharmaceutical chemistry. [ABSTRACT FROM AUTHOR]

A mechanochemical synthesis of sulfonimidamides by iron(II)‐catalyzed exogenous ligand‐free N‐acyl nitrene transfer to sulfinamides is reported. The one‐step method tolerates a wide range of sulfinamides with various substituents under solvent‐free ambient conditions. Compared to its solution‐phase counterpart, this mechanochemical approach shows better conversion and chemoselectivity. Mechanistic investigations by ESI‐MS revealed the generation of crucial nitrene iron intermediates. [ABSTRACT FROM AUTHOR]

This article discusses the practical asymmetric synthesis of sulfoximines and sulfimides from sulfinamides. The authors highlight the importance of sulfur-containing functional groups in various fields and the relevance of chiral sulfoximines and sulfimides in agrochemicals and pharmaceuticals. They describe their own research in developing sulfur-selective alkylation and arylation reactions to achieve the desired transformations, and demonstrate the synthesis of various enantioenriched sulfoximines and sulfimides. The authors acknowledge the contributions of Prof. K. Maruoka and Dr. Y. Aota to this research. [Extracted from the article]

Sulfur monoxide (SO) is a highly reactive species that cannot be isolated in bulk. However, SO can play a pivotal role as a fundamental building block in organic synthesis. Reported herein is the design and application of a sulfinylhydrazine reagent as an easily prepared sulfur monoxide surrogate. We show facile thermal SO transfer from this reagent to dienes where a reaction using a mechanistic probe suggests the generation of singlet SO. Combined with Grignard reagents and appropriate carbon or nitrogen electrophiles, the reagent serves as an effective "SO" donor to enable the one‐pot, three‐component synthesis of sulfoxides and sulfinamides. [ABSTRACT FROM AUTHOR]

Monoterpene thiols are one of the classes of natural flavors that impart the smell of citrus fruits, grape must and wine, black currants, and guava and are used as flavoring agents in the food and perfume industries. Synthetic monoterpene thiols have found an application in asymmetric synthesis as chiral auxiliaries, derivatizing agents, and ligands for metal complex catalysis and organocatalysts. Since monoterpenes and monoterpenoids are a renewable source, there are emerging trends to use monoterpene thiols as monomers for producing new types of green polymers. Monoterpene thioderivatives are also known to possess antioxidant, anticoagulant, antifungal, and antibacterial activity. The current review covers methods for the synthesis of acyclic, mono-, and bicyclic monoterpene thiols, as well as some investigations related to their usage for the preparation of the compounds with antimicrobial properties. [ABSTRACT FROM AUTHOR]

3 Conclusions and Future Directions A versatile sulfinylative cross-coupling for the synthesis of sulfoxides and sulfinamides was developed employing easily prepared, bench-stable sulfoxide reagents B 1a b and B 1b b . Keywords: sulfinylative cross-coupling; Grignard reagents; one-pot synthesis; sulfinamides; sulfoxides EN sulfinylative cross-coupling Grignard reagents one-pot synthesis sulfinamides sulfoxides 1939 1942 4 10/09/23 20231024 NES 231024 Graph 1 Introduction Sulfoxides and sulfinamides represent versatile sulfur functional groups in medicinal and synthetic chemistry, and, as a result, considerable efforts have been made toward their synthesis. Optimization of conditions allowed the isolation of sulfoxide B 8 b in 77% yield (Scheme 2), while sulfoxide B 1b b , a Cl-substituted variant of B 1a b , was identified as another viable SO-donating reagent. Despite the demonstrated utility of sulfoxides B 1a b and B 1b b , minor side reactions, such as sulfoxide/magnesium exchange [49] were observed for some of the Grignard reagents tested. [Extracted from the article]

ω-transaminase has attracted growing attention for chiral amine synthesis, although it commonly suffers from severe by-product inhibition. ω-transaminase CrmG is critical for the biosynthesis of Caerulomycin A, a natural product that possesses broad bioactivity, including immunosuppressive and anti-cancer. Compared to L-Arg, amino donor L-Glu, L-Gln or L-Ala is more preferred by CrmG. In this study, we determined the crystal structure of CrmG in complex with amino donor L-Arg, unveiling the detailed binding mode. Specifically, L-Arg exhibits an extensive contact with aromatic residues F207 and W223 on the roof of CrmG active site via cation-π network. This interaction may render the deamination by-product of L-Arg to be an inhibitor against PMP-bound CrmG by stabilizing its flexible roof, thus reducing the reactivity of L-Arg as an amino donor for CrmG. These data provide further evidence to support our previous proposal that CrmG can overcome inhibition from those by-products that are not able to stabilize the flexible roof of active site in PMP-bound CrmG. Thus, our result can not only facilitate the biosynthesis of CRM A but also be beneficial for the rational design of ω-transaminase to bypass by-product inhibition. • Crystal structure of CrmG in complex with amino donor L-Arg is reported. • L-Arg interacts with the roof of CrmG active site via unique cation-π network. • The interaction with the roof impairs reactive efficiency of L-Arg as CrmG amino donor. [ABSTRACT FROM AUTHOR]

Finally, -sulfoximine esters with alkyl substituents ( I tert i -butyl, cyclohexyl, butyl) were investigated under the standard reaction conditions and afforded the corresponding sulfoximine B 4h b - B j b in moderate yields (42-56%). Keywords: sulfoximines; S-alkylation; sulfinamides; sulfoximine esters EN sulfoximines S-alkylation sulfinamides sulfoximine esters 1829 1833 5 08/29/23 20230915 NES 230915 Graph The development of modern synthetic chemistry not only facilitates the construction of compound libraries, studies on structure-activity relationships, and developments of the synthesis process, but also considerably improves the rate of generation of small-molecule drugs and provides efficient support for the discovery of candidate drug compounds. Synthesis of Sulfoximines through Selective Sulfur Alkylation of Sulfinamides Generated In Situ from -Sulfoximine Esters The reaction then proceeds smoothly through a selective S-alkylation, rather than an N-alkylation, with readily available alkyl bromides to give the corresponding sulfoximines in reasonable yields (Scheme 1c). [Extracted from the article]

The crystal structure of four cyclic sulfinamides is studied. While belonging to different space groups, all four crystals contain homochiral chains of the same type formed by classical N–H⋯O hydrogen bonds. Within the considered series, the homochiral recognition is shown to transform from the 1D level (chains) through the 2D level (layers) to the 3D level (network). The role of intermolecular interactions in the formation of associates of different stereochemical types is revealed. [ABSTRACT FROM AUTHOR]

Sulfoxides and sulfinamides play important roles in the pharmaceutical industry, organic synthesis and fine chemicals. This review will demonstrate that, under catalysis by transition metals, β-sulfinyl esters, as nucleophilic reagents, react with a variety of electrophilic reagents to produce sulfoxides and sulfinamides. The important prospect of the asymmetric catalytic synthesis of chiral sulfur-containing molecules in this field is described.

Sulfoxides and sulfinamides play important roles in the pharmaceutical industry, organic synthesis and fine chemicals. This review will demonstrate that, under catalysis by transition metals, β-sulfinyl esters, as nucleophilic reagents, react with a variety of electrophilic reagents to produce sulfoxides and sulfinamides. The important prospect of the asymmetric catalytic synthesis of chiral sulfur-containing molecules in this field is described. [ABSTRACT FROM AUTHOR]

The chemistry of cyclic sulfinic acid derivatives (sultines and cyclic sulfinamides) was underdeveloped for a long time due to their inaccessibility. Considering the importance of cyclic sulfinate esters and amides in the fields of chemistry, pharmaceutical science, and material science, synthesis strategies involving cyclic sulfinic acid derivatives have been paid more attention in recent years, and have been widely used in the synthesis of sulfur-containing compounds such as sulfoxides, sulfones, sulfinates and thioethers. Despite the impressive improvements that have been made in last twenty years with the new strategies, to date, no reviews have been published, to the best of our knowledge, dealing with the preparation of cyclic sulfinic acid derivatives. This review summarizes the latest advances in the development of new synthesis methods to access cyclic sulfinic acid derivatives in the last two decades. The synthetic strategies are reviewed by highlighting their product diversity, selectivity and applicability, and the mechanistic rationale is presented where possible. We wish to bring readers a comprehensive understanding of the state-of-play of cyclic sulfinic acid derivative formation and make a contribution to future research. [ABSTRACT FROM AUTHOR]

Chiral sulfimides, the aza‐analogues of sulfoxides, are valuable compounds in organic synthesis and medicinal chemistry. Herein, we report an efficient method for preparing chiral sulfimides from easily available enantioenriched sulfinamides. The key step of this method is a stereospecific oxygen‐selective alkylation of enantioenriched sulfinamides, which is accomplished by using isopropyl iodide, K2CO3, and DMPU. The resulting chiral sulfinimidate esters are transformed to chiral sulfimides by the nucleophilic addition of the Grignard reagents under simple conditions. This transformation enables access to the enantioenriched diaryl or dialkyl sulfimides bearing two similar carbon substituents, which are difficult to synthesize by previous methods. [ABSTRACT FROM AUTHOR]

The development of NH transfer reactions using hypervalent iodine and simple sources of ammonia has facilitated the synthesis of sulfoximines and sulfonimidamides for applications across the chemical sciences. Perhaps most notably, the methods have been widely applied in medicinal chemistry and in the preparation of biologically active compounds, including in the large-scale preparation of an API intermediate. This review provides an overview of the development of these synthetic methods involving an intermediate iodonitrene since our initial report in 2016 on the conversion of sulfoxides into sulfoximines. This review covers the NH transfer to sulfoxides and sulfinamides, and the simultaneous NH/O transfer to sulfides and sulfenamides to form sulfoximines and sulfonimidamides, respectively. The mechanism of the reactions and the identification of key intermediates are discussed. Developments in the choice of reagents, and in the reaction conditions and setups used are described. [ABSTRACT FROM AUTHOR]

α‐Amino acid derivatives are key components of the molecules of life. The synthesis of α‐amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we report a practical method for the preparation of α‐amino acid derivatives via direct hydrative amination of activated alkynes under mild conditions, relying on sulfinamides as the nitrogen source. Computational studies suggest that the reaction is enabled by a new type of sulfonium [2,3]‐sigmatropic rearrangement. [ABSTRACT FROM AUTHOR]

Sulfoxides and sulfinamides represent versatile sulfur functional groups found in ligands, chiral auxiliaries, and bioactive molecules. Canonical two‐component syntheses, however, rely on substrates with a preinstalled C−S bond and impede efficient and modular access to these sulfur motifs. Herein is presented the application of an easily prepared, bench‐stable sulfoxide reagent for one‐pot, three‐component syntheses of sulfoxides and sulfinamides. The sulfoxide reagent donates the SO unit upon the reaction with a Grignard reagent (RMgX) as a sulfenate anion (RSO−). While subsequent trapping reactions of this key intermediate with carbon electrophiles provide sulfoxides, a range of tertiary, secondary, and primary sulfinamides can be prepared by substitution reactions with electrophilic amines. The syntheses of sulfinamide analogs of amide‐ and sulfonamide‐containing drugs illustrate the utility of the method for the rapid preparation of medicinally relevant molecules. [ABSTRACT FROM AUTHOR]

C−N bond formation takes on a critical significance in reactions of organic synthesis, material production and pharmaceutical manufactory. Chan‐Lam has proposed a useful methodology to furnish secondary arylamides under mild conditions. However, when chiral sulfinamides serve as the coupling precursors, the Cu‐catalyzed coupling reaction is found with low efficacy. Complex side‐products are generated under classic conditions. Moreover, it led to the racemization of the coupling product. In this study, an optimized Ni‐catalyzed Chan‐Lam type coupling conditions were proposed, which resulted in clean conversion from chiral sulfinamides and arylboronic acids to offer N‐aryl sulfinamides efficiently and enantioretentively. The trans‐N1,N2‐dimethylcyclohexane‐1,2‐diamine was proven as the most efficient ligand. Under the optimized conditions, a series of chiral N‐aryl sulfinamides was prepared with high chemical yield without racemization. Furthermore, a plausible and novel mechanism was proposed. Interestingly, the method could efficiently furnish a wide variety of C−X bonds by coupling arylboronic acids with different nucleophiles. [ABSTRACT FROM AUTHOR]

The growing interest in novel sulfur pharmacophores led to recent advances in the synthesis of some S(IV) and S(VI) motifs. However, preparation and isolation of uncommon primary sulfinamidines, the aza‐analogues of sulfinamides, is highly desirable. Here we report a multistep continuous flow synthesis of poorly explored NH2‐sulfinamidines by nucleophilic attack of organometallic reagents to in situ prepared N‐(trimethylsilyl)‐N‐trityl‐λ4‐sulfanediimine (Tr−N=S=N−TMS). The transformation can additionally be realized under mild conditions, at room temperature, via a highly chemoselective halogen‐lithium exchange of aryl bromides and iodides with n‐butyllithium. Moreover, the synthetic potential of the methodology was assessed by exploring further manipulations of the products and accessing novel S(IV) analogues of celecoxib, tasisulam, and relevant sulfinimidoylureas. [ABSTRACT FROM AUTHOR]

The aim of this research was to improve the operational stability and enable the reusability of ω-transaminase for synthesis of new enantiopure chiral amines of steroids. Dihydrotestosterone was used to optimize the synthetic procedure of corresponding amino-steroid on a larger scale. The obtained product 3α-amino-5α-androstan-17β-ol was isolated and characterized. The enzyme was immobilized on a methacrylate-based carrier, giving the specific activity of 1.84 U/g of dry polymer. Higher residual activity of the immobilized enzyme in comparison to the soluble form (100 % versus 35%) after 24 h incubation in 35 % dimethylformamide (DMF) was obtained. The soluble enzyme retained 19 % of the initial activity after 2 h incubation in 35 % DMF at 70 °C, while the activity of the immobilized enzyme decreased only to 75 %. Immobilized retained 85 % of initial activity after ten consecutive cycles of 3α-amino-5α-androstan-17β-ol synthesis. We have tested the specificity of the ArRMut11 variant, further increased its stability by immobilization, and used it in several cycles for the synthesis of 3α-amino-5α-androstan-17β-ol. We showed that the enzyme previously evolved for higher stability as the immobilized variant showed more increased stability and high reusability that can more effectively be applied for the biosynthesis of amino steroids. [Display omitted] • ArRMut11 omega-transaminase was tested for amination of steroid compounds. • 3α-amino-5α-androstan-17β-ol was synthesized and characterized. • The enzyme was further stabilized by immobilization onto macroporous copolymer. • Synthetic process was performed in ten consecutive cycles with immobilized enzyme. [ABSTRACT FROM AUTHOR]

Although the power of chiral sulfinamide reagents in synthetic chemistry has long been recognized, methods for their synthesis are still auxiliary‐based approaches which possess the disadvantages of poor atom economy and limited substrate universality. Due to the weak nucleophilicity of amides, it is more difficult to prepare chiral N‐acylsulfinamides by traditional methods. Herein, we describe an example of catalytic asymmetric synthesis of N‐acyl sulfinamides. In this work, N‐acyl sulfenamides act as useful substrates, because of the indispensable N−H bond, which could form an efficient hydrogen bond with chiral phosphoric acid. H2O2 (35%) was used as the terminal oxidant for preparation of sulfinamides in high yields and enantioselectivities, which could be easily derivatized to sulfoxides without loss of the enantioselectivity. [ABSTRACT FROM AUTHOR]

Nitrogen additive is an important factor for chiral lactic acid fermentation for low-cost and high optical purity of final chiral lactic acid product. This study tried to formulate a low-cost and racemic lactic acids-free nitrogen ingredient for lactic acid bacterium strain using wheat straw as carbon source. Eight available plant proteins were evaluated as potential nitrogen additives for chiral lactic acid fermentation by proteinase catalyzed hydrolysis to release the free amino acids and short peptides. Soybean meal was selected as the most promising nitrogen additive by its high protein content and lactic acids free composition. The plant proteins derived nitrogen additives was found that the inherent deficiency of amino acids in plant proteins led to the insufficient lactic acid fermentation. A minimal yeast extract was added to the plant protein hydrolysates to compensate the amino acid deficiency, and the use of the combinational nitrogen ingredients resulted in the final cellulosic L-lactic acid titer reached 122.9 ± 0.4 g/L with the yield of 88.1% and the optical purity of 99.7% using wheat straw feedstock. Comparing with yeast extract as nitrogen additive, the combinational ingredients substituted 75% of yeast extract with 56.7% cost reduction. This study provides a cost-effective solution of nitrogen ingredients for cellulosic chiral lactic acid production in industrial biorefinery process. • Plant proteins were screened as racemic lactic acids-free nitrogen additives. • A combinational nitrogen ingredient was designed for chiral cellulosic lactic acid fermentation. • 75% of yeast extract was substituted by plant proteins with 56.7% cost reduction. [ABSTRACT FROM AUTHOR]

[Display omitted] Chiral sulfinamides have emerged as versatile tools in various asymmetric reactions, especially in the generation of chiral amines through asymmetric C C bond formation reactions involving chiral sulfinyl imines derived from sulfinamides and aldehyde or ketones. The prospect of employing sulfinamide auxiliaries in stereoselective carbon–heteroatom bond formation reactions has received considerable attention. This review examines recent advancements in stereoselective reactions involving chiral sulfinamide reagents, focusing on C N, C O, and C S bond formation reactions. The article elucidates the mechanisms and stereocontrol aspects underlying these asymmetric reactions, highlighting their utility in the synthesis of bioactive compounds. [ABSTRACT FROM AUTHOR]

We report a novel asymmetric radical cyclization of alkenes via stereospecific homolytic substitution of sulfinamides. This reaction produces a variety of cyclic sulfinamides with excellent stereocontrol. The protocol features broad functional group tolerance, high product diversity, and easy accessibility to feedstocks, and outlines a new pathway for the synthesis of chiral cyclic sulfinamides. [ABSTRACT FROM AUTHOR]

An efficient diastereoselective route for the preparation of chiral oxathiazine 2‐oxide scaffolds as sulfinyl transfer agents, using tert‐butanesulfinamide (tBSA) both as the source of chirality and as the precursor to the required nitrogen electron withdrawing group on the scaffold, was developed. This methodology allows the introduction of different substituents on the chiral scaffold, using commercially available reagents and standard synthetic transformations. The synthesized scaffolds were tested in the preparation of enantioenriched sulfinamides, providing results comparable to the sulfinyl transfer agents so far proposed in the literature, and opening the possibility to further elaborate these scaffolds, with the aim to support them on solid phases so to facilitate their recovery and reuse. [ABSTRACT FROM AUTHOR]

Effective biocatalysts for the synthesis of optically pure amines from keto precursors are highly required in organic synthesis. Transaminases are a large group of PLP-dependent enzymes, which can be utilized for production of chiral amines or amino acids. The bioinformatic approach previously made to search for promising transaminases with unusual characteristics surprisingly revealed mysterious genes in some Gram-negative bacteria, which products were annotated as aminotransferases, but they lacked the key catalytic lysine residue required for covalent binding of the PLP-cofactor. To address the question of which products these genes encode, we obtained the first structure of such a type of protein from the bacterium Variovorax paradoxus (VP5454) and provided its comprehensive analysis. We demonstrated that VP5454 has a typical aminotransferase fold and architecture of the active site, where substitution of the catalytic lysine with asparagine was observed. Despite that no covalent adduct can be formed between PLP and asparagine residue, using X-ray analysis and molecular dynamic (MD) simulation, we demonstrated that VP5454 is able to bind the PLP molecule in the transaminase in a specific manner, with PLP coordinated via its phosphate moiety. Taking into account a number of sequences homologous to VP5454 with a substituted catalytic lysine found in the genomes of various bacteria, we speculate that the proteins encoded by these sequences may have hidden functional roles. [ABSTRACT FROM AUTHOR]

A biocatalytic approach has been designed for the synthesis of optically active piperazinones and 1,4‐diazepanones in aqueous medium under mild conditions. The method described herein is based on a biocatalytic transamination of an easily accessible N‐(2‐oxopropyl) amino acid ester and the subsequent spontaneous cyclization of the initially formed amine. Both enantiomers of the synthesized piperazinones can be prepared by the selection of amine transaminases of opposite selectivity. The reaction conditions were optimised and eight selected processes were performed on a preparative scale. Thus, seven optically active piperazinones were synthesized in high isolated yields (70–90%) and a 1,4‐diazepanone in a moderate yield (51%), being the ee ≥99% in all the cases. [ABSTRACT FROM AUTHOR]

Redox signaling, wherein reactive and diffusible small molecules are channeled into specific messenger functions, is a critical component of signal transduction. A central principle of redox signaling is that the redox modulators are produced in a highly controlled fashion to specifically modify biotargets. Thiols serve as primary mediators of redox signaling as a function of the rich variety of adducts, which allows initiation of distinct cellular effects. Coupling the inherent reactivity of thiols with highly sensitive and selective chemical analysis protocols can facilitate identification of redox signaling agents, both in solution and in cultured cells. Here, we describe use of capillary zone electrophoresis to both identify and quantify sulfinamides, which are specific markers of the reaction of thiols with nitroxyl (HNO), a putative biologically relevant reactive nitrogen species. • The natural reactivity of thiols facilitates trapping of reactive molecules. • Modified thiols can be identified and quantified by capillary zone electrophoresis. • Sulfinamides serve as specific markers of the reaction of thiols with nitroxyl (HNO). • A procedure to detect HNO through formation of glutathione sulfinamide is described. [ABSTRACT FROM AUTHOR]

A robust Pd(0)-catalyzed decarboxylation alkylation has been developed to construct quaternary stereocenters through the use of chiral tert -butanesulfinamide as the directing group. This strategy provides a simple and efficient route to the construction of quaternary chiral centers at the α-position of chiral sulfinamides, with high diastereoselectivities and high yields. [ABSTRACT FROM AUTHOR]

We present (3+2)‐ and (4+2)‐cycloadditions of donor–acceptor (D–A) cyclopropanes and cyclobutanes with N‐sulfinylamines and a sulfur diimide, along with a one‐pot, two‐step strategy for the formal insertion of HNSO2 into D–A cyclopropanes. These are rare examples of cycloadditions with D–A cyclopropanes and cyclobutanes whereby the 2π component consists of two different heteroatoms, thus leading to five‐ and six‐membered rings containing adjacent heteroatoms. [ABSTRACT FROM AUTHOR]

A new synthetic methodology has been developed for the synthesis of N-alkyl and N-aryl arenesulfinamides. The methodology involved reacting arenesulfinic acids (R = -Me, -H, -Cl) with 1,1'-carbonyldiimidazole (CDI) to form the reactive intermediate, an arenesulfinylimidazole. This intermediate was then reacted with both primary and secondary amines to yield the corresponding N-alkyl sulfinamides in yields up to 90%. While the overall yields ranged from 52% to 90%, the level of diastereoselection with racemic or enantiomerically enriched amines only reached a level of 54:46 favoring the major diastereomer as determined by analysis of the 500 MHz 1H NMR spectra. A series of aniline derivatives were also investigated as coupling partners and were found to form the N-aryl arenesulfinamide in good yield. [ABSTRACT FROM AUTHOR]

Sulfinamides, especially enantiopure sulfinamides, are widely used in organic and medicinal synthesis. Syntheses and transformations of racemic and enantioenriched sulfinamides have achieved great progress. Especially sulfinamides demonstrate interesting and valuable reactivity, which deserves to be pertinent. This review summarizes the latest development in the synthesis and transformation of sulfinamides and will be helpful for future related research. 1 Introduction 2 Synthesis of Sulfinamides 2.1 Synthesis of Racemic Sulfinamides 2.2 Synthesis of Enantiomerically Pure Sulfinamides 2.3 Synthesis of Other Sulfinamides 3 Transformations of Sulfinamides 3.1 Condensation with Aldehydes and Ketones 3.2 Reaction with Alkynes 3.3 Reaction with Alkenes 3.4 Reaction with Aryl and Alkyl Halides 3.5 Reaction with Alcohols, Dibenzyl Ether, and Benzyl Mercaptan 3.6 Synthesis of tert -Butyldisulfanyl-Substituted Hetarenes 3.7 Synthesis of Asymmetric Sulfides 3.8 Synthesis of N -Phosphino-sulfinamide Ligands 3.9 Asymmetric Synthesis of γ-Amino Acids 3.10 Sulfonylation of Heterocyclic Compounds 4 Summary and Outlook [ABSTRACT FROM AUTHOR]

Chiral o-aminobenzylamines are synthons for many chiral ligands and catalysts that have been widely used in asymmetric synthesis. Here, we report a highly efficient and stereoselective addition of Grignard reagents to N -[(o -aminophenyl)methylene]sulfinamides to give a range of o -aminosulfinylimines in good yields with good to excellent diastereoselectivities. [ABSTRACT FROM AUTHOR]

Cascade reactions appeared as a cutting‐edge strategy to streamline the assembly of complex structural scaffolds from naturally available precursors in an atom‐, as well as time, labor‐ and cost‐efficient way. We herein report a strategy to control cationic cyclization cascades by exploiting the ability of anchoring dynamic substrates in the active site of terpene cyclases via designed hydrogen bonding. Thereby, it is possible to induce "directed" cyclizations in contrast to established "non‐stop" cyclizations (99:1) and predestinate cascade termination at otherwise catalytically barely accessible intermediates. As a result, we are able to provide efficient access to naturally widely occurring apocarotenoids, value‐added flavors and fragrances in gram‐scale by replacing multi‐stage synthetic routes to a single step with unprecedented selectivity (>99.5 % ee) and high yields (up to 89 %). [ABSTRACT FROM AUTHOR]

The crystal structures of four representatives of sulfinamides of the thiazine series are comparatively analyzed for the occurrence of different supramolecular associates, inter- and intramolecular interactions. With a similar molecular geometry, different packing motifs occur in the crystals yielding different-type supramolecular associates due to classical N–H⋯O hydrogen bonds. The features of transferring the sulfinamide open-chain supramolecular synthon from racemic to homochiral environment consisting in the appearance of "secondary cross-linking" are studied. [ABSTRACT FROM AUTHOR]

For years, metal–nitrene-transfer reactions have been mainly directed toward C=C bond aziridination or C–H bond amidation reactions. In the last decade, multiple efforts have been made to develop new synthetic approaches to expand the applicability of this powerful tool, resulting in the synthesis of complex structures from relatively simple starting materials. Here, we present our contributions to the area with several novel and, to some degree, unexpected transformations developed by our research group. The catalysts for these nitrene-transfer reactions are copper or silver complexes bearing hydrotrispyrazolyl (scorpionate) ligands. These transformations have contributed to an expansion of the scope of organic compounds accessible by nitrene-transfer reactions and to an understanding of the reactivity of metallonitrene species toward the oxidation of less-explored organic substrates. 1 Introduction 2 Synthesis of 1,2-Dihydropyridines from Furans 3 Regio- and Stereoselective Aziridination of Dienes 4 Chemoselective Synthesis of Aminimides from Amines 5 Synthesis of Sulfinamides and Isothiazoles from Alkynes 6 Formation of Azetidines and Methylene Aziridines from Allenes 7 Conclusion [ABSTRACT FROM AUTHOR]

Sulfoximines are widely used as medicines, agricultural chemicals, chiral precursors, and chiral ligands in asymmetric synthesis, as well as pivotal intermediates for the construction of heterocyclic compounds. NH‐sulfoximines may be synthesized from thioethers, sulfoxides, sulfilimines, and sulfinamides. NH‐sulfoximines can undergo various transformations, such as arylations, alkylations, vinylations, and alkynylations. Here, we review the methods that have been applied to the syntheses and transformations of NH‐sulfoximines. [ABSTRACT FROM AUTHOR]

An iron catalyzed reaction for the selective transformation of thiols (‐SH) to sulfinamides (‐SONH2) by a direct transfer of ‐O and free ‐NH2 groups has been developed. The reaction operates under mild conditions using a bench stable hydroxylamine derived reagent, exhibits broad functional group tolerance, is scalable and proceeds without the use of any precious metal catalyst or additional oxidant. This novel, practical reaction leads to the formation of two distinct new bonds (S=O and S−N) in a single step to chemoselectively form valuable, unprotected sulfinamide products. Preliminary mechanistic studies implicate the role of the alcoholic solvent as an oxygen atom donor. [ABSTRACT FROM AUTHOR]

A series of amino alcohols have been prepared in a chemo‐, diastereo‐ and enantioselective fashion starting from the corresponding (het)aryl diketones, avoiding tedious chemical protection and deprotection steps. Different alcohol dehydrogenases have been able to selectively reduce the more reactive trifluoroacetyl groups under optimized conditions, while amine transaminases catalyzed the biotransamination of the less hindered acetyl groups. Based on the different reactivity of the acetyl and trifluoroacetyl groups, the design of sequential and concurrent cascades was investigated. The proper selection of the enzymes permits the synthesis of amino alcohol stereoisomers in high to excellent yields (86–>99% conversion) and remarkable stereocontrol (up to >99% de and >99% ee) using an aqueous medium and mild reaction conditions. [ABSTRACT FROM AUTHOR]

• A bi-functional redox biocatalyst was obtained by co-immobilization of ene-reductase and glucose dehydrogenase. • The bi-functional biocatalyst showed increased conversion compared to the combined use of individual catalysts. • Excellent reusability of the co-immobilized biocatalyst was shown over 10 cycles. • Preparative-scale synthesis allowed access to important chemical building blocks in high enantiopurity. An immobilized bi-functional redox biocatalyst was designed for the asymmetric reduction of alkenes by nicotinamide-dependent ene-reductases. The biocatalyst, which consists of co-immobilized ene-reductase and glucose dehydrogenase, was implemented in biotransformations in the presence of glucose as source of reducing equivalents and catalytic amounts of the cofactor. Enzyme co-immobilization employing glutaraldehyde activated Relizyme HA403/M as support material was performed directly from the crude cell-free extract obtained after protein overexpression in E. coli and cell lysis, avoiding enzyme purification steps. The resulting optimum catalyst showed excellent level of activity and stereoselectivity in asymmetric reduction reactions using either OYE3 from Saccharomyces cerevisiae or NCR from Zymomonas mobilis in the presence of organic cosolvents in up to 20 vol%. The bi-functional redox biocatalyst, which demonstrated remarkable reusability over several cycles, was applied in preparative-scale synthesis at 50 mM substrate concentration and provided access to three industrially relevant chiral compounds in high enantiopurity (ee up to 97 %) and in up to 42 % isolated yield. The present method highlights the potential of (co-)immobilization of ene-reductases, notorious for their poor scalability, and complements the few existing methods available for increasing productivity in asymmetric bioreduction reactions. [ABSTRACT FROM AUTHOR]