Electrochemical strategies for N-alkylation and N-acylation of NH-sulfoximines via the decarboxylation and deoxygenation of carboxylic acids

Abstract

The functionalization of NH-sulfoximines to construct N–C bonds from common carboxylic acids remains underdeveloped. Herein, electrochemical strategies were utilized to enable the chemoselective decarboxylation or deoxygenation of carboxylic acids for the synthesis of N-alkyl and N-acyl sulfoximines. The advantages of these methods include mild reaction conditions, no electrode sacrifice, no external oxidants or metal catalysts, and easy scalability to gram-scale production. Furthermore, 67 diverse sulfoximine derivatives, particularly those incorporating motifs from amino acids and drug molecules, were obtained.

---

Introduction

Sulfoximines, the mono-aza analogues of sulfones, are obtained by substituting one oxygen atom of sulfoxides with a nitrogen atom.¹ Due to their chiral sulfur center and coordination ability with metal ions, sulfoximines were initially used primarily as chiral auxiliaries or ligands in asymmetric reactions and catalysis.^2–8 More recently, sulfoximines have garnered increasing attention for their potential applications in the fields of agrochemicals^9,10 and medicinal chemistry.^11–15 Therefore, the synthesis and modification of sulfoximines have witnessed rapid progress.

Unlike sulfones, the presence of a nitrogen atom in sulfoximines can provide more potential for derivatization via the modification of N-substituents, thus resulting in structures with finely tuned chemical and physical properties.^16–25 Recently, the structural diversification of NH-sulfoximines through efficient N-functionalization has garnered significant interest to construct an array of N–C and N–X (X = Br, S, P, etc.) bonds.^26–39 Among these, considerable efforts have been dedicated to converting N–H to N–C, due to the substantial impact of such modifications on the properties of sulfoximines, such as solubility, H-bonding capability, and metabolic stability.^14,40,41

Several examples have been reported to achieve this conversion through the dehydrogenative coupling of N–H bonds between sulfoximines and (halogenated) alkanes,^31,42–47 as well as the difunctionalization of alkenes^48–55 to synthesize N-alkylated sulfoximines under metal-catalyzed (copper, iron), photocatalytic or electrochemical conditions (Scheme 1a). As for N-acylation of NH-sulfoximines (Scheme 1b), it has been traditionally achieved using pre-activated coupling partners, such as acyl chlorides.⁵⁶ Efficient carboxyl activation agents (such as DCC or EDC) and boron catalysts like boric acid or 1,3-dioxane-2,4,6-triborane (DATB) also facilitate the formation of N-acyl sulfoximines from carboxylic acids.^56–58 However, these methods inevitably produce excess and undesired chemical waste and require high temperatures. By utilizing external chemical oxidants or transition metal catalysts, NH-sulfoximines can undergo oxidative cross-coupling reactions with aldehydes,⁵⁹ methyl aromatics,⁶⁰ and α-keto acids⁶¹ to afford N-acylated sulfoximines. Additionally, several photochemical and electrochemical methods have also been developed to enable the formation of N-acylation products with thioacids,⁶² hydroxamic acids⁶³ and α-keto acids,⁶⁴ respectively.

Scheme 1 Approaches for the N-alkylation and N-acylation of sulfoximines.

Despite the fruitful results, a general protocol for N–C(alkyl) construction from NH-sulfoximines and common carboxylic acids, which are usually stable, inexpensive, and widely available in bioactive molecules like amino acids, has not been disclosed. This seemed strange since recent advancements in the derivatization of either sulfoximines or carboxylic acids have been substantial, separately.^25,65–71

Due to the continuing interest of our group^35,36,48 in the N–H functionalization of sulfoximines and the ongoing development of electrochemical synthesis strategies,^72–75 it was questioned whether the construction of N–C(alkyl) was feasible using sulfoximines and carboxylic acids. Theoretically, the selective decarboxylation and deoxygenation of carboxylic acids would afford N-alkylation and N-acylation products of sulfoximines, respectively, thus providing a diverse range of sulfoximine derivatives with potential applications.

Herein, the corresponding results were disclosed to showcase the feasibility of this strategy for the first time. Under electrochemical conditions without sacrificial electrodes, chemical oxidants, or metal catalysts, the N-alkylation of NH-sulfoximines with carboxylic acids was achieved. Meanwhile, by adding triphenylphosphines to the electrochemical system, N-acylation products were obtained with chemoselectivity (Scheme 1c).

Results and discussion

Initially, S,S-diaryl sulfoximine 1a and N-Boc-D-proline 2a were chosen as model substrates to screen the reaction conditions for the envisioned electrochemical decarboxylative N-alkylation reaction. After extensive experimentation to screen an array of variables systematically, including current, electrode, and electrolyte, the best result was obtained by conducting the electrolysis at room temperature and a constant current of 3.0 mA in an undivided cell equipped with a graphite anode and a nickel cathode in dry dichloromethane containing ⁿBu₄NPF₆ as a supporting electrolyte, with 2,4,6-collidine as a non-oxidizable base and 4 Å molecular sieves as dehydrating agents. Under these conditions, the desired product 3a was obtained in 90% isolated yield (Table 1, entry 1). As shown in Table 1, the absence of current resulted in no target product (entry 2), demonstrating its crucial role in the decarboxylative N-alkylation process. Among the electrode materials screened, when graphite plates or platinum sheets were used as both cathode and anode, the yield of 3a greatly decreased. When a graphite plate was used as the anode and a platinum sheet as the cathode, the yield of 3a decreased slightly (entry 3). With respect to the solvent, the yield of 3a decreased to 69% when acetonitrile was used; however, no desired transformation occurred when methanol was used as the solvent (entry 4). After that, different electrolytes were screened. The conversion efficiency of ⁿBu₄NClO₄ was similar to that of ⁿBu₄NPF₆, while the use of ⁿBu₄NOAc was found to significantly affect the efficiency of the reaction (entry 5). Shortening the reaction time to 8 h was found to be detrimental to the isolated yield, leading to 65% of 3a, while prolonging it to 12 h did not enhance the yield further (entry 6). Increasing or decreasing the current intensity led to a relatively lower yield (entry 7). The absence of 2,4,6-collidine was detrimental to the yield (25%, entry 8). The addition of 4 Å molecular sieves improved the yield of 3a (entry 9), probably by suppressing the hydration of the possible carbocation intermediates (for more information on the screening of conditions, see ESI section 3†).

Table 1 Optimization of the reaction conditions^a

Entry	Variations from the ‘standard’ conditions	Yield of 3a ^b (%)
a Standard conditions A: 1a (0.2 mmol), 2a (0.6 mmol), 2,4,6-collidine (0.6 mmol), ^nBu4NPF6 (0.1 M), dry DCM (4.0 mL), 4 Å MS (100 mg), constant current = 3.0 mA under air for 10 hours. b Isolated yields. c No reaction.
1	None	90
2	No current	N.R.^c
3	C/C, Pt/Pt, or C/Pt as the electrode	41, 59, 82
4	MeCN or MeOH as the solvent	63, N.R.
5	^nBu4NClO4 or ^nBu4NOAc as the electrolyte	85, 17
6	8 h or 12 h as the reaction time	65, 89
7	2 mA, 5 mA, or 7 mA as the current	51, 64, 65
8	No 2,4,6-collidine	25
9	No 4 Å MS	67

---

With the optimized conditions in hand, the scope of the reaction was then explored by first varying the carboxylic acid substrates (Scheme 2). Commercially available cyclic N-protected α-amino acids, such as proline, pyroglutamic acid, and six-membered cyclic α-amino acids, reacted well with S,S-diaryl sulfoximine 1a to give the desired decarboxylation products (3a–3d) in 81%–95% yields. Similarly, acyclic amino acid derivatives, including valine (2e) and alanine (2f), were also suitable substrates for this decarboxylative transformation, yielding products 3e (95%) and 3f (98%), respectively. In addition, α-heteroatom acids such as tetrahydropyran-2-carboxylic acid (2g) and N-Cbz-2-morpholinecarboxylic acid (2h) could be converted to the target products 3g (41%) and 3h (52%) with moderate yields. Fortunately, peptides underwent decarboxylation to yield the corresponding products in high yields under optimal conditions (3i–3k, 81%–97%). Indomethacin and flurbiprofen, two carboxylic acid-based drug molecules, afforded the corresponding sulfoximine derivatives under these electrochemical conditions (3l, 60%; 3m, 55%). Furthermore, secondary and tertiary benzylic carboxylic acids (2n–2t) underwent a direct decarboxylative N-alkylation process in this transformation, affording the target products 3n–3t (40%–87%). However, we did not observe any product formations when using non-benzyl carboxylic acids (benzoic acid, cyclohexanecarboxylic acid and 4-phenylbutyric acid).

Scheme 2 Substrate scope of the electrochemical decarboxylation and N-alkylation of carboxylic acids and sulfoximines. Standard conditions A: N–H sulfoximines (0.2 mmol), carboxylic acids (0.6 mmol), 2,4,6-collidine (0.6 mmol), Bu₄NPF₆ (0.1 M), dry DCM (4.0 mL), 4 Å MS (100 mg), constant current = 3 mA under air for 10 hours, in an undivided cell.

We next explored the compatibility of a series of NH-sulfoximines with this electrochemical decarboxylative system. Various NH-diphenylsulfoximines with ortho-, meta-, or para-substituents, such as electron-donating groups (–Me, –OMe) and electron-withdrawing groups (–Cl, –CN, –CO₂Me), could afford the desired products (3u–3za) with yields ranging from 30% to 87%. There was a significant electronic effect among these substrates. Substrates 1x and 1y, which have strong electron-withdrawing groups (–CN, –CO₂Me), only provide target products 3x and 3y with yields of 30% and 60%, respectively, under this electrochemical transformation. The conversion efficiency of NH-sulfoximines with weak electron-withdrawing groups (–Cl) and electron-donating groups (–Me, –OMe) was similar. When comparing the results of different positional isomers, it had little influence on the yields (3u, 82% vs. 3z, 87% vs. 3za, 86%). Naphthalene-substituted NH-sulfoximine was also a suitable substrate and delivered the target product in 80% yield (3zb). In the reactions of S-aryl-S-methyl sulfoximines, both alkoxy and bromide were well tolerated under the optimal conditions, affording the corresponding products 3zc–3ze with dr values of approximately 1 : 1 and yields ranging from 60% to 91%. Moreover, S-3,5-dichlorophenyl-S-methyl sulfoximines, S-aryl-S-cyclopropyl sulfoximines and S,S-diethyl sulfoximines all transformed to the expected products 3zf (70%, dr ∼1 : 1.2), 3zg (79%, dr ∼ 1 : 1.1) and 3zh (65%), respectively. These results demonstrated the robustness of this procedure toward the steric and electronic variations of the sulfoximine counterpart.

We observed that carboxylic acids can not only directly decarboxylate to form C–X bonds but can also undergo acylation via deoxygenation with the assistance of PPh₃.^76–79 Subsequently, we investigated the N-acylation of sulfoximines with carboxylic acids. Initially, we attempted to use PPh₃ to deoxygenate amino acids (such as 2a, 2f) for N-acylation, but instead, we obtained decarboxylated products. We then focused on primary carboxylic acids, and after preliminary attempts with phenylacetic acid (5d) reacting with sulfoximine, we successfully achieved N-acylation. Through a series of optimization conditions (for more information on the screening of conditions, see ESI section 4†), we identified the optimal conditions for PPh₃-assisted electrochemical deoxygenation N-acylation of sulfoximines. After extensive experimentation to screen the current, electrode, electrolyte, etc., the best result was obtained by conducting the electrolysis at room temperature under a constant current of 3.0 mA in an undivided cell equipped with a graphite anode and a nickel cathode in solvent dry acetonitrile containing ⁿBu₄NPF₆ as the supporting electrolyte, with 2,6-lutidine as a non-oxidizable base. Under these conditions, the desired product 6d was obtained in 94% isolated yield (standard conditions B).

We subsequently evaluated the substrate scope and functional group compatibility of the N-acylation strategy using PPh₃ additives (Scheme 3). Similarly, the scope and tolerance of the reaction were explored initially by varying the carboxylic acids. A range of phenylacetic acids with electron-donating (6a, –Me; 6b, –OMe) or electron-withdrawing (6c, –F; 6d, –Cl; 6e, –Br; 6f, –CF₃) groups located at the para-position were effectively converted to the corresponding products (87%–96%).

Scheme 3 Substrate scope of the electrochemical deoxygenation and N-acylation of carboxylic acids and sulfoximines. Standard conditions B: N–H sulfoximines (0.2 mmol), carboxylic acids (0.6 mmol), 2,6-lutidine (0.6 mmol), Bu₄NPF₆ (0.1 M), PPh₃ (0.6 mmol), dry MeCN (4.0 mL), constant current = 3 mA under air for 10 hours, in an undivided cell.

Comparing the results of positional isomers, there was little influence on the yields (6a, 90% vs. 6i, 87%; 6b, 87% vs. 6g, 93%; 6c, 93% vs. 6h, 71%; 6d, 94% vs. 6j, 65%). Naphthylacetic acid was also converted with an 85% yield. Phenoxyacetic acids with various substituents were also transformed into the expected products (6l–6o, 60%–84%). Notably, thiopheneacetic acid, diphenylacetic acid, and 4-pentenoic acid also participated in this transformation, with corresponding product yields of 90%, 91%, and 41%, respectively.

Next, a diverse array of sulfoximines proved to be effective substrates for the construction of the corresponding N-acylated compounds. First, S-aryl-S-methyl sulfoximines were investigated and it was found that para-substituted alkoxy and bromide were effectively converted to the corresponding products 6s–6u with yields ranging from 85% to 92%. Furthermore, S-3,5-dichlorophenyl-S-methyl sulfoximine, S-pyridyl-S-methyl sulfoximine, S-aryl-S-cyclopropyl sulfoximine and S,S-diethyl sulfoximine all reacted efficiently and were transformed to the expected products 6v (78%), 6w (89%), 6x (88%) and 6y (72%), respectively. As for NH-diphenylsulfoximines, electron-donating groups (–Me, –OMe) and weakly electron-withdrawing groups (–Cl) performed well (81%–94%), while strongly electron-withdrawing groups (6zc, –CN) only provided a 45% yield of the target product. Furthermore, the substrates with substituents at the meta or ortho positions proceeded effectively, affording the desired products in similar yields to those with para-substituents (6z, 94% vs. 6zd, 88% vs. 6ze, 81%). Additionally, we found that naphthalene-substituted NH-sulfoximine (6zf, 65%) and sulfonimidamide (6zg, 53%) were well tolerated under the optimal reaction conditions.

To examine the practicability and scalability of the decarboxylative and deoxygenative transformations between sulfoximines and carboxylic acids, 10-fold scaled reactions were conducted by simply amplifying the dosages of every reagent under the optimal conditions, respectively. As shown in Scheme 4, both the decarboxylation and deoxygenation proceeded smoothly, yielding 0.62 g of N-alkyl sulfoximine 3a (80%) and 0.64 g of N-acyl sulfoximine 6d (86%), respectively.

Scheme 4 Gram-scale synthesis of 3a and 6d.

Subsequently, we performed several mechanistic experiments to gain more insight into the reaction process. For the decarboxylative N-alkylation reaction, under standard conditions, the addition of 3.0 equivalents of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy), a well-known radical scavenger, significantly inhibited the formation of 3a. Alkyl radical trapping products were detected via HRMS. The transformation did not proceed when using butylated hydroxytoluene (BHT) as a radical scavenger. This indicated that 2a was decarboxylated to generate alkyl radicals under electrode oxidation (Scheme 5a). To verify the formation of a carbocation, sulfoximine 1a and diphenylacetic acid 2n were reacted under standard conditions with the addition of 10 μL of water and without 4 Å molecular sieves. This resulted in a 61% yield of the target product 3n and diphenyl ketone 7 (Scheme 5b). This implied that diphenylmethyl radicals, after the generation via radical decarboxylation, were further oxidized to carbocations, which could then be simultaneously trapped by both sulfoximines and water as nucleophiles. Additionally, methanol and ethanol could also act as nucleophiles to trap carbocation intermediates, yielding (diphenylmethyl) methyl ether (73% yield) and (diphenylmethyl) ethyl ether (80% yield), respectively. These results provided strong evidence for the involvement of carbocation intermediates. For the N-acylation of sulfoximines, the use of TEMPO and BHT as radical scavengers also significantly inhibited the formation of the target product. HRMS analysis detected the trapping products of acyl radicals and sulfoximine nitrogen radicals, respectively (Scheme 5c), indicating the possibility that both these radical species were generated and participated in the reaction mechanism.

Scheme 5 Mechanistic studies. (a) N-Alkylation radical trapping experiments of sulfoximines. (b) Demonstration of carbocation formation. (c) N-Acylation radical trapping experiments of sulfoximines.

Based on the above experimental results, we postulated two distinct pathways as shown in Scheme 6. Path A involves the decarboxylative N-alkylation process (green square). Under basic conditions, carboxylate anion I is initially formed, followed by oxidation at the anode to generate carboxyl radical intermediate II. Rapid decarboxylation then forms alkyl radical III, which yields carbocation IV upon further anodic oxidation. Simultaneously, sulfoximines lose a proton under basic conditions to form sulfoximine anion V, which then nucleophilically attacks carbocation IV to yield the final product 3. For N-acylation (Scheme 6, path B, pink square), initially, the anodic oxidation of triphenylphosphine generates its cationic radical, which reacts with the carboxylic acid to form a P–O bond, yielding radical intermediate VI. Then, VI undergoes β-scission to produce acyl radical VII and triphenylphosphine oxide. Simultaneously, the single electron transfer (SET) of sulfoximines anion V at the anode produces N-centered radical VIII. Subsequently, N-centered radical VIII and acyl radical VII combined via direct radical coupling to yield the desired product 6.

Scheme 6 Proposed mechanism.

Conclusions

In summary, a controllable electrochemical strategy has been developed to achieve N-alkylation and N-acylation reactions of sulfoximines with readily available carboxylic acids. This method addresses a crucial gap in green synthesis by enabling efficient N–C bond formation at room temperature and without the need for external oxidants, metal catalysts, or sacrificial electrodes. A simple undivided cell setup using commercially available inexpensive electrodes, coupled with easy scalability, highlights the practicality of this reaction. Besides the recoverable phosphine oxide, hydrogen and carbon dioxide are relatively green and clean by-products. This N-functionalization of sulfoximines via the decarboxylation and deoxygenation of carboxylic acids can deliver a series of products that have not been accessed previously and is expected to broaden the availability and application of sulfoximine derivatives.

Data availability

All relevant data are available within the manuscript and its ESI.†

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We thank the National Natural Science Foundation of China (22061036) and the Scientific and Technological Talent Project of the Corps (2024DB005) for financial support.

References

1. H. R. Bentley, E. E. Mcdermott and J. K. Whitehead, Action of Nitrogen Trichloride on Proteins: a Synthesis of the Toxic Factor from Methionine., Nature, 1950, 165, 735.
2. C. Bolm and O. Simić, Highly Enantioselective Hetero-Diels-Alder Reactions Catalyzed by a C2-Symmetric Bis(sulfoximine) Copper(II) Complex, J. Am. Chem. Soc., 2001, 123, 3830–3831.
3. M. Harmata and S. K. Ghosh, A New, Chiral Bis-Benzothiazine Ligand, Org. Lett., 2001, 3, 3321–3323.
4. C. Bolm, M. Martin, L. Simic and M. Verrucci, C2-Symmetric Bissulfoximines as Ligands in Copper-Catalyzed Enantioselective Diels−Alder Reactions, Org. Lett., 2003, 5, 427–429.
5. C. Bolm, M. Verrucci, O. Simic, P. G. Cozzi, G. Raabe and H. Okamura, A new class of C1-symmetric monosulfoximine ligands for enantioselective hetero Diels–Alder reactions, Chem. Commun., 2003, 2826–2827.
6. C. Bolm, M. Martin, G. Gescheidt, C. Palivan, D. Neshchadin, H. Bertagnolli, M. Feth, A. Schweiger, G. Mitrikas and J. Harmer, Spectroscopic Investigations of Bis(sulfoximine) Copper(II) Complexes and Their Relevance in Asymmetric Catalysis, J. Am. Chem. Soc., 2003, 125, 6222–6227.
7. M. Langner and C. Bolm, C1−Symmetric Sulfoximines as Ligands in Copper–Catalyzed Asymmetric Mukaiyama–Type Aldol Reactions, Angew. Chem., Int. Ed., 2004, 43, 5984–5987.
8. M. Langner, P. Rémy and C. Bolm, Highly Modular Synthesis of C1−Symmetric Aminosulfoximines and Their Use as Ligands in Copper–Catalyzed Asymmetric Mukaiyama–Aldol Reactions, Chem. – Eur. J., 2005, 11, 6254–6265.
9. Y. Zhu, M. R. Loso, G. B. Watson, T. C. Sparks, R. B. Rogers, J. X. Huang, B. C. Gerwick, J. M. Babcock, D. Kelley, V. B. Hegde, B. M. Nugent, J. M. Renga, I. Denholm, K. Gorman, G. J. DeBoer, J. Hasler, T. Meade and J. D. Thomas, Discovery and Characterization of Sulfoxaflor, a Novel Insecticide Targeting Sap-Feeding Pests, J. Agric. Food Chem., 2010, 59, 2950–2957.
10. J. M. Babcock, C. B. Gerwick, J. X. Huang, M. R. Loso, G. Nakamura, S. P. Nolting, R. B. Rogers, T. C. Sparks, J. Thomas, G. B. Watson and Y. Zhu, Biological characterization of sulfoxaflor, a novel insecticide, Pest Manage. Sci., 2010, 67, 328–334.
11. P. Mäder and L. Kattner, Sulfoximines as Rising Stars in Modern Drug Discovery? Current Status and Perspective on an Emerging Functional Group in Medicinal Chemistry, J. Med. Chem., 2020, 63, 14243–14275.
12. U. Lücking, Neglected sulfur(VI) pharmacophores in drug discovery: exploration of novel chemical space by the interplay of drug design and method development, Org. Chem. Front., 2019, 6, 1319–1324.
13. U. Lücking, Sulfoximines: A Neglected Opportunity in Medicinal Chemistry, Angew. Chem., Int. Ed., 2013, 52, 9399–9408.
14. M. Frings, C. Bolm, A. Blum and C. Gnamm, Sulfoximines from a Medicinal Chemist's Perspective: Physicochemical and in vitro Parameters Relevant for Drug Discovery, Eur. J. Med. Chem., 2017, 126, 225–245.
15. Y. Han, K. Xing, J. Zhang, T. Tong, Y. Shi, H. Cao, H. Yu, Y. Zhang, D. Liu and L. Zhao, Application of sulfoximines in medicinal chemistry from 2013 to 2020, Eur. J. Med. Chem., 2021, 209, 112885–112898.
16. C. Bohnen and C. Bolm, N-Trifluoromethylthiolated Sulfoximines, Org. Lett., 2015, 17, 3011–3013.
17. H. Wang, M. Frings and C. Bolm, Halocyclizations of Unsaturated Sulfoximines, Org. Lett., 2016, 18, 2431–2434.
18. N. Sharma and G. Sekar, Palladium nanoparticles catalyzed aroylation of NH-sulfoximines with aryl iodides, RSC Adv., 2016, 6, 37226–37235.
19. S. K. Aithagani, S. Dara, G. Munagala, H. Aruri, M. Yadav, S. Sharma, R. A. Vishwakarma and P. P. Singh, Metal-Free Approach for the Synthesis of N-Aryl Sulfoximines via Aryne Intermediate, Org. Lett., 2015, 17, 5547–5549.
20. C. A. Dannenberg, L. Fritze, F. Krauskopf and C. Bolm, Access to N-cyanosulfoximines by transition metal-free iminations of sulfoxides, Org. Biomol. Chem., 2017, 15, 1086–1090.
21. H. Wang, D. Zhang and C. Bolm, Sulfoximidations of Benzylic C−H bonds by Photocatalysis, Angew. Chem., Int. Ed., 2018, 57, 5863–5866.
22. Z. Li, M. Frings, H. Yu and C. Bolm, Organocatalytic Synthesis of Sulfoximidoyl-Containing Carbamates from Sulfoximines and Morita–Baylis–Hillman Carbonates, Org. Lett., 2019, 21, 3119–3122.
23. C. Wang, Y. Tu, D. Ma and C. Bolm, Photocatalytic Fluoro Sulfoximidations of Styrenes, Angew. Chem., Int. Ed., 2020, 59, 14134–14137.
24. C. Wang, H. Wang and C. Bolm, Sulfoximines with α–Ketoester Functionalities at Nitrogen from Cyanoacetates and Air, Adv. Synth. Catal., 2020, 363, 747–750.
25. M. Andresini, A. Tota, L. Degennaro, J. A. Bull and R. Luisi, Synthesis and Transformations of NH–Sulfoximines, Chem. – Eur. J., 2021, 27, 17293–17321.
26. J. Huang, F. Liu, F. Du, L. Zeng and Z. Chen, Cp*Rh/Ag catalyzed C–H activation/cyclization sequences of NH-sulfoximines to fused aza-polyheterocycles under gentle conditions, Green Synth. Catal., 2023, 4, 160–168.
27. Y. Hirata, D. Sekine, Y. Kato, L. Lin, M. Kojima, T. Yoshino and S. Matsunaga, Cobalt(III)/Chiral Carboxylic Acid–Catalyzed Enantioselective Synthesis of Benzothiadiazine–1−oxides via C−H Activation, Angew. Chem., Int. Ed., 2022, 61, e202205341.
28. D. Liu, Z. R. Liu, C. Ma, K. J. Jiao, B. Sun, L. Wei, J. Lefranc, S. Herbert and T. S. Mei, Nickel–Catalyzed N–Arylation of NH–Sulfoximines with Aryl Halides via Paired Electrolysis, Angew. Chem., Int. Ed., 2021, 60, 9444–9449.
29. S. Banerjee, M. Mishra and T. Punniyamurthy, Copper-Catalyzed C7-Selective C–H/N–H Cross-Dehydrogenative Coupling of Indolines with Sulfoximines, Org. Lett., 2022, 24, 7997–8001.
30. M. Song, L. Zhang, D. Wei, Y. He, J. Jia, H. Li and B. Yuan, Ultrafast N-arylation of sulfoximines enabled by micellar catalysis in water, Green Chem., 2022, 24, 6119–6124.
31. J. Dong, Q. Su, D. Li and J. Mo, Visible-Light-Induced One-Pot Cross Coupling of NH-Sulfoximines with Toluene, Org. Lett., 2022, 24, 8447–8451.
32. D. Ma, C. Wang, D. Kong, Y. Tu, P. Shi and C. Bolm, Palladium–Catalyzed Carbonylation in the Synthesis of N–Ynonylsulfoximines, Adv. Synth. Catal., 2021, 363, 1330–1334.
33. P. Shi, Y. Tu, C. Wang, D. Ma and C. Bolm, Visible Light-Promoted Synthesis of β-Keto Sulfoximines from N-Tosyl-Protected Sulfoximidoyl Chlorides, J. Org. Chem., 2022, 87, 3817–3824.
34. X. Wang, K. Rissanen and C. Bolm, A One-Pot Domino Reaction Providing Fluorinated 5,6-Dihydro-1,2-thiazine 1-Oxides from Sulfoximines and 1-Trifluoromethylstyrenes, Org. Lett., 2023, 25, 1569–1572.
35. J. Huang, X. Li, Y. Wei, Z. Lei and L. Xu, Organoboron/iodide-catalyzed photoredox N-functionalization of NH-sulfoximines/sulfonimidamides, Chem. Commun., 2023, 59, 13643–13646.
36. X. Li, J. Huang, L. Xu, J. Liu and Y. Wei, Electrochemical Oxidative Dehydrogenative Coupling of Sulfoximines to Construct N–sulfenyl and N–phosphinyl Sulfoximines, Adv. Synth. Catal., 2023, 365, 4647–4653.
37. D. Kong, D. Ma, P. Wu and C. Bolm, Mechanochemical Solvent-Free N-Sulfenylations of Sulfoximines and Sulfonimidamides, ACS Sustainable Chem. Eng., 2022, 10, 2863–2867.
38. C. Wang, P. Shi and C. Bolm, Visible light-promoted NH-halogenation of sulfoximines with dichloromethane or dibromomethane, Org. Chem. Front., 2021, 8, 2919–2923.
39. Y. Lin, Y. Liu, Y. Zheng, R. Nie, L. Guo and Y. Wu, Green and Efficient Synthesis of N-Sulfenyl Sulfoximines in Water, ACS Sustainable Chem. Eng., 2018, 6, 13644–13649.
40. F. W. Goldberg, J. G. Kettle, J. Xiong and D. Lin, General synthetic strategies towards N-alkyl sulfoximine building blocks for medicinal chemistry and the use of dimethylsulfoximine as a versatile precursor, Tetrahedron, 2014, 70, 6613–6622.
41. E. Boulard, V. Zibulski, L. Oertel, P. Lienau, M. Schäfer, U. Ganzer and U. Lücking, Increasing Complexity: A Practical Synthetic Approach to Three–Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties, Chem. – Eur. J., 2020, 26, 4378–4388.
42. X. Kong, Y. Tian, X. Chen, Y. Chen and W. Wang, Electrochemical Oxidative C(sp3)–H/N–H Coupling of Diarylmethanes with Sulfoximines or Benzophenone Imine, J. Org. Chem., 2021, 86, 13610–13617.
43. Q.-R. Zhu, P.-Z. Zhang, X. Sun, H. Gao, P.-L. Wang and H. Li, Electrochemical N(sp2)–H/C(sp3)–H cross-coupling reaction between sulfoximines and alkylarenes, Green Chem., 2024, 26, 5824–5831.
44. F. Teng, S. Sun, Y. Jiang, J.-T. Yu and J. Cheng, Copper-catalyzed oxidative C(sp³)–H/N–H coupling of sulfoximines and amides with simple alkanes via a radical process, Chem. Commun., 2015, 51, 5902–5905.
45. Y. Cheng, W. Dong, L. Wang, K. Parthasarathy and C. Bolm, Iron-Catalyzed Hetero-Cross-Dehydrogenative Coupling Reactions of Sulfoximines with Diarylmethanes: A New Route to N-Alkylated Sulfoximines, Org. Lett., 2014, 16, 2000–2002.
46. Y. F. Zhang, J. H. Wang, N. Y. Yang, Z. Chen, L. L. Wang, Q. S. Gu, Z. L. Li and X. Y. Liu, Copper-Catalyzed Enantioconvergent Radical C(sp3)−N Cross-Coupling: Access to α,α–Disubstituted Amino Acids, Angew. Chem., Int. Ed., 2023, 62, e202302983.
47. Y.-F. Zhang, X.-Y. Dong, J.-T. Cheng, N.-Y. Yang, L.-L. Wang, F.-L. Wang, C. Luan, J. Liu, Z.-L. Li, Q.-S. Gu and X.-Y. Liu, Enantioconvergent Cu-Catalyzed Radical C–N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines, J. Am. Chem. Soc., 2021, 143, 15413–15419.
48. X. Li, J. Huang, L. Xu, P. Liu and Y. Wei, Synthesis of β-Arylseleno Sulfoximines: A Metal-Free Three-Component Reaction Mediated by Tetrabutylammonium Tribromide, J. Org. Chem., 2022, 87, 10684–10697.
49. X.-Y. Cheng, Y.-F. Zhang, J.-H. Wang, Q.-S. Gu, Z.-L. Li and X.-Y. Liu, A Counterion/Ligand-Tuned Chemo- and Enantioselective Copper-Catalyzed Intermolecular Radical 1,2-Carboamination of Alkenes, J. Am. Chem. Soc., 2022, 144, 18081–18089.
50. C. Wang, Y. Tu, D. Ma, C. A. Tarint and C. Bolm, Photocatalytic Synthesis of Difluoroacetoxy-containing Sulfoximines, Org. Lett., 2021, 23, 6891–6894.
51. D. Ma, D. Kong, P. Wu, Y. Tu, P. Shi, X. Wang and C. Bolm, Introduction of Lipophilic Side Chains to NH-Sulfoximines by Palladium Catalysis Under Blue Light Irradiation, Org. Lett., 2022, 24, 2238–2241.
52. C. Wang and T. Jia, Photocatalytic N–Alkylation of NH–Sulfoximines via Anti–Markovnikov Hydroamination of Alkenes, Adv. Synth. Catal., 2023, 365, 3666–3673.
53. H.-C. Li, G.-N. Li, H.-S. Wang, Y. Tan, X.-L. Chen and B. Yu, Photoredox-catalyzed difunctionalization of alkenes with oxime esters and NH-sulfoximines, Org. Chem. Front., 2024, 11, 135–141.
54. J.-L. Wan and J.-M. Huang, Electrochemically Enabled Sulfoximido-Oxygenation of Alkenes with NH-Sulfoximines and Alcohols, Org. Lett., 2022, 24, 8914–8919.
55. H. Chen, L. Chen, Z. He and Q. Zeng, Blue light-promoted radical sulfoximido-chalcogenization of aliphatic and aromatic alkenes, Green Chem., 2021, 23, 2624–2627.
56. C. P. R. Hackenberger, G. Raabe and C. Bolm, Synthetic and Spectroscopic Investigation of N–Acylated Sulfoximines, Chem. – Eur. J., 2004, 10, 2942–2952.
57. M. Harmata and A. Garimallaprabhakaran, Boric Acid Mediated N-Acylation of Sulfoximines, Synlett, 2011, 361–364.
58. H. Noda, Y. Asada, M. Shibasaki and N. Kumagai, Direct N-acylation of sulfoximines with carboxylic acids catalyzed by the B3NO2 heterocycle, Chem. Commun., 2017, 53, 7447–7450.
59. L. Wang, D. L. Priebbenow, L. H. Zou and C. Bolm, The Copper–Catalyzed Oxidative N–Acylation of Sulfoximines, Adv. Synth. Catal., 2013, 355, 1490–1494.
60. Y. Zou, J. Xiao, Z. Peng, W. Dong and D. An, Transition metal-free aroylation of NH-sulfoximines with methyl arenes, Chem. Commun., 2015, 51, 14889–14892.
61. C. Pimpasri, L. Sumunnee and S. Yotphan, Copper-catalyzed oxidative decarboxylative coupling of α-keto acids and sulfoximines, Org. Biomol. Chem., 2017, 15, 4320–4327.
62. P. Qiu, X. Duan, M. Li, Y. Zheng and W. Song, Visible-Light-Induced N-Acylation of Sulfoximines, Org. Lett., 2022, 24, 2733–2737.
63. W. Huang, S. Wang, M. Li, L. Zhao, M. Peng, C. Kang, G. Jiang and F. Ji, Electrochemical N-Acylation of Sulfoximine with Hydroxamic Acid, J. Org. Chem., 2023, 88, 17511–17520.
64. C. Kang, M. Li, W. Huang, S. Wang, M. Peng, L. Zhao, G. Jiang and F. Ji, Electrochemical N-acylation and N-α-ketoacylation of sulfoximines via the selective decarboxylation and dehydration of α-ketoacids, Green Chem., 2023, 25, 8838–8844.
65. A. Varenikov, E. Shapiro and M. Gandelman, Decarboxylative Halogenation of Organic Compounds, Chem. Rev., 2020, 121, 412–484.
66. Y. Wei, P. Hu, M. Zhang and W. Su, Metal-Catalyzed Decarboxylative C–H Functionalization, Chem. Rev., 2017, 117, 8864–8907.
67. P. Xiao, X. Pannecoucke, J.-P. Bouillon and S. Couve-Bonnaire, Wonderful fusion of organofluorine chemistry and decarboxylation strategy, Chem. Soc. Rev., 2021, 50, 6094–6151.
68. V. Ramadoss, Y. Zheng, X. Shao, L. Tian and Y. Wang, Advances in Electrochemical Decarboxylative Transformation Reactions, Chem. – Eur. J., 2020, 27, 3213–3228.
69. S.-H. Shi, Y. Liang and N. Jiao, Electrochemical Oxidation Induced Selective C–C Bond Cleavage, Chem. Rev., 2020, 121, 485–505.
70. M. T. Passia, J.-H. Schöbel and C. Bolm, Sulfondiimines: synthesis, derivatisation and application, Chem. Soc. Rev., 2022, 51, 4890–4901.
71. W. Zheng, X. Chen, F. Chen, Z. He and Q. Zeng, Syntheses and Transformations of Sulfoximines, Chem. Rec., 2020, 21, 396–416.
72. S. Lv, X. Han, J. Y. Wang, M. Zhou, Y. Wu, L. Ma, L. Niu, W. Gao, J. Zhou, W. Hu, Y. Cui and J. Chen, Tunable Electrochemical C−N versus N−N Bond Formation of Nitrogen–Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications, Angew. Chem., Int. Ed., 2020, 59, 11583–11590.
73. L. Ma, X. Gao, X. Liu, X. Gu, B. Li, B. Mao, Z. Sun, W. Gao, X. Jia and J. Chen, Recent advances in organic electrosynthesis using heterogeneous catalysts modified electrodes, Chin. Chem. Lett., 2023, 34, 107735–107752.
74. P. Zhang, B. Li, L. Niu, L. Wang, G. Zhang, X. Jia, G. Zhang, S. Liu, L. Ma, W. Gao, D. Qin and J. Chen, Scalable Electrochemical Transition–Metal–Free Dehydrogenative Cross–Coupling Amination Enabled Alkaloid Clausines Synthesis, Adv. Synth. Catal., 2020, 362, 2342–2347.
75. S. Lv, G. Zhang, J. Chen and W. Gao, Electrochemical Dearomatization: Evolution from Chemicals to Traceless Electrons, Adv. Synth. Catal., 2019, 362, 462–477.
76. R. Mao, S. Bera, A. Cheseaux and X. Hu, Deoxygenative trifluoromethylthiolation of carboxylic acids, Chem. Sci., 2019, 10, 9555–9559.
77. W. Xu, C. Fan, X. Hu and T. Xu, Deoxygenative Transformation of Alcohols via Phosphoranyl Radical from Exogenous Radical Addition, Angew. Chem., Int. Ed., 2024, 63, e202401575.
78. X. Shao, Y. Zheng, V. Ramadoss, L. Tian and Y. Wang, Recent advances in PIII-assisted deoxygenative reactions under photochemical or electrochemical conditions, Org. Biomol. Chem., 2020, 18, 5994–6005.
79. X.-Q. Hu, Y.-X. Hou, Z.-K. Liu and Y. Gao, Recent advances in phosphoranyl radical-mediated deoxygenative functionalisation, Org. Chem. Front., 2020, 7, 2319–2324.

---

Footnote

† Electronic supplementary information (ESI) available. CCDC 2368952 and 2368953. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d5qo00068h

---