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Synlett 2021; 32(13): 1262-1268
DOI: 10.1055/a-1506-5532
cluster account
Perspectives on Organoheteroatom and Organometallic Chemistry

Modern Organoselenium Catalysis: Opportunities and Challenges

Lihao Liao
,
Xiaodan Zhao  ∗

We thank the National Natural Science Foundation of China (91856109 and 21772239), the Fundamental Research Funds for the Central Universities (20lgzd21), and the Leading Scientific, Technical and Innovation Talents of Guangdong Special Support Program (2019TX05Y638), and the China Postdoctoral Science Foundation (2020M683018) for the financial support.
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Abstract

Organoselenium catalysis has attracted increasing interest in recent years. This Cluster highlights recent key advances in this area regarding the functionalization of alkenes, alkynes, and arenes by electrophilic selenium catalysis, selenonium salt catalysis, selenium-based chalcogen-bonding catalysis, and Lewis basic selenium catalysis. These achievements might inspire and help future research.

1 Introduction

2 Electrophilic Selenium Catalysis

3 Selenonium Salt Catalysis

4 Selenium-Based Chalcogen-Bond Catalysis

5 Lewis Basic Selenide Catalysis

6 Conclusion


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Key words

organoselenium catalysis - electrophilic selenium - selenonium salt - chalcogen bonding - Lewis basic selenium

Biographical Sketches

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Prof. Dr. Xiaodan Zhao received his bachelor’s degree from Hubei University in 2002 and finished his PhD under the supervision of Prof. Zhengkun Yu at Dalian Institute of Chemical Physics, Chinese Academy of Sciences in 2007, during which he studied in Prof. Howard Alper’s group at University of Ottawa as an exchange student for almost one year. Then he carried out postdoctoral research in the group of Prof. Vy M. Dong at University of Toronto (2008-2010) and the group of Prof. Tomislav Rovis at Colorado State University (2010-2013). In 2013, he started his independent career in Sun Yat-Sen University. His research interests mainly focus on asymmetric catalysis, chalcogenide catalysis, and fluorine chemistry.

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Dr. Lihao Liao received his bachelor’s degree from Sun Yat-Sen University in 2015 and finished his PhD under the supervision of Prof. Xiaodan Zhao at the same university in 2020. Currently, he is a post-doctoral research associate working with Prof. Xiaodan Zhao. His current research interests mainly focus on development of new methods and halogen chemistry.

1

Introduction

Organoselenium compounds play important roles in different fields, especially in synthetic chemistry.[1] In synthetic transformations, stoichiometric organoselenium reagents are generally utilized to produce selenenylated synthetic intermediates, followed by oxidation and elimination of selenium unities to give nonselenium-containing molecules.[2] These selenium-mediated transformations have good chemoselectivities, regioselectivities, and stereoselectivities. Besides, organoselenium compounds can serve as catalysts to catalyze organic reactions for synthetic purposes because of their unique properties.[3] [4] However, the development of organoselenium catalysis has been quite slow in the past decades. Until the last eight years, this field has attracted more and more attention from chemists and has developed into several branches based on various selenium species (Scheme [1]). Great progresses have been made, particularly focusing on the transformations of unsaturated hydrocarbons. This Cluster Account will selectively highlight and comment recent key advances regarding the functionalization of alkenes, alkynes, and arenes by electrophilic selenium catalysis, selenonium salt catalysis, selenium-based chalcogen-bonding catalysis, and Lewis basic selenium catalysis. It is hoped that it will inspire and help future research. Other subtypes of organoselenium catalysis that have been paid less attention in recent years, such as selenium oxacid catalysis,[5] selenium radical catalysis,[6] and selenium anion catalysis,[7] will not be discussed although they have potentials in organic synthesis as well.

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Scheme 1 Directions in modern organoselenium catalysis

# 2

Electrophilic Selenium Catalysis

Electrophilic selenium catalysis,[3d] [4b] [c] , [8] [9] [10] [11] [12] which goes through the electrophilic selenenylation and oxidative deselenenylation process, is the beginning of the modern organoselenium catalysis. Since Sharpless and co-workers disclosed the chlorination of alkenes in the presence of PhSeSePh as pre-catalyst and N-chlorosuccinimide (NCS) as oxidant and chlorine source in 1979,[8a] this field has gradually attracted scientists’ attention. The development of this field largely depends on the discovery of new oxidative systems, such as persulfate-involved,[8b] hypervalent-iodide-involved,[8d] and electrochemical oxidation systems.[8c] [l] In 2013, Breder and co-workers reported an interesting oxidative allylic and vinylic amination of alkenes using N-fluorobenzenesulfonimide (NFSI) by this catalysis.[8e] Although both NFSI and NCS are electrophilic halogen reagents, NFSI played a role of nitrogen source instead of halogen (fluorine) source in this reaction.

In consideration of different redox potentials of various N–F reagents and reaction compatibility of anions derived from oxidants,[8h] [i] in 2018, Zhao and co-workers envisioned that bulky N–F reagent might be an ideal candidate to serve as the oxidant and fluorine source (Scheme [2]).[8k] After test of various N–F reagents, as expected, they found the desired allylic fluoride was formed in good yield when N-fluoro-2,4,6-trimethylpyridinium triflate was utilized as the oxidant in selenium-catalyzed olefin fluorination (Scheme [2a]). A possible mechanism is depicted in Scheme [2b]. Pre-catalyst PhSeSePh was oxidized by N–F reagent to form PhSe+ and potential nitrogen and fluorine nucleophiles (Scheme [2b], top). PhSe+ activates alkene to generate seleniranium ion intermediate, which might be attacked by nitrogen or fluorine nucleophiles to furnish the corresponding amination or fluorination (Scheme [2b], middle). When bulky N–F reagent N-fluoro-2,4,6-trimethylpyridinium triflate is used as oxidant, the formed 2,4,6-collidine with weak nucleophilicity and large steric hindrance can suppress the undesired amination, which provides a good opportunity for the fluorination (Scheme [2b], bottom). Success of this fluorination might promote rational design of selenium-catalyzed new reactions to introduce various functional groups into alkenes.

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Scheme 2 Oxidative allylic fluorination via electrophilic selenium catalysis

Another important progress is the electrophilic selenium-catalyzed asymmetric transformation. Although asymmetric electrophilic selenium catalysis has been reported for a long time, the results are not satisfactory.[9] On the one hand, the rigidity of traditional chiral selenium catalysts is often maintained by the noncovalent interaction between selenium and heteroatom on the catalyst, which is sensitive to reaction conditions. On the other hand, the reactions often require chiral diselenides as catalyst precursors, which are difficult to be synthesized. To solve these problems, in 2016, Maruoka and co-workers designed and synthesized an indanol-based chiral selenide, which exhibited excellent effect for the enantioselective oxidative cyclization of unsaturated carboxylic acids.[10a] This advantageous chiral catalyst offered a new platform for asymmetric electrophilic selenium catalysis. In 2019, Denmark and co-workers reported an enantioselective syn-diamination of alkenes with bistosyl urea as nitrogen source by asymmetric electrophilic selenium catalysis (Scheme [3]).[10d] After screening different chiral selenium catalysts, the authors found the tetralin-based diselenides provided better enantioselectivity than the indanol-based ones (Scheme [3a]). The authors considered that the mechanism was similar to the selenium-catalyzed oxidative syn-dichlorination of alkenes.[8g] [10c] After intermolecular nucleophilic ring opening of seleniranium by urea, a selenenylated amino intermediate was formed; followed by oxidation and stereoselective intramolecular SN2 displacement, the desired vicinal diaminated product was formed (Scheme [3b]).

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Scheme 3 Enantioselective syn-diamination of alkenes via electrophilic selenium catalysis

Alkenes are most commonly used substrates in electrophilic selenium catalysis. Although alkynes have a similar π bond to alkenes, electrophilic selenium-catalyzed functionalization of alkynes was considered to be challenging.[4e] The main reason for hindering the development of electrophilic selenium-catalyzed alkyne functionalization might be the difficulty of deselenenylation of vinyl selenium species intermediate, which blocked the catalytic cycle. To solve this issue, in 2018, Zhao and co-works reported three types of oxidative alkyne functionalization by this catalysis via diverse conversion of vinyl selenium intermediates (Scheme [4]).[11a] When propargyl-phosphonates were used as substrates, phosphonate-substituted ynones were formed via unusual C–C triple-bond migration (Scheme [4a], top). Mechanistic studies revealed that the reaction went through the intramolecular oxygen transfer and the oxidative elimination of vinyl selenium species under heating (Scheme [4a], bottom). When ynamides were used as substrates under nitriles as solvent, multisubstituted oxazoles with high regioselectivity were formed via formal N,O-difunctionalization of triple bonds (Scheme [4b], top). This reaction might go through the tautomerization of enamine intermediate and SN2 displacement (Scheme [4b], bottom). In addition, when N-propargylamides were utilized as substrates, cyclization gave oxazole aldehydes smoothly (Scheme [4c], top). The key to this transformation was considered to be aromatization-driven isomerization and further oxidation as well as nucleophilic substitution (Scheme [4c], bottom). These discoveries enriched the mechanism of electrophilic selenium catalysis and promoted further design of new reactions for alkyne functionalization.[11b] [c]

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Scheme 4 Oxidative functionalization of alkynes via electrophilic selenium catalysis

Aryl selenium cations generated from oxidation of diaryl diselenides are classical catalysts in electrophilic selenium catalysis. However, the development of new electrophilic selenium catalysts beyond the catalysts based on aryl selenium cations is a new trend. In 2018, Michael and co-workers hypothesized that the aryl group acted as a ligand for selenium rather than a substituent on the aryl selenium cation catalysts. Replacement of the aryl group by other common ligands such as N-heterocyclic carbenes (NHC) and phosphines might act as new catalysts in electrophilic selenium catalysis (Scheme [5a]).[12a] By this strategy, they achieved phosphine selenide catalyzed aza-Heck reactions of terminal alkenes and selenophosphoramide-catalyzed diamination and oxyamination of alkenes, which were difficult to be realized by aryl selenium cation catalysis.[12a] [b] Recently, Michael and co-workers disclosed an oxidative allylic C–H amination of terpenoids by phosphine selenide or selenourea catalysis (Scheme [5b], top).[12c] In this catalytic system, sulfonamides or sulfamates were used as nitrogen source and iodobenzene diacetate PhI(OAc)2 was used as oxidant. A possible mechanism is depicted in Scheme [5b], bottom. Selenium bis(imide) is formed by oxidation of the phosphine selenide by PhI(OAc)2/sulfonamides. Possibly, phosphine oxide can be formed in this process and coordinate to selenium bis(imide), which helps to stabilize the Se(IV) species. Followed by ene reaction, [2,3]-sigmatropic shift, and oxidative turnover, the aminated product is formed and selenium bis(imide) is regenerated. The new system using selenoureas or phosphine selenides as catalysts is a good progress in electrophilic selenium catalysis. These reactions are generally initiated by Se(IV) species, different from the Se(II)-species-initiated process.

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Scheme 5 Oxidative allylic C–H amination via selenium catalysis

# 3

Selenonium Salt Catalysis

Due to the existence of weakly coordinated anions, trisubstituted tetravalent selenonium salts with definite structure exhibit Lewis acidity to some degree, which can be used as Lewis acid catalysts. From 2006 to 2009, ­Lenardão and co-workers synthesized a series of selenonium salts via alkylation of selenides and applied them as Lewis acid catalysts in hetero-Diels–Alder reactions, thioacetalations, and Baylis–Hillman reactions.[13] Although there are background reactions in some of these transformations, the addition of selenonium salt catalyst can promote the reactions to a certain extent.

In 2018, a stable electron-deficient methyl di(p-trifluoromethylphenyl) selenonium tetrafluoroborate salt was used as Lewis acid catalyst by Yeung, Ke, and co-workers in the electrophilic bromination and aldol-type reactions (Scheme [6a] and 6b).[14] The key to the success of these reactions might be ascribed to the carbonyl activation of the electrophiles or the substrates. To confirm this point, the authors preformed the NMR experiments using an equimolar amount of mixture of N,N-dimethylacetamide (DMA) and selenonium salts (Scheme [6c]). An obvious downfield shift of the carbonyl carbon signal on DMA was observed according to the 13C NMR experiment. Meanwhile, the selenium signal of selenonium salts showed a downfield shift, owing to the anisotropic effect resulting from the interaction between selenium and the oxygen atom on carbonyl. Besides, high-resolution mass analysis of this mixture traced the putative selenonium–DMA adduct successfully. These studies clearly indicated that selenonium catalysts had relatively strong Lewis acidity. Although not much attention has been paid to selenonium salt catalysis, this field has potentials in catalytic synthesis. New selenonium salt catalysts might be able to trigger new organic transformations.

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Scheme 6 Carbonyl activation via selenonium catalysis

# 4

Selenium-Based Chalcogen-Bond Catalysis

Chalcogen bonding, one of the σ-hole interactions discovered from crystal structures, is considered as the interaction between a positively polarized chalcogen (including sulfur, selenium, tellurium, but not oxygen) atom and a Lewis base.[15] Nevertheless, this noncovalent interaction is typically employed in the solid state and scarcely applied in catalysis. Since chalcogen bonding provides similar characteristics to hydrogen bonding and halogen bonding, an increased interest using it in catalysis has been awaken in recent years.

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Scheme 7 Transfer hydrogenation of quinolines via chalcogen bond catalysis

In 2017, Matile and co-workers developed a series of neutral benzodiselenazole catalysts with high-precision selenium donors of variable strength.[16a] By using these catalysts, transfer hydrogenation of quinoline derivatives with Hantzsch ester could be realized successfully (Scheme [7a]). The chalcogen bonding between selenium atom on the catalyst and nitrogen atom on quinoline was considered to be the key for activation of the quinoline derivatives (Scheme [7b]). The strong electron-withdrawing sulfonyl and cyano groups on the catalyst could enhance the positive charges of selenium atoms effectively, thus enhancing this chalcogen bonding. Success of this work promoted more and more research about selenium-based chalcogen bonding in catalysis.[16`] [c] [d] [e] This is a new research area of organoselenium catalysis launched a few years ago. More studies are required to deeply understand the details in this catalysis.


# 5

Lewis Basic Selenide Catalysis

Lewis basic selenide catalysis is a rising big branch in organoselenium catalysis.[3i] [4a] [d] For this catalysis, the reaction mode involves two steps: activation of electrophiles by selenide to form selenide-captured electrophilic intermediates and transfer of the intermediates to nucleophilic substrates. For example, in 2004, Tunge and co-workers reported diphenyl diselenide catalyzed bromolactonization of alkenes via nucleophilic activation of electrophilic halogenating reagents by diphenyl diselenide.[17] Until recent years, this field has gained a rapid progress. Most studies focused on asymmetric catalysis, such as asymmetric electrophilic functionalization of alkenes and alkynes.[18] However, it is quite challenging to realize enantioselective aromatic electrophilic functionalization by Lewis basic selenide catalysis.

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Scheme 8 Enantioselective aromatic chlorination via selenide catalysis

Since P-chirogenic compounds have been applied in different fields,[19] developing efficient approach to access such molecules is highly desirable. In 2020, Zhao and co-workers reported chiral selenide-catalyzed enantioselective electrophilic aromatic chlorination of prochiral arylphosphine compounds, which provided a new method for the efficient synthesis of chiral phosphine molecules (Scheme [8]).[20] By using chiral selenide catalysts, enantioselective chlorination occurred on the aryl ring on triaryl phosphine oxides and diaryl phosphinates (Scheme [8a]). Based on the control experiments, the possible intermediates in enantioselective control steps are shown in Scheme [8b]. For triaryl phosphine oxides, intermediate Int-I is preferred as the phenyl of substrate faces to the aryl of selenide catalyst (Scheme [8b], top left). If the phenyl group faces the opposite direction, the formed intermediate Int-I′ is not preferred owing to the steric hindrance (Scheme [8b], top right). For diaryl phosphinates, Int-II is preferred due to the less steric hindrance compared with Int-II′ with the methoxy group close to the aryl of the selenide (Scheme [8b], bottom). This work is complementary for the synthesis of chiral phosphine molecules and guides Lewis basic selenide catalysis toward electrophilic functionalization of arenes to construct chiral molecules.


# 6

Conclusion

In the past few years, organoselenium catalysis has developed rapidly. A few different branches have appeared as modern catalysis. They provides a great convenience for the synthesis of a variety of molecules and brought organic synthesis to a new height. Despite these great achievements, organoselenium catalysis is still at its infancy stage. Limitations remain, such as limited substrate scopes and reaction models as well as less successful asymmetric transformation examples. Developing new catalysts and reaction models based on the unique properties of selenium compounds to realize challenging transformations will be a major task in the future.


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Conflict of Interest

The authors declare no conflict of interest.


Corresponding Author

Xiaodan Zhao
Institute of Organic Chemistry and MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University
Guangzhou 510275
P. R. of China   

Publication History

Received: 11 April 2021

Accepted: 11 May 2021

Accepted Manuscript online:
11 May 2021

Article published online:
08 June 2021

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Scheme 1 Directions in modern organoselenium catalysis
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Scheme 2 Oxidative allylic fluorination via electrophilic selenium catalysis
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Scheme 3 Enantioselective syn-diamination of alkenes via electrophilic selenium catalysis
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Scheme 4 Oxidative functionalization of alkynes via electrophilic selenium catalysis
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Scheme 5 Oxidative allylic C–H amination via selenium catalysis
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Scheme 6 Carbonyl activation via selenonium catalysis
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Scheme 7 Transfer hydrogenation of quinolines via chalcogen bond catalysis
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Scheme 8 Enantioselective aromatic chlorination via selenide catalysis