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Review

Multicomponent Reactions between Heteroatom Compounds and Unsaturated Compounds in Radical Reactions

by
Akiya Ogawa
1,* and
Yuki Yamamoto
2
1
Organization for Research Promotion, Osaka Metropolitan University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan
2
Graduate Faculty of Interdisciplinary Research, University of Yamanashi, 4-4-37 Takeda, Kofu 400-8510, Japan
*
Author to whom correspondence should be addressed.
Molecules 2023, 28(17), 6356; https://doi.org/10.3390/molecules28176356
Submission received: 3 July 2023 / Revised: 18 August 2023 / Accepted: 25 August 2023 / Published: 30 August 2023
(This article belongs to the Special Issue Multicomponent Reactions in Organic Synthesis)
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Abstract

:
In this mini-review, we present our concepts for designing multicomponent reactions with reference to a series of sequential radical reactions that we have developed. Radical reactions are well suited for the design of multicomponent reactions due to their high functional group tolerance and low solvent sensitivity. We have focused on the photolysis of interelement compounds with a heteroatom–heteroatom single bond, which readily generates heteroatom-centered radicals, and have studied the photoinduced radical addition of interelement compounds to unsaturated compounds. First, the background of multicomponent radical reactions is described, and basic concepts and methodology for the construction of multicomponent reactions are explained. Next, examples of multicomponent reactions involving two interelement compounds and one unsaturated compound are presented, as well as examples of multicomponent reactions involving one interelement compound and two unsaturated compounds. Furthermore, multicomponent reactions involving intramolecular cyclization processes are described.

1. Introduction

Currently, as the importance of environmentally friendly manufacturing practices increases, there is a strong need to reduce waste and improve elemental efficiency in organic synthesis. In particular, one-pot multicomponent reactions are expected to be an effective method for reducing the complexity of isolation operations in multistep reactions consisting of multiple components [1,2]. However, the suppression of side reactions among multicomponent substrates is an important issue in one-pot reactions of multicomponent reactions. In order to further increase atomic efficiency, it is expected to be effective to utilize addition-type reactions that can ideally incorporate all substrates into the product, rather than substitution-type reactions that involve the byproduction of leaving groups. Although acid/base catalysts and transition metal catalysts have been widely used in conventional addition reactions, these reactions are easily affected by solvents. In contrast, the utilization of radical reactions with high tolerance for a variety of solvents is expected to be effective in order to uniformly dissolve substrates of multiple components [3,4,5,6,7,8]. Furthermore, we have come to believe that radical addition reactions that can be induced by light are the most effective reaction systems for multicomponent reactions, avoiding the use of radical initiators whose residues are waste products [9,10,11,12,13,14,15]. In particular, light irradiation in the near-ultraviolet to visible region is considered preferable to suppress side reactions of unsaturated compounds such as polymerization.
Based on this idea, we have been studying multicomponent radical addition reactions to carbon–carbon and carbon–nitrogen unsaturated compounds by selecting inter-element compounds having absorption in the near-ultraviolet to visible regions. This mini-review deals with an overview of the following three categories of multicomponent radical reactions that we have studied: (1) a reaction using multicomponent interelement compounds to one unsaturated compound, (2) a reaction using multicomponent unsaturated compounds to one interelement compound, and (3) a multicomponent reaction incorporating cyclization reactions.

2. General Concept for Photoinduced Radical Addition of Interelement Compounds to Unsaturated Bonds

Interelement compounds with heteroatom–heteroatom single bonds, in which a solitary electron pair exists on the heteroatom, usually have absorption based on n→σ* transitions in the near-UV to visible region, homolysis of the interelement bond proceeds upon photoirradiation in this region, and the corresponding heteroatom-centered radicals are generated. When carbon–carbon unsaturated compounds coexist in this reaction system, the radical addition reaction of interelement compounds to unsaturated compounds is expected to proceed with the generated heteroatom-centered radicals as the key active species. This radical addition reaction consists of the following two-step reaction process: step 1: the formation of carbon radicals by the addition of heteroatom-centered radicals to carbon–carbon unsaturated bonds, and step 2: capturing the formed carbon radicals by an interelement compound. As an alternative pathway for step 2, the coupling reaction between the carbon radical and the heteroatom-centered radical can be considered. However, the concentration of heteroatom radicals in the reaction system is relatively very low because heteroatom radicals easily dimerize each other at a diffusion-controlled rate to regenerate the starting interelement compounds, and thus the radical coupling pathway is not the major reaction process. In step 1, low-period heteroatom radicals are more reactive than high-period heteroatom radicals of the same family, while in step 2, high-period interelement compounds have a higher ability to capture carbon radicals than low-period interelement compounds of the same family because the binding energy of the high-period interelement bonds is relatively smaller. Thus, if the low-period interelement compound is used alone for photoinduced radical addition to alkenes, the undesirable polymerization reaction would be expected to proceed in preference to the radical addition reaction due to the lower carbon-radical-capturing ability of the low-period interelement compound. In contrast, when high-period interelement compounds are used alone, the desired radical addition reaction is expected to be less likely to proceed due to the lower reactivity of the high-period heteroatom radicals. To solve these problems and to make the radical addition reaction highly selective, it is expected that a combination of high-period and low-period interelement compounds will be promising: namely, a highly reactive low-period heteroatom radical selectively attacks alkenes, and the carbon radicals generated by this attack are selectively trapped by high-period interelement compounds.
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Taking disulfide and diselenide as examples to illustrate radical addition to 1-hexene, it is clear that when disulfide or diselenide is used alone, the radical addition reaction proceeds inefficiently: the 1,2-dithio- and 1,2-diseleno-hexenes were obtained in 7% and 9% yields, respectively. In the disulfide–diselenide binary system, however, the thioselenation product is obtained regioselectively in high yield (89% yield) [16]. This is because the highly reactive thiyl radical regioselectively attacks the terminal position of the alkene, and the generated carbon radical is selectively captured by the diselenide (Equation (1)). Based on this concept, we developed a series of radical addition reactions of interelement compounds to various unsaturated compounds such as alkynes, alkenes, allenes, conjugate dienes, isocyanides, etc. Some related works were successfully developed by other researchers [17,18,19,20,21,22,23,24,25,26].
When designing radical reactions of interelement compounds, it is necessary to consider not only the period but also the group. In the case of group 17 interelement compounds, which are molecular halogens, the resulting halogeno radicals have no substituent, and therefore, it is required to control the radical addition reaction by the properties of the element itself. Furthermore, halogeno radicals are highly reactive, and with alkenes, the hydrogen abstraction reaction at the allylic position of alkenes usually proceeds in preference to the desired radical addition reaction. In sharp contrast, group 16 interelement compounds, which are organic dichalcogenides such as (PhS)2, (PhSe)2, and (PhTe)2, can control the reaction by means of substituents. Since chalcogeno radicals such as PhS•, PhSe•, and PhTe• are less reactive than halogeno radicals, hydrogen abstraction at the allylic position usually does not occur, and the radical addition reaction proceeds preferentially. In addition, since chalcogeno radicals have only one substituent, the steric hindrance is not so important when the radical addition is performed. Organic dichalcogenides have their absorption in the near-ultraviolet to visible region based on the n→σ* transition and can generate the corresponding radical species by homolysis. In particular, organic diselenides and ditellurides can undergo homolysis upon sunlight irradiation.
Group 15 interelement compounds, which are organic dipnictogenides such as (Ph2P)2, have two substituents on each phosphorus group, making them susceptible to steric hindrance. In addition, trivalent species readily convert into pentavalent species upon exposure to air or moisture, so there are many factors that control the reaction. Furthermore, arsenic and antimony have problems such as high toxicity. Although (Ph2Bi)2 is a known compound, its synthesis and handling require specialized techniques.
Group 14 and 13 interelement compounds do not have lone pairs, so the homolysis of interelement bonds using the n→σ* transition cannot be used. In the case of group 14 interelement compounds, steric hindrance is a major problem due to the large number of substituents. In the case of group 13 interelement compounds, since there is an empty orbital, if homolysis is performed as it is, it becomes a 5-electron radical species, which is far away from the octet and becomes unstable. In addition, side reactions due to the coordination of Lewis bases to empty orbitals must be controlled.
Note that many second-period inter-element compounds with isolated electron pairs are unstable due to the short bonding distances of the interelement bonds and the large electronic repulsion between adjacent isolated electron pairs, and some peroxides and diazo compounds are explosive.
Keeping in mind the above considerations regarding the group and period, radical addition reactions to unsaturated bonds using mixed systems of multiple interelement compounds are discussed in the next section.

3. Photoinduced Radical Addition to Unsaturated Bonds Using Mixed Systems of Interelement Compounds

Addition reactions to terminal alkynes by binary systems of group 15–17 interelement compounds that have a lone pair of electrons and can generate heteroatom radicals upon irradiation with near-ultraviolet to visible light were investigated. In the case of group 16–17 binary systems, molecular halogens (X2) act as oxidizing agents for organic dichalcogenides (RCh-ChR) to generate the corresponding chalcogenyl halides (RChX), which are well-known to add to alkynes via an ionic process such as electrophilic addition.
In the case of group 16 binary systems, photoinduced radical addition to terminal alkynes successfully occurs with (PhS)2-(PhSe)2, (PhS)2-(PhTe)2, and (PhSe)2-(PhTe)2, affording the corresponding thioselenation [27], thiotelluration, and selenotelluration [28] products, in good yields, respectively [29,30,31,32]. In these reactions, highly reactive chalcogeno radicals attack the terminal position of alkynes, whereas dichalcogenides bearing a higher carbon-radical-capturing ability preferentially capture the alkenyl radicals formed at the inner position of alkynes. Accordingly, the relative reactivities of chalcogeno radicals and dichalcogenides are as follows: PhS• > PhSe• > PhTe•; (PhTe)2 > (PhSe)2 > (PhS)2. These orders of reactivities are fully supported by the several kinetic studies reported (Scheme 1).
Since organic diselenides have an excellent carbon-radical-capturing ability, a radical addition of (PhSe)2 and organic peroxide such as benzoyl peroxide (BPO, (PhC(=O)O)2) to alkynes was attempted under thermal conditions (Equation (2)) [33,34,35,36]. Thermal decomposition of BPO generates PhC(=O)O•, which is safely trapped with (PhSe)2 to form PhC(=O)SePh as a key electrophilic reagent. In the case of internal alkynes, benzoyloxyselenation of the alkynes successfully proceeded, as shown in Equation (2). In the case of terminal alkynes, the benzoyloxy group was eliminated with the acetylenic proton of terminal alkynes to afford the corresponding alkynyl selenides (R-C≡C-SePh) in good yields.
Molecules 28 06356 i002
In the case of group 15–16 binary systems, a similar photoinduced radical addition to terminal alkynes was examined using binary systems of tetraphenyl diphosphine and diphenyl dichalcogenides. As can be seen from the results of Scheme 1, the desired radical addition reactions proceed successfully affording the corresponding thiophosphination [37,38], selenophosphination [39], and phosphinotelluration [40] products, respectively, with excellent regioselectivity [41,42,43,44,45].
Accordingly, the relative reactivity of the heteroatom-centered radicals is as follows: PhS• > PhSe• > Ph2P• > PhTe•. Although Ph2P• might be more reactive than PhSe•, the presence of two substituents on the phosphorus center might contribute to the relative reactivity between PhSe• and Ph2P•. Since there is no kinetic detail about the carbon-radical trapping ability of (Ph2P)2 and chalcogeno phosphines such as Ph2P–YPh (Y = S, Se, and Te), the relative reactivity of carbon-radical trapping is unclear at present.
In the case of interelement compounds including group 14 elements, the generation of radical species is difficult due to the strong bond dissociation energy. As rare examples, interelement compounds bearing a carbon–heavy-element bond such as C–I, C–Te, and C–Bi can generate the corresponding carbon radicals upon photoirradiation or in the presence of a radical initiator. For example, the combination of perfluoroalkyl iodide (RFI) and (PhSe)2 or (PhTe)2 leads to a regioselective perfluoroalkyl-selenation or -telluration of alkynes (Equations (3) and (4)) [46,47,48].
Molecules 28 06356 i003
Molecules 28 06356 i004
In sharp contrast, a mixed system of RFI and (Ph2P)2 did not work well with the radical addition to alkynes probably because (Ph2P)2 is bulkier than (PhSe)2. In place of the radical addition product, P-fluorous phosphine (RFPPh2) was obtained in almost quantitative yield [49,50,51]. The synthesized P-fluorous phosphine can be used as an excellent ligand for transition metal catalysts. For example, palladium catalysts having RFPPh2 as a ligand can be employed as recycling catalysts for several cross-coupling reactions such as Sonogashira coupling using a fluorous biphasic system (FBS) (Equation (5)) [52,53].
Molecules 28 06356 i005
Molecules 28 06356 i006
As with the group 13–16 binary system such as (Bpin)2 and (PhS)2, very interestingly, radical addition of (Bpin)2 to terminal alkynes proceeded successfully, despite that the radical addition did not occur in the absence of (PhS)2 (Equation (6)) [54,55,56,57,58,59,60].
When Ph3P was used as an additive, lower yields but excellent stereoselectivity were observed (e.g., 32% [91/9] (R = nHex); 39% [91/9] (MeO2C(CH2)3)). Unfortunately, (PhSe)2 and (PhTe)2 were ineffective for the photoinduced diboration of alkynes. This is probably because the coordination ability of (PhSe)2 and (PhTe)2 to (Bpin)2 is relatively lower than that of (PhS)2. In the absence of additives, the formed radicals such as •B(pin) have 5-electron radical species that are unstable because they are far away from the octet. However, 7-electron radical species formed by the coordination of (PhS)2 or PPh3 are conceivably more stable.
Using a (PhS)2-(PhSe)2 binary system as a representative mixed system of interelement compounds, we next examined a photoinduced radical addition to a series of unsaturated compounds such as allenes, conjugate dienes, alkenes, vinylcyclopropanes, and isocyanides (for the detailed Scheme, see ref. [61]).
Among these unsaturated compounds, allenes exhibit the highest reactivity toward heteroatom-centered radicals. For example, (PhSe)2 alone cannot efficiently add to alkenes, conjugated dienes, vinylcyclopropanes, and isocyanides upon irradiation, due to the low reactivity of PhSe• with respect to ordinary unsaturated bonds. (PhSe)2 can photochemically add to alkynes under high concentration conditions [62]. However, the photoinduced addition of (PhSe)2 to allenes was complete within 1 h even under dilute conditions.
Compared to (PhS)2, (PhSe)2 has a greater absorption in the near-UV to visible region. Therefore, in the (PhS)2-(PhSe)2 binary system, (PhSe)2 preferentially undergoes homolysis to form PhSe• when irradiated with the light of this region. In the case of ordinary unsaturated compounds such as alkenes and alkynes, the generated PhSe• preferentially attacks (PhS)2 to generate PhS•, which in turn attacks alkenes and alkynes. In contrast, in the case of allenes, PhSe• preferentially reacts with allenes to give the diselenide adduct first. Upon continued photoirradiation, the diselenide adduct gradually transformed into the corresponding thioselenation product by replacing the phenylseleno group at the allylic position with a thio group [63,64].
The photoinduced thioselenation of conjugate dienes proceeded via the generation of allylic radical by the attack of the thiyl radical, followed by trapping the allylic radical with (PhSe)2 [65]. Similarly, the photoinduced thioselenation of vinylcyclopropanes involved the generation of cyclopropylcarbinyl radicals by the attack of the thiyl radical and the subsequent ring opening to generate the terminal carbon radical, which was captured with (PhSe)2 [28]. The thioselenation method could be applied to aromatic isocyanides [66,67,68,69].
In general, the photoinduced reaction of conjugate dienes in the presence of (PhS)2 induces polymerization of the dienes. Very interestingly, however, when the same reaction was conducted in the presence of 30 mol% of (PhSe)2, the polymerization was suppressed, and instead, the dithiolation products were obtained selectively (Equation (7)) [65].
Molecules 28 06356 i007
The present (PhSe)2-assisted dithiolation could be applied to the dithiolation of aliphatic isocyanides. Moreover, the photoinduced dithiolation of allenes could be attained by the coexistence of 30 mol% of (PhTe)2 [63].

4. Photoinduced Radical Addition of Interelement Compounds to Several Unsaturated Compounds

Based on the insight into the efficacy of interelement compounds bearing excellent carbon-radical-capturing ability and the relative reactivity of a series of unsaturated compounds, we next demonstrated the multicomponent reactions using two or more unsaturated compounds. As discussed in Section 3, the relative reactivity of unsaturated compounds toward heteroatom-centered radicals is shown as follows: (highly reactive) allene > alkyne > diene > alkene (less reactive). In addition, the order of the carbon-radical-capturing ability is as follows: (PhTe)2 > (PhSe)2 > (PhS)2. In the case of the low carbon-radical-capturing ability such as (PhS)2, radical polymerization is also expected to proceed. Although (PhTe)2 has an excellent carbon-radical-capturing ability, the weaker bond energy of C–Te (47.8 kcal/mol) compared with those of C–S and C–Se (65.1 and 56.0 kcal/mol, respectively) might induce the living polymerization of unsaturated compounds. Accordingly, (PhSe)2 is the best choice of mediator for the desired sequential addition to muticomponent unsaturated compounds.
To attain such muticomponent radical reactions, it is of great importance to consider the stability of carbon radical species, which can be estimated by comparing the bond dissociation energy of a series of C–H bonds: 105 kcal/mol (CH3–H); 101 kcal/mol (RCH2–H, primary); 98.5 kcal/mol (R2CH–H, secondary); 96.5 kcal/mol (R3C–H, tertiary); 87 kcal/mol (RCH=CHCH(R)–H, allylic); 112 kcal/mol (Ph–H, phenyl (or arylic)); 87 kcal/mol (PhCH2–H, benzylic). As can be seen from these data, aryl radicals (Ar•) are the most powerful radical species, whereas allylic or benzylic radicals are relatively stable carbon radicals, in which it is difficult to induce further addition to usual unsaturated compounds intermolecularly.
Next, we need to consider which unsaturated compounds are suitable for multicomponent radical addition of interelement compounds. In the case of allenes, powerful heteroatom-centered radicals such as PhS• attack both terminal and internal positions of allenes, resulting in poor regioselectivity (central attack/internal attack = 75/25). In contrast, less reactive heteroatom-centered radicals such as PhSe• and PhTe• predominantly attack the central carbon of allenes, generating allylic radicals that are difficult to add to other unsaturated compounds. Allenes are therefore not suitable candidates for unsaturated compounds attacked first by heteroatom-centered radicals in multicomponent radical addition reactions.
When a mixture of alkyne and alkene is employed in multicomponent radical addition reactions, carbon radicals irreversibly add to both alkyne and alkene with an alkene/alkyne ratio of ca. 1.2 (Scheme 2). In the case of heteroatom-centered radicals, however, the addition proceeds reversibly, preferring the more stable β-heteroatom-substituted alkenyl radicals over β-heteroatom-substituted alkyl radicals. This is most probably because the dissociation energy of the sp2 carbon-heteroatom bond is stronger than that of the sp3 carbon-heteroatom bond. Based on these considerations, the reaction of heteroatom-centered radicals with a mixture of alkyne and alkene might preferentially generate β-heteroatom-substituted alkenyl radicals as a key species for the multicomponent reactions.
Thus, we examined the photoinduced sequential addition of (PhSe)2 to 1-hexene using several alkynes (Scheme 3). Aliphatic and aromatic alkynes such as 1-octyne and phenylacetylene, which generate vinylic σ- and π-radicals, respectively, were both ineffective in the sequential addition with 1-hexene, and the diselenide adducts to the alkynes were mainly obtained. However, when an electron-deficient alkyne such as ethyl propiolate was employed, the desired sequential addition product was obtained with a decrease in the formation of the diselenide adduct. The sequential addition might proceed via the selective attack of the seleno radical to ethyl propiolate, followed by the addition of the formed vinyl radical to 1-hexene. Then, the formed alkyl radical is captured with (PhSe)2. The electron-withdrawing group might prolong the lifetime of the vinyl radical species to further react with alkenes. This can be explained by the orbital interaction, as shown in Scheme 4 [70].
The singly occupied molecular orbital (SOMO) of radical species can be stabilized by the electron-withdrawing group and close to the highest occupied molecular orbital (HOMO) of alkene. To emphasize the SOMO-HOMO interaction, the electron-donating group is introduced into the alkene.
Based on this concept, we attempted the photoinduced reaction of ethyl propiolate with vinylic ethers such as butyl vinyl ether and methyl 2-propenyl ether, which successfully afforded the sequential addition products in high yields upon shorter photoirradiation (Scheme 4).
Furthermore, photoinduced sequential addition of (PhSe)2 to ethyl propiolate and conjugate diene or vinylcyclopropane was also examined. Even using excess amounts of conjugate diene or vinylcyclopropane, PhSe• selectively attacked ethyl propiolate to generate the corresponding vinylic radical that was sequentially added to conjugate diene or vinylcyclopropane. The resulting allylic radical or primary carbon radical formed by the ring opening of the cyclopropane was captured by (PhSe)2 to afford the corresponding multicomponent coupling products in good yields (Equations (8) and (9)) [70,71].
Molecules 28 06356 i008
Molecules 28 06356 i009
When excess amounts of isocyanides are used for this sequential addition of (PhSe)2 to ethyl or methyl propiolate, the generated vinyl radicals are trapped with isocyanides to afford the corresponding α,β-unsaturated imine derivatives in good yields (Equation (10)) [72]. As can be seen from Scheme 5, in the case of isocyanide having (EtO)2P(O)-group, a similar imine derivative was formed in 58% yield. The following reaction of this imine derivative with the in situ generated ketene (MeO–CH=C=O) successfully led to the formation of a β-lactam derivative (85% yield), the hydrolysis of which afforded the corresponding β-lactam derivative having formyl group (51% yield). This β-lactam derivative is a key intermediate for the synthesis of carbapenem analogs by conducting a Wittig-type reaction [72].
Molecules 28 06356 i010
Scheme 5 also indicates the synthetic utility of a series of multicomponent coupling products bearing seleno groups. A vinylic seleno group can be converted into not only a formyl group but also alkyl groups by the reaction with organocuprates (e.g., nBu2CuLi, Et2O, −110 °C~r.t., 1 h, 84% [E/Z = 7/93] from the vinyl selenide [E/Z = 10/90]) [70]. On the other hand, alkyl selenides can lead to the corresponding alkenes by selenoxide syn-elimination or can be removed by reduction with NiCl2/NaBH4.

5. Photoinduced Multicomponent Reactions of Interelement Compounds Involving Cyclization Process

In general, intramolecular reactions are 1000 times faster than intermolecular reactions. Therefore, by incorporating intramolecular reactions into the radical addition reactions of interelement compounds, it is expected that more advanced multicomponent reactions can be designed. 5-Exo cyclization is one of the most important intramolecular radical reactions. For example, 5-hexenyl radical undergoes 5-exo cyclization to generate cyclopentylmethyl radical (k = 2.3 × 105 s−1). Considering the sequential addition to an alkyne and alkene by a seleno radical, a 5-hexenyl radical might be synthesized by the sequential addition to an alkyne and two molecules of alkenes (Scheme 6). As mentioned in Section 4, the seleno radical first attacks ethyl propionate and then the electron-rich alkene, producing a carbon radical with an alkoxy group at the α-position. Now then, what kind of alkene is desirable as the next alkene to be attacked by this carbon radical? It is expected that the SOMO energy level of the carbon radicals with an alkoxy group at the α-position is higher. If the LUMO of an alkene interacts with this SOMO, it would be preferable to use an alkene with an electron-withdrawing group which lowers the energy level of the LUMO.
Thus, we examined the photoinduced reaction of (PhSe)2 with ethyl propiolate, methyl 2-propenyl ether, and acrylate derivatives or acrylonitrile (Scheme 7). The incorporation of 5-exo cyclization prevented further addition (or oligomerization), providing the corresponding cyclic diselenides that were obtained in moderate yields [73,74,75,76,77,78,79,80,81,82,83].
In this reaction, interestingly, five-membered cyclization products incorporating two electron-poor alkenes were also formed as byproducts in 15–17% yields. This means the carbon radical intermediates bearing electron-withdrawing groups are stable enough to induce the sequential addition of two molecules of the alkenes, and in addition, the presence of the 5-exo cyclization process can inhibit further addition (or oligomerization), resulting in the formation of the corresponding five-membered cyclization product as a stereoisomeric mixture (Equation (11)).
Molecules 28 06356 i011
When a mixture of N-aryl isocyanides having an o-alkenyl group, (PhS)2, and (PhTe)2 was irradiated with visible light, a novel dithiolation incorporating 5-exo-type cyclization proceeded successfully to afford the corresponding 2-(phenylthiol)-3-(phenylthiomethyl)indene derivatives in good yields (Scheme 8). In this reaction, PhTe• formed by the visible light irradiation attacks (PhS)2 to generate PhS•, which adds to the isocyano group producing the imidoyl radical. In general, photoinduced thiotelluration of PhNC is difficult to take place due to the instability of the thiotelluartion product under the photoirradiation condition. Surprisingly, however, the 5-exo-type cyclization could induce the radical addition of (PhS)2 to the aryl isocyanide, providing the indene disulfide by trapping the indenylmethyl radical with PhSTePh [84,85,86,87,88,89,90,91,92,93,94,95,96].
Furthermore, when bis(o-aminophenyl) disulfide was used for the (PhTe)2-mediated reaction with o-alkenylphenyl isocyanide having an electron-withdrawing group at the terminal position of the o-alkenyl group, multicyclic compounds could be synthesized via ionic intramolecular cyclization processes (Scheme 9).
Thiyl radical attacks the isocyano group to generate an imidoyl radical, which is selectively trapped with (PhTe)2. Since the telluro group introduced is a good leaving group, the o-amino group induces nucleophilic substitution intramolecularly. Furthermore, Michael-type addition occurs between the amino group and the alkenyl group to directly construct a tetracyclic ring system. This one-pot sequential reaction is very interesting because ionic intramolecular cyclization reactions can be incorporated into a multicomponent radical reaction system.

6. Conclusions

This mini-review focuses on multicomponent reactions between unsaturated compounds and mutual component compounds by radical addition and cyclization reactions. Radical reactions have high tolerance to functional groups and low sensitivity to solvents, making them very suitable for designing multicomponent reactions [97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133].
To construct highly selective multicomponent radical reactions, it is important to consider the following: (1) the relative stability of carbon radicals based on the bond dissociation energy; (2) orbital interactions between SOMO and HOMO or LUMO; (3) kinetic data on addition, cyclization, etc.; (4) the characteristics of heteroatoms, especially upon photoirradiation; (5) the relative reactivity of heteroatom-centered radicals; (6) the relative carbon-radical-capturing ability of interelement compounds; (7) the control of the reaction by the optimization of the substrate concentration; (8) the use of heteroatom mixed reaction systems; and (9) the use of intramolecular reactions.
We hope that this mini-review will help researchers develop new multicomponent reactions in an environmentally friendly manner.

Author Contributions

Conceptualization, A.O.; writing—original draft preparation, A.O.; writing—review and editing, A.O. and Y.Y.; funding acquisition, A.O. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by JSPS KAKENHI Grant Number JP22H02124, the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Zhu, J.; Bienaymé, E. Multicomponent Reactions; Wiley-VCH: Weinheim, Germany, 2005; pp. 1–468. [Google Scholar]
  2. Qiu, G.; Ding, Q.; Wu, J. Recent advances in isocyanide insertion chemistry. Chem.Soc. Rev. 2013, 42, 5257–5269. [Google Scholar] [CrossRef]
  3. Ryu, I.; Sonoda, N.; Curran, D.P. Tandem Radical Reactions of Carbon Monoxide, Isocyanides, and Other Reagent Equivalents of the Geminal Radical Acceptor/Radical Precursor Synthon. Chem. Rev. 1996, 96, 177–194. [Google Scholar] [CrossRef] [PubMed]
  4. Heinrich, M.R. Intermolecular olefin functionalization involving aryl radicals generated from arenediazonium salts. Chem. Eur. J. 2009, 15, 820–833. [Google Scholar] [CrossRef]
  5. Dömling, A.; Ugi, I. Multicomponent Reactions with Isocyanides. Angew. Chem. Int. Ed. 2000, 39, 3168–3210. [Google Scholar] [CrossRef]
  6. Godineau, E.; Landais, Y. Radical and Radical-Ionic Multicomponent Processes. Chem. Eur. J. 2009, 15, 3044–3055. [Google Scholar] [CrossRef] [PubMed]
  7. Wille, U. Radical cascades initiated by intermolecular radical addition to alkynes and related triple bond systems. Chem. Rev. 2013, 113, 813–853. [Google Scholar] [CrossRef] [PubMed]
  8. Sumino, S.; Fusano, A.; Fukuyama, T.; Ryu, I. Carbonylation reactions of alkyl iodides through the interplay of carbon radicals and Pd catalysts. Acc. Chem. Res. 2014, 47, 1563–1574. [Google Scholar] [CrossRef]
  9. Sumino, S.; Ryu, I. Bromine-Radical-Mediated Bromoallylation of C-C unsaturated Bonds: A Facile Access to 1,4-, 1,5-, 1,6-, and 1,7-Dienes and Related Compounds. Synlett 2023, 34, 1001–1011. [Google Scholar]
  10. Trowbridge, A.; Reich, D.; Gaunt, M.J. Multicomponent synthesis of tertiary alkylamines by photocatalytic olefin-hydroaminoalkylation. Nature 2018, 561, 522–527. [Google Scholar] [CrossRef]
  11. Coppola, G.A.; Pillitteri, S.; Van der Eycken, E.V.; You, S.-L.; Sharm, U.K. Multicomponent reactions and photo/electrochemistry join forces: Atom economy meets energy efficiency. Chem. Soc. Rev. 2022, 51, 2313–2382. [Google Scholar] [CrossRef]
  12. Garbarino, S.; Ravelli, D.; Protti, S.; Basso, A. Photoinduced multicomponent reactions. Angew. Chem. Int. Ed. 2016, 55, 15476–15484. [Google Scholar] [CrossRef] [PubMed]
  13. Russo, C.; Brunelli, F.; Tron, G.C.; Giustiniano, M. Isocyanide-Based Multicomponent Reactions Promoted by Visible Light Photoredox Catalysis. Chem. Eur. J. 2023, 29, e202203150. [Google Scholar] [CrossRef]
  14. Wu, J.; Xia, H.; Pan, X. Recent advances in photoinduced trifluoromethylation and difluoroalkylation. Org. Chem. Front. 2016, 3, 1163–1185. [Google Scholar]
  15. Oh, E.H.; Kim, H.J.; Han, S.B. Recent Developments in Visible-Light-Catalyzed Multicomponent Trifluoromethylation of Unsaturated Carbon-Carbon Bonds. Synthesis 2018, 50, 3346–3358. [Google Scholar]
  16. Ogawa, A.; Tanaka, H.; Yokoyama, H.; Obayashi, R.; Yokoyama, K.; Sonoda, N. A highly selective thioselenation of olefins using disulfide-diselenide mixed system. J. Org. Chem. 1992, 57, 111–115. [Google Scholar] [CrossRef]
  17. Toru, T.; Seko, T.; Maekawa, T. Addition of S-Benzoyl Phenylselenosulfide to Olefins: Selenothiocarboxylation. Tetrahedron Lett. 1985, 26, 3263–3266. [Google Scholar] [CrossRef]
  18. Toru, T.; Seko, T.; Maekawa, T.; Ueno, Y. Reaction of Olefins with Se-Phenyl (Selenothioperoxy)benzoate: A New Anti-Markownikoff Benzeneselenenylation. J. Chem. Soc. Perkin Trans. I. 1988, 26, 575–581. [Google Scholar] [CrossRef]
  19. Denes, F.; Pichowicz, M.; Povie, G.; Renaud, P. Thiyl radicals in organic synthesis. Chem. Rev. 2014, 114, 2587–2693. [Google Scholar] [CrossRef]
  20. Perin, G.; Lenardão, E.J.; Jacob, R.G.; Panatieri, R.B. Synthesis of Vinyl Selenides. Chem. Rev. 2009, 109, 1277–1301. [Google Scholar] [CrossRef]
  21. Procter, D.J. The synthesis of thiols, selenols, sulfides, selenides, sulfoxides, selenoxides, sulfones and selenones. J. Chem. Soc. Perkin Transactions 1 1999, 6, 641–668. [Google Scholar] [CrossRef]
  22. Comasseto, J.V.; Ling, L.W.; Petragnani, N.; Stefani, H.A. Vinylic selenides and tellurides—Preparation, reactivity and synthetic applications. Synthesis 1997, 1997, 373–403. [Google Scholar] [CrossRef]
  23. Curran, D.P.; Eichenberger, E.; Collis, M.; Roepel, M.G.; Thoma, G. Group Transfer Addition Reactions of Methyl(phenylseleno)malononitrile to Alkenes. J. Am. Chem. Soc. 1994, 116, 4279–4288. [Google Scholar] [CrossRef]
  24. Zong, Y.; Lang, Y.; Yang, M.; Li, X.; Fan, X.; Wu, J. Synthesis of β-Sulfonyl Amides through a Multicomponent Reaction with the Insertion of Sulfur Dioxide under Visible Light Irradiation. Org. Lett. 2019, 21, 1935–1938. [Google Scholar] [CrossRef] [PubMed]
  25. Tlahuext-Aca, A.; Garza-Sanchez, A.R.; Glorius, F. Multicomponent Oxyalkylation of Styrenes Enabled by Hydrogen-Bond-Assisted Photoinduced Electron Transfer. Angew. Chem. Int. Ed. 2017, 56, 3708–3711. [Google Scholar] [CrossRef] [PubMed]
  26. Hofman, K.; Liu, N.-W.; Manolikakes, G. Radicals and Sulfur Dioxide: A Versatile Combination for the Construction of Sulfonyl-Containing Molecules. Chem. Eur. J. 2018, 24, 11852–11863. [Google Scholar] [CrossRef]
  27. Ogawa, A.; Obayashi, R.; Ine, H.; Tsuboi, Y.; Sonoda, N.; Hirao, T. Highly regioselective thioselenation of acetylenes by using a (PhS)2-(PhSe)2 binary system. J. Org. Chem. 1998, 63, 881–884. [Google Scholar] [CrossRef]
  28. Ogawa, A.; Ogawa, I.; Obayashi, R.; Umezu, K.; Doi, M.; Hirao, T. Highly Selective Thioselenation of Vinylcyclopropanes with a (PhS)2−(PhSe)2 Binary System and Its Application to Thiotelluration. J. Org. Chem. 1999, 64, 86–92. [Google Scholar] [CrossRef]
  29. Taniguchi, T.; Fujii, T.; Idota, A.; Ishibashi, H. Reductive Addition of the Benzenethiyl Radical to Alkynes by Amine-Mediated Single Electron Transfer Reaction to Diphenyl Disulfide. Org. Lett. 2009, 11, 3298–3301. [Google Scholar] [CrossRef]
  30. Yu, J.; Mao, R.; Wanga, Q.; Wu, J. Synthesis of β-keto sulfones via a multicomponent reaction through sulfonylation and decarboxylation. Org. Chem. Front. 2017, 4, 617–621. [Google Scholar] [CrossRef]
  31. Zeni, G.; Lüdtke, D.S.; Penatieri, R.B.; Braga, A.L. Vinylic Tellurides: From Preparation to Their Applicability in Organic Synthesis. Chem. Rev. 2006, 106, 1032–1076. [Google Scholar] [CrossRef]
  32. Kippo, T.; Hamaoka, K.; Ryu, I. Bromine Radical-Mediated Sequential Radical Rearrangement and Addition Reaction of Alkylidenecyclopropanes. J. Am. Chem. Soc. 2013, 135, 632–635. [Google Scholar] [CrossRef] [PubMed]
  33. Kodama, S.; Saeki, T.; Mihara, K.; Higashimae, S.; Kawaguchi, S.; Sonoda, M.; Nomoto, A.; Ogawa, A. A Benzoyl Peroxide/Diphenyl Diselenide Binary System for Functionalization of Alkynes Leading to Alkenyl and Alkynyl Selenides. J. Org. Chem. 2017, 82, 12477–12484. [Google Scholar] [CrossRef] [PubMed]
  34. Sun, L.; Yuan, Y.; Yao, M.; Wang, H.; Wang, D.; Gao, M.; Chen, Y.-H.; Lei, A. Electrochemical Aminoselenation and Oxyselenation of Styrenes with Hydrogen Evolution. Org. Lett. 2019, 21, 1297–1300. [Google Scholar] [CrossRef]
  35. Sonawane, A.D.; Sonawane, R.A.; Ninomiya, M.; Koketsu, M. Synthesis of Seleno-Heterocycles via Electrophilic/RadicalCyclization of Alkyne Containing Heteroatoms. Adv. Synth. Catal. 2020, 362, 3485–3515. [Google Scholar] [CrossRef]
  36. Schweitzer-Chaput, B.; Demaerel, J.; Engler, H.; Klussmann, M. Acid-Catalyzed Oxidative Radical Addition of Ketones to Olefins. Angew. Chem. Int. Ed. 2014, 53, 8737–8740. [Google Scholar] [CrossRef] [PubMed]
  37. Shirai, T.; Kawaguchi, S.; Nomoto, A.; Ogawa, A. Photoinduced highly selective thiophosphination of alkynes using a (PhS)2/(Ph2P)2 binary system. Tetrahedron Lett. 2008, 49, 4043–4046. [Google Scholar] [CrossRef]
  38. Wada, T.; Kondoh, A.; Yorimitsu, H.; Oshima, K. Intermolecular Radical Addition of Alkylthio- and Arylthiodiphenylphosphines to Terminal Alkynes. Org. Chem. 2008, 10, 1155–1157. [Google Scholar] [CrossRef]
  39. Kawaguchi, S.; Shirai, T.; Ohe, T.; Nomoto, A.; Sonoda, M.; Ogawa, A. Highly regioselective simultaneous introduction of phosphino and seleno groups into unsaturated bonds by the novel combination of (Ph2P)2 and (PhSe)2 upon photoirradiation. J. Org. Chem. 2009, 74, 1751–1754. [Google Scholar] [CrossRef]
  40. Kawaguchi, S.; Ohe, T.; Shirai, T.; Nomoto, A.; Sonoda, M.; Ogawa, A. Highly selective phosphinotelluration of terminal alkynes using a (Ph2P)2-(PhTe)2 mixed system upon visible light irradiation: Straightforward access to 1-phosphino-2-telluro-alkenes. Organometallics 2010, 29, 312–316. [Google Scholar] [CrossRef]
  41. Pan, X.-Q.; Zou, J.-P.; Yi, W.-B.; Zhang, W. Recent advances in sulfur- and phosphorous-centered radical reactions for the formation of Se–C and P–C bonds. Tetrahedron 2015, 71, 7481–7529. [Google Scholar] [CrossRef]
  42. Yorimitsu, H. Homolytic substitution at phosphorus for C–P bond formation in organic synthesis. Beilstein J. Org. Chem. 2013, 9, 1269–1277. [Google Scholar] [CrossRef]
  43. Lamas, M.-C.; Studer, A. Radical Alkylphosphanylation of Olefins with Stannylated or Silylated Phosphanes and Alkyl Iodides. Org. Lett. 2011, 13, 2236–2239. [Google Scholar] [CrossRef] [PubMed]
  44. Ueda, M.; Miyabe, H.; Sugino, H.; Miyata, O.; Naito, T. Tandem Radical-Addition–Aldol-Type Reactionof an α,β-Unsaturated Oxime Ether. Angew. Chem. Int. Ed. 2005, 44, 6190–6193. [Google Scholar] [CrossRef] [PubMed]
  45. Xu, Y.; Zhou, X.; Chen, L.; Maa, Y.; Wu, G. The copper-catalyzed radical aminophosphinoylation of maleimides with anilines and diarylphosphine oxides. Org. Chem. Front. 2022, 9, 2471–2476. [Google Scholar] [CrossRef]
  46. Tamai, T.; Nomoto, A.; Tsuchii, K.; Minamida, Y.; Mitamura, T.; Sonoda, M.; Ogawa, A. Highly selective perfluoroalkylchalcogenation of alkynes by the combination of iodoperfluoroalkanes and organic dichalcogenides upon photoirradiation. Tetrahedron 2012, 68, 10516–10522. [Google Scholar] [CrossRef]
  47. Postigo, A. Electron Donor-Acceptor Complexes in Perfluoroalkylation Reactions. Eur. J. Org. Chem. 2018, 2018, 6391–6404. [Google Scholar] [CrossRef]
  48. Ye, J.-H.; Zhu, L.; Yan, S.-S.; Miao, M.; Zhang, X.-C.; Zhou, W.-J.; Li, J.; Lan, Y.; Yu, D.-G. Radical Trifluoromethylative Dearomatization of Indoles and Furans with CO2. ACS Catalysis 2017, 7, 8324–8330. [Google Scholar] [CrossRef]
  49. Kawaguchi, S.; Minamida, Y.; Ohe, T.; Nomoto, A.; Sonoda, M.; Ogawa, A. Synthesis and properties of perfluoroalkyl phosphine ligands: Photoinduced reaction of diphosphines with perfluoroalkyl iodides. Angew. Chem. Int. Ed. 2013, 52, 1748–1752. [Google Scholar] [CrossRef]
  50. Horváth, I.T.; Rábai, J. Facile Catalyst Separation without Water: Fluorous Biphase Hydroformylation of Olefins. Science 1994, 266, 72–75. [Google Scholar] [CrossRef]
  51. Betzemeier, B.; Knochel, P. Palladium-Catalyzed Cross-Coupling of Organozinc Bromides with Aryl Iodides in Perfluorinated Solvents. Angew. Chem. Int. Ed. Engl. 1997, 36, 2623–2624. [Google Scholar] [CrossRef]
  52. Kawaguchi, S.; Minamida, Y.; Okuda, T.; Sato, Y.; Saeki, T.; Yoshimura, A.; Nomoto, A.; Ogawa, A. Photoinduced Synthesis of P-Perfluoroalkylated Phosphines from Triarylphosphines and Their Application in the Copper-Free Cross-Coupling of Acide Clorides and Terminal Alkynes. Adv. Synth. Catal. 2015, 357, 2509–2519. [Google Scholar] [CrossRef]
  53. Gladysz, J.A.; Curran, D.P.; Horváth, I.T. Handbook of Fluorous Chemistry; Wiley-VCH: Weinheim, Germany, 2004. [Google Scholar]
  54. Yoshimura, A.; Takamachi, Y.; Han, L.-B.; Ogawa, A. Organosulfide-Catalyzed Diboration of Terminal Alkynes under Light. Chem. Eur. J. 2015, 21, 13930–13933. [Google Scholar] [CrossRef] [PubMed]
  55. Neeve, E.C.; Geier, S.J.; Mkhalid, I.A.I.; Westcott, S.A.; Marder, T.B. Diboron(4) Compounds: From Structural Curiosity to Synthetic Workhorse. Chem. Rev. 2016, 116, 9091–9161. [Google Scholar] [CrossRef] [PubMed]
  56. Cuenca, A.B.; Shishido, R.; Ito, H.; Fernández, E. Transition-metal-free B–B and B–interelement reactions with organic molecules. Chem. Soc. Rev. 2017, 46, 415–430. [Google Scholar] [CrossRef]
  57. Cheng, Y.; Mück-Lichtenfeld, C.; Studer, A. Transition Metal-Free 1,2-Carboboration of Unactivated Alkenes. J. Am. Chem. Soc. 2018, 140, 6221–6225. [Google Scholar] [CrossRef]
  58. Tian, Y.-M.; Guo, X.-N.; Braunschweig, H.; Radius, U.; Marder, T.B. Photoinduced Borylation for the Synthesis of Organoboron Compounds. Chem. Rev. 2021, 121, 3561–3597. [Google Scholar] [CrossRef]
  59. Ren, S.-C.; Zhang, F.-L.; Qi, J.; Huang, Y.-S.; Xu, A.-Q.; Yan, H.-Y.; Wang, Y.-F. Radical Borylation/Cyclization Cascade of 1,6-Enynes for the Synthesis of Boron-Handled Hetero- and Carbocycles. J. Am. Chem. Soc. 2017, 139, 6050–6053. [Google Scholar] [CrossRef]
  60. Friese, F.W.; Studer, A. New avenues for C–B bond formation via radical intermediates. Chem. Sci. 2019, 10, 8503–8518. [Google Scholar] [CrossRef]
  61. Yamamoto, Y.; Ogawa, A. Metal-Free One-Pot Multi-Functionalization of Unsaturated Compounds with Interelement Compounds by Radical Process. Molecules 2023, 28, 787. [Google Scholar] [CrossRef]
  62. Back, T.G.; Krishna, M.V. Free-radical addition of diselenides to dimethyl acetylenedicarboxylate, methyl propiolate, and dimethyl maleate. J. Org. Chem. 1988, 53, 2533–2536. [Google Scholar] [CrossRef]
  63. Ogawa, A.; Obayashi, R.; Doi, M.; Sonoda, N.; Hirao, T. A Novel Photoinduced Thioselenation of Allenes by Use of a Disulfide−Diselenide Binary System. J. Org. Chem. 1998, 63, 4277–4281. [Google Scholar] [CrossRef]
  64. Liu, L.; Ward, R.M.; Schomaker, J.M. Mechanistic Aspects and Synthetic Applications of Radical Additions to Allenes. Chem. Rev. 2019, 119, 12422–12490. [Google Scholar] [CrossRef]
  65. Ogawa, A.; Obayashi, R.; Sonoda, N.; Hirao, T. Diphenyl diselenide-assisted dithiolation of 1,3-dienes with diphenyl disulfide upon irradiation with near-UV light. Tetrahedron Lett. 1998, 39, 1577–1578. [Google Scholar] [CrossRef]
  66. Tsuchii, K.; Tsuboi, Y.; Kawaguchi, S.-i.; Takahashi, J.; Sonoda, N.; Nomoto, A.; Ogawa, A. Highly Selective Double Chalcogenation of Isocyanides with Disulfide−Diselenide Mixed Systems. J. Org. Chem. 2007, 72, 415–423. [Google Scholar] [CrossRef] [PubMed]
  67. Giustiniano, M.; Basso, A.; Mercalli, V.; Massarotti, A.; Novellino, E.; Tron, G.C.; Zhu, J. To each his own: Isonitriles for all flavors. Functionalized isocyanides as valuable tools in organic synthesis. Chem. Soc. Rev. 2017, 46, 1295–1357. [Google Scholar] [CrossRef] [PubMed]
  68. Lei, J.; Huang, J.; Zhu, Q. Recent progress in imidoyl radical-involved reactions. Org. Biomol. Chem. 2016, 14, 2593–2602. [Google Scholar] [CrossRef]
  69. Lygin, A.V.; De Meijere, A. Isocyanides in the synthesis of nitrogen heterocycles. Angew. Chem. Int. Ed. 2010, 49, 9094–9124. [Google Scholar] [CrossRef]
  70. Ogawa, A.; Doi, M.; Ogawa, I.; Hirao, T. Highly selective three-component coupling of ethyl propiolate, alkenes, and diphenyl diselenide under visible-light irradiation. Angew. Chem. Int. Ed. 1999, 38, 2027–2029. [Google Scholar] [CrossRef]
  71. Ogawa, A.; Ogawa, I.; Sonoda, N. A novel three-component coupling of alkynes, vinylcyclopropanes, and diphenyl diselenide under visible-light irradiation. J. Org. Chem. 2000, 65, 7682–7685. [Google Scholar] [CrossRef]
  72. Ogawa, A.; Doi, M.; Tsuchii, K.; Hirao, T. Selective sequential addition of diphenyl diselenide to ethyl propiolate and isocyanides upon irradiation with near-UV light. Tetrahedron Lett. 2001, 42, 2317–2319. [Google Scholar] [CrossRef]
  73. Tsuchii, K.; Doi, M.; Hirao, T.; Ogawa, A. Highly selective sequential addition and cyclization reactions involving of diphenyl diselenide, an alkyne, and alkenes under visible-light irradiation. Angew. Chem. Int. Ed. 2003, 42, 3490–3493. [Google Scholar] [CrossRef] [PubMed]
  74. Lee, E.; Hur, C.U.; Rhee, Y.H.; Park, Y.C.; Kim, S.Y. Propiolate-Olefin-Olefin Three-Component Annulation Mediated by the Addition of Stannyl Radicals. J. Chem. Soc.. Chem. Commun. 1993, 19, 1466–1468. [Google Scholar] [CrossRef]
  75. Bowman, W.R.; Bridge, C.F.; Brookes, P. Synthesis of heterocycles by radical cyclisation. J. Chem. Soc. Perkin Trans. 1 2000, 1, 1–14. [Google Scholar] [CrossRef]
  76. Naito, T. Heteroatom radical addition-cyclization and its synthetic application. Heterocycles 1999, 50, 505–541. [Google Scholar] [CrossRef]
  77. Kerry Gilmore, K.; Alabugin, I.V. Cyclizations of Alkynes: Revisiting Baldwin’s Rules for Ring Closure. Chem. Rev. 2011, 111, 6513–6556. [Google Scholar] [CrossRef]
  78. Godineau, E.; Landais, Y. Multicomponent Radical Processes: Synthesis of Substituted Piperidinones. J. Am. Chem. Soc. 2007, 129, 12662–12663. [Google Scholar] [CrossRef]
  79. Rueping, M.; Vila, C. Visible Light Photoredox-Catalyzed Multicomponent Reactions. Org. Lett. 2013, 15, 2092–2095. [Google Scholar] [CrossRef]
  80. Joseph, D.; Idris, M.A.; Chen, J.; Lee, S. Recent Advances in the Catalytic Synthesis of Arylsulfonyl Compounds. ACS Catal. 2021, 11, 4169–4204. [Google Scholar] [CrossRef]
  81. Ryu, I.; Tani, A.; Fukuyama, T.; Ravelli, D.; Fagnoni, M.; Albini, A. Atom-Economical Synthesis of Unsymmetrical Ketones through Photocatalyzed C-H Activation of Alkanes and Coupling with CO and Electrophilic Alkenes. Angew. Chem. 2011, 123, 1909–1912. [Google Scholar] [CrossRef]
  82. Lipp, B.; Kammer, L.M.; Kücükdisli, M.; Luque, A.; Kühlborn, J.; Pusch, S.; Matulevičiūtė, G.; Schollmeyer, D.; Šačkus, A.; Opatz, T. Visible Light-Induced Sulfonylation/Arylation of Styrenes in a Double Radical Three-Component Photoredox Reaction. Chem. Eur. J. 2019, 25, 8965–8969. [Google Scholar] [CrossRef]
  83. Liautard, V.; Robert, F.; Landais, Y. Free-Radical Carboalkynylation and Carboalkenylation of Olefins. Org. Lett. 2011, 13, 2658–2661. [Google Scholar] [CrossRef] [PubMed]
  84. Mitamura, T.; Iwata, K.; Ogawa, A. Photoinduced intramolecular cyclization of o-ethenylaryl isocyanides with organic disulfides mediated by diphenyl ditelluride. J. Org. Chem. 2011, 76, 3880–3887. [Google Scholar] [CrossRef] [PubMed]
  85. Zhang, B.; Studer, A. Recent advances in the synthesis of nitrogen heterocycles via radical cascade reactions using isonitriles as radical acceptors. Chem. Soc. Rev. 2015, 44, 3505–3521. [Google Scholar] [CrossRef] [PubMed]
  86. Zhang, B.; Daniliuc, C.G.; Studer, A. 6-Phosphorylated Phenanthridines from 2-Isocyanobiphenyls via Radical C-P and C-C Bond Formation. Org. Lett. 2014, 16, 250–253. [Google Scholar] [CrossRef] [PubMed]
  87. Sadjadi, S.; Heravi, M.M.; Nazari, N. Isocyanide-based multicomponent reactions in the synthesis of heterocycles. RSC Adv. 2016, 6, 53203–53272. [Google Scholar] [CrossRef]
  88. Zhang, B.; Studer, A. 2-Trifluoromethyated Indoles via Radical Trifluoromethylation of Isonitriles. Org. Lett. 2014, 16, 1216–1219. [Google Scholar] [CrossRef]
  89. Jiang, H.; Cheng, Y.; Wang, R.; Zheng, M.; Zhang, Y.; Yu, S. Synthesis of 6-alkylated phenanthridine derivatives using photoredox neutral somophilic isocyanide insertion. Angew. Chem. Int. Ed. 2013, 52, 13289–13292. [Google Scholar] [CrossRef]
  90. An, X.-D.; Yu, S. Visible-Light-Promoted and One-Pot Synthesis of Phenanthridines and Quinolines from Aldehydes and O-Acyl Hydroxylamine. Org. Lett. 2015, 17, 2692–2695. [Google Scholar] [CrossRef]
  91. Zamudio-Medina, A.; García-González, M.C.; Padilla, J.; González-Zamora, E. Synthesis of a tetracyclic lactam system of Nuevamine by four-component reaction and free radical cyclization. Tetrahedron Lett. 2010, 51, 4837–4839. [Google Scholar] [CrossRef]
  92. Shen, Z.-J.; Wu, Y.-N.; He, C.-L.; He, L.; Hao, W.-J.; Wang, A.-F.; Tu, S.-J.; Jiang, B. Stereoselective synthesis of sulfonated 1-indenones via radical-triggered multi-component cyclization of β-alkynyl propenones. Chem. Commun. 2018, 54, 445–448. [Google Scholar] [CrossRef]
  93. Fang, Y.; Zhu, Z.-L.; Xu, P.; Wang, S.-Y.; Ji, S.-J. Aerobic radical-cascade cycloaddition of isocyanides, selenium and imidamides: Facile access to 1,2,4-selenadiazoles under metal-free conditions. Green Chem. 2017, 19, 1613–1618. [Google Scholar] [CrossRef]
  94. Liu, Y.-Y.; Yu, X.-Y.; Chen, J.-R.; Qiao, M.-M.; Qi, X.; Shi, D.-Q.; Xiao, W.-J. Visible-Light-Driven Aza-ortho-quinone Methide Generation for the Synthesis of Indoles in a Multicomponent Reaction Angew. Chem. Int. Ed. 2017, 56, 9527–9531. [Google Scholar] [CrossRef] [PubMed]
  95. Kaicharla, T.; Thangaraj, M.; Biju, A.T. Practical Synthesis of Phthalimides and Benzamides by a Multicomponent Reaction Involving Arynes, Isocyanides, and CO2/ H2O. Org. Lett. 2014, 16, 1728–1731. [Google Scholar] [CrossRef] [PubMed]
  96. Yin, Z.-B.; Ye, J.-H.; Zhou, W.-J.; Zhang, Y.-H.; Ding, L.; Gui, Y.-Y.; Yan, S.-S.; Li, J.; Yu, D.-G. Oxy-Difluoroalkylation of Allylamines with CO2 via Visible-Light Photoredox Catalysis. Org. Lett. 2018, 20, 190–193. [Google Scholar] [CrossRef]
  97. Rossi, B.; Pastori, N.; Clerici, A.; Punta, C. Free-radical hydroxymethylation of ketimines generated in situ: A one-pot multicomponent synthesis of β,β-disubstituted-β-aminoalcohols. Tetrahedron 2012, 68, 10151–10156. [Google Scholar] [CrossRef]
  98. Matcha, K.; Antonchick, A.P. Cascade Multicomponent Synthesis of Indoles, Pyrazoles, and Pyridazinones by Functionalization of Alkenes. Angew. Chem. Int. Ed. 2014, 53, 11960–11964. [Google Scholar] [CrossRef]
  99. Liu, Z.; Liu, Z.-Q. An Intermolecular Azidoheteroarylation of Simple Alkenes via Free-Radical Multicomponent Cascade Reactions. Org. Lett. 2017, 29, 5649–5652. [Google Scholar] [CrossRef]
  100. Beniazza, R.; Liautard, V.; Poittevin, C.; Ovadia, B.; Mohammed, S.; Robert, F.; Landais, Y. Free-Radical Carbo-Alkenylation of Olefins: Scope, Limitations and Mechanistic Insights. Chem. Eur. J. 2017, 23, 2439–2447. [Google Scholar] [CrossRef]
  101. Kanazawa, J.; Maeda, K.; Uchiyama, M. Radical Multicomponent Carboamination of [1.1.1]Propellane. J. Am. Chem. Soc. 2017, 139, 17791–17794. [Google Scholar] [CrossRef]
  102. Liu, Q.; Liu, J.-J.; Cheng, L.; Wang, D.; Liu, L. TEMPO promoted direct multi-functionalization of terminal alkynes with 2-oxindoles/benzofuran-2(3H)-one. Org. Biomol. Chem. 2018, 16, 5228–5231. [Google Scholar] [CrossRef]
  103. Liu, H.; Fang, Y.; Wang, S.-Y.; Ji, S.-J. TEMPO-Catalyzed Aerobic Oxidative Selenium Insertion Reaction: Synthesis of 3-Selenylindole Derivatives by Multicomponent Reaction of Isocyanides, Selenium Powder, Amines, and Indoles under Transition-Metal-Free Conditions. Org. Lett. 2018, 20, 930–933. [Google Scholar] [CrossRef] [PubMed]
  104. Chen, H.; Ding, R.; Tang, H.; Pan, Y.; Xu, Y.; Chen, Y. Simultaneous Construction of C−Se And C−S Bonds via the Visible-Light-Mediated Multicomponent Cascade Reaction of Diselenides, Alkynes, and SO2. Chem. Asian J. 2019, 14, 3264–3268. [Google Scholar] [CrossRef]
  105. Pramanik, M.M.D.; Yuan, F.; Yan, D.-M.; Xiao, W.-J.; Chen, J.-R. Visible-Light-Driven Radical Multicomponent Reaction of 2-Vinylanilines, Sulfonyl Chlorides, and Sulfur Ylides for Synthesis of Indolines. Org. Lett. 2020, 22, 2639–2644. [Google Scholar] [CrossRef] [PubMed]
  106. Yu, X.; Daniliuc, C.G.; Alasmary, F.A.; Studer, A. Direct Access to α-Aminosilanes Enabled by Visible-Light-Mediated Multicomponent Radical Cross-Coupling. Angew. Chem. Int. Ed. 2021, 60, 23335–23341. [Google Scholar] [CrossRef]
  107. Deneny, P.J.; Kumar, R.; Gaunt, M.J. Visible light-mediated radical fluoromethylation via halogen atom transfer activation of fluoroiodomethane. Chem. Sci. 2021, 12, 12812–12818. [Google Scholar] [CrossRef] [PubMed]
  108. Ma, N.; Guo, L.; Qi, D.; Gao, F.; Yang, C.; Xia, W. Visible-Light-Induced Multicomponent Synthesis of γ-Amino Esters with Diazo Compounds. Org. Lett. 2021, 23, 6278–6282. [Google Scholar] [CrossRef] [PubMed]
  109. Cabrera-Afonso, M.J.; Sookezian, A.; Badir, S.O.; Khatib, M.E.; Molander, G.A. Photoinduced 1,2-dicarbofunctionalization of alkenes with organotrifluoroborate nucleophiles via radical/polar crossover. Chem. Sci. 2021, 12, 9189–9195. [Google Scholar] [CrossRef]
  110. Shen, J.; Xu, J.; He, L.; Ouyang, Y.; Huang, L.; Li, W.; Zhu, Q.; Zhang, P. Photoinduced Rapid Multicomponent Cascade Reaction of Aryldiazonium Salts with Unactivated Alkenes and TMSN3. Org. Lett. 2021, 23, 1204–1208. [Google Scholar] [CrossRef]
  111. Chen, L.; Wang, Z.; Liu, H.; Li, X.; Wang, B. tert-Butyl nitrite triggered radical cascade reaction for synthesizing isoxazoles by a one-pot multicomponent strategy. Chem. Commun. 2022, 58, 9152–9155. [Google Scholar] [CrossRef]
  112. Huang, J.; Liu, F.; Zeng, L.-H.; Li, S.; Chen, Z.; Wu, J. Accessing chiral sulfones bearing quaternary carbon stereocenters via photoinduced radical sulfur dioxide insertion and Truce–Smiles rearrangement. Nat. Commun. 2022, 13, 7081. [Google Scholar] [CrossRef]
  113. Li, Y.; Yang, J.; Geng, X.; Tao, P.; Shen, Y.; Su, Z.; Zheng, K. Modular Construction of Unnatural α-Tertiary Amino Acid Derivatives by Multicomponent Radical Cross-Couplings. Angew. Chem. Int. Ed. 2022, 61, e202210755. [Google Scholar] [CrossRef] [PubMed]
  114. Xie, D.-T.; Chen, H.-L.; Wei, D.; Wei, B.-Y.; Li, Z.-H.; Zhang, J.-W.; Yu, W.; Han, B. Regioselective Fluoroalkylphosphorylation of Unactivated Alkenes by Radical-Mediated Alkoxyphosphine Rearrangement. Angew. Chem. Int. Ed. 2022, 61, e202203398. [Google Scholar] [CrossRef] [PubMed]
  115. Kim, M.; You, E.; Kim, J.; Hong, S. Site-Selective Pyridylic C−H Functionalization by Photocatalytic Radical Cascades. Angew. Chem. Int. Ed. 2022, 61, e202204217. [Google Scholar] [CrossRef]
  116. Burykina, J.V.; Kobelev, A.D.; Shlapakov, N.S.; Kostyukovich, A.Y.; Fakhrutdinov, A.N.; König, B.; Ananikov, V.P. Intermolecular Photocatalytic Chemo-, Stereo- and Regioselective Thiol–Yne–Ene Coupling Reaction. Angew. Chem. Int. Ed. 2022, 61, e202116888. [Google Scholar] [CrossRef]
  117. Su, Y.-L.; Liu, G.-X.; Angelis, L.D.; He, R.; Al-Sayyed, A.; Schanze, K.S.; Hu, W.-H.; Qiu, H.; Doyle, M.P. Radical Cascade Multicomponent Minisci Reactions with Diazo Compounds. ACS Catal. 2022, 12, 1357–1363. [Google Scholar] [CrossRef]
  118. Yang, N.; Mao, C.; Zhang, H.; Wang, P.; Li, S.; Xie, L.; Liao, S. FSO2 Radical-Initiated Tandem Addition Reaction of Two Different Olefins: A Facile Access to Multifunctional Aliphatic Sulfonyl Fluorides. Org. Lett. 2023, 25, 4478–4482. [Google Scholar] [CrossRef] [PubMed]
  119. Wang, L.; Shen, Y.-T.; Wang, Y.-X.; Wang, H.-Y.; Hao, W.-J.; Jiang, B. Multicomponent Annulative SO2 Insertion of Heteroatom-Linked 1,7-Diynes for Accessing Tricyclic Sulfones. Adv. Synth. Catal. 2023, 365, 1693–1698. [Google Scholar] [CrossRef]
  120. Venditto, N.J.; Boerth, J.A. Photoredox-Catalyzed Multicomponent Synthesis of Functionalized γ-Amino Butyric Acids via Reductive Radical Polar Crossover. Org. Lett. 2023, 25, 3429–3434. [Google Scholar] [CrossRef]
  121. Huang, W.; Keess, S.; Molander, G.A. A General and Practical Route to Functionalized Bicyclo[1.1.1]Pentane-Heteroaryls Enabled by Photocatalytic Multicomponent Heteroarylation of [1.1.1]Propellane. Angew. Chem. Int. Ed. 2023, 62, e202302223. [Google Scholar] [CrossRef]
  122. Sun, B.; Tang, X.-L.; Zhuang, X.; Ling, L.; Huang, P.; Wang, J.; Jin, C. Visible-Light-Driven Multicomponent Radical Cascade Versatile Alkylation of Quinoxalinones Enabled by Electron Donor Acceptor Complex in Water. Adv. Synth. Catal. 2023, 365, 1020–1026. [Google Scholar] [CrossRef]
  123. Zhang, K.-Y.; Long, F.; Peng, C.-C.; Liu, J.-H.; Hu, Y.-C.; Wu, L.-J. Multicomponent Sulfonylation of Alkenes to Access β-Substituted Arylsulfones. J. Org. Chem. 2023, 88, 3772–3780. [Google Scholar] [CrossRef]
  124. Sookezian, A.; Molander, G.A. Photoinduced Vicinal 1,2-Difunctionalization of Olefins for the Synthesis of Alkyl Sulfonamides. Org. Lett. 2023, 25, 1014–1019. [Google Scholar] [CrossRef]
  125. Bhat, V.S.; Lee, A. Three-Component Synthesis of 3-(Arylsulfonyl)benzothiophenes Using Acetic Acid as a Quencher for Methyl Radical-Mediated Side Reactions. Adv. Synth. Catal. 2023, 365, 1514–1520. [Google Scholar] [CrossRef]
  126. Cukalovic, A.; Monbaliu, J.-C.M.R.; Stevens, C. Microreactor Technology as an Efficient Tool for Multicomponent Reactions. Synth. Heterocycles Via Multicomponent React. I 2010, 23, 161–198. [Google Scholar]
  127. Zhang, W.; Yi, W.-B. Pot, Atom, and Step Economy (PASE) Synthesis; Springer: Berlin/Heidelberg, Germany, 2019. [Google Scholar]
  128. Magnus Rueping, M.; Vila, C.; Bootwicha, T. Continuous Flow Organocatalytic C−H Functionalization and Cross-Dehydrogenative Coupling Reactions: Visible Light Organophotocatalysis for Multicomponent Reactions and C−C, C−P Bond Formations. ACS Catal. 2013, 3, 1676–1680. [Google Scholar] [CrossRef]
  129. Maya Shankar Singh, M.S.; Chowdhury, S. Recent developments in solvent-free multicomponent reactions: A perfect synergy for eco-compatible organic synthesis. RSC Adv. 2012, 2, 4547–4592. [Google Scholar] [CrossRef]
  130. Verma, C.; Haque, J.; Quraishi, M.A.; Ebenso, E.E. Aqueous phase environmental friendly organic corrosion inhibitors derived from one step multicomponent reactions: A review. J. Mol. Liq. 2019, 275, 18–40. [Google Scholar] [CrossRef]
  131. Zhang, X.; Smith, R.T.; Le, C.; McCarver, S.J.; Shireman, B.T.; Carruthers, N.I.; MacMillan, D.W.C. Copper-mediated synthesis of drug-like bicyclopentanes. Nature 2020, 580, 220–226. [Google Scholar] [CrossRef] [PubMed]
  132. Campo, J.; García-Valverde, M.; Marcaccini, S.; Rojoa, M.J.; Torroba, T. Synthesis of indole derivatives via isocyanides. Org. Biomol. Chem. 2006, 4, 757–765. [Google Scholar] [CrossRef]
  133. Zhang, X.; Cui, T.; Zhao, X.; Liu, P.; Sun, P. Electrochemical Difunctionalization of Alkenes by a Four-Component Reaction Cascade Mumm Rearrangement: Rapid Access to Functionalized Imides. Angew. Chem. Int. Ed. 2020, 59, 3465–3469. [Google Scholar] [CrossRef]
Molecules 28 06356 sch001
Scheme 1. Simultaneous introduction of two different heteroatom groups into alkynes.
Scheme 1. Simultaneous introduction of two different heteroatom groups into alkynes.
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Scheme 2. Considerations for the selection of unsaturated compounds for multicomponent reactions.
Scheme 2. Considerations for the selection of unsaturated compounds for multicomponent reactions.
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Scheme 3. Diselenide-mediated addition to 1-hexene using several alkynes.
Scheme 3. Diselenide-mediated addition to 1-hexene using several alkynes.
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Scheme 4. Diselenide-mediated sequential addition to ethyl propiolate and vinyl ethers.
Scheme 4. Diselenide-mediated sequential addition to ethyl propiolate and vinyl ethers.
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Scheme 5. Synthetic utility of multicomponent coupling products bearing seleno groups.
Scheme 5. Synthetic utility of multicomponent coupling products bearing seleno groups.
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Scheme 6. Strategy for multicomponent reaction incorporating radical cyclization.
Scheme 6. Strategy for multicomponent reaction incorporating radical cyclization.
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Scheme 7. (PhSe)2–induced multicomponent reaction via radical cyclization.
Scheme 7. (PhSe)2–induced multicomponent reaction via radical cyclization.
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Scheme 8. (PhTe)2-mediated dithiolative cyclization of o-alkenylphenyl isocyanide.
Scheme 8. (PhTe)2-mediated dithiolative cyclization of o-alkenylphenyl isocyanide.
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Scheme 9. (PhTe)2-mediated synthesis of multi-cyclic compounds from o-alkenylphenyl isocyanide.
Scheme 9. (PhTe)2-mediated synthesis of multi-cyclic compounds from o-alkenylphenyl isocyanide.
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Ogawa, A.; Yamamoto, Y. Multicomponent Reactions between Heteroatom Compounds and Unsaturated Compounds in Radical Reactions. Molecules 2023, 28, 6356. https://doi.org/10.3390/molecules28176356

AMA Style

Ogawa A, Yamamoto Y. Multicomponent Reactions between Heteroatom Compounds and Unsaturated Compounds in Radical Reactions. Molecules. 2023; 28(17):6356. https://doi.org/10.3390/molecules28176356

Chicago/Turabian Style

Ogawa, Akiya, and Yuki Yamamoto. 2023. "Multicomponent Reactions between Heteroatom Compounds and Unsaturated Compounds in Radical Reactions" Molecules 28, no. 17: 6356. https://doi.org/10.3390/molecules28176356

APA Style

Ogawa, A., & Yamamoto, Y. (2023). Multicomponent Reactions between Heteroatom Compounds and Unsaturated Compounds in Radical Reactions. Molecules, 28(17), 6356. https://doi.org/10.3390/molecules28176356

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