Article pubs.acs.org/accounts
Synthetic Utilization of α‑Aminoalkyl Radicals and Related Species in Visible Light Photoredox Catalysis Published as part of the Accounts of Chemical Research special issue “Photoredox Catalysis in Organic Chemistry”. Kazunari Nakajima, Yoshihiro Miyake,*,† and Yoshiaki Nishibayashi* Department of Systems Innovation, School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan CONSPECTUS: Single electron oxidation of amines provides an efficient way to access synthetically useful α-aminoalkyl radicals as reactive intermediates. After the single electron oxidation of amines, fragmentation of the resulting radical cations proceeds to give the α-aminoalkyl radicals along with generation of a proton. In the synthetic utilization of the αaminoalkyl radicals, precise control of single electron transfer is essential, because further oxidation of the α-aminoalkyl radicals occurs more easily than the starting amines and the αaminoalkyl radicals are converted into the corresponding iminium ions. As a result, photoinduced single electron transfer is quite attractive in the synthetic utilization of the α-aminoalkyl radicals. Recently, visible light-photoredox catalysis using transition metal−polypyridyl complexes and other dyes as catalysts has attracted considerable attention, where useful molecular transformations can be achieved through the single electron transfer process between the excited catalysts and substrates. In this context, MacMillan et al. (Science 2011, 334, 1114, DOI: 10.1126/ science.1213920) reported an aromatic substitution reaction of cyanoarenes with amines, where α-aminoalkyl radicals work as key reactive intermediates. Pandey and Reiser et al. (Org. Lett. 2012, 14, 672, DOI: 10.1021/ol202857t) and our group (Nishibayashi et al. J. Am. Chem. Soc. 2012, 134, 3338, DOI: 10.1021/ja211770y) independently reported reactions of amines with α,β-unsaturated carbonyl compounds, where addition of α-aminoalkyl radicals to alkenes is a key step. After these earliest examples, nowadays, a variety of transformations using the α-aminoalkyl radicals as reactive intermediates have been reported by many groups. The α-aminoalkyl radicals are usually produced from amines by single electron oxidation and the subsequent deprotonation of the C−H bond adjacent to the nitrogen atom. In addition, the α-aminoalkyl radicals are also produced from α-silylamines and αamino acids in high efficiency through desilylation or decarboxylation after the single electron oxidation. The generated α-aminoalkyl radicals are utilized in a variety of reaction systems. In fact, reactions based on the addition of αaminoalkyl radicals to alkenes and other unsaturated bonds have been extensively studied. Aromatic and other types of substitution reactions have also been investigated. Some of these transformations are achieved by combination of photoredox catalysts and other catalysts such as Brønsted and Lewis acids, organocatalysts, and transition metal catalysts. It is also noteworthy that the enantioselective reactions have been accomplished by combination of photoredox catalysts and chiral catalysts. The strategy for the generation of α-aminoalkyl radicals can be applied to utilize other types of alkyl radicals. In the generation of α-aminoalkyl radicals, the bond dissociation of the radical cations occurs at the α-position of amines. In relation to this process, synthetic utilization of other types of alkyl radicals generated by the bond dissociation of the radical cations at a remote position has been also investigated. These alkyl radicals have been applied to molecular transformations in a manner similar to the αaminoalkyl radicals. Recently, organic synthesis using the α-aminoalkyl radicals and related alkyl radicals has been studied extensively. In this Account, we describe recent advances in photoredox-catalyzed synthetic utilization of these alkyl radicals.
1. INTRODUCTION
organic chemistry,1,2 because synthetically useful radical species
Single electron oxidation of neutral organic compounds is a straightforward and efficient way to access highly reactive radical cationic intermediates. Among various known reactivities of radical cations, fragmentation into neutral radical species and cationic species is quite attractive from the viewpoint of synthetic
can be obtained by dissociation of inert bonds such as carbon−
© XXXX American Chemical Society
hydrogen (C−H) and carbon−carbon (C−C) bonds. Received: May 25, 2016
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Accounts of Chemical Research Scheme 2. Generation of α-Aminoalkyl Radicals
Among the functional groups in organic compounds, amines are one of the most electron rich ones; therefore, easy access to the corresponding radical cations has been eagerly studied. A representative oxidative fragmentation process of amines is shown in Scheme 1. Neutral amines are converted into the Scheme 1. Radical Cation Fragmentation of Amines
radical cations via single electron oxidation. After generation of the radical cation, the C−H bonds adjacent to the nitrogen atom are greatly acidified (pKa ca. 8), and deprotonation easily occurs to give α-aminoalkyl radicals and a proton.3,4 If the electron transfer is reversible in the reaction system, the inverse process to reproduce the starting amines from α-aminoalkyl radicals is possible, though such a process is slow.5 Another important feature of this process is the second oxidation of α-aminoalkyl radicals. α-Aminoalkyl radicals are more readily oxidized (E1/2 = −1.03 V vs SCE) than the starting amines (E1/2 = +1.15 V vs SCE) and are rapidly converted into the iminium ions in the presence of an excess amount of oxidants.6 Therefore, precise control of single electron transfer is key to utilize α-aminoalkyl radicals as reactive intermediates. Photoinduced electron transfer between excited molecules and amines is a reliable method for synthetic utilization of αaminoalkyl radicals. Synthetic use of α-aminoalkyl radicals under UV light irradiation has been studied for decades. This process is typically initiated by the direct excitation of substrates or via the employment of catalytic or stoichiometric amounts of chromophores.7−10 On the other hand, visible light-mediated reaction systems with transition metal−polypyridyl complexes and other dyes (photoredox catalysts) have emerged in recent years as a powerful synthetic tool for organic chemistry.11−13 Typical photoredox catalysts are summarized in Figure 1.
2a). Additionally, desilylation of α-silylamines or decarboxylation of α-amino acids affords the corresponding α-aminoalkyl radicals more efficiently (Scheme 2b,c).9,17
3. ADDITION TO UNSATURATED BONDS 3.1. Addition to Alkenes
Among the vast range of reactivity of α-aminoalkyl radicals, addition to electron-deficient alkenes is the most densely studied transformation in both UV and visible light-mediated reaction systems.9,10,17 Photoredox-catalyzed reactions of this type were first accomplished by Pandey and Reiser et al. (Scheme 3) and Scheme 3. Reactions of 1,2,3,4-Tetrahydroisoquinolines with α,β-Unsaturated Carbonyl Compounds
our group independently (Scheme 4).15,16 Reactions of amines with α,β-unsaturated carbonyl compounds in the presence of photoredox catalysts under visible light illumination gave the corresponding radical addition products. In the report by Pandey and Reiser et al., the scope of amines was limited to N-aryl1,2,3,4-tetrahydroisoquinoline derivatives, while our group succeeded in the use of various cyclic and acyclic amines. From a mechanistic point of view, determination of the quantum yield is quite important. Previously, Hoffmann et al. reported a similar reaction of trialkylamines with furanones catalyzed by 4,4′-dimethoxybenzophenone under UV light irradiation, where the quantum yield is above unity (Φ = 4), clearly indicating the involvement of a radical chain mechanism.10,18 On the other hand, we determined the quantum yield of our photoredox-catalyzed reaction system to be below unity (Φ = 0.32). In addition, we also examined the reactions in the presence of common radical initiators under heating conditions, and the corresponding products were not obtained. As a result, we concluded that the contribution of radical chain mechanism is negligible in our reaction system. A plausible reaction pathway is shown in Scheme 4. The initial step is the single electron oxidation of amines by the
Figure 1. Typical photoredox catalysts.
MacMillan et al. reported photoredox-catalyzed aromatic substitution reactions of cyanoarenes with amines via αaminoalkyl radicals.14 Pandey and Reiser et al. and our group, independently, reported reactions of α,β-unsaturated carbonyl compounds with amines, where the addition of α-aminoalkyl radicals to alkenes is a key step.15,16 After these earliest examples, a variety of photoredox-catalyzed reactions via α-aminoalkyl radicals have been reported to date. In this Account, we describe recent advances in visible light-mediated synthetic utilization of α-aminoalkyl radicals and the related species.
2. GENERATION OF α-AMINOALKYL RADICALS Representative reaction pathways to access α-aminoalkyl radicals are shown in Scheme 2. As mentioned above, the single electron oxidation of amines and subsequent deprotonation of the C−H bond α to the nitrogen atom is a well-known process (Scheme B
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Accounts of Chemical Research Scheme 4. Reactions of Amines with α,β-Unsaturated Carbonyl Compounds
Melchiorre et al. have reported asymmetric variants of reactions of cyclic enones with amines based on the combination of photoredox catalysts and chiral organocatalysts bearing a carbazole moiety (Scheme 6).27 In this reaction system, cyclic Scheme 6. Asymmetric Reactions of Amines with Cyclic Enones
photoexcited catalysts (*cat) to give α-aminoalkyl radicals (A) after deprotonation along with the reduced catalyst (cat−). Subsequent addition of the α-aminoalkyl radical A to the electron-deficient alkene occurs. The resulting radical intermediates (B) are reduced by cat−, and subsequent protonation affords the corresponding addition products. It is also noteworthy that reduction of the radical intermediates B to the corresponding anion by cat− is extremely exothermic.19,20 After the publication of these works, several groups also reported similar reactions under modified reaction conditions.21−23 In addition, Oguri et al. reported an intramolecular cyclization in the diversification of an indole alkaloid mimetic structure (Scheme 5a).24 Xu and Li et al. reported the reaction of amines with allenoates (Scheme 5b),25 while Melchiorre et al. reported the reaction between amines and 2-vinylpyridine derivatives (Scheme 5c).26
enones are activated by the chiral organocatalyst by formation of the iminium ions. After the enantioselective addition of the αaminoalkyl radicals to the iminium ions, the resulting α-iminyl radicals are stabilized by intramolecular electron transfer from the carbazole moiety. The catalytic cycle is completed by the reduction of the resulting radical cationic carbazole moiety. The quantum yield of this reaction system was determined to be Φ = 0.4. Our group has succeeded in the synthetic utilization of αaminoalkyl radicals generated from α-silylamines toward addition to α,β-unsaturated carbonyl compounds (Scheme 7).28 In this reaction system, α-aminoalkyl radicals were generated selectively by dissociation of the C−Si bond even in the use of trialkylamine-derived α-silylamines having multiple C−H bonds. Furthermore, the quantum yield of the typical reaction is quite high (Φ = 0.68), reflecting the high generation efficiency of α-aminoalkyl radicals from α-silylamines. In the use of α-silylamines, desilylation leads to the formation of α-aminoalkyl radicals (Scheme 2b). We also succeeded in the isolation of a silyl enol ether as the primary product from the reaction system, where the silyl group is not just an auxiliary group, but it is also incorporated into the products in a useful form. In advance of our report, Mariano et al. had extensively studied reactions of α-silylamines with α,β-unsaturated carbonyl compounds under UV light irradiation.9,17 In these reports, however, silyl enol ethers could not be generated because an alcoholic solvent is used to capture silyl fragments. Our group also succeeded in the utilization of α-aminoalkyl radicals derived from α-silyl secondary amines (Scheme 8).29 After reactions of α-silyl secondary amines with α,β-unsaturated
Scheme 5. Reactions of Amines with Various Types of Alkenes
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Accounts of Chemical Research Scheme 7. Reactions of α-Silyl Amines with α,β-Unsaturated Carbonyl Compounds
Scheme 9. Photoredox- and Chiral Lewis Acid-Catalyzed Reactions of α-Silylamines with α,β-Unsaturated Carbonyl Compounds
Scheme 10. Reactions of α-Silylamines with 3Alkylideneinodol-2-ones in the Presence of a Chiral Template Scheme 8. Utilization of α-Silyl Secondary Amines in the OnePot Synthesis of Heterocycles
esters under visible light-photoredox catalysis, treatment of the reaction mixture with potassium tert-butoxide produces the corresponding γ-lactam via intramolecular cyclization. The photochemical reactions proceeded in good quantum yield (Φ = 0.21). The synthesis of pyrroles through the reaction of amines with α,β-unsaturated ketones were also successful. It is noteworthy that synthetic utilization of α-aminoalkyl radicals derived from secondary amines has been strictly limited even in the UV-mediated reaction systems, probably due to the competing side reactions to form aminyl radicals via deprotonation of the N−H bond of the radical cations.30 An asymmetric variant of this type of reaction was achieved by Yoon et al. through employment of both photoredox catalysts and chiral Lewis acid catalysts (Scheme 9).31 Reactions of αsilylamines with α,β-unsaturated amide derivatives in the presence of both [Ru(bpy)3]Cl2 and Sc(III)-PyBox catalyst afforded the corresponding addition products with excellent enantioselectivity. Bach et al. also succeeded in the enantioselective reactions of α-silylamines with 3-alkylideneindolin-2-ones in the presence of a chiral template (Scheme 10).32 In this reaction system, the chiral template induces the enantioselective addition of α-aminoalkyl radicals to 3-alkylideneindolin-2-ones through hydrogen bonding between the chiral template and 3alkylideneindolin-2-ones. As shown in Scheme 2c, α-amino acids are also useful to generate α-aminoalkyl radicals. The reaction of α-amino acids
with electron deficient alkenes via decarboxylation was reported by MacMillan et al. (Scheme 11).33 Synthetic utilization of other aliphatic carboxylic acids via decarboxylation was also achieved under the same reaction conditions. Koike and Akita et al. found that the photoredox-catalyzed single electron oxidation of alkyl borates affords the correspondScheme 11. Reactions of α-Amino Acids with α,β-Unsaturated Carbonyl Compounds
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Accounts of Chemical Research ing alkyl radicals.34 In the presence of a photoredox catalyst, reactions of aminomethylborates with α,β-unsaturated esters gave the corresponding addition products (Scheme 12).35
Scheme 14. Reactions of Amines with Azodicarboxylate Esters
Scheme 12. Reactions of Aminomethylborates with α,βUnsaturated Carbonyl Compounds
that the reaction proceeds via radical−radical coupling beween αaminoalkyl radicals and radical anions of azodicarboxylate esters. Li et al. reported reactions of amines with isocyanates and isothiocyanates (Scheme 15).41 A photoredox catalyst of iridium complex bearing the picolinato ligand was quite effective in this reaction system.
After the addition of α-aminoalkyl radicals to alkenes, subsequent transformations utilizing the newly generated radical can be performed. Yu and Bian et al. reported oxidative cyclization of N,N-dialkylanilines with maleimides via αaminoalkyl radicals (Scheme 13).36 In this reaction, alkyl radical
Scheme 15. Reactions of N,N-Dimethylanilines with Isocyanates or Isothiocyanates
Scheme 13. Oxidative Cyclization Reactions of N,NDimethylanilines with Maleimides
Asymmetric reactions via addition of α-aminoalkyl radicals to imines were achieved by Ooi et al. through the combination of a photoredox catalyst and a chiral phosphonium catalyst (Scheme 16).42 In this reaction, single electron reduction of the imines Scheme 16. Enantioselective Addition of Amines to Imines
intermediates generated by addition of α-aminoalkyl radicals to maleimides are trapped by the neighboring aniline ring. Subsequent oxidation and deprotonation give the corresponding 1,2,3,4-tetrahydroquinoline derivatives. Similar reactions under modified reaction conditions have been reported by several groups.21,37−39 3.2. Addition to Nitrogen-Containing Double Bonds
After our reports on reactions of amines with electron-deficient alkenes, we succeeded in the reaction of amines with azodicarboxylate esters (Scheme 14).40 In this reaction, the use of cyclic amines such as 1,2,3,4-tetrahydroquinolines and indolines gave the corresponding amination products in high yields compared with acyclic amines. The quantum yield of a typical reaction was determined to be Φ = 0.27. Stern−Volmer analyses revealed that both the oxidation of amines and the reduction of azodicarboxylate esters were possible, indicating E
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Accounts of Chemical Research occurred to give radical anions along with the formation of αaminoalkyl radicals by oxidation of the amines. After the formation of an ion pair between the imine radical anion and phosphonium catalyst, enantiocontrolled addition of α-aminoalkyl radical is achieved. Rueping et al. also reported the reactions of amines with N-arylimines in the presence of lithium carbonate (Scheme 17a),43a while, in the presence of benzoic acid, the
Scheme 18. Intramolecular Cyclization Reactions Based on Addition of α-Aminoalkyl Radicals to Alkynes
Scheme 17. Reactions of Amines with Imines or Aldehydes
Scheme 19. Functionalization of Fullerene and Corannulene Based on Addition of α-Aminoalkyl Radicals
reactions of amines with aromatic aldehydes were also successful. Meggers et al. reported the asymmetric variant of reactions of trifluoromethylketones with amines catalyzed by chiral iridium complex (Scheme 17b).43b The quantum yield of the typical reaction was determined to be 0.09.
Although addition reactions of alkyl lithiums and dihalocarbenes to corannulene have already been reported,47,48 this is the first successful example of addition of radicals to corannulene.
3.3. Addition to Alkynes
5. SUBSTITUTION REACTIONS
Compared with the reactions of amines with alkenes and other double bonds, reactions with alkynes are limited. Zhou et al. reported an intramolecular cyclization under air as shown in Scheme 18.44 After the addition of α-aminoalkyl radicals to the alkyne moiety, the resulting vinyl radicals were trapped by dioxygen to give the corresponding indol-3-yl ketones.
5.1. Aromatic Substitution Reactions
MacMillan et al. reported photoredox-catalyzed aromatic substitution reactions of cyanoarenes with amines via αaminoalkyl radicals (Scheme 20).14,49 In this reaction, a radical−radical coupling reaction between cyanoarene radical anions and α-aminoalkyl radicals takes place followed by decyanation to afford the alkylated cyanoarenes. The use of heteroaryl halides instead of cyanoarenes was also achieved under similar reaction systems.50,51 Synthetic utilization of α-aminoalkyl radicals in combined reaction system of photoredox catalysts and nickel catalysts was reported by Doyle and MacMillan et al. They reported the first dual catalytic system to employ both photoredox and nickel catalysts to perform a cross-coupling reaction between an aryl halide and an α-aminoalkyl radical (Scheme 21a).52 Furthermore, an asymmetric variant of this reaction was achieved by using a chiral nickel catalyst (Scheme 21b).53 Molander et al. also reported a photoredox- and nickel-catalyzed cross-coupling
4. ADDITION TO AROMATIC RINGS Utilization of α-aminoalkyl radicals toward photoredox-catalyzed functionalization of π-conjugated aromatic compounds has been achieved by our group. Reactions of fullerene (C60) with αsilylamines in the presence of photoredox catalysts and water in 1,2-dichlorobenzene under illumination of visible light (λ = 440 nm) gave the corresponding addition products in good yields (Scheme 19a).45 The quantum yield of a typical reaction is determined to be Φ = 4 × 10−3. Our group also succeeded in the functionalization of corannulene by α-aminoalkyl radicals (Scheme 19b).46 The quantum yield of a typical reaction is determined to be Φ = 0.06. F
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Accounts of Chemical Research Scheme 20. Reactions of Amines with Cyanoarenes
Scheme 21. Reactions of Amines with Aryl Bromides
between aryl bromides and aminomethylborate derivatives (Scheme 21c).54,55 Stephenson et al. reported oxidative coupling reactions of nitrogen heterocycles with amines via α-aminoalkyl radicals as key reactive intermediates (Scheme 22).56 In this reaction, addition of α-aminoalkyl radicals to nitrogen heterocycles and subsequent oxidative aromatization are key steps. 5.2. Vinylic Substitution Reactions
Noble and MacMillan succeeded in the photoredox-catalyzed vinylic substitution reactions of vinyl sulfones with amines (Scheme 23a).57 Instead of vinyl sulfones, vinyl halides could be used to achieve the same transformation with nickel and photoredox dual catalysis (Scheme 23b).58 5.3. Allylic Substitution Reactions
Photoredox-catalyzed allylic substitution reactions were reported by Xu and Li et al.23 Their group applied allyl acetate-type α,βunsaturated esters in the reaction of amines (Scheme 24). In this reaction, elimination of the acetoxy group occurs after the addition of α-aminoalkyl radicals to alkenes and subsequent single electron reduction of the resulting radical species. Lu and Xiao et al. have succeeded in the allylic substitution reactions through the combination of photoredox and palladium catalysts (Scheme 25).59 In this reaction, generation of allyl radicals by the reduction of π-allyl palladium intermediates is considered to be a key step, and radical−radical coupling between allyl radicals and α-aminoalkyl radicals gives the corresponding products.
Scheme 22. Preparation and Diversification of JAK2 Inhibitor LY2784544
5.4. Substitution Reactions of Alkynyl Halides
UV light (315−400 nm) rather than visible light (fluorescent light bulb).
Reactions of alkynyl iodides with amines were reported by Hashmi et al. to give α-alkynyl amines (Scheme 26).60 The reaction pathway is proposed to go through a radical−radical coupling between α-aminoalkyl radicals and alkynyl radicals. In this reaction, a bimetallic gold complex was used as a photocatalyst, and the reactions were performed under sunlight. However, it is noteworthy that the reactions were promoted by
6. SYNTHETIC UTILIZATION OF ALKYL RADICALS GENERATED AT THE REMOTE POSITIONS On generation of α-aminoalkyl radicals, deprotonation of the radical cations occurs at the α-position of amines as shown in Scheme 2. Contrary to this reaction process, bond dissociation at a remote position is also attractive to generate reactive radical G
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Accounts of Chemical Research Scheme 23. α-Vinylation Reactions of Amines with Vinyl Sulfones and Vinyl Halides
Scheme 26. Substitution Reactions of Alkynyl Iodides with Amines
Scheme 27. Generation of Alkyl Radicals at a Remote Position
Scheme 28. β-Functionalization of Aldehydes via Enamines
Scheme 24. Allylic Substitution Reactions of Allyl AcetateType α,β-Unsaturated Carbonyl Compounds with Amines
affords the corresponding radical cation. Subsequent deprotonation of the C−H bond occurs at the β-position of the original aldehyde to give the corresponding alkyl radical as reactive species. The generated alkyl radicals were utilized in aromatic substitution reactions of cyanoarenes in a manner similar to the α-aminoalkyl radicals (Scheme 28).61 Additionally, this strategy was applied to reactions with electron-deficient alkenes and imines.62,63 Our group succeeded in the generation and utilization of paraaminobenzyl radicals by oxidation of para-aminophenylacetic acids toward the addition to electron-deficient alkenes (Scheme 29).64 In this reaction system, introduction of para-amino groups in phenylacetic acids is critical for the decarboxylation to occur, indicating that decarboxylation is triggered by oxidation of an amine moiety. The quantum yield of the typical raction was determined to be Φ = 0.21. Tunge et al. reported allylic substitution reactions via decarboxylation of allyl para-aminophenylacetate via dual photoredox and palladium catalysis (Scheme 30).65 Oxidative addition of palladium across the allyl ester gives the aminophenylacetate, which is subsequently oxidized and converted into the corresponding benzyl radicals via decarboxylation, while the resulting π-allyl palladium is reduced to give the allyl radical. The product was obtained by a radical−radical coupling between these two species.
Scheme 25. Photoredox- and Palladium-Catalyzed Allylic Substitution Reactions
species (Scheme 27). In this section, reactions using such related radical species are described. MacMillan et al. reported β-functionalization of aldehydes and ketones based on oxidation of enamines generated by secondary amine catalysts (Scheme 28).61−63 This reaction proceeds through the condensation of the secondary amine catalyst with the aldehyde. Then, single electron oxidation of the enamine H
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Accounts of Chemical Research Scheme 29. Utilization of para-Aminobenzyl Radicals via Decarboxylation
other cations. However, synthetic use of the reverse process, where nitrogen-containing fragments are converted into cations along with formation of reactive alkyl radicals, has not been reported until recently. Our group has succeeded in the utilization of 4-alkyl-1,4-dihydropyridines as alkylation reagents as shown in Scheme 32.67 In this reaction system, various alkyl radicals can be generated along with formation of pyridinium cations. Scheme 32. Single Electron Oxidation-Induced C−C Bond Cleavage of 4-Alkyl-1,4-Dihydropyridines
Scheme 30. Photoredox- and Palladium-Catalyzed Allylic Substitution Reactions via Decarboxylation
Our group has developed aromatic substitution reactions of cyanoarenes with 4-alkyl-1,4-dihydropyridines as alkylating reagents (Scheme 33).67 In this reaction system, benzyl radicals, Scheme 33. Aromatic Substitution Reactions of Cyanoarenes with 4-Alkyl-1,4-Dihydropyridines
Pandey et al. reported the utilization of benzylic radicals at the γ-position of amines (Scheme 31).66 Reactions of a cyclic amine, N-methyl-9,10-dihydroacridine, with electron deficient alkenes gave the remote C−H functionalized products. Scheme 31. C−H Functionalization of 9,10-Dihydroacridine heteroatom-substituted alkyl radicals, and simple secondary alkyl radicals can be used to give the corresponding products in high yields. The quantum yield of the typical reaction was determined to be Φ = 0.19, indicating that these reactions proceed in similar efficiency to the utilization of α-aminoalkyl radicals.
8. SUMMARY In this Account, we have described the photoredox-catalyzed utilization of α-aminoalkyl radicals and related species based on the oxidative fragmentation of amines. Photochemical single electron transfer process of amines with excited-state molecules is quite effective to generate these reactive radical species. Photoredox catalysis has been extensively studied and combined with organocatalysts, transition metal catalysts, and Brønsted and Lewis acids to perform complex transformations. These efforts will further expand the synthetic utility of α-aminoalkyl radicals and the related species.
7. SYNTHETIC UTILIZATION OF ALKYL RADICALS GENERATED BY OXIDATION OF 4-ALKYL-1,4-DIHYDROPYRIDINES As discussed above, photoredox-catalyzed oxidative fragmentation of amines is an efficient way to generate α-aminoalkyl radicals and other related radical species. In this fragmentation process of radical cations into alkyl radicals and cations, nitrogencontaining fragments are converted into alkyl radicals such as αaminoalkyl radicals after deprotonation or the generation of
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DOI: 10.1021/acs.accounts.6b00251 Acc. Chem. Res. XXXX, XXX, XXX−XXX
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Accounts of Chemical Research *E-mail:
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Present Address †
Y.M.: Department of Applied Chemistry Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan. Notes
The authors declare no competing financial interest. Biographies Kazunari Nakajima received his Ph.D. in 2013 from the University of Tokyo under the direction of Professor Yoshiaki Nishibayashi. He has been an assistant professor at the University of Tokyo since 2013. Yoshihiro Miyake received his Ph.D. in 2002 from Kyoto University under the supervision of Professor Sakae Uemura. He became an assistant professor at Tokyo Metropolitan University in 2002 and moved to the University of Tokyo in 2005. Since 2013, he has been an associate professor at Nagoya University, working with Professor Hiroshi Shinokubo. Yoshiaki Nishibayashi received his Ph.D. in 1995 from Kyoto University under the supervision of Professor Sakae Uemura. He became an assistant professor at the University of Tokyo in 1995 and moved to Kyoto University in 2000. In 2005, he became an associate professor at the University of Tokyo as PI. Since 2016, he has been a full professor at the University of Tokyo. His current research interests are focused on organic and organometallic chemistry.
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ACKNOWLEDGMENTS This work was supported by CREST, JST. We thank JSPS KAKENHI Grant Numbers 26288044, 15H05798, 26870120, 16K05767, and 16KT0160 from the Japan Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).
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