Construction of C-N Bond via Visible-Light-Mediated Difunctionalization of Alkenes

In the last few years, the photo-redox process via single-electron transfer (SET) has received substantial attention for the synthesis of targeted organic compounds due to its environmental friendliness and sustainability. Of late visible-light-medi-ated difunctionalization of alkenes has gained much attention because of its step economy, which allows the consecutive installation of two functional groups across the C=C bond in a single operation. The construction of N -containing compounds has always been important in organic synthesis. Molecules containing C-N bonds are found in many building blocks and are important precursors to other functional groups. Meanwhile, C-N bond formation via the addition of the C=C double bond is gaining prominence. Therefore, considering the influence and synthetic potential of the C-N bond, here we provide a summary of the state of the art on visible-light-driven difunctionalizations of alkene. We hope that the construction of the C-N bond via visible-light-mediated difunctionalization of alkenes will be useful for medicinal and synthetic organic chemists and will inspire further reaction development in this interesting area.


Introduction
Of late, photo-redox catalysis has been utilized as a flexible and demanding synthetic protocol in the realm of modern organic chemistry due to its environmental friendliness and sustainability [1]. This visible-light-driven protocol essentially affords a large number of nitrogen centred radicals via a single electron transfer (SET) process or energy transfer process under mild reaction conditions, compared to the traditional radical reactions that use high-energy ultraviolet (UV) light or highly toxic and expensive radical initiators [2]. Therefore, visible-lightmediated photo-redox catalysis has been widely applied for the synthesis of natural products, synthetic methodologies, enantioselective catalysis, and polymerization reactions. The success of any photochemical reactions relies on the ability of photocatalysts, usually transition-metal based complexes, organic dyes or heterogeneous semiconductors which promote single-electron transfer (SET) with organic molecules upon excitation with visible light [3]. An alkene difunctionalization can introduce two functional groups in a signal operation across the double bond (Figure 1) [4]. In this context, the radical-mediated C-N bond formation has emerged as a powerful strategy to construct valuable molecules that have found application in different fields [5]. Therefore, this chapter focuses mainly on the difunctionalization of C=C bonds emphasizing the C-N bond formation using visible-light photo-redox catalysis.

Photocatalysts
Photocatalysts are organic or inorganic substances that absorb light and get excited to a higher energy level and transfer this energy to a reacting partner thereby triggering a chemical reaction. Few commonly used photocatalysts for the difunctionalization of alkenes [6] are shown in (Figures 2 and 3). These photocatalysts can be divided into two categories: (A) Transition-metal complexes and (B) Organic dyes.
A. Transition-Metal Complex Photocatalysts: The widely used visible-lightmediated photocatalyst are well-defined ruthenium (II) polypyridine complexes or Ir-cyclometalated derivatives. They facilitate redox reactions due to their ability to cause single electron transfer (SET) under a mild reaction condition in the presence of a visible light source [7].
B. Organic Dye: Since the beginning of organic synthesis, the formation of carbon-heteroatom bonds in a controlled and efficient manner is the heart of organic synthesis. Organic dyes using visible light has been playing a key role  in the formations of carbon-heteroatom bond in the difunctionalization of alkene. Compared to metal-containing photocatalyst, organic dyes require mild reaction conditions as it uses visible light of low power source and therefore the number of organic dyes have been employed as photo redox catalysts [8].

General mechanism
In general, at first, a photocatalyst (P.C) is converted to its excited state (*P.C) by irradiation of visible light and undergoes an energy transfer or a redox path. In the reductive quench path, the (*P.C) absorbs an electron from the electron donor to produce a reduced photo catalyst (P.C À ). Which is a good reductant for the oneelectron reduction of the substrate (S) or transition metal (M n+ ). Simultaneously, the photocatalyst is regenerate to the ground state and the reduced species radical anion (S À. ) or M (nÀ1)+ undergo further reaction. In the oxidative quench pathway, the (*P.C) loses an electron to the electron acceptor to generate an oxidized photo catalyst (P.C + ) which is a good oxidant for the one-electron oxidation of the substrate (S) or transition metal (M n+ ). The photo catalyst is regenerated and oxidative species radical cation (S +. ) or M (n + 1) + could undergo further transformations. Both of these cycles produce D +• and A À• radicals in a single operation through SET to  make the overall process neutral. Here, the reductive path refers to the reduction of the excited photo catalyst (*P.C) where the external electron donor D is oxidized, whereas the oxidative path defines oxidation of the excited photo catalyst (*P.C) with concomitant reduction of the external electron acceptor A (Figure 4).

Ru-catalyzed C-N bond formations
Several methodologies have been developed for various difunctionalizations of which transition-metal based photocatalytic C-N bond formations is in high demand. Dagousset et al. in 2014 reported a metal-catalyzed azido-and aminotrifluoromethylation of alkenes (2) from alkene (1), azidotrimethylsilane and Umemoto's reagent ( Figure 5) [9]. The radical-mediated difunctionalization of alkene is promoted under the irradiations of blue LEDs in the presence of a Rucatalyst. According to the proposed reaction mechanism in the presence of visible light the catalyst Ru(bpy) 3 2+ form an excites species [Ru(bpy) 3 2+ ] *which generates the CF 3 radical via a single electron transfer (SET) from Umemoto's reagent. The CF 3 radical reacts with the alkene (1) providing the radical species with subsequent oxidation to a cation via a SET process from [Ru(bpy) 3 3+ ]. Finally, the nucleophilic addition of this β-trifluoromethylated carbocation by TMSN 3 or amine afforded the corresponding trifluoro methylated product (2).
Yasu et al. in 2013 reported a metal-catalyzed facile intermolecular aminotrifluoromethylation of alkenes (Figure 6) [10]. This is a highly efficient bifunctional reaction taking place between alkene (3), and Umemoto's reagent in MeCN. Here MeCN acts as a N-nucleophile, known as an aminative carbocation trap agent (Ritter-type reaction) and Umemoto's reagent serving as the CF 3 source. The reaction takes place via initial SET processes in the presence of blue LEDs through excitation of [Ru(bpy) 3 ] 2+ to *[Ru(bpy) 3 ] 2+ which reduce the Umemoto's reagent to produce a CF 3 radical. Then this CF 3 radical attacks alkene (3) to give a radical which is further oxidized by [Ru(bpy) 3 ] 3+ to form a trifluoromethylated carbocation through another SET process. Finally, the additions of RCN, to the   (Figure 7) [11]. Herein, the CF 3 radical is generated from the Togni reagent via a reductive photo redox path under a single electron transfer process. Then the addition of enecarbamates (5) generates α-amido radical which is rapidly oxidized to an acyliminium cation by a SET process. Finally, nucleophilic additions of NaN 3 affords the product (6).
Bearing the importance of C-N bonds in mind Yang et al. in 2020 developed an efficient alkylazidation (8) using alkene (7), sodium azide and heteroareniumsalts as functionalized alkyl reagents for the synthesis of 2-azido-1-(1,4-dihydropyridin-4-yl)-ethane's (8). This reaction permits the incorporation of both azido and 1,4dihydropyridin-4-yl group via difunctionalization of alkenes to construct C-C and C-N bonds in a single operation (Figure 8) [12]. The [Ru(bpy) 3 ] 2+ specie is excited to [Ru(bpy) 3 ] 2+ * by irradiated it with visible-light and undergoes single-electron transfer (SET) with NaN 3 to form an azido radical (N 3 ). The addition of azido radical across the C=C bond of alkene (7) generates an alkyl radical which is followed by the addition of the pyridinyl ring of pyridinium and finally, reductions by the [Ru(bpy) 3 ] + species gives a product (8) and regenerates the active catalyst.
Yu et al. in 2016 disclose a Ru-catalyzed visible-light-mediated synthesis of azotrifluoromethylation (10) in the presence of alkenes (9) with aryldiazonium salts and sodium trifluoromethanesulfinate (Figure 9) [13]. This reaction is successful for unactivated alkene. Both electron-donating and electron-withdrawing groups of alkene and aryldiazonium salts give their product (10) in good yields. These trifluoromethylated azo products are useful building blocks for many heterocycles and nitrogen-containing compounds. As per the suggested mechanism in (Figure 9) in the presence of blue light, photoexcitation of the photocatalyst   [Ru(bpy) 3 ] 2+ generates the excited state *[Ru(bpy) 3 ] 2+ species. This active species is transferred into the oxidizing photocatalyst [Ru(bpy) 3 ] 3+ via SET oxidation by the phenyldiazonium salt. This active species serves as a strong oxidant to oxidize Langlois' reagent to produce CF 3 radical upon removal of SO 2 and returning the photocatalyst to its ground state. At this time, the CF 3 radical undergoes addition to the alkene (9)  Since vicinal diamine are found in many pharmaceuticals and various biologically active compounds hence the development of newer methodologies is deemed worthy. Considering their biological importance and ongoing demand Govaerts et al. in 2020 demonstrated a Ru-catalyzed diamination of alkene (11) in the presence of blue LEDs (Figure 10) [14]. This methodology exploits the generation of aminium radicals from the in situ generated N-chloroamines and their capability to react with alkenes via anti-Markovnikov addition.
According to the depicted mechanism ( Figure 10 (Figure 11) for the synthesis of functionalized amide (14) using diazonium salt as the cheap and environment-friendly arylation partner and alkene (13). [15] The photo Meerwein arylation reaction is applied only for the formation of aryl-alkene coupling products. As suggested in the mechanism, initially an aryl radical is formed via a single-electron transfer (SET) from the excited state of the photocatalyst [Ru(bpy) 3 ] 2 + * to a diazonium salt. Then the addition of aryl radical to alkene (13) generates another radical intermediate which undergoes oxidation to provide a carbenium species. Finally, the attack of a nitrile (R 3 CN) to the carbenium species followed by hydrolysis gives the amino-arylated product (14).
Considering the biological importance of sulfoximines containing compounds, Prieto et al. in 2019 demonstrated a method for the formation of N-chloro Sfluoroalkyl sulfoximines (16) from alkene (15) and sulfoximine through an atom transfer radical addition (ATRA) mechanism. A broad reaction scope was demonstrated, and various functionalised sulfoximines were well tolerated in the present protocol ( Figure 12) [16]. Herein the photoexcited catalyst reacts with sulfoximine by SET reduction to give the sulfoximidoyl radical which is then followed by reaction with the alkene providing the alkyl radical. At this time, two different paths are possible, one is via the radical-chain path and another the catalytic path. In the radical-chain pathway the alkyl radical abstracts a chlorine atom from sulfoximine to give the compound (16) and generate a new sulfoximidoyl radical. In the catalytic pathway, the intermediate alkyl radical undergo oxidation by the   oxidized form of PC into a cationic species and restore the photocatalyst. Finally, the addition of chlorine atom to the cationic species afforded the compound (16).
Ouyang et al. in 2018 established an elegant method in which a photo-induced three-component reaction of styrenes (17) with alkyl N-hydroxyphthalimide (NHP) esters and amine leads to 1,2-alkylamine (18) (Figure 13) [17]. In this reaction, the alkyl NHP esters act as an alkylating agent to give 1,2-alkyl amine products from their respective alkenes. The plausible mechanism involves a visiblelight excitation of the photo redox catalyst thereby decomposing the alkyl NHP ester to an alkyl radical, CO 2 , and phthalimide anion. Then the addition of alkyl radical across the C=C bond of arylalkene (17) generates another alkyl radical which upon single electron transfer through oxidation of the [Ru(bpy) 3 ] 3+ species provide the alkyl cation. Finally, the nucleophilic attack of amine to the cationic species delivers the final product (18).  (19) by photo redox catalysis (Figure 14) [18]. Here N-protected 1-aminopyridinium salt is the key compound that provides an amidyl radical precursor in the presence of Ir-photocatalyst. The reaction proceeds via an Ir-catalyzed radical-mediated path in the presence of acetone and water under the irradiations of blue LEDs providing difunctionalized alkenes. The proposed mechanism is shown in (Figure 14). In the presence of visible light, the photocatalyst Ir III is excited to *Ir III , which undergoes single electron transfer (SET) to an aminopyridinium to provide a stabilized radical (A) and a highly oxidizable Ir species Ir IV . The generated amidyl radical from intermediate (A) reacts with alkene (19) in a regiospecific manner to give a radical intermediate (B). Then Ir III is oxidized to form an Ir IV species and afford β-amino carbocation intermediate (C)  and regenerate the Ir photocatalyst to its ground state Ir III . Finally, the nucleophilic attack of H 2 O to the carbocation intermediate (C) produce the product 1,2aminoalcohol (20).

Ir-catalyzed C-N bond formations
Xu and Cai in 2019 reported a metal-catalyzed visible-light-mediated difunctionalization of alkene (21) where BrCF 2 CO 2 Et and amines are the coupling partner (Figure 15) [19]. The present strategy is equally successful for electron-poor, electron-rich, and internal alkenes. The Csp 3 -Csp 3 and Csp 3 -N bonds are simultaneously formed under mild conditions. According to the proposed mechanism in (Figure 15) initially, in the presence of visible light, fac-Ir III (ppy) 3 is excited to fac-Ir III (ppy) 3 *, which then reacts with BrCF 2 CO 2 Et by the SET pathway to generate the ethyl difluoroacetate radical (A) and the oxidized photocatalyst fac-Ir IV (ppy) 3 (Figure 17) [21]. These reactions take place in the presence of tert-butanol and irradiations of 90 W blue LEDs. Electron-withdrawing and electron-donating group of alkene and cyanopyridine react smoothly to give the product (26). According to the proposed mechanism, irradiation of Ir(ppy) 2 (dtbbpy)PF 6 produce an excited state Ir* which would capture a single-electron from azide to generate the azido radical intermediate (A) and reducing photocatalyst Ir II (27) in the presence of N-aminopyridinium and TMSNCS to affords 1,2aminoisothiocyanation products (28) in high chemo-and regio-selective manner with broad substrate scope and good functional group tolerance (Figure 18) [22]. According to the proposed mechanism ( Figure 18 (Figure 19) [23]. This visible-light-mediated vicinal aminosulfonylation of an alkene with the insertion of SO 2 giving rise to β-sulfonyl amides (30) with high efficiency and excellent chemoselectivity, in moderate to good yields.
As depicted in Figure 19 the plausible mechanism involves the interaction of aryldiazonium tetrafluoroborate with DABCOÁ(SO 2 ) 2 to generate aryl radical, sulfur dioxide, nitrogen, and DABCO radical cation. Then the aryl radical is captured by sulfur dioxide to generate an aryl sulfonyl radical intermediate Ge et al. in 2020 developed a metal-catalyzed three-component reaction of alkene (31), using a selenium ylides-based trifluoromethylation reagent, and nucleophiles such as azide, amine, alcohol, water via a radical process to trifluoromethylative amination product (32) under mild conditions (Figure 20) [24]. The trifluoromethylation reagent act as a trifluoromethyl radical source. The process takes place in the presence of a Lewis acid scandium(III) trifluoromethanesulfonate Sc(OTf) 3    ( Figure 21) [25]. Here o-acyl hydroxylamines are the key reacting partner for difunctionalization. Here solvent also play a pivotal role as different solvent gave different products. A plausible mechanism for the Ir-catalyzed radical diamination and α-amino ketone of active olefins is shown in (Figure 21) (Figure 22) [26]. Here Nchlorosulfonamides served both as nitrogen and chlorine source. This methodology provides regioselective, efficient, and atom-economic method for the preparation of vicinal halo amines. The reaction goes via the generation of a nitrogen-centered radical from N-chlorosulfonamide by oxidative quenching of the Ir-catalyzed which is excited in the presence of blue LEDs. This nitrogen centered radical then adds to the olefin (35) to produce an alkyl radical which is further oxidized to a carbocation intermediate with the regeneration of Ir III . Finally, the addition of chloride anion to the carbocation gives chloraminated product (36).

Cu and Pd-catalyzed C-N bond formations
Wu et al. in 2019 depicted (Figure 23) a visible-light-mediated Cu-catalyzed difunctionalization of alkene (37) to give azidation product (38) [27]. Here the azidobenziodoxole acts as an azidating agent in the presence of acetonitrile and [Cu(dap) 2 ]PF 6 complex as the photocatalyst. While the reactions produced three types of difunctionalized products, which correspond to reaction patterns of amidoazidation, diazidation and benzoyloxy-azidation. The electronic factor of the aryl group attached to the alkene play a vital role in determining the reaction outcome. When the aryl group is rich in electron, the reaction afforded benzoyloxy-azidation product and highly electron-deficient vinyl arenes, generated diazidation products in moderate yields. When the aryl group is electron-deficient or moderately electron-rich, give predominantly amido-azidation product. Based on the proposed mechanism the reaction is initiated via single electron transfer (SET) between IBA-N 3 and [Cu(dap) 2 ] + *, which provided an azidyl radical and [Cu(dap) 2 ] 2+ . The azide radical then attacks the alkene to produce a radical which would couple with the CH 3 CN-[Cu] 2+ complex followed by reductive elimination to give Ritter-type intermediate. The latter is readily captured by the o-iodo benzoyloxylate anion and further rearrangement formed product (38). In another path, the radical generated from alkene is oxidized to the corresponding carbocation by IBA-N 3 . Then addition with o-iodo benzoyloxylate anion afforded the oxy-azidation products (38 0 ). When the vinyl group is attached to a strong electron-withdrawing group intermediate generated from alkene abstracts an azidyl group from IBA-N 3 to give the diazidation product (38″).
Similarly     Cheung et al. in 2020 disclose a Pd-catalyzed visible-light-mediated synthesis of aminoalkylations derivative (46) via 1,2-carbofunctionalization of conjugated dienes (45) using alkyl iodides and amines as the coupling partners (Figure 27) [31]. This methodology is subsequently utilizing for the late-stage derivatization of complex molecules which is useful in drugs discovery. The multi-component reaction uses readily available reaction partners with broad substrate scope and does not require any exogenous photosensitizers or external oxidants.
The proposed mechanism is shown in (Figure 27

Rose Bengal and 9-Fluorenone catalyzed C-N bond formation
Wei et al. in 2018 reported a new and facile visible-light-mediated synthesis of αazido ketones (48) via oxyazidation of alkenes (47) with TMSN 3 in the air at room temperature (Figure 28) [32]. Rose Bengal is a metal-free photocatalyst, used for the synthesis of α-azido ketones. This difunctionalized products are easily and efficiently obtained in moderate to excellent yields via the formation of C-N and C=O bonds. The proposed mechanism is shown in (Figure 28). At first, visible-light irradiation of Rose Bengal generated the excited RB*. Subsequently, a single electron transfer (SET) process takes place between TMSN 3 and RB* to produce an azido radical and RB •À radical anions. Then, the ground state Rose Bengal and O 2 •À is formed through the oxidation of RB •À by molecular oxygen (air). Furthermore, the attack of azido radical to alkene (47) (Figure 29) [33]. This transformation occurs via metalfree and redox neutral conditions and applies to a wide range of alkenes. The βazido alkyl hydrazines are used for the preparations of many valuable synthetic building blocks. As per mechanism (Figure 29) initially, photo-excited fluorenone generates a N 3 radical via the catalytic oxidation of azide source with the formation of a reductive ketyl radical species (B). Then, the azide radical attacks the alkene to    (Figure 30) [34]. This protocol provides a new synthetic method for unsymmetrical azo compounds and applies to different aryldiazonium salts and alkenes. According to the proposed mechanism (Figure 30) initially, in the presence of visible light, the photocatalyst 'Mes' undergoes an excited state (*Mes) and take parts in a single electron transfer (SET) process with TMSN 3 to generate the azido radical and 'Mes' À radical anion. Subsequently, the azido radical attacked the alkene (51) to produce an alkyl radical intermediate (A), which is trapped by the aryldiazonium salt to generate a radical cation intermediate (B). Finally, another SET process between the radical cation (B) and the 'Mes' À radical anion provide the product (52) with simultaneous regeneration of the photocatalyst 'Mes'.
Yang and Lu in 2017 established a suitable method for the formation of hydroxyazidation derivative (54) from the reaction of alkenes (53) under visible light photo redox catalysis (Figure 31) [35]. The important features of the reaction are low catalyst loading, room temperature, broad substrate scope. Readily available starting materials, such as alkenes and air, to construct valuable β-azido alcohols.
Wang et al. in 2020, demonstrated a metal-free method for the synthesis of β-trifluoromethyl hydrazines (56) by reacting alkene (55) with sodium trifluoromethanesulfonate as the CF 3 source. (Figure 32) [36]. This methodology enabled a radical cascade that incorporates a trifluoromethyl and a hydrazine group across the C=C double bond. Moon et al. in 2020 demonstrated an atom-economical visible-light-mediated synthesis of aminopyridylationproduct (56) in the presence of alkenes (55) and N-aminopyridinium ylides (Figure 33) [37]. This environmentally friendly method   applies to a wide range of substrates with good functional group tolerance. Both activated, unactivated alkenes and pyridine are smoothly reacted and gave their desired products in moderate to good yields at room temperature.

Eosin-Y-catalyzed C-N bond formation
Moon et al. in 2019 demonstrated an Eosin Y mediated photocatalytic strategy for the synthesis of aminoethyl pyridine derivatives (60) in the presence of alkenes (59) using a variety of N-aminopyridinium salts as both aminating and pyridylating agents (Figure 34) [38]. Here concomitant incorporations of amino and pyridyl groups take place into alkenes under mild reaction conditions. In this protocol alkene bearing both electron-withdrawing and electron-donating groups are well tolerated. According to the possible mechanism (Figure 34) initially, in the presence of LEDs photocatalyst EY excited to the EY*, which subsequently form the Alam et al. in 2020 developed an elegant visible-light-mediated synthesis of Nhydroxybenzimidoyl cyanides from aromatic terminal alkenes using Eosin Y as a metal-free photocatalyst (Figure 35) [39]. DFT calculation supports a biradical pathway with successive incorporation of two nitrogen atoms, one each from tertbutyl nitrite (TBN) and ammonium acetate. The difunctionalization product is accomplished by the concomitant installation of an oxime and a nitrile group.
As determined from the DFT calculation and few control experiments a plausible mechanism has been proposed (Figure 35). In the influence of visible light Eosin Y (EY) undergoes excitation and generates a PINO radical from NHPI via hydrogen atom transfer (HAT) and returns to the ground state. The PINO radical adds to the

Conclusion
In summary, this chapter focus on the recent advancements in visible-lightmediated transition-metal and organic dye catalyzed difunctionalization of alkene leading to the formation of C-N bond. The utilization of visible light by photo catalysis is a burgeoning field in contemporary organic synthesis The ubiquitous nature of the C-N bond predominates the synthetic chemist community. In this regard visible-light-mediated difunctionalization of alkene reactions have emerged as an efficient strategy for the synthesis of functionalized molecules, giving a high atom economy. Organic dye mediated C-N bond formations is even more promising compared to metal-catalyzed C-N bond formation because they overcome the