Reductive Heck reactions have emerged as a powerful tool for efficient construction of saturated C—C bonds,^[1] which enable cross-coupling between aryl (pseudo)halides and alkenes followed by protonation or coupling with a hydride, while avoiding the use of highly reactive and air- sensitive organometallics. To this end, palladium-catalyzed reductive Heck reactions including asymmetric versions have been widely developed.^[2] Unlike palladium, nickel is an earth-abundant, extremely cheap transition metal, which is more electropositive than palladium. In Heck reactions, the migration insertion of Ni^II species to alkenes is more favorable than Pd, while β-hydride elimination of alkyl nickel species is calculated to have higher barriers than Pd.^[3] Thus, nickel has also been viewed as an efficient catalyst for reductive Heck reaction.^[4] Recent progress has been achieved in the field of nickel-catalyzed reductive Heck cyclization.^[5] And very recently, Zhou and co- workers^[6] reported the first example of asymmetric intermolecular reductive Heck reaction by nickel catalysis. Despite of a progress achieved, the reductive Heck reactions require elevated temperatures and stoichiometric amounts of metal reductant such as Mn or Zn (Scheme 1, a), which results in a large disposal of metal waste and a high risk in practical synthesis. Therefore, further exploration of reductive Heck reaction under mild conditions without requirement of metallic reductants is highly desirable.

Compared to metal reductants, organic reductants are mild, cheap, and user environmentally friendly.^[7] Taking advantage of photoexcited chemistry, a sort of organic reductants could be applied in metal-catalyzed reductive cross-coupling reactions to replace traditional metal reductants,^[8] while the application in reductive Heck reaction remains underdeveloped. In this regard, our group has developed several examples of photo-assisted nickel-cataly- zed reductive cross-coupling in the aid of organic reductant, such as tertiary amine or Hantzsch ester (HEH).^[9] Previously, we reported a photo-induced nickel-catalyzed reductive acyl-coupling without photoredox catalyst by using HEH as a potent organic reductant.^[9c] Recently, Yang and co-workers^[10] reported a photoexcited Ni^II-aryl complex- mediated Giese addition of aryl radicals to alkenes enabled by nickel/photoredox dual catalysis, in which HEH was used as reductant. Inspired by these works, we envisioned that the excited-state of HEH* [E_ox(HEH^•＋/HEH*)=－2.28 V vs. SCE]^[11] could potentially reduce Ni(II) [E_red(Ni^II/Ni⁰)=－1.2 V vs. SCE]^[12] back to Ni(0) to furnish the catalytic cycle, meanwhile the protons releasing from HEH during the reductive process could protonate alkyl Ni(II) species to afford hydroarylation products. Herein, we reported the first photo-induced nickel-cataly- zed reductive Heck arylation of alkenes in the presence of HEH as organic reductant under extremely mild conditions (Scheme 1, b). HEH was identified as a unique bifunctional reagent which serves as a reductant and proton source. This method obviates the use of metal-based reductants and provides a complementary approach for reductive Heck reaction.

4-Iodo-1,1'-biphenyl (1a) and methyl acrylate (2a) were chosen as model substrate to test the hypothesis. To our delight, after a detailed survey of reaction conditions, the reductive Heck product 3 could be detected in 78% GC yield when performing the reaction in the presence of Ni(PPh₃)₂Br₂ as catalyst, 6,6'-dmbpy (L1) as ligand, Hantzsch ester (HEH) as organic reductant, i-Pr₂NH as base, in dimethyl adipate (DMA) under 1.5 W purple LED irradiation for 24 h (Table 1, Entry 1). Nickel catalyst has an important effect on the reactivity. Replacing Ni(PPh₃)₂- Br₂ to other nickel sources led to decreased yields (Entries 2, 3). Interestingly, the direct use of Ni⁰ precatalyst such as Ni(cod)₂ could also give 65% yield (Entry 3). Ligand screening showed that the bipyridyl ligand bearing di-ortho-methyl substituents is critical to the reaction as moving methyl group to para or meta position resulted in very low efficiency (Entries 4, 5). The use of terpyridyl ligand L4 largely decreased the reactivity (Entry 6). The survey of different solvents indicated that N,N-dimethyl- formamide (DMF), dimethyl sulfoxide (DMSO), and tetrahydrofuran (THF) were all inferior to the reaction (Entries 7~9). The purple light was important for the reaction process as using 456 nm blue LED irradiation led to no reaction (Entry 10). Control experiments suggested that nickel, ligand, purple light, and base were all indispensable for the reductive Heck reaction (Entry 11).

With the optimized reaction conditions in hand, we started to examine the substrate scope. First, the substrate scope of electron-deficient alkenes was investigated (Table 2). Acrylates bearing methyl (3), ethyl (4), isopropyl (5), tert-butyl (6), benzyl (7), isobutyl (8) and cyclohexyl (9) substituent reacted smoothly, affording the corresponding products in good yields (66%~80% isolated yields). Besides, phenyl acrylate (10), allyl acrylate (11), and 2- methoxyethyl acrylate (12) were all valid substrates. Gratifyingly, methyl methacrylate reacted as well (13). Moreover, acrylonitrile (14) was also proven to be a valid substrate for the nickel-catalyzed reductive Heck reaction. While acrylamides reacted with largely decreased yields. Unfortunately, acrolein, α,β-unsaturated ketones, β-sub- stituted or α,β-disubstituted acrylates were incompatible to the standard conditions.

Next, the scope generality of aryl halides was investigated (Table 3). Aryl iodides with different electronic and steric natures of substituents have no significant influence on the reactivity. Aryl iodides irrespective of para, meta, or ortho substituents all successfully engaged in the reaction. Not only electron-withdrawing groups but also electron-donating groups were reacted smoothly, affording desired products in moderate to good yields (15~23). The reaction tolerated a variety of functional groups, such as CF₃ (15), OCF₃ (18), fluoride (19, 23), chloride (20), thioether (21), and tert-butyldimethylsilyl ether (OTBS) (22).

Besides of phenyl iodides, 1-iodonaphthalene and 2-iodo- naphthalene were proven to be suitable substrates (24, 25). Presumably due to the steric hindrance effect, ortho-sub- stituted aryl iodides provided generally lower reactivity (20 and 24). Gratifyingly, heteroaryl halide, such as 5-iodo- benzo[d][1,3]dioxole (26) was also successfully participated in the reaction to give the expected product in good yield. Besides of aryl iodides, aryl bromides and aryl triflates were valid substrates.

In order to give an insight into the mechanism, the related mechanistic experiments were carried out. when D₂O was added, 20% yield of deuterated reductive Heck product d-3 was isolated with 21% deuterium incorporation (Scheme 2). The low deuterium incorporation might be contributed to the competitive protonation by HE. This result indicated the formation of C—Ni bond adjacent to the ester group by reductive Heck reaction of 1a and 2a. Moreover, the radical-trapping experiment was performed with butylated hydroxytoluene (BHT) as a radical inhibitor, while the reaction still proceeded smoothly without detection of aryl radical-trapped adducts by HRMS (Scheme 2), suggesting that the radical pathway was most unlikely involved. The Stern-Volmer quenching experiments were performed and the results revealed that the oxidative quenching of the excited state of HEH* by nickel catalyst was existed in the reaction system, suggesting a single electron-transfer (SET) between HEH* and Ni^II (Figure 1).

Based on the experimental results, a plausible mechanism was proposed in Scheme 3. The ground-state of HEH was irradiated by purple light to reach its excited state HEH*, which is a strong reductant that can potentially reduce Ni^II to Ni⁰. Then Ni⁰ undergoes oxidative addition with aryl halide to get aryl-Ni^II species, followed by migration insertion of alkenes to form α-carbonyl Ni^II species. Final single electron reduction of the resulting Ni^II by HEH* regenerates Ni⁰ to complete the catalytic cycle.

In summary, a photo-induced nickel-catalyzed reductive Heck reaction of aryl halides with electron-deficient alkenes under very mild conditions was developed. Hantzsch ester (HEH) was disclosed as a mild organic reductant to replace traditionally used metal reductants for reductive Heck reaction. The photoexcited state of HEH* possessing strong reductive potential can reduce Ni^II back to Ni⁰ to furnish the catalytic cycle. The reaction shows relatively broad scope of aryl halides and tolerates a variety of functional groups.