N-Iodosuccinimide as a Precatalyst for Direct Cross-Coupling of Alcohols with C-Nucleophiles under Solvent-Free Reaction Conditions

C–C bond formation is one of the most important implements in synthetic organic chemistry. In pursuit of effective synthetic routes functioning under greener pathways to achieve direct C–C bond formation, we report N-iodosuccinimide (NIS) as the most effective precatalyst among the N-halosuccinimides (NXSs) for the direct cross-coupling of benzyl alcohols with C-nucleophiles under solvent-free reaction conditions (SFRC). The protocol is metal-free, and air- and water-tolerant, providing a large-scale synthesis with almost quantitative yields.


Introduction
C-C bond formation is one of the most significant approaches for the synthesis of complex organic compounds such as pharmaceuticals and agrochemicals [1]. Alcohols are readily available and one of the most abundant organic compounds. Their employment for direct cross-coupling reactions with other partners is highly desirable, producing water as the only by-product, making the protocol environmentally benign. Since hydroxyl moieties are a weak leaving group, often an additional activation is unavoidable [2].
The hydroxyl group's activation employing a substoichiometric amount of Brønsted acids, metal ions, Lewis/Brønsted acid combinations, or other promoters has been shown by several excellent reviews [1,[3][4][5][6][7][8][9] and recent advanced related reports [10][11][12][13][14]. Nevertheless, the necessity of hazardous or costly reagents, environmentally unfriendly solvents, multiple-step synthesis, a high amount of the catalyst, or high temperatures make such a synthetic procedure less preferable than the green chemical standpoint. Therefore, planning organic reactions and processes following the principles of green chemistry [15] is one of the main challenges in organic synthesis. As a result, solvent-free synthetic methods have attracted significant interest not only in laboratory synthesis but also in the chemical industry due to their simplicity and cost-efficiency. With this in mind, it is becoming essential to develop efficient, selective, and environmentally benign catalytic systems for direct dehydrative C-C coupling.
Recently, we presented the introduction of N-halosuccinimides (NXSs) (chloro, bromo, and iodo), as the catalyst for the transformation of organic compounds bearing the hydroxyl functional group in one pot, constructing new carbon-carbon or carbon-heteroatom bonds [16]. N-iodosuccinimide (NIS) in substoichiometric amounts was favored as the most effective and selective catalyst among the NXSs. In continuation of our research on developing greener synthetic transformation [17][18][19] herein, we reported the expanding role of NIS as a non-metal, commercially available, and eco-friendly precatalyst for direct dehydrative C-C coupling between various benzyl alcohols and different type of observed and established the quantitative formation of the corresponding product 18 (entry 8, Table  1). No transformation was observed in the case of triphenylmethanol 6 with 9 catalyzed by NIS under SFRC. Additionally, the effective transformation was obtained between 1,3-bis(4-methoxyphenyl)propane-1,3-dione 19 and 1, furnishing the respective product 20 in excellent yield (entry 9, Table 1).
To establish the synthetic value of the reported methodology, the following reaction was performed on the 10 mmol scales. Coupling of 1 with 2 under the above-mentioned optimal reaction conditions afforded the corresponding product 4 in quantitative yield (99%).  . No transformation was observed in the case of triphenylmethanol 6 with 9 catalyzed by NIS under SFRC. Additionally, the effective transformation was obtained between 1,3-bis(4-methoxyphenyl)propane-1,3-dione 19 and 1, furnishing the respective product 20 in excellent yield (entry 9, Table 1). To establish the synthetic value of the reported methodology, the following reaction was performed on the 10 mmol scales. Coupling of 1 with 2 under the above-mentioned optimal reaction conditions afforded the corresponding product 4 in quantitative yield (99%). 1). No transformation was observed in the case of triphenylmethanol 6 with 9 catalyzed by NIS under SFRC. Additionally, the effective transformation was obtained between 1,3-bis(4-methoxyphenyl)propane-1,3-dione 19 and 1, furnishing the respective product 20 in excellent yield (entry 9, Table 1). To establish the synthetic value of the reported methodology, the following reaction was performed on the 10 mmol scales. Coupling of 1 with 2 under the above-mentioned optimal reaction conditions afforded the corresponding product 4 in quantitative yield (99%). 1). No transformation was observed in the case of triphenylmethanol 6 with 9 catalyzed by NIS under SFRC. Additionally, the effective transformation was obtained between 1,3-bis(4-methoxyphenyl)propane-1,3-dione 19 and 1, furnishing the respective product 20 in excellent yield (entry 9, Table 1). To establish the synthetic value of the reported methodology, the following reaction was performed on the 10 mmol scales. Coupling of 1 with 2 under the above-mentioned optimal reaction conditions afforded the corresponding product 4 in quantitative yield (99%). under SFRC. Additionally, the effective transformation was obtained between 1,3-bis(4-methoxyphenyl)propane-1,3-dione 19 and 1, furnishing the respective product 20 in excellent yield (entry 9, Table 1). To establish the synthetic value of the reported methodology, the following reaction was performed on the 10 mmol scales. Coupling of 1 with 2 under the above-mentioned optimal reaction conditions afforded the corresponding product 4 in quantitative yield (99%).  Inspired by these results, we investigated NIS's efficiency as the catalyst for the direct coupling of phenyl substituted alkene with secondary benzyl alcohol under solvent-free conditions. NIS, as an effective catalyst, was observed to promote the direct coupling of 1,1 diphenylethene 21 with phenyl(p-tolyl) methanol 11 under SFRC, producing the corresponding substituted alkene 23 in nearly quantitative yield (Scheme 1).  Inspired by these results, we investigated NIS's efficiency as the catalyst for the direct coupling of phenyl substituted alkene with secondary benzyl alcohol under solvent-free conditions. NIS, as an effective catalyst, was observed to promote the direct coupling of 1,1 diphenylethene 21 with phenyl(p-tolyl) methanol 11 under SFRC, producing the corresponding substituted alkene 23 in nearly quantitative yield (Scheme 1).
Catalysts 2020, 10, x FOR PEER REVIEW 4 of 8 Inspired by these results, we investigated NIS's efficiency as the catalyst for the direct coupling of phenyl substituted alkene with secondary benzyl alcohol under solvent-free conditions. NIS, as an effective catalyst, was observed to promote the direct coupling of 1,1 diphenylethene 21 with phenyl(p-tolyl) methanol 11 under SFRC, producing the corresponding substituted alkene 23 in nearly quantitative yield (Scheme 1).  Inspired by these results, we investigated NIS's efficiency as the catalyst for the direct coupling of phenyl substituted alkene with secondary benzyl alcohol under solvent-free conditions. NIS, as an effective catalyst, was observed to promote the direct coupling of 1,1 diphenylethene 21 with phenyl(p-tolyl) methanol 11 under SFRC, producing the corresponding substituted alkene 23 in nearly quantitative yield (Scheme 1).
Catalysts 2020, 10, x FOR PEER REVIEW 4 of 8 Inspired by these results, we investigated NIS's efficiency as the catalyst for the direct coupling of phenyl substituted alkene with secondary benzyl alcohol under solvent-free conditions. NIS, as an effective catalyst, was observed to promote the direct coupling of 1,1 diphenylethene 21 with phenyl(p-tolyl) methanol 11 under SFRC, producing the corresponding substituted alkene 23 in nearly quantitative yield (Scheme 1).
Catalysts 2020, 10, x FOR PEER REVIEW 4 of 8 Inspired by these results, we investigated NIS's efficiency as the catalyst for the direct coupling of phenyl substituted alkene with secondary benzyl alcohol under solvent-free conditions. NIS, as an effective catalyst, was observed to promote the direct coupling of 1,1 diphenylethene 21 with phenyl(p-tolyl) methanol 11 under SFRC, producing the corresponding substituted alkene 23 in nearly quantitative yield (Scheme 1). Effective transformation with β-diketone 2 was observed in the reaction with additional classes of secondary benzyl alcohols, including derivatives of diphenylmethanol bearing electron-donating or Catalysts 2020, 10, 850 4 of 8 electron-withdrawing substituents on the aromatic rings 11 and 13, and established the quantitative formation of the corresponding products 12 and 14 (entries 2 and 3, Table 1).
Furthermore, we checked the reaction of the primary benzyl alcohol bearing electron-donating group with 2. 4-methoxybenzyl alcohol 15 was efficiently and selectively converted into the 2-(4-methoxybenzyl)-1,3-diphenylpropane-1,3-dione 16 (entry 4, Table 1). We further investigated the corresponding reactions of alcohols with benzoylacetone 7. In the case of the reaction of primary benzyl alcohol 5 with 7 in the presence of NIS as the catalyst under solvent-free conditions, no transformation took place. Effective and selective transformation with 7 was observed in the reaction with phenyl(p-tolyl)methanol 11, providing the quantitative formation of the corresponding product 17 (entry 6, Table 1). No transformation was observed with sterically bulkier triphenylmethanol 6 with 7 catalyzed by NIS under SFRC.
Moreover, we investigated the corresponding reactions of alcohols with acetylacetone 9. In the case of the reaction of unsubstituted benzyl alcohol 5 with 9 catalyzed by NIS under SFRC, no transformation took place. Effective transformation of phenyl(p-tolyl)methanol 11 with 9 was observed and established the quantitative formation of the corresponding product 18 (entry 8, Table 1). No transformation was observed in the case of triphenylmethanol 6 with 9 catalyzed by NIS under SFRC. Additionally, the effective transformation was obtained between 1,3-bis(4-methoxyphenyl)propane-1,3-dione 19 and 1, furnishing the respective product 20 in excellent yield (entry 9, Table 1).
To establish the synthetic value of the reported methodology, the following reaction was performed on the 10 mmol scales. Coupling of 1 with 2 under the above-mentioned optimal reaction conditions afforded the corresponding product 4 in quantitative yield (99%).
Inspired by these results, we investigated NIS's efficiency as the catalyst for the direct coupling of phenyl substituted alkene with secondary benzyl alcohol under solvent-free conditions. NIS, as an effective catalyst, was observed to promote the direct coupling of 1,1 diphenylethene 21 with phenyl(p-tolyl) methanol 11 under SFRC, producing the corresponding substituted alkene 23 in nearly quantitative yield (Scheme 1).
Catalysts 2020, 10, x FOR PEER REVIEW 4 of 8 Inspired by these results, we investigated NIS's efficiency as the catalyst for the direct coupling of phenyl substituted alkene with secondary benzyl alcohol under solvent-free conditions. NIS, as an effective catalyst, was observed to promote the direct coupling of 1,1 diphenylethene 21 with phenyl(p-tolyl) methanol 11 under SFRC, producing the corresponding substituted alkene 23 in nearly quantitative yield (Scheme 1). It is well-known that alkenes can be readily achieved by dehydration of tertiary alcohols bearing a vicinal hydrogen atom. Inspired by this finding, we performed the reaction between 1,1-diphenylethanol 24 and 1 catalyzed by NIS under SFRC. We observed that the direct coupling of two alcohols, 1 and 24, forming the corresponding product 22 as the major product took place, accompanied by a trace amount of side products identified as benzophenone and dimeric ether 3, (Scheme 2). It is well-known that alkenes can be readily achieved by dehydration of tertiary alcohols bearing a vicinal hydrogen atom. Inspired by this finding, we performed the reaction between 1,1-diphenylethanol 24 and 1 catalyzed by NIS under SFRC. We observed that the direct coupling of two alcohols, 1 and 24, forming the corresponding product 22 as the major product took place, accompanied by a trace amount of side products identified as benzophenone and dimeric ether 3, (Scheme 2).
Electron-rich benzocyclenes with a general structure (X=NAc, O) were chosen as potential partners for the NIS-promoted reactions with benzyl alcohols under SFRC. The reaction of diphenylmethanol 1 with 1,2-dihydronaphthalene 25 catalyzed by NIS under SFRC performed the corresponding substituted alkene 26, accompanied by a small amount of dimeric ether 3, was observed. Different parameters such as the loading of the NIS as the catalyst and the reaction temperature for the reaction of 1 with 1,2-dihydronaphthalene 25 under SFRC were first studied, and the results are shown in the Supplementary Materials (Tables S8 and S9). Moreover, during the optimization of reaction conditions, we found that equimolar of 1 and 25 provided the best result in terms of efficiency and selectivity.  (Tables S8 and S9). Moreover, during the optimization of reaction conditions, we found that equimolar of 1 and 25 provided the best result in terms of efficiency and selectivity.
To verify the presumption that the symmetric ether 3 could be the intermediate of the cross-coupling [21], we independently performed the reaction between symmetric ether 3 as a source of benzylic cation, which was synthesized from 1 catalyzed by NIS (2 mol%) at 70-75 °C, for 3.5 h under SFRC. Then, alkylation of the dimeric ether 3 by dihydronaphthalene 25 took place, providing the corresponding product 26 in quantitative yield. Another possible pathway might be a direct reaction of carbocation derived from alcohol 1 and followed by nucleophile displacement (Scheme 3).

Scheme 3. Control reactions.
According to the results of the control reaction shown in Scheme 3, a potential explanation suggests a decomposition of the precatalyst NIS to form HOI in alcoholic reaction media, which could be responsible for NIS's mediation activity [22][23][24][25]. The X2 forms HOI and HI in aqueous media, providing the regeneration of HOI for the following catalysis. Therefore, it was reasonable to assume that the water produced as the only by-product of the process could act as a supporting factor in the acceleration of the reaction, since no conversion was observed in the reaction between diphenylmethanol 1 and 1,3-diphenylpropane-1,3-dione 2 catalyzed by NIS in aqueous media. The presumption that NIS was actually a precatalyst forming HOI, I2, and protons during the process, which might catalyze nucleophilic substitutions, showed to be reasonable [16,26].
The generality of this methodology for C-C hetero coupling approaches with heteroatom benzocyclenes 27 and 29 with 1, catalyzed by NIS under SFRC, was further examined. The results of  (Tables S8 and S9). Moreover, during the optimization of reaction conditions, we found that equimolar of 1 and 25 provided the best result in terms of efficiency and selectivity.
To verify the presumption that the symmetric ether 3 could be the intermediate of the cross-coupling [21], we independently performed the reaction between symmetric ether 3 as a source of benzylic cation, which was synthesized from 1 catalyzed by NIS (2 mol%) at 70-75 °C, for 3.5 h under SFRC. Then, alkylation of the dimeric ether 3 by dihydronaphthalene 25 took place, providing the corresponding product 26 in quantitative yield. Another possible pathway might be a direct reaction of carbocation derived from alcohol 1 and followed by nucleophile displacement (Scheme 3).

Scheme 3. Control reactions.
According to the results of the control reaction shown in Scheme 3, a potential explanation suggests a decomposition of the precatalyst NIS to form HOI in alcoholic reaction media, which could be responsible for NIS's mediation activity [22][23][24][25]. The X2 forms HOI and HI in aqueous media, providing the regeneration of HOI for the following catalysis. Therefore, it was reasonable to assume that the water produced as the only by-product of the process could act as a supporting factor in the acceleration of the reaction, since no conversion was observed in the reaction between diphenylmethanol 1 and 1,3-diphenylpropane-1,3-dione 2 catalyzed by NIS in aqueous media. The presumption that NIS was actually a precatalyst forming HOI, I2, and protons during the process, which might catalyze nucleophilic substitutions, showed to be reasonable [16,26].
The generality of this methodology for C-C hetero coupling approaches with heteroatom benzocyclenes 27 and 29 with 1, catalyzed by NIS under SFRC, was further examined. The results of According to the results of the control reaction shown in Scheme 3, a potential explanation suggests a decomposition of the precatalyst NIS to form HOI in alcoholic reaction media, which could be responsible for NIS's mediation activity [22][23][24][25]. The X 2 forms HOI and HI in aqueous media, providing the regeneration of HOI for the following catalysis. Therefore, it was reasonable to assume that the water produced as the only by-product of the process could act as a supporting factor in the acceleration of the reaction, since no conversion was observed in the reaction between diphenylmethanol 1 and 1,3-diphenylpropane-1,3-dione 2 catalyzed by NIS in aqueous media. The presumption that NIS was actually a precatalyst forming HOI, I 2 , and protons during the process, which might catalyze nucleophilic substitutions, showed to be reasonable [16,26].
The generality of this methodology for C-C hetero coupling approaches with heteroatom benzocyclenes 27 and 29 with 1, catalyzed by NIS under SFRC, was further examined. The results of the reactions carried out under SFRC are collected in Table 2. NIS catalyzed the direct coupling of 1 with an N-based heteroarene such as 1-acetylindole 23 under SFRC, affording C-3 alkylated product in high yield (28, entry 1, Table 2). The direct coupling of 1 with an O-containing heteroarene such as 2,3-benzofuran 29 underwent smooth coupling to provide the C-2 alkylated product in good yield (30, entry 2, Table 2). It could be seen that the electrophilic substitution in 1-acetylindole 27 took place at C-3 and not at C-2. This orientation could be explained by comparing the stability of the carbocation resulting from the electrophilic attack at C-2, which was less favorable than the carbocation from the electrophilic attack at C-3. The electrophilic substitution at C-2 in benzofuran 29 could also be explained in the same way. with an N-based heteroarene such as 1-acetylindole 23 under SFRC, affording C-3 alkylated product in high yield (28, entry 1, Table 2). The direct coupling of 1 with an O-containing heteroarene such as 2,3-benzofuran 29 underwent smooth coupling to provide the C-2 alkylated product in good yield (30, entry 2, Table 2). It could be seen that the electrophilic substitution in 1-acetylindole 27 took place at C-3 and not at C-2. This orientation could be explained by comparing the stability of the carbocation resulting from the electrophilic attack at C-2, which was less favorable than the carbocation from the electrophilic attack at C-3. The electrophilic substitution at C-2 in benzofuran 29 could also be explained in the same way. To gain clearer insight into NIS's thermal stability, thermal gravimetric analysis (TGA) on the precatalyst was carried out. It was observed that the degradation did not happen to the precatalyst at temperatures 25-200 °C [16].

Materials and Methods
All starting materials and NIS were commercially available and used without further purification (Merck, Darmstadt, Germany; Sigma Aldrich, St. Louis, MO, USA). Reactions were performed in 4 mL screw-capped vials. All reactions were observed by thin-layer chromatography (TLC, mobile phase: dichloromethane/hexane 9:1) (with silica gel/TLC cards; DC-Alufolien-Kieselgel, Sigma-Aldrich, St. Louis, MO, USA) and visualized by UV lamp (254 nm, Camag, Muttenz, Switzerland). 1 H and 13 C NMR spectra were measured on Varian INOVA 300 NMR instrument, using a solution of CDCl3 as the solvent with SiMe4 as an internal reference standard. Melting points were measured by Buchi 535 equipment. Purification of a few products was performed by column chromatography (CC) using silica gel 60 (particle size: 0.063-0.200 mm).
General procedure for new C-C bond construction through β-diketone or electron-rich C=C bonds in organic molecule catalyzed by NIS on half mmol scale: The mixture of benzyl alcohol (0.5 mmol), β-diketone, or alkene (0.5 mmol) and NIS (1-10 mol%), after being powdered in a mortar in the case of solid-state reactants, was transferred to a 4 mL screw-capped vial and heated at 70-75 °C for 24 h. TLC monitored the progress of the reaction mixture. The crude reaction mixture was cooled down to room temperature and diluted with a mixture of (3 × 5 mL EtOAc), (2 × 3 mL saturated Na2S2O3), (2 × 3 mL saturated NaHCO3), and (2 × 5 with an N-based heteroarene such as 1-acetylindole 23 under SFRC, affording C-3 alkylated product in high yield (28, entry 1, Table 2). The direct coupling of 1 with an O-containing heteroarene such as 2,3-benzofuran 29 underwent smooth coupling to provide the C-2 alkylated product in good yield (30, entry 2, Table 2). It could be seen that the electrophilic substitution in 1-acetylindole 27 took place at C-3 and not at C-2. This orientation could be explained by comparing the stability of the carbocation resulting from the electrophilic attack at C-2, which was less favorable than the carbocation from the electrophilic attack at C-3. The electrophilic substitution at C-2 in benzofuran 29 could also be explained in the same way. To gain clearer insight into NIS's thermal stability, thermal gravimetric analysis (TGA) on the precatalyst was carried out. It was observed that the degradation did not happen to the precatalyst at temperatures 25-200 °C [16].

Materials and Methods
All starting materials and NIS were commercially available and used without further purification (Merck, Darmstadt, Germany; Sigma Aldrich, St. Louis, MO, USA). Reactions were performed in 4 mL screw-capped vials. All reactions were observed by thin-layer chromatography (TLC, mobile phase: dichloromethane/hexane 9:1) (with silica gel/TLC cards; DC-Alufolien-Kieselgel, Sigma-Aldrich, St. Louis, MO, USA) and visualized by UV lamp (254 nm, Camag, Muttenz, Switzerland). 1 H and 13 C NMR spectra were measured on Varian INOVA 300 NMR instrument, using a solution of CDCl3 as the solvent with SiMe4 as an internal reference standard. Melting points were measured by Buchi 535 equipment. Purification of a few products was performed by column chromatography (CC) using silica gel 60 (particle size: 0.063-0.200 mm).
General procedure for new C-C bond construction through β-diketone or electron-rich C=C bonds in organic molecule catalyzed by NIS on half mmol scale: The mixture of benzyl alcohol (0.5 mmol), β-diketone, or alkene (0.5 mmol) and NIS (1-10 mol%), after being powdered in a mortar in the case of solid-state reactants, was transferred to a 4 mL screw-capped vial and heated at 70-75 °C for 24 h. TLC monitored the progress of the reaction mixture. The crude reaction mixture was cooled down to room temperature and diluted with a mixture of (3 × 5 mL EtOAc), (2 × 3 mL saturated Na2S2O3), (2 × 3 mL saturated NaHCO3), and (2 × 5 in high yield (28, entry 1, Table 2). The direct coupling of 1 with an O-containing heteroarene such as 2,3-benzofuran 29 underwent smooth coupling to provide the C-2 alkylated product in good yield (30, entry 2, Table 2). It could be seen that the electrophilic substitution in 1-acetylindole 27 took place at C-3 and not at C-2. This orientation could be explained by comparing the stability of the carbocation resulting from the electrophilic attack at C-2, which was less favorable than the carbocation from the electrophilic attack at C-3. The electrophilic substitution at C-2 in benzofuran 29 could also be explained in the same way. To gain clearer insight into NIS's thermal stability, thermal gravimetric analysis (TGA) on the precatalyst was carried out. It was observed that the degradation did not happen to the precatalyst at temperatures 25-200 °C [16].

Materials and Methods
All starting materials and NIS were commercially available and used without further purification (Merck, Darmstadt, Germany; Sigma Aldrich, St. Louis, MO, USA). Reactions were performed in 4 mL screw-capped vials. All reactions were observed by thin-layer chromatography (TLC, mobile phase: dichloromethane/hexane 9:1) (with silica gel/TLC cards; DC-Alufolien-Kieselgel, Sigma-Aldrich, St. Louis, MO, USA) and visualized by UV lamp (254 nm, Camag, Muttenz, Switzerland). 1 H and 13 C NMR spectra were measured on Varian INOVA 300 NMR instrument, using a solution of CDCl3 as the solvent with SiMe4 as an internal reference standard. Melting points were measured by Buchi 535 equipment. Purification of a few products was performed by column chromatography (CC) using silica gel 60 (particle size: 0.063-0.200 mm).
General procedure for new C-C bond construction through β-diketone or electron-rich C=C bonds in organic molecule catalyzed by NIS on half mmol scale: The mixture of benzyl alcohol (0.5 mmol), β-diketone, or alkene (0.5 mmol) and NIS (1-10 mol%), after being powdered in a mortar in the case of solid-state reactants, was transferred to a 4 mL screw-capped vial and heated at 70-75 °C for 24 h. TLC monitored the progress of the reaction mixture. The crude reaction mixture was cooled down to room temperature and diluted with a mixture of (3 × 5 mL EtOAc), (2 × 3 mL saturated Na2S2O3), (2 × 3 mL saturated NaHCO3), and (2 × 5 To gain clearer insight into NIS's thermal stability, thermal gravimetric analysis (TGA) on the precatalyst was carried out. It was observed that the degradation did not happen to the precatalyst at temperatures 25-200 • C [16].

Materials and Methods
All starting materials and NIS were commercially available and used without further purification (Merck, Darmstadt, Germany; Sigma Aldrich, St. Louis, MO, USA). Reactions were performed in 4 mL screw-capped vials. All reactions were observed by thin-layer chromatography (TLC, mobile phase: dichloromethane/hexane 9:1) (with silica gel/TLC cards; DC-Alufolien-Kieselgel, Sigma-Aldrich, St. Louis, MO, USA) and visualized by UV lamp (254 nm, Camag, Muttenz, Switzerland). 1 H and 13 C NMR spectra were measured on Varian INOVA 300 NMR instrument, using a solution of CDCl 3 as the solvent with SiMe 4 as an internal reference standard. Melting points were measured by Buchi 535 equipment. Purification of a few products was performed by column chromatography (CC) using silica gel 60 (particle size: 0.063-0.200 mm).
General procedure for new C-C bond construction through β-diketone or electron-rich C=C bonds in organic molecule catalyzed by NIS on half mmol scale: The mixture of benzyl alcohol (0.5 mmol), β-diketone, or alkene (0.5 mmol) and NIS (1-10 mol%), after being powdered in a mortar in the case of solid-state reactants, was transferred to a 4 mL screw-capped vial and heated at 70-75 • C for 24 h. TLC monitored the progress of the reaction mixture. The crude reaction mixture was cooled down to room temperature and diluted with a mixture of (3 × 5 mL EtOAc), (2 × 3 mL saturated Na 2 S 2 O 3 ), (2 × 3 mL saturated NaHCO 3 ), and (2 × 5 mL distilled water). The organic phase was dried Na 2 SO 4 , and the organic solvent was removed under reduced pressure, leaving the resultant residue.