{'fraction_non_alphanumeric': 0.04014492284799275, 'fraction_numerical': 0.024973312198751336, 'mean_word_length': 5.081841432225064, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Manganese(I)-Catalyzed Cross-Coupling of Ketones and Secondary Alcohols with Primary Alcohols.

Catalytic cross-coupling of ketones and secondary alcohols with primary alcohols is reported. An abundant manganese-based pincer catalyst catalyzes the reactions. Low loading of catalyst (2 mol %) and catalytic use of a mild base (5-10 mol %) are sufficient for efficient cross-coupling. Various aryl and heteroaryl ketones are catalytically cross-coupled with primary alcohols to provide the selective α-alkylated products. Challenging α-ethylation of ketones is also attained using ethanol as an alkylating reagent. Further, direct use of secondary alcohols in the reaction results in in situ oxidation to provide the ketone intermediates, which undergo selective α-alkylation. The reaction proceeds via the borrowing hydrogen pathway. The catalyst oxidizes the primary alcohols to aldehydes, which undergo subsequent aldol condensation with ketones, promoted by catalytic amount of Cs2CO3, to provide the α,β-unsaturated ketone intermediates. The hydrogen liberated from oxidation of alcohols is used for hydrogenation of α,β-unsaturated ketone intermediates. Notably either water or water and dihydrogen are the only byproducts in these environmentally benign catalytic processes. Mechanistic studies allowed inferring all of the intermediates involved. Dearomatization-aromatization metal-ligand cooperation in the catalyst facilitates the facile O-H bond activation of both primary and secondary alcohols, and the resultant manganese alkoxide complexes produce corresponding carbonyl compounds, perhaps via β-hydride elimination. The manganese(I) hydride intermediate plays dual role as it hydrogenates α,β-unsaturated ketones and liberates molecular hydrogen to regenerate the catalytically active dearomatized intermediate. Metal-ligand cooperation allows all of the manganese intermediates to exist in same oxidation state (+1) and plays an important role in these catalytic cross-coupling reactions.


INTRODUCTION
Efficient and catalytic construction of C−C bond is an important transformation in organic synthesis. Among C−C bond formation methods, α-alkylation of ketones is one of the pivotal routes for the synthesis of several biologically active, heterocyclic compounds and natural product building blocks. 1 Conventional methods involved use of reactive alkyl halides as alkylating reagents in the presence of stoichiometric amount of base that resulted in generation of toxic waste, which limited their sustainable applications. 2 Advancement in catalysis, in particular introduction of "borrowing hydrogen" or "hydrogen autotransfer" methods, allowed to overcome these drawbacks. In recent years, borrowing hydrogen strategy for C−C bond formation has received significant attention for the construction of functionalized organic molecules. 3 Typical borrowing hydrogen method involves catalytic dehydrogenation of alcohol to aldehyde and ketones, followed by basemediated aldol reaction, which generates the corresponding α,β-unsaturated ketone intermediate with elimination of water. Further, catalytic and selective transfer hydrogenation of the enone intermediates using the hydrogen obtained from the oxidation of alcohols affords α-alkylated ketones with high atom efficiency. Liberated molecular hydrogen and water are the only byproducts from this transformation (Scheme 1). 4 In general, this catalytic alkylation of ketones using alcohols is implemented using noble metals such as ruthenium, 5 palladium, 6 osmium, 7 iridium, 8 etc. Accordingly nonprecious first-row transition metals 9 have drawn much attention. Recently, Beller and co-workers have reported an aliphatic electron-rich PNP tridentate manganese(I) catalyst for alkylation of ketones. 10 More recently, α-alkylated ketones have been synthesized by direct dehydrogenative coupling of readily available and cheap secondary alcohols with primary alcohols. 10b,c Dehydrogenative cross-coupling of secondary alcohols and primary alcohols using Rh, Ru, and Ir catalysts has been reported. 5,8b,11 Thus, earth-abundant, inexpensive, more eco-friendly base metals like Mn-, Fe-, and Co-catalyzed crosscoupling of primary and secondary alcohols to α-alkylated ketones is desirable. In this direction, recently, Lang and coworkers have reported ligand-controlled copper(I)-catalyzed cross-coupling of secondary and primary alcohols. 11b Eminent research groups have designed and developed various manganese pincer catalysts, which catalyzed an assortment of organic transformations. 12−19 Manganese pincer-based catalysis has become more attractive because of new selectivity patterns in known reactions; different products are obtained just by altering the base. 20 Recently, Yu and coworkers 21 have reported manganese-catalyzed cross-coupling of secondary alcohols with primary alcohols, which provided the Guerbet β-alkylated secondary alcohol products in good yields. Kempe and co-workers 14c reported the multicomponent synthesis of pyrimidines from alcohols and amidines that proceeded via β-alkylation of alcohols. Using ruthenium pincer catalyst, we have reported the cross-coupling of secondary alcohols. 22a Selective α-alkylation and α-olefination of nitrile compounds with primary alcohols and secondary alcohols, respectively, were also reported using ruthenium catalyst. 22b,c Very recently, we have also reported manganese-catalyzed selective α-alkenylation of ketones using primary alcohols. 22d In continuation of our quest to devise and develop atomeconomical and sustainable catalytic transformations, herein, we report the selective cross-coupling of ketones and secondary alcohols with primary alcohols, which provided the α-alkylated ketone products in good to excellent yields. These dehydrogenative and dehydrative cross-coupling reactions are catalyzed by the manganese(I) pincer-based Kempe catalyst [(PN 5 P)Mn(CO) 2 Br] (1) together with catalytic amount of a mild base.

RESULTS AND DISCUSSION
During the development of selective α-alkenylation of ketones using primary alcohols, we have found that catalyst 1 with phenyl substituent in the catalyst backbone favorably produced the α-alkylated ketone products, while similar catalyst with 4methyl substitution promoted the selective α-olefination reaction. 22d Thus, catalytic α-alkylation of ketones by primary alcohols using manganese pincer catalyst 1 was investigated. At the outset of our studies, acetophenone and benzyl alcohol were chosen as benchmark substrates to find the optimal reaction conditions for the PN 5 P triazine-based manganese catalyst 1, and the results are presented in Table 1. Reaction of acetophenone and benzyl alcohol (each 0.5 mmol) was performed in the presence of 2 mol % catalyst 1 and 5 mol % Cs 2 CO 3 as base in tert-amyl alcohol solvent, which delivered the desired alkylated product in 63% yield (entry 1, Table 1). Upon increase of base load to 10 mol %, alkylated product 2a was isolated in 75% yield (entry 2, Table 1). When the amount of alcohol was increased from 1 to 1.2 equiv, the outcome was optimal, where the desired 2a was isolated in 86% yield with more than 99% conversion of acetophenone (entry 3, Table 1). Further, lowering the catalyst load to 1 mol % resulted in diminished yield of the product (entry 4, Table 1). Use of different solvents like 1,4-dioxane and toluene provided the alkylated product 2a in 84 and 51% yield, respectively (entries 5 and 6, Table 1). Reactions were tested with different bases. Upon use of sodium carbonate, product 2a was isolated in 11% yield (entry 7, Table 1). Although use of potassium carbonate as a base provided 97% conversion of acetophenone, the desired product 2a was isolated in 47% yield (entry 8, Table  1). Further, use of strong base sodium tert-butoxide provided the moderate conversion (80%) and yield (71%, entry 9, Table  1). When the reaction was carried out in the absence of catalyst 1 and in the presence of base alone, the product was obtained in 20% yield along with other undesired side products (entry 10, Table 1). When alkylation reactions were carried out with catalyst 1 in the absence of base and in the absence of both catalyst and base (entries 11 and 12, Table 1), no product was observed, implying that catalyst and base are essential for the alkylation of ketones using alcohols.

ACS Omega
Article alkylated product 2h, perhaps due to steric hindrance in proximity to alcohol functionality. Then, we explored the scope of different aryl ketones in the catalytic α-alkylation reactions using various primary alcohols (Table 3). Initially, different acetophenone derivatives bearing electron-withdrawing and electron-donating substituents were subjected to alkylation with benzyl alcohol. 4-Methylacetophenone provided the desired alkylated product 3a in 94% isolated yield. In general, aryl ketones having poor electron-aryl motifs provided the corresponding alkylated products in lower yields (3b−e) than electron-rich aryl ketones. Gratifyingly, heteroaryl ketone, 2-acetylthiophene, was transformed to the desired alkylated product. Upon reaction with benzyl alcohol, 65% of the alkylated product 3e was isolated. Despite 3-(pyridin-2-yl)propan-1-ol provided good conversion, its catalytic α-alkylation with 4-methylacetophenone resulted in 45% of 3f. With piperonyl alcohol as alkylating partner, 4methoxyacetophenone yielded 62% of the corresponding alkylated product 3g. 1-Tetralone and 4-methyl-1-tetralone were converted quantitatively to the α-alkylated products 3h and 3i in 78 and 88% yields, respectively. Remarkably, this manganese-catalyzed α-alkylation reaction is highly chemoselective. Even in the presence of amine functionality, alkylation occurred exclusively on a carbon α to carbonyl group. Upon catalytic α-alkylation of 2′-aminoacetophenone with 1-hexanol and 1-heptanol, the corresponding alkylated products were obtained in 53 and 46% yields (3j and 3k). Notably, the N-alkylated product was not observed in this condition, which indicates the chemoselective C-alkylation over N-alkylation.
To further explore the scope of manganese-catalyzed αalkylation of ketones with primary alcohols, alkylation using ethanol is demonstrated (Table 4). Acetophenone and ethanol under the optimized catalytic conditions yielded 58% of the ethylated product 4a. 4′-Methylacetophenone and 4′-chloroacetophenone provided 65 and 63% yields of the corresponding ethylated product 4b and 4c. β-Napthyl methyl ketone provided the ethylated product 4d in 66% yield. However, when 3-acetyl quinoline was examined under standard experimental conditions, only 23% of the ethylated product 4e was isolated. Similar catalytic results were obtained by Table 2. Manganese-Catalyzed α-Alkylation of Acetophenone Using Primary Alcohols a a Reaction conditions: ketone (0.5 mmol), alcohol (0.6 mmol), tertamyl alcohol (2 mL), catalyst 1 (2 mol %), and Cs 2 CO 3 (10 mol %) were heated at 140°C under open condition with an argon flow. Yields were calculated for isolated products after column chromatography. Conversion of ketones was determined by gas chromatography (GC) analysis using toluene as an internal standard and given within parentheses.  Table 4. Manganese-Catalyzed α-Alkylation of Ketones Using Ethanol a a Reaction conditions: ketone (0.5 mmol), ethanol (1 mL), tert-amyl alcohol (1 mL), catalyst 1 (2 mol %), and Cs 2 CO 3 (10 mol %) were heated at 140°C in a sealed tube. Yields were calculated for isolated products after column chromatography. Conversion of ketones was determined by GC analysis using toluene as an internal standard and given within parentheses.
In situ monitoring of the reaction progress by GC on the catalytic α-alkylation reaction of acetophenone using 4methylbenzyl alcohol catalyzed by 1 allowed to infer the intermediates involved. As reaction proceeded, decrease in concentration of acetophenone (black line) can be corroborated with increasing concentration of product 2b (blue line). Notably, upon oxidation of 4-methylbenzyl alcohol, the in situ formed intermediate 4-methylbenzyl aldehyde (green line) was only short-lived as it undergoes rapid condensation with acetophenone to provide intermediate A (α,β-unsaturated ketones, red line). Reaction kinetics also indicated that hydrogenation of α,β-unsaturated ketone intermediate A to the corresponding alkylated product was rapid at the outset of the reaction and became slower over time ( Figure 1).
In an attempt to further develop these benign catalytic alkylation reactions, cross-coupling of secondary alcohols with primary alcohols, which can result in selective β-alkylation of secondary alcohols leading to the exclusive formation of αalkylated ketones, was envisaged. Thus, using catalyst 1, the cross-coupling reaction between 1-phenyl-1-ethanol and benzyl alcohol was subjected to optimization studies, and the results are presented in Table 5. Initial experiments with different loads of catalyst 1 (3−1 mol %) and base (Cs 2 CO 3 , 10 mol %) provided moderate to complete conversions (entries 1−3, Table 5). Spectral analyses of the isolated product clearly indicated the formation of α-alkylated ketone product, 1,3diphenylpropan-1-one (2a). Upon performing the experiment using 2 mol % catalyst 1 and 5 mol % Cs 2 CO 3 , quantitative conversion of 1-phenyl-1-ethanol was observed and the alkylated product 2a was isolated in 90% yield (entry 4, Table 5). Further decrease of the catalyst and base loads turned out to be detrimental to the progress of the reaction as incomplete conversions were observed after 20 h (entries 5−6,

ACS Omega
Article Table 5). Control experiments using only catalyst 1, base (Cs 2 CO 3 ) alone, and an experiment without catalyst and base (entries 7−9, Table 5) proved that this alkylation requires a catalyst and a base. Further, under similar reaction conditions, the effect of different bases was also explored. K 2 CO 3 and KOH provided moderate yields of product (83 and 40%, respectively). However, use of bases such as NaH, NaOH, Na 2 CO 3 , and KO t Bu resulted in poor conversion of secondary alcohols. Surprisingly, the in situ generation of ketones from the oxidation of secondary alcohols provided facile α-alkylation reactions by primary alcohols. Using only 5 mol % base, the reaction was completed in 20 h compared to the requirement of higher load of base, higher temperature, and longer reaction time required for the direct ketone alkylation by primary alcohols (see Table 1).
As shown in Table 6, a wide range of primary alcohols was subjected to manganese-catalyzed β-alkylation of 1-phenyl-1ethanol, which provided α-alkylated ketones in moderate to excellent yields. Reaction of different benzyl alcohols with 2 mol % catalyst 1 and 5 mol % Cs 2 CO 3 resulted in good conversion of 1-phenyl-1-ethanol, and the β-alkylated products (2a−c and 2l−n) were isolated in 73−90% yields. Further, a series of primary aliphatic alcohols (nonbenzylic) such as 4phenyl-1-butanol, 3-(pyridin-2-yl)propan-1-ol, 1-hexanol, 1octanol, 3,5,5-trimethylhexanol, and 2-cyclohexylethanol were investigated as alkylating partners and, in general, excellent conversions as well as yields were obtained (2o, 2p, 2g, 2i, and 2j; Table 6). Manganese-catalyzed cross-coupling of 1-phenyl-1-ethanol with benzyl alcohols was reported using strong base KO t Bu. 10b Next, substrate scope of structurally diverse secondary alcohols was investigated in the catalytic cross-coupling reactions with various primary alcohols. Initially, different secondary alcohol derivatives bearing electron-donating and electron-withdrawing substituents were subjected to coupling with benzylic and aliphatic alcohol (Table 7). In general, nonactivated primary aliphatic alcohols provided the corresponding alkylated products 3m−p in higher yields than aryl alcohols. Notably, electron-withdrawing halogen-containing secondary alcohols underwent facile β-alkylation reaction and provided the corresponding alkylated products 3q−s and 3c in 66−95% yields. Remarkably, as observed in ketone alkylation  Conversion of 1-phenyl-1-ethanol was determined by GC using toluene as an internal standard. c Isolated yields after column chromatography. d A minor amount of (E)-chalcone formation also observed. Table 6. Manganese-Catalyzed Cross-Coupling of 1-Phenyl-1-ethanol with Primary Alcohols a a Reaction conditions: 1-phenyl-1-ethanol (0.5 mmol), primary alcohol (0.6 mmol), tert-amyl alcohol (2 mL), catalyst 1 (0.01 mmol), and Cs 2 CO 3 (0.025 mmol) were heated at 135°C in open condition under an argon flow. Yield of the products corresponds to isolated pure compounds after column chromatography. Conversion of 1-phenyl-1-ethanol was determined by GC using toluene as an internal standard and given within parentheses.

ACS Omega
Article reactions, the amine functionality is tolerated in the catalytic alkylation reactions. When (4-bromophenyl)-1-ethanol was reacted with (4-aminophenyl)methanol, the desired alkylated product 3t was obtained in 61% yield. Notably, the N-alkylated product was not observed in this condition, which indicates the chemoselective C-alkylation over N-alkylation. Heteroaryl secondary alcohols were also successfully alkylated using this manganese catalysis and alkylated heteroaryl ketones 3u, 3v, and 3e were isolated in moderate to good yields (Table 7). Nickel-catalyzed cross-coupling of secondary alcohols with primary alcohols is reported, which required the use of higher load of base (KOH, 50 mol %). 10c Further, the substrate scope was extended to cyclic secondary alcohols (Table 8). Thus, the reactions of 1-indanol with 1-hexanol and 1-octanol resulted in the corresponding alkylated products 5a and 5b in 98 and 97% isolated yields. Gratifyingly, 1,2,3,4-tetrahydronaphthalen-1-ol and its derivatives efficiently reacted with 1-hexanol and 4-phenyl-1-butanol and afforded the alkylated products 5c, 3h, and 3i in 85−95% isolated yields, respectively ( Table 8).
The reaction progress on β-alkylation reaction of 1-phenyl-1-ethanol with 3-phenyl-1-propanol catalyzed by 1 was monitored using GC, which indicated zero-order kinetics for the conversion of secondary alcohols as well for the formation of β-alkylated ketone product 2o (Figure 2). Notably, upon oxidation of 3-phenyl-1-propanol, the in situ formed intermediate hydrocinnamaldehyde was observed in a trace amount. Further, the rapid condensation of aldehyde with in situ generated acetophenone from 1-phenyl-1-ethanol provides α,β-unsaturated ketone intermediate. However, ketone and α,β-unsaturated ketone intermediates were not observed in the reaction; perhaps they undergo concomitant condensation and hydrogenation reactions, respectively.
In a further attempt to identify the intermediates involved in this transformation, the catalytic reaction of 1-phenyl-1-ethanol with benzyl alcohol was intervened and the reaction mixture was subjected to 1 H NMR analysis, which resonated a characteristic singlet at δ 10.05 ppm and a distinct doublet at δ 7.85 ppm with a coupling constant J = 16 Hz that corresponds to aldehyde proton of benzaldehyde and olefin protons of (E)-chalcone, respectively. 23 Moreover, a mercury poisoning experiment was performed to examine the involvement of any metal nanoparticles formed from complex 1. When the dehydrogenative and dehydrative coupling of 1-phenyl-1-ethanol with benzyl alcohol was carried out in the presence of mercury (2 equiv, relative to substrate), nearly 93% conversion of 1-phenyl-1-ethanol was observed and the alkylated ketone 2a was obtained in 87% (see Scheme 3), indicating the involvement of molecular intermediates. Further, when 1-(4-methoxyphenyl)ethanol independently reacted with catalyst 1 under optimized experimental conditions, exclusive formation of 1-(4-methoxyphenyl)ethanone was observed in 74% yield, confirming the catalytic oxidation of secondary alcohols to ketones.
On the basis of these observations and the experimental studies involving catalyst 1 in recent reports, 14b,22d the plausible catalytic cycle is proposed in Scheme 4. In the presence of catalytic amount of base, the dearomatized coordinatively unsaturated intermediate I is generated from catalyst 1 upon amine deprotonation and debromination from the metal center. O−H activation of the primary and

CONCLUSIONS
In summary, manganese pincer 1 catalyzed cross-coupling of ketones and secondary alcohols with primary alcohols leading to the selective α-alkylation of ketones. Primary alcohols serve as alkylating reagents. Remarkably, using a minimal catalyst load (2 mol %) and base (5−10 mol %), various ketones and secondary alcohols can be efficiently alkylated with an assortment of linear primary alcohols in excellent yields. Ethylation of ketones using ethanol is also demonstrated. Chemoselective α-alkylation of ketones is observed with primary alcohol in the presence of nonbenzylic secondary alcohol. Moreover, chemoselective catalytic C-alkylations of ketone and secondary alcohols over N-alkylation of aryl amine are achieved. Mechanistic studies confirm the formation of aldehyde, ketone, and α,β-unsaturated ketone intermediates. Accordingly, a catalytic cycle incorporating the formation of these intermediates eventually leading to the α-alkylated ketones is proposed. One equivalent of hydrogen liberated from oxidation of primary and secondary alcohols is utilized by the catalyst for the hydrogenation of α,β-unsaturated ketones to deliver the β-alkylated ketones. Overall, the catalytic coupling of ketones with alcohol releases 1 equiv of water, while the cross-coupling of secondary and primary alcohols produces 1 equiv of water and molecular hydrogen from the reactions as the only byproducts.

EXPERIMENTAL SECTION
4.1. General Information. All stoichiometric reactions were performed in nitrogen atmosphere. All catalytic reactions were performed under nitrogen atmosphere using standard Schlenk techniques. Dry solvents were prepared according to standard procedures. 1 H, 13  Inside a glovebox, a 15 mL sealed tube was charged with a stir bar, 2,4-diamino-6-phenyl-1,3,5triazine (2 mmol, 0.374 g), and dry tetrahydrofuran (THF) (8 mL) under nitrogen atmosphere. The solution was cooled to 0°C and then chlorodiisopropylphosphine (4.2 mmol, 0.665 mL) was added dropwise into the reaction mixture. Triethylamine (8 mmol, 1.112 mL) was added to the reaction mixture. The reaction mixture was allowed to warm to room temperature and stirred vigorously for 16 h at 60°C. The suspension was filtered over a glass filter frit with a pad of Celite (3 cm) and washed with 10 mL of THF. The combined organic phase was concentrated in vacuo yielding (4-Ph)Tr(NHP(iPr) 2 ) 2 as a colorless solid (712 mg, 85%). 1    4.3. General Procedure for α-Alkylation of Acetophenone Using Alcohols. Inside a nitrogen atmosphere glovebox, a 25 mL Schlenk tube was charged with a stir bar, catalyst 1 (0.01 mmol), base (0.05 mmol), acetophenone (0.5 mmol), solvent (2 mL), and alcohol (0.6 mmol) in the same order. The reaction flask was taken out of the glovebox and then refluxed (oil bath temperature, 140°C) with stirring in an open system under argon flow for 24 h. The reaction mixture was then cooled down to room temperature. The solvent was evaporated under reduced pressure, and 0.5 mmol internal standard (toluene) was added into the reaction mixture and then diluted with 0.8 mL of acetone. An aliquot of the solution was passed through a small Celite plug and analyzed by GC. The solvent was evaporated under reduced pressure and the crude reaction mixture was purified by column chromatography over silica gel (60−120 mesh) using ethyl acetate/pet ether mixture as an eluent. The conversion of acetophenone was calculated using GC analysis, and yields of pure products were determined after column chromatography.
4.4. General Procedure for Dehydrogenative Cross-Coupling of Alcohols. Inside a nitrogen atmosphere glovebox, a 25 mL Schlenk tube was charged with a stir bar, catalyst 1 (0.01 mmol), Cs 2 CO 3 (0.025 mmol), secondary alcohol (0.5 mmol), tert-amyl alcohol (2 mL), and primary alcohol (0.6 mmol) in the same order. The reaction flask was taken out of the glovebox and refluxed (oil bath temperature 135°C) with stirring in an open system under argon flow for 24 h. The reaction mixture was then cooled down to room temperature. The solvent was evaporated under reduced pressure and 0.5 mmol internal standard (toluene) was added into the reaction mixture and then diluted with 0.8 mL of acetone. An aliquot of the solution was passed through a small Celite plug and analyzed by GC. The solvent was evaporated under reduced pressure, and the crude reaction mixture was purified by column chromatography over silica gel (60−120 mesh) using ethyl acetate/pet ether mixture as an eluent. The conversion of secondary alcohol was calculated using GC analysis, and yields of pure products were determined after column chromatography.    3061, 2930, 1686, 1618, 1597, 1449, 1325, 1163, 1121, 1067   The reaction mixture was then cooled to room temperature. The solvent was evaporated under reduced pressure, and 0.5 mmol internal standard (toluene) was added into the reaction mixture and then diluted with 0.8 mL of acetone. Afterward, an aliquot of this reaction mixture was quickly filtered through a small plug of Celite and analyzed by GC. The solvent was evaporated under reduced pressure, and the crude reaction mixture was purified by column chromatography over silica gel (60−120 mesh) using ethyl acetate/pet ether mixture as an eluent. The conversion of product was calculated using GC analysis, and the yield of pure product was determined after column chromatography. 4.8. Chemoselective α-C-Alkylation of Acetophenone by Primary Alcohols over Secondary Alcohols. Inside a glovebox, a 25 mL Schlenk tube was charged with a magnetic stir bar, catalyst 1 (0.01 mmol), Cs 2 CO 3 (0.05 mmol), acetophenone (0.5 mmol), tert-amyl alcohol (2 mL), 1-hexanol (0.6 mmol), and 3-pentanol (0.6 mmol) sequentially under nitrogen atmosphere. The reaction flask was taken out of the glovebox and then refluxed (oil bath temperature, 140°C) with stirring in an open system under argon flow for 24 h. The reaction mixture was then cooled to room temperature. The solvent was evaporated under reduced pressure, and 0.5 mmol internal standard (toluene) was added into the reaction mixture and then diluted with 0.8 mL of acetone. Afterward, an aliquot of this reaction mixture was quickly filtered through a small plug of Celite and analyzed by GC. The solvent was evaporated under reduced pressure, and the crude reaction mixture was purified by column chromatography over silica gel (60−120 mesh) using ethyl acetate/pet ether mixture as an eluent. The conversion of product was calculated using GC analysis, and the yield of pure product was determined after column chromatography.
4.9. Chemoselective α-C-Alkylation of Acetophenone by Primary Alcohols over N-Alkylation of Aniline. Inside a nitrogen atmosphere glovebox, a 25 mL Schlenk tube was

ACS Omega
Article charged with a stir bar, catalyst 1 (0.01 mmol), Cs 2 CO 3 (0.05 mmol), acetophenone (0.5 mmol), tert-amyl alcohol (2 mL), 1-hexanol (0.6 mmol), and aniline (0.5 mmol) in the same order. The reaction flask was taken out of the glovebox, equipped with a condenser, and the reaction mixture was refluxed (oil bath temperature, 140°C) with stirring in an open system under the flow of argon for 24 h. The reaction mixture was then cooled down to room temperature. The solvent was evaporated under reduced pressure and 0.5 mmol internal standard (toluene) was added into the reaction mixture and the solution was quickly filtered through a small plug of Celite. Afterward, an aliquot of this reaction mixture was dissolved in 0.8 mL of acetone and analyzed by GC analysis. The solvent was evaporated under reduced pressure, and the crude reaction mixture was purified by column chromatography over silica gel (60−120 mesh) using ethyl acetate/pet ether mixture as an eluent. The conversion of product was calculated using GC analysis, and the yield of pure product was determined after column chromatography.
sequentially. The reaction flask was taken out of the glovebox and equipped with a condenser, and the solution was refluxed (oil bath temperature, 135°C) with stirring in open system under the flow of argon. Aliquots were collected from reaction mixture periodically, further diluted with acetone (0.5 mL), and analyzed by GC. The conversion of 1-phenyl-1-ethanol and yield of 2h were calculated using GC analysis.
4.11. Mercury Poisoning Test. Inside a nitrogen atmosphere glovebox, a 25 mL Schlenk tube was charged with a stir bar, catalyst 1 (0.01 mmol), Cs 2 CO 3 (0.025 mmol), 1-phenyl-1-ethanol (0.5 mmol), solvent (2 mL), benzyl alcohol (0.6 mmol), and mercury (2 equiv 200 mg) in the same order. The reaction flask was taken out of the glovebox and then refluxed (oil bath temperature 135°C) with stirring in an open system under argon flow for 24 h. The reaction mixture was then cooled down to room temperature. The solvent was evaporated under reduced pressure and 0.5 mmol of an internal standard (toluene) was added into the reaction mixture and then diluted with 0.8 mL of acetone. An aliquot of the solution was passed through a small Celite plug and analyzed by GC. The solvent was evaporated under reduced pressure, and the crude reaction mixture was purified by column chromatography over silica gel (60−120 mesh) using ethyl acetate/pet ether mixture as an eluent. The conversion of 1-phenyl-1-ethanol was calculated using GC analysis, and the yield of pure product was determined after column chromatography.
4.12. Observation of Ketone Intermediate. In a glovebox, a 25 mL Schlenk tube was charged with a stir bar, catalyst 1 (0.01 mmol), Cs 2 CO 3 (0.025 mmol), 1-(4methoxyphenyl)ethanol (0.5 mmol), and solvent (2 mL) under nitrogen atmosphere. The flask was taken out of the glovebox, equipped with a condenser, and the solution was refluxed (oil bath temperature 135°C) with stirring in an open system under a flow of argon for 20 h. After cooling to room temperature, 0.5 mmol of an internal standard (dodecane) was added and the reaction mixture was subjected GC analysis. The solvent was evaporated, and the crude reaction mixture was purified by column chromatography over silica gel (100− 200 mesh) using ethyl acetate/pet ether as an eluent. The conversion of 1-(4-methoxyphenyl)ethanol was calculated using GC analysis, and yield of pure products after column chromatography.

* S Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.9b01246. 1 H and 13 C NMR spectra of the products (PDF)

Notes
The authors declare no competing financial interest.