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DOI: 10.1055/s-0036-1588928
t-BuONa-Mediated Transition-Metal-Free Autoxidation of Diarylmethanes to Ketones
Publication History
Received: 29 October 2016
Accepted after revision: 04 December 2016
Publication Date:
30 January 2017 (online)
Abstract
Autoxidative sp3 C–H transformation of diarylmethanes has been demonstrated using O2-mediation by t-BuONa. This protocol enables an alternative route for the access to diaryl ketones from benzyl derivatives in good to excellent yields under mild reaction conditions, without transition metal catalysts or additional chemical oxidants.
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Benzylic oxidative C–H functionalization is among the most widely used and fundamental transformations in academic and industrial areas,[1] which allows the production of various carbonyl compounds such as aldehydes, ketones, and carboxylic acid derivatives. For this oxidation process, molecular oxygen (O2) is considered to be of the best choice thanks to its low cost and the emission of water as a unique by-product.[2] However, it is not reactive enough to inert C–H bonds and cannot be readily inserted into unactivated C–H bonds. Thus, the presence of transition metal catalysts has usually been required to promote oxidative reaction efficiency,[1] albeit with the problem of the metal residue and environmental pollution.[3] During the past decades, great progress has been made in the benzylic C–H functionalization;[4] nevertheless, there remains a high need to seek simple, green and efficient synthetic methods for the accomplishment of such transformations.
Aryl ketones, in general, serve as structural units in numerous pharmaceuticals, naturally-occurring products, and organic functional materials.[5] Also, they are widely used as useful intermediates in the construction of new C-based chemical bonds or heterocycles.[6] Traditionally, the synthetic methods of aryl ketones[6a] include classical Friedel–Crafts acylation of arenes,[7] oxidation of secondary alcohols,[8] CO insertion reactions[9] and transition-metal-catalyzed coupling reactions.[10] Notably, the latter has been well developed with the advancement of C–H activation strategies. However, toxic or expensive metal catalysts, harmful oxidants and harsh reaction conditions are still involved in most of the transformations. In addition, the oxygenative carbonylation of benzylic sp 3 C–H bonds is an alternative powerful tool to access aryl ketones. The well-documented strategies employed for such a transformation include oxidation using various stoichiometric chemical oxidants,[11] photo-oxygenation mediated by light,[12] and electrosynthesis by electroxidative C–H activation.[13] Recently, transition-metal-free autoxidative coupling has been attracting extensive interest from chemists.[14] We envisioned that the autoxidative carbonylation of benzyl derivatives using O2 without transition metal catalysts or chemical oxidants would occur. Herein, we demonstrate a transition-metal-free oxygenation of benzylic sp3 C–H bonds by base using an O2-promoted process, allowing the construction of diaryl ketones from benzyl derivatives under mild conditions.
Initially, we set out to optimize the reaction conditions for the autoxidative conversion of diarylmethanes to the carbonylation products using diphenylmethane (1a) as the model substrate. To achieve the optimal reaction parameters, a series of factors such as temperature, bases, solvents, molecular oxygen sources and so on were investigated, and the results are summarized in Scheme [1] and Table [1]. Considering the poor reactivity of diphenylmethane sp 3 C–H bonds to the direct insertion of molecular oxygen, the strong base t-BuONa was chosen to deprotonate the substrate so as to form a carbanion, which is very reactive to molecular oxygen. Delightedly, the use of t-BuONa in anhydrous DMSO at room temperature under O2 balloon smoothly delivered the carbonylation product 2a in moderate yield (52%; Table [1], entry 1), albeit with part of 1a unconverted. Thus, different reaction temperatures were attempted. It turned out that with the temperature increasing, the efficiency climbed up to the best yield (92%) at the range of 50–60 °C (Table [1], entries 4 and 5), and the reaction underwent to completion within less than one hour. From the viewpoint of energy consumption, we chose 50 °C as our preferred reaction temperature in this autoxidative reaction.
a Reactions were carried out using diphenylmethane (0.2 mmol) and base (0.4 mmol) in anhyd solvent (0.5 mL) under O2 balloon for the indicated time.
b Carried out in an open flask.
Later on, screening other strong bases such as t-BuOK, NaH, KOH and NaOH showed that slightly lower efficiencies were observed (Table [1], entries 6–9). This suggests that the addition of a strong base accelerated the oxidation reaction without a long induction period as required in usual C–H bond autoxidation. However, the use of weaker bases such as K2CO3 and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) failed to give the desired product with 1a intact (Table [1], entries 10 and 11), in spite of the prolonged reaction time. It may result from their inability to effectively snatch hydrogen atom from 1a. Furthermore, tuning the amount of t-BuONa (see Supporting Information) indicated that decreasing the amount (< 2 equiv) led to the remarkable erosion of the yield due to the incomplete conversion of 1a. Further increasing the base amount did not give higher yield.
As for the solvents, the reaction underwent smoothly in aprotic and highly polar solvents (Table [1], entries 1–9 and 12). For example, DMSO furnished the best yield (see Supporting Information). By contrast, the transformation did not occur in protic solvents or aprotic but lower polar solvents (MeOH, MeCN, EtOAc, THF and CH2Cl2), with the starting material quantitatively recovered (Table [1], entries 13–17).
The molecular oxygen source also exerted a significant impact on the efficiency (Table [1], entry 18). The reaction in an open flask for five hours provided a medium yield (Table [1], entry 18). It is worthwhile to note that extreme removal of water or moisture in solvent, oxygen, and reaction system favored the efficiency, probably due to the suppression of the oxidative fission of benzophenone C(C=O)–C bond.[15]
Having established the optimal reaction conditions,[16] we attempted to investigate the scope of the benzyl compounds. The data listed in Scheme [1] reveals that this autoxidative reaction underwent smoothly for the various substrates tested, all giving good to excellent yields. It appears that the presence of electron-withdrawing groups increased the oxidation reactivity and selectivity of the benzylic C–H bonds in the presence of a strong base (2h–l), while the introduction of electron-donating substituents decreased the reaction efficiencies (2b–g). This may result from the acidity enhancement of the benzylic C–H bonds by electron-withdrawing groups, and as a consequence the ease to abstract the hydrogen atom by base, and thus the susceptibility of carbanion to oxygen. Meanwhile, the electron-drawing substituents suppressed the oxidation of aromatic rings, whereas the electron-donating substituents gave rise to an opposite impact. Unlike the electronic effects, however, steric effects exerted no significant influence. For instance, Me, OMe located at ortho- or para-position offered similar yields (2b vs 2c, 2f vs 2g). Furthermore, this protocol was successfully applicable to the substitutions on the two arenes (2m–v). When both benzene rings of the substrates possessed electron-donating groups such as methyl, the reaction gave a lower but nonetheless good yield (2c vs 2m).
When an electron-withdrawing group was introduced to the system bearing an electron-donating group, the yield occurred between that of the system with only electron-donating group and that with only electron-withdrawing one (2d vs 2p, 2e vs 2o). When connected with both electron-withdrawing groups, the yields turned out to be excellent and amounted up to 98% (2v).
In particular, the electron-donating groups such as Me or OMe were well tolerated in this reaction although they possess benzylic C–H bonds and are prone to oxidation. The C-halo groups were compatible with this procedure and the oxygenation products were obtained in excellent isolated yields (2h–k,n–v). The NO2 group delivered the desired ketone almost quantitatively (2l) due to its strong activation of the benzylic C–H bonds and the nature of strongly retarding the oxidation of aromatic rings. Importantly, the compatibility of halo and nitro groups allow the possibility for further post-functionalization based on the C-halo activation[17] or hydrogen-borrowing strategies.[18]
With the successful oxygenation of diarylmethanes, we had expected to expand this protocol to the oxygenative carbonylation of the monoaryl systems. Much to our disappointment, however, 1,2,3,4-tetrahydronaphthalene, 1-(4-ethylphenyl)ethan-1-one, ethylbenzene, or 1-ethyl-4-nitrobenzene were inert in such transformation, even on increasing the amount of base or elevating the reaction temperature (up to 100 °C). Similarly, dibenzyl ether was an inert substrate, which could not furnish its corresponding benzyl benzoate.
To gain an insight into the mechanism for the autoxidative reaction, several control experiments were conducted (Scheme [2]). First, the traditional radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) was used in this transformation. Although the reaction was not completely inhibited, the isolated yield was remarkably reduced to 30% using two equivalents of TEMPO. Moreover, the TEMPO-adduct was isolated and confirmed by 1H NMR and 13C NMR spectra. This suggested that the reaction likely involved a radical process. Second, when we monitored the reaction process using TLC and GC–MS analysis, the presence of benzhydrol was observed, which reminded us of the benzyl alcohols being a possible intermediate in the autoxidative formation of the ketones. Thus, we used benzhydrol as the substrate under the standard conditions. It turned out that the reaction completed within 30 minutes, and resulted in an almost quantitative conversion into the corresponding ketone 2a.
Finally, we attempted to carry out this standard reaction under argon atmosphere using anhydrous air-degassed DMSO, via three oxygen-evacuating/argon-refilling cycles. The TLC and GC–MS analyses showed that no reaction occurred, with only the starting material detected. This means that in this transformation, molecular oxygen is indispensable.
Base-mediation suggests that this autoxidative carbonylation most likely involves an anion-radical oxidation rather than a pure free-radical process. Based on the documented reports[12a] [19] and our experimental observations, a tentative mechanism is proposed for this base-promoted autoxidative formation of diaryl ketones,[20] as shown in Scheme [3]. In the case of diphenylmethane (1a), the t-BuO anion initially abstracts the hydrogen atom from 1a to form a carbanionic intermediate 3, which is oxidized by oxygen to intermediate free radical 4. The radical 4 would be rapidly converted into a peroxy radical 5 in the presence of excess oxygen. Undoubtedly, this rapid consumption of 4 accounts for the absence of the homocoupled product. Then, the peroxy radical 5 can be readily transformed into a hydroperoxidate intermediate 6 by the proton abstraction from the species such as t-BuOH or 1a in the reaction system. Next, this intermediate 6 loses one water molecule to yield the desired ketone 2 or otherwise converts to the benzyl alcohol 7, which undergoes further autoxidative transformation mediated by base to finally produce the ketone 2.
In conclusion, we have demonstrated an autoxidative oxygenation of diarylmethanes sp3 C–H bonds in the presence of O2-mediation by t-BuONa. This protocol allows for an alternative method for ready access to diaryl ketones from benzyl derivatives in good to excellent yields. The transformation smoothly undergoes under mild reaction conditions without transition metal catalysts or additional chemical oxidants. Extensive investigation on the autoxidative reactions of other sp3 C–H bonds is still underway.
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Acknowledgment
This work was supported by the National Natural Science Foundation of China (21202010 & 21376031), the Hunan Provincial Natural Science Foundation of China (2015JJ3012), the Scientific Research Fund of Hunan Provincial Education Department (16B003), the Hunan Provincial Science and Technology Project (2013FJ3076), the Hunan Provincial Key Laboratory of Materials Protection for Electric Power and Transportation (2015CL05), Changsha University of Science & Technology, P. R. of China.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org.accesdistant.sorbonne-universite.fr/10.1055/s-0036-1588928.
- Supporting Information
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References and Notes
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- 1b Sheldon R. Metal-catalyzed Oxidations of Organic Compounds: Mechanistic Principles and Synthetic Methodology Including Biochemical Processes. Elsevier; Amsterdam: 2012
- 2 Campbell AN, Stahl SS. Acc. Chem. Res. 2012; 45: 851
- 3 Garrett CE, Prasad K. Adv. Synth. Catal. 2004; 346: 889
- 4a Li B.-J, Shi Z.-J. Chem. Soc. Rev. 2012; 41: 5588
- 4b Scheuermann CJ. Chem. Asian J. 2010; 5: 436
- 4c Girard SA, Knauber T, Li C.-J. Angew. Chem. Int. Ed. 2014; 53: 74
- 4d Sakamoto R, Inada T, Selvakumar S, Moteki SA, Maruoka K. Chem. Commun. 2016; 52: 3758
- 4e Zhang L, Yi H, Wang J, Lei A. Green Chem. 2016; 18: 5122
- 4f Zhang W, Wang F, McCann SD, Wang D, Chen P, Stahl SS, Liu G. Science 2016; 353: 1014
- 4g Li J.-S, Xue Y, Fu D.-M, Li D.-L, Li Z.-W, Liu W.-D, Pang H.-L, Zhang Y.-F, Cao Z, Zhang L. RSC Adv. 2014; 4: 54039
- 4h Mao D, Zhu X, Hong G, Wu S, Wang L. Synlett 2016; 27: 2481
- 5a Wu S.-B, Long C, Kennelly EJ. Nat. Prod. Rep. 2014; 31: 1158
- 5b Belluti F, De Simone A, Tarozzi A, Bartolini M, Djemil A, Bisi A, Gobbi S, Montanari S, Cavalli A, Andrisano V, Bottegoni G, Rampa A. Eur. J. Med. Chem. 2014; 78: 157
- 5c Vooturi SK, Cheung CM, Rybak MJ, Firestine SM. J. Med. Chem. 2009; 52: 5020
- 5d Lee SY, Yasuda T, Yang YS, Zhang Q, Adachi C. Angew. Chem. Int. Ed. 2014; 53: 6402
- 5e Ryabchun A, Sakhno O, Wegener M. RSC Adv. 2016; 6: 51791
- 6a Larock RC. Comprehensive Organic Transformations: A Guide to Functional Group Preparations. Wiley; New York: 1999
- 6b Li J.-S, Fu D.-M, Xue Y, Li Z.-W, Li D.-L, Da Y.-D, Yang F, Zhang L, Lu C.-H, Li G. Tetrahedron 2015; 71: 2748
- 6c Li J.-S, Cai F.-F, Li Z.-W, Liu W.-D, Simpson J, Xue Y, Pang H.-L, Huang P.-M, Cao Z, Li D.-L. RSC Adv. 2014; 4: 474
- 6d Li J.-S, Xue Y, Li Z.-W, Liu W.-D, Lu C.-H, Zhao P.-X. Synlett 2013; 24: 2003
- 7 Sartori G, Maggi R. Advances in Friedel–Crafts Acylation Reactions: Catalytic and Green Processes. CRC Press; Boca Raton: 2009
- 8 Tojo G, Fernández MI. Oxidation of Alcohols to Aldehydes and Ketones: A Guide to Current Common Practice. Springer Science & Business Media; New York: 2006
- 9a Colquhoun H, Thompson D, Twigg MV. Carbonylation: Direct Synthesis of Carbonyl Compounds. Springer Science & Business Media; New York: 1991
- 9b Beller M, Wu X.-F. Transition-Metal-Catalyzed Carbonylation Reactions. Springer; Berlin/Heidelberg: 2013
- 10a Sharma S, Mishra NK, Shin Y, Kim IS. Curr. Org. Chem. 2016; 20: 471
- 10b Wu X.-F. Chem. Eur. J. 2015; 21: 12252
- 10c Pan C, Jia X, Cheng J. Synthesis 2012; 44: 677
- 11a Zarghani M, Akhlaghinia B. RSC Adv. 2016; 6: 38592
- 11b He C, Zhang X, Huang R, Pan J, Li J, Ling X, Xiong Y, Zhu X. Tetrahedron Lett. 2014; 55: 4458
- 12a Yi H, Bian C, Hu X, Niu L, Lei A. Chem. Commun. 2015; 51: 14046
- 12b Muehldorf B, Wolf R. Chem. Commun. 2015; 51: 8425
- 13 Meng L, Su J, Zha Z, Zhang L, Zhang Z, Wang Z. Chem. Eur. J. 2013; 19: 5542
- 14a Luo K, Chen YZ, Chen LX, Wu L. J. Org. Chem. 2016; 81: 4682
- 14b Klussmann M, Schweitzer-Chaput B. Synlett 2016; 27: 190
- 14c Lu QQ, Yi H, Lei AW. Acta Chim. Sinica 2015; 73: 1245
- 14d Ueda H, Yoshida K, Tokuyama H. Org. Lett. 2014; 16: 4194
- 14e Huo C, Yuan Y, Wu M, Jia X, Wang X, Chen F, Tang J. Angew. Chem. Int. Ed. 2014; 53: 13544
- 14f Xu Q.-L, Gao H, Yousufuddin M, Ess DH, Kürti L. J. Am. Chem. Soc. 2013; 135: 14048
- 14g Pinter A, Sud A, Sureshkumar D, Klussmann M. Angew. Chem. Int. Ed. 2010; 49: 5004
- 15a Gassman PG, Lumb JT, Zalar FV. J. Am. Chem. Soc. 1967; 89: 946
- 15b Swan GA. J. Chem. Soc. 1948; 1408
- 16 Typical Procedure for t-BuONa-Mediated Autoxidation of Diarylmethanes to Ketones: To a predried 5-mL round-bottom flask diarylmethane 1a (0.4 mmol, 67 mg, 1 equiv), anhyd DMSO (0.4 mol/L), and t-BuONa (0.8 mmol, 77 mg, 2 equiv) were subsequently added as soon as possible. The reaction system was sealed by a rubber septum with a needle connected to an O2 balloon, and then stirred at 50 °C for 1 h. During this period, the reaction system suffered complex color changes. The usual workup afforded the desired ketone 2a as a white solid (yield: 92%, 67 mg); mp 48–49 °C. 1H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 7.7 Hz, 4 H), 7.59 (t, J = 7.3 Hz, 2 H), 7.48 (t, J = 7.5 Hz, 4 H). 13C NMR (101 MHz, CDCl3): δ = 196.8, 137.6 (2 × C), 132.4 (2 × C), 130.1 (4 × C), 128.3 (4 × C). EI–MS: m/z = 182.0 [M]+.
- 17a De Meijere A, Bräse S, Oestreich M. Metal-Catalyzed Cross-Coupling Reactions and More. John Wiley & Sons; New York: 2013
- 17b Ribas X. CH and CX Bond Functionalization: Transition Metal Mediation. Royal Society of Chemistry; London: 2013
- 18a Xie Y, Liu S, Liu Y, Wen Y, Deng G.-J. Org. Lett. 2012; 14: 1692
- 18b Xiao F, Liu Y, Tang C, Deng G.-J. Org. Lett. 2012; 14: 984
- 19 Miao C, Zhao H, Zhao Q, Xia C, Sun W. Catal. Sci. Technol. 2016; 6: 1378
- 20 Chebolu R, Bahuguna A, Sharma R, Mishra VK, Ravikumar PC. Chem. Commun. 2015; 51: 15438
-
References and Notes
- 1a Trost BM, Fleming I. Comprehensive Organic Synthesis: Selectivity, Strategy & Efficiency in Modern Organic Chemistry. Vol. 7. Pergamon Press; Oxford: 2007
- 1b Sheldon R. Metal-catalyzed Oxidations of Organic Compounds: Mechanistic Principles and Synthetic Methodology Including Biochemical Processes. Elsevier; Amsterdam: 2012
- 2 Campbell AN, Stahl SS. Acc. Chem. Res. 2012; 45: 851
- 3 Garrett CE, Prasad K. Adv. Synth. Catal. 2004; 346: 889
- 4a Li B.-J, Shi Z.-J. Chem. Soc. Rev. 2012; 41: 5588
- 4b Scheuermann CJ. Chem. Asian J. 2010; 5: 436
- 4c Girard SA, Knauber T, Li C.-J. Angew. Chem. Int. Ed. 2014; 53: 74
- 4d Sakamoto R, Inada T, Selvakumar S, Moteki SA, Maruoka K. Chem. Commun. 2016; 52: 3758
- 4e Zhang L, Yi H, Wang J, Lei A. Green Chem. 2016; 18: 5122
- 4f Zhang W, Wang F, McCann SD, Wang D, Chen P, Stahl SS, Liu G. Science 2016; 353: 1014
- 4g Li J.-S, Xue Y, Fu D.-M, Li D.-L, Li Z.-W, Liu W.-D, Pang H.-L, Zhang Y.-F, Cao Z, Zhang L. RSC Adv. 2014; 4: 54039
- 4h Mao D, Zhu X, Hong G, Wu S, Wang L. Synlett 2016; 27: 2481
- 5a Wu S.-B, Long C, Kennelly EJ. Nat. Prod. Rep. 2014; 31: 1158
- 5b Belluti F, De Simone A, Tarozzi A, Bartolini M, Djemil A, Bisi A, Gobbi S, Montanari S, Cavalli A, Andrisano V, Bottegoni G, Rampa A. Eur. J. Med. Chem. 2014; 78: 157
- 5c Vooturi SK, Cheung CM, Rybak MJ, Firestine SM. J. Med. Chem. 2009; 52: 5020
- 5d Lee SY, Yasuda T, Yang YS, Zhang Q, Adachi C. Angew. Chem. Int. Ed. 2014; 53: 6402
- 5e Ryabchun A, Sakhno O, Wegener M. RSC Adv. 2016; 6: 51791
- 6a Larock RC. Comprehensive Organic Transformations: A Guide to Functional Group Preparations. Wiley; New York: 1999
- 6b Li J.-S, Fu D.-M, Xue Y, Li Z.-W, Li D.-L, Da Y.-D, Yang F, Zhang L, Lu C.-H, Li G. Tetrahedron 2015; 71: 2748
- 6c Li J.-S, Cai F.-F, Li Z.-W, Liu W.-D, Simpson J, Xue Y, Pang H.-L, Huang P.-M, Cao Z, Li D.-L. RSC Adv. 2014; 4: 474
- 6d Li J.-S, Xue Y, Li Z.-W, Liu W.-D, Lu C.-H, Zhao P.-X. Synlett 2013; 24: 2003
- 7 Sartori G, Maggi R. Advances in Friedel–Crafts Acylation Reactions: Catalytic and Green Processes. CRC Press; Boca Raton: 2009
- 8 Tojo G, Fernández MI. Oxidation of Alcohols to Aldehydes and Ketones: A Guide to Current Common Practice. Springer Science & Business Media; New York: 2006
- 9a Colquhoun H, Thompson D, Twigg MV. Carbonylation: Direct Synthesis of Carbonyl Compounds. Springer Science & Business Media; New York: 1991
- 9b Beller M, Wu X.-F. Transition-Metal-Catalyzed Carbonylation Reactions. Springer; Berlin/Heidelberg: 2013
- 10a Sharma S, Mishra NK, Shin Y, Kim IS. Curr. Org. Chem. 2016; 20: 471
- 10b Wu X.-F. Chem. Eur. J. 2015; 21: 12252
- 10c Pan C, Jia X, Cheng J. Synthesis 2012; 44: 677
- 11a Zarghani M, Akhlaghinia B. RSC Adv. 2016; 6: 38592
- 11b He C, Zhang X, Huang R, Pan J, Li J, Ling X, Xiong Y, Zhu X. Tetrahedron Lett. 2014; 55: 4458
- 12a Yi H, Bian C, Hu X, Niu L, Lei A. Chem. Commun. 2015; 51: 14046
- 12b Muehldorf B, Wolf R. Chem. Commun. 2015; 51: 8425
- 13 Meng L, Su J, Zha Z, Zhang L, Zhang Z, Wang Z. Chem. Eur. J. 2013; 19: 5542
- 14a Luo K, Chen YZ, Chen LX, Wu L. J. Org. Chem. 2016; 81: 4682
- 14b Klussmann M, Schweitzer-Chaput B. Synlett 2016; 27: 190
- 14c Lu QQ, Yi H, Lei AW. Acta Chim. Sinica 2015; 73: 1245
- 14d Ueda H, Yoshida K, Tokuyama H. Org. Lett. 2014; 16: 4194
- 14e Huo C, Yuan Y, Wu M, Jia X, Wang X, Chen F, Tang J. Angew. Chem. Int. Ed. 2014; 53: 13544
- 14f Xu Q.-L, Gao H, Yousufuddin M, Ess DH, Kürti L. J. Am. Chem. Soc. 2013; 135: 14048
- 14g Pinter A, Sud A, Sureshkumar D, Klussmann M. Angew. Chem. Int. Ed. 2010; 49: 5004
- 15a Gassman PG, Lumb JT, Zalar FV. J. Am. Chem. Soc. 1967; 89: 946
- 15b Swan GA. J. Chem. Soc. 1948; 1408
- 16 Typical Procedure for t-BuONa-Mediated Autoxidation of Diarylmethanes to Ketones: To a predried 5-mL round-bottom flask diarylmethane 1a (0.4 mmol, 67 mg, 1 equiv), anhyd DMSO (0.4 mol/L), and t-BuONa (0.8 mmol, 77 mg, 2 equiv) were subsequently added as soon as possible. The reaction system was sealed by a rubber septum with a needle connected to an O2 balloon, and then stirred at 50 °C for 1 h. During this period, the reaction system suffered complex color changes. The usual workup afforded the desired ketone 2a as a white solid (yield: 92%, 67 mg); mp 48–49 °C. 1H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 7.7 Hz, 4 H), 7.59 (t, J = 7.3 Hz, 2 H), 7.48 (t, J = 7.5 Hz, 4 H). 13C NMR (101 MHz, CDCl3): δ = 196.8, 137.6 (2 × C), 132.4 (2 × C), 130.1 (4 × C), 128.3 (4 × C). EI–MS: m/z = 182.0 [M]+.
- 17a De Meijere A, Bräse S, Oestreich M. Metal-Catalyzed Cross-Coupling Reactions and More. John Wiley & Sons; New York: 2013
- 17b Ribas X. CH and CX Bond Functionalization: Transition Metal Mediation. Royal Society of Chemistry; London: 2013
- 18a Xie Y, Liu S, Liu Y, Wen Y, Deng G.-J. Org. Lett. 2012; 14: 1692
- 18b Xiao F, Liu Y, Tang C, Deng G.-J. Org. Lett. 2012; 14: 984
- 19 Miao C, Zhao H, Zhao Q, Xia C, Sun W. Catal. Sci. Technol. 2016; 6: 1378
- 20 Chebolu R, Bahuguna A, Sharma R, Mishra VK, Ravikumar PC. Chem. Commun. 2015; 51: 15438
