Chinese Chemical Letters  2016, Vol.27 Issue (04): 571-574   PDF    
Copper-catalyzed decarboxylative hydroboration of phenylpropiolic acids under ligand-free or both ligand- and base-free conditions
Ying-Wei Zhao, Qiang Feng, Qiu-Ling Song     
Institute of Next Generation Matter Transformation, College of Chemical Engineering, Huaqiao University, Xiamen 361021, China
Abstract: An efficient copper-catalyzed decarboxylative hydroboration of phenylpropiolic acids with bis(pinacolato) diboron was developed, affording β-vinylboronates as the only products in high yields. Extra hydrogen sources such as methanol are not needed in this catalytic system. This reaction could be performed successfully under ligand- and base-free conditions. It demonstrated that phenylpropiolic acids can be employed as alkyne synthons in the hydroboration reaction and exhibited good reactivity and higher selectivity than terminal alkynes.
Key words: Decarboxylation     Hydroboration     Ligand-free     Base-free     Copper-catalysis    
1. Introduction

Alkenylboron compounds are especially versatile building blocks that are widely employed as vinyl anionic or cationic synthons in a myriad of coupling reactions [1], as well as they can be readily transformed into various vinylic derivatives [2]. Over the past years, the transition-metal-catalyzed addition of boron to carbon-carbon triple bonds presents a convenient and important strategy for alkenylboron synthesis [3]. Among them, coppercatalyzed hydroboration of alkynes has attracted much attention due to the readily availability, low cost, and low toxicity of copper salts. Great progress has been made by Miyaura [4], Yun [5], Li [6], Haveyda [7], and others [8]. However, some limitations still exist, such as the requirement of ligand, base, and special hydrogen source, thus the development of more efficient method with much wide applicability to prepare vinylboronates via copper-catalyzed regioselective hydroboration of aryl alkynes is still a challenge for synthetic organic chemistry. On the other hand, alkynyl carboxylic acids are regarded as ideal substitutions for terminal alkynes and have been widely applied in the transition-metal-catalyzed construction of C-C and C-heteroatoms bonds via decarboxylation [9]. In particular, alkynyl carboxylic acids exhibit superiority to terminal alkynes in the reactions: they are often more reactive, and they can efficiently suppress the Glaser coupling reaction that frequently occurs in the Sonogashira reactions. As part of our ongoing research into the development of highly efficient and versatile copper-catalyzed decarboxylative reactions [10], and in conjunction with our work on oxidative decarboxylative coupling of arylpropiolic acids with dialkyl H-phosphonates [11], we decided to expand this strategy in the copper-catalyzed hydroborations. Recently, we have achieved the synthesis of bisdeuterated β-borylated α, β-styrene derivatives from the reaction of alkynyl acids with bis(pinacolato)diboron under base-free conditions [12]. Herein, we report our results on the general hydroboration using alkynyl acids as the substrates under ligandfree or both ligand- and base-free conditions.

2. Experimental

All experiments were conducted with a Schlenk tube. Flash column chromatography was performed over silica gel (200-300 mesh). 1H NMR spectra were recorded on a Bruker AVⅢ-400M or AVⅢ-500M spectrometers. Chemical shifts (in ppm) were referenced to CDCl3 (δ 7.26) as an internal standard. 13C NMR spectra were obtained by using the same NMR spectrometers and were calibrated with CDCl3 (δ 77.0). Unless otherwise noted, materials obtained from commercial suppliers were used without further purification. Anhydrous dioxane was obtained by refluxing for at least 12 h over sodium and freshly distilled prior to use.

General procedure for the synthesis of (E)-4, 4, 5, 5-tetramethyl- 2-styryl-1, 3, 2-dioxaborolane (3a): A Schlenk tube with a magnetic stirring bar was charged with 3-phenylpropiolic acid (1a, 68 mg, 0.5 mmol), bis(pinacolato)diboron (2a, 152 mg, 0.6 mmol), Cu(TFA)2 (29 mg, 10 mol%), Na2CO3 (127 mg, 1.2 mmol), and 1, 4-dioxane (2 mL) under N2. The reaction mixture was stirred at 80 ℃ for 18 h (monitored by TLC and GC). Upon completion of the reaction, the reaction mixture was then cooled to ambient temperature, diluted with ethyl acetate (20 mL), filtered through a plug of silica gel, and washed with ethyl acetate (20 mL). The organic layer was washed with saturated brine (20 mL × 2) and dried over anhydrous Na2SO4. The solvents were removed via rotary evaporator and the residue was purified by flash chromatography (silica gel, ethyl acetate: petroleum ether = 1:30) to give 89.7 mg of desired product 3a in 78% yield as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.48-7.50 (m, 2H), 7.41 (d, 1H, J = 18.5 Hz), 7.29-7.32 (m, 3H), 6.18 (d, 1H, J = 18.4 Hz), 1.32 (s, 12H). 13C NMR (100 MHz, CDCl3): δ 148.5, 136.4, 127.9, 127.5, 126.0, 82.3, 23.8.

3. Results and discussion

We chose 3-phenylpropiolic acid (1a) and bis(pinacolato)- diboron (2a) as the model substrates. Initially, the reaction was conducted in the presence of 10 mol% of Cu(OTf)2 and 1.2 equiv. of Na2CO3 in benzene at 80 ℃ underN2 atmosphere and no extra ligand and hydrogen source were used. To our delight, bborylated α, β-styrene with E-configuration (3aa) was formed in =% yield as the single product (Table 1, entry 1). When the reaction temperature was raised to 90 ℃, a slight decrease on the product yieldwas observed and no reaction occurred at room temperature (Table 1, entries 2 and 3). Further screening of the solvents showed that acetonitrile and 1, 4-dioxane are good choice for this reaction (Table 1, entries 5-9).We also employed other copper catalysts and copper trifluoroacetate (Cu(TFA)2) exhibited the best activity (Table 1, entry 12). The yield of 3aa could be further enhanced to 83% when 2.2 equiv. of Na2CO3 was employed. To our surprise, in the absence of the base Na2CO3, also 37% yield could be obtained (Table 1, entry 14). Then we screened the copper catalyst again under base-free condition and found out that Cu2O could lead to satisfied result, probably because of its potential basicity (Table 1, entry 18). Considering that actually a double amount of [Cu] was involved for Cu2O, a loading of 5 mol% was used and a little lower yield was obtained (Table 1, entry 20). Further increasing the reaction temperature to 100 ℃ made the product being formed nearly quantitatively (Table 1, entry 21). Finally, this reaction performed smoothly at room temperature if a phosphorous ligand was added (Table 1, entry 22). It is noteworthy that the solvents we used were actually wet. When the reaction under the conditions as in entry 19 was performed in anhydrous dioxane, only 7% of 3aa was obtained. If extra 0.25 mmol of water (0.5 equiv.) was added to anhydrous dioxane, the yield was 31%. Only when more than 1 equiv. of water was used, acceptable around 60% yield could be achieved, indicating that water content in the wet dioxane we used was higher than 0.4%.

Table 1
Optimization of the reaction conditions.a

After establishing the optimized reaction conditions of the different catalytic systems, a variety of alkynyl carboxylic acids and diboron reagents were subjected (Table 1, entries 13 and 21) to evaluate the scope of the copper-catalyzed decarboxylative regioselective hydroboration reaction. As shown in Scheme 1, phenylpropiolic acids with both electron-rich and electrondeficient substituents on the aromatic ring could be smoothly converted into the desired products. The position of the substitutes on the aromatic rings had some influence on yields (3b-3c, 3d-3e, 3m-3o, 3p-3q), with ortho-substitutions usually giving lower yields of β-borylated α, β-styrene when compared to meta- and para-substitutions, probably because of steric hindrance. It is noteworthy that most halo-substituted aryl groups survived well, leading to halo-substituted aromatic β-borylated α, β-styrene in good yields which could be used for further transformations (3m- 3r). In addition, 4-phenyl, 1-naphthyl, 4-trifluoromethyl, 4-cyano substituted 3-phenylpropiolic acid and 3-(thiophen-2-yl)propiolic acid were transformed into corresponding β-borylated α, bstyrenes smoothly as well (3h-3l).

Scheme 1.Substrate scope. Reaction conditions: (a) 1 (0.5 mmol), 2 (1.2 equiv., 0.6 mmol), Cu(TFA)2 (10 mol%), Na2CO3 (2.2 equiv., 1.1 mmol), 1, 4-dioxane (2 mL) under N2, 80 ℃, 18 h, isolated yield; (b) 1 (0.5 mmol), 2 (1.2 equiv., 0.6 mmol), Cu2O (10 mol%), 1, 4-dioxane (2 mL) under N2, 100 ℃, 18 h, isolated yield.

In order to understand the reactionmechanism, some control experiments were performed. When potassium 3-phenylpropiolate was performed as starting material in anhydrous solvent (Scheme 2, eq. 1), only trace of hydroboration product was formed. This result indicates that the hydrogen of alkynyl carboxylic acids and water in the solvent under ‘‘standard condition’’ offers the protons as the electrophilic source. When D2O was added to the standard reaction system, high deuterium incorporation for both olefinic protons in 3a-D2 was obtained (Scheme 2, eq. 2). Utilizing phenylacetylene instead of 3- phenylpropiolic acid as the substrate to perform the reactions with D2O under the standard conditions resulted in a slight lower reactivity and poorer deuterium incorporation than alkynyl carboxylic acids (Scheme 2, eq. 3).

Scheme 2.Control experiments.

Based on previous copper-catalyzed hydroboration reactions and our own work, we suggested that the reation may be performed through the addition of copper-boron species (Ⅰ) to the C-C triple bond of (phenylethynyl) copper intermediate (Ⅱ) which is generated via decarboxylation of phenylpropiolic acid under base-free condition, followed by the formation of (E)- alkenyl-bis-copper reactive intermediate (Ⅲ) which has two reactive positions with two copper atoms on. Finally, it can be trapped by protons to afford the (E)-β-borylated α, β-styrene (Scheme 3).

Scheme 3.Proposed mechanism.
4. Conclusion

In conclusion, we have developed efficient catalytic systems to synthesize alkenylboronates via copper-catalyzed decarboxylative regioselective hydroboration of alkynyl carboxylic acids under ligand-free or both ligand and base-free conditions. The application of alkynyl carboxylic acids instead of terminal alkynes can lead to a highly active and selective hydroboration reaction. Mechanic investigations supported the formation of an alkenyl-bis-copper reactive intermediate. This novel strategy has great potential in the development of bis-functionalization of carbon-carbon triple bond. Further studies on exploration of the reaction scope, mechanistic elucidation, and synthetic application of this protocol are ongoing in our laboratory.


Financial support from the National Science Foundation of China (No. 21202049), the Recruitment Program of Global Experts (1000 Talents Plan) and Fujian Hundred Talents Plan and Program of Innovative Research Team of Huaqiao University are gratefully acknowledged. We also thank Instrumental Analysis Center of Huaqiao University for analysis support.

[1] B. Carboni, L. Monnier, Recent developments in the chemistry of amine- and phosphine-boranes, Tetrahedron 55(1999) 1197-1248.
[2] (a) H.C. Brown, T. Hamaoka, N. Ravindran, Reaction of alkenylboronic acids with iodine under the influence of base. Simple procedure for the stereospecific conversion of terminal alkynes into trans-1-alkenyl iodides via hydroboration, J. Am. Chem. Soc. 95(1973) 5786-5788;(b) G.A. Molander, N.M. Ellis, Highly stereoselective synthesis of cis-alkenyl pinacolboronates and potassium cis-alkenyltrifluoroborates via a hydroboration/protodeboronation approach, J. Org. Chem. 73(2008) 6841-6844;(c) R.E. Shade, A.M. Hyde, J.C. Olsen, C.A. Merlic, Copper-promoted coupling of vinyl boronates and alcohols:a mild synthesis of allyl vinyl ethers, J. Am. Chem. Soc. 132(2010) 1202-1203;(d) P.J. Riss, S. Lu, S. Telu, F.I. Aigbirhio, V.W. Pike, CuI-catalyzed 11C carboxylation of boronic acid esters:a rapid and convenient entry to 11C-labeled carboxylic acids, esters, and amides, Angew. Chem. Int. Ed. 51(2012) 2698-2702;(e) N.R. Candeias, F. Montalbano, P.M.S.D. Cal, P.M.P. Gois, Boronic acids and esters in the Petasis-borono Mannich multicomponent reaction, Chem. Rev. 110(2010) 6169-6193;(f) M. Tredwell, S.M. Preshlock, N.J. Taylor, et al., A general copper-mediated nucleophilic 18F fluorination of arenes, Angew. Chem. Int. Ed. 53(2014) 7751-7755.
[3] (a) Y.D. Bidal, F. Lazreg, C.S.J. Cazin, Copper-catalyzed regioselective formation of Tri- and tetrasubstituted vinylboronates in air, ACS Catal. 4(2014) 1564-1569;(b) C. Gunanathan, M. Hö lscher, F. Pan, W. Leitner, Ruthenium catalyzed hydroboration of terminal alkynes to Z-vinylboronates, J. Am. Chem. Soc. 134(2012) 14349-14352.
[4] K. Takahashi, T. Ishiyama, N. Miyaura, A borylcopper species generated from bis(pinacolato)diboron and its additions to α,β-unsaturated carbonyl compounds and terminal alkynes, J. Organomet. Chem. 625(2001) 47-53.
[5] (a) J.E. Lee, J. Kwon, J. Yun, Copper-catalyzed addition of diboron reagents to[small alpha],[small beta]-acetylenic esters:efficient synthesis of β-boryl-α,bethylenic esters, Chem. Commun. (2008) 733-734;(b) H.R. Kim, I.G. Jung, K. Yoo, et al., Bis(imidazoline-2-thione)-copper(i) catalyzed regioselective boron addition to internal alkynes, Chem. Commun. 46(2010) 758-760;(c) H.R. Kim, J. Yun, Highly regio- and stereoselective synthesis of alkenylboronic esters by copper-catalyzed boron additions to disubstituted alkynes, Chem. Commun. 47(2011) 2943-2945;(d) H.Y. Jung, J. Yun, Copper-catalyzed double borylation of silylacetylenes:highly regio- and stereoselective synthesis of syn-vicinal diboronates, Org. Lett. 14(2012) 2606-2609;(e) J. Yun, Copper(Ⅰ)-catalyzed boron addition reactions of alkynes with diboron reagents, Asian J. Org. Chem. 2(2013) 1016-1025.
[6] J. Zhao, Z. Niu, H. Fu, Y. Li, Ligand-free hydroboration of alkynes catalyzed by heterogeneous copper powder with high efficiency, Chem. Commun. 50(2014) 2058-2060.
[7] (a) H. Jang, A.R. Zhugralin, Y. Lee, A.H. Hoveyda, Highly selective methods for synthesis of internal (α-) vinylboronates through efficient NHC-Cu-catalyzed hydroboration of terminal alkynes. Utility in chemical synthesis and mechanistic basis for selectivity, J. Am. Chem. Soc. 133(2011) 7859-7871;(b) Y. Lee, H. Jang, A.H. Hoveyda, Vicinal diboronates in high enantiomeric purity through tandem site-selective NHC-Cu-catalyzed boron-copper additions to terminal alkynes, J. Am. Chem. Soc. 131(2009) 18234-18235.
[8] (a) W. Yuan, S. Ma, CuCl-K2CO3-catalyzed highly selective borylcupration of internal alkynes-ligand effect, Org. Biomol. Chem. 10(2012) 7266-7268;(b) K. Semba, T. Fujihara, J. Terao, Y. Tsuji, Copper-catalyzed highly regio-and stereoselective directed hydroboration of unsymmetrical internal alkynes:controlling regioselectivity by choice of catalytic species, Chem. Eur. J. 18(2012) 4179-4184;(c) A.L. Moure, R. Gómez Arrayás, D.J. Cárdenas, I. Alonso, J.C. Carretero, Regiocontrolled CuI-catalyzed borylation of propargylic-functionalized internal alkynes, J. Am. Chem. Soc. 134(2012) 7219-7222.
[9] (a) W. Jia, N. Jiao, Cu-Catalyzed oxidative amidation of propiolic acids under air via decarboxylative coupling, Org. Lett. 12(2010) 2000-2003;(b) D.L. Priebbenow, P. Becker, C. Bolm, Copper-catalyzed oxidative decarboxylative couplings of sulfoximines and aryl propiolic acids, Org. Lett. 15(2013) 6155-6157;(c) X. Li, F. Yang, Y. Wu, Y. Wu, Copper-mediated oxidative decarboxylative coupling of arylpropiolic acids with dialkyl H-phosphonates in water, Org. Lett. 16(2014) 992-995;(d) D. Zhao, C. Gao, X. Su, et al., Copper-catalyzed decarboxylative cross-coupling of alkynyl carboxylic acids with aryl halides, Chem. Commun. 46(2010) 9049-9051;(e) L. Zhang, Z. Hang, Z.Q. Liu, A free-radical-promoted stereospecific decarboxylative silylation of α,β-unsaturated acids with silanes, Angew. Chem. Int. Ed. 55(2016) 236-239.
[10] (a) Q. Song, Q. Feng, M. Zhou, Copper-catalyzed oxidative decarboxylative arylation of benzothiazoles with phenylacetic acids and (α-hydroxyphenylacetic acids with O2 as the sole oxidant, Org. Lett. 15(2013) 5990-5993;(b) Q. Feng, Q. Song, Copper-catalyzed decarboxylative C-N triple bond formation:direct synthesis of benzonitriles from phenylacetic acids under O2 atmosphere, Adv. Synth. Catal. 356(2014) 1697-1702;(c) Q. Feng, Q. Song, Aldehydes and ketones formation:copper-catalyzed aerobic oxidative decarboxylation of phenylacetic acids and (α-hydroxyphenylacetic acids, J. Org. Chem. 79(2014) 1867-1871;(d) Q. Song, Q. Feng, K. Yang, Synthesis of primary amides via copper-catalyzed aerobic decarboxylative ammoxidation of phenylacetic acids and α-hydroxyphenylacetic acids with ammonia in water, Org. Lett. 16(2014) 624-627.
[11] M. Zhou, M. Chen, Y. Zhou, et al., β-Ketophosphonate formation via aerobic oxyphosphorylation of alkynes or alkynyl carboxylic acids with H-phosphonates, Org. Lett. 17(2015) 1786-1789.
[12] Q. Feng, K. Yang, Q. Song, Highly selective copper-catalyzed trifunctionalization of alkynyl carboxylic acids:an efficient route to bis-deuterated β-borylated α,β-styrene, Chem. Commun. 51(2015) 15394-15397.