Ruthenium-Catalyzed Anti-Markovnikov Selective Hydroboration of

Research Article pubs.acs.org/acscatalysis

Ruthenium-Catalyzed Anti-Markovnikov Selective Hydroboration of Olefins Sesha Kisan, Varadhan Krishnakumar, and Chidambaram Gunanathan* School of Chemical Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar 752050, India S Supporting Information *

ABSTRACT: Ruthenium-catalyzed selective hydroboration of styrenes and aliphatic olefins with pinacolborane (HBpin) is reported. This efficient transformation provided products with exclusive anti-Markovnikov selectivity, and this hydroboration protocol is compatible with olefins having electronic and steric divergence as well as diverse functional groups. Hydroboration occurred at room temperature under solvent-free conditions with minimal catalyst load (0.05 mol %) and provided high TON (>1980; >990 per Ru). Mechanistic studies confirmed the involvement of intermediate [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)] (2). A catalytic cycle including a mononuclear ruthenium intermediate is proposed. The rationale for observed anti-Markovnikov selectivity is provided from reversible 1,3-hydride transfer leading to the regioselective 1,2-insertion on olefins. KEYWORDS: hydroboration, ruthenium, borane, anti-Markovnikov addition, green synthesis

■

INTRODUCTION Alkylboronic esters have found widespread application in organic synthesis, as the C−B bond can be further utilized in many organic transformations such as C−C, C−N, C−O, and C−X bond forming reactions.1 Alkylboronates are preferred over other organometallic reagents due to their stability, nontoxicity, and ability to be stored in air.2 The conventional synthesis of alkylboronates results in the formation of copious waste.3 Dialkylboranes readily react with olefins, whereas reactions of dialkoxyboranes require catalysts. Thus, catalytic hydroboration of olefins resulting in alkylboronates has become attractive. However, for practical applications, catalytic hydroboration reactions should provide products with exclusive regioselectivity and in high efficiency. The first catalytic hydroboration of olefins was performed with Wilkinson’s catalyst,4 and these reactions are in general dominated by Rh and Ir catalysts.5 Alternatively, alkylboronates were also obtained by Ir- and Rh-catalyzed direct borylation of alkanes under harsh experimental conditions.6 In addition, catalytic borylation of alkyl halides with B2Pin2 to provide alkylboronate esters was developed.7 Hydroboration of olefins with pinacolborane is a more attractive, atom-economical approach to alkylboronates. Huang, Szymczak, Chirik, and Ritter reported the iron-catalyzed hydroboration of unactivated alkenes with pinacolborane.8 Chirik, Huang, Fout, Turculet, and co-workers developed the highly active cobalt-catalyzed isomerization−hydroboration of alkenes with pinacolborane (Scheme 1).9 Similarly, Lu and Huang established the cobaltcatalyzed enantioselective 1,1-disubstituted hydroboration of alkenes, which provided optically pure alkylboronate products.10 Such catalytic methods present synthetic versatilities of hydroboration of olefins; however, they require a metal complex composed of designed ligands and activators (Grignard reagents and NaBHEt3; 2−3-fold excess relative to catalyst) and © XXXX American Chemical Society

often provide minor amounts of Markovnikov products that can make the isolation of a single regioisomer tedious. For example, Huang demonstrated the cobalt pincer catalyzed hydroboration of alkenes with pinacolborane, which provided excellent selectivity and high yields.11 However, the electronrich phosphine coordinated cobalt catalyst [(iPrPNN)CoCl2] is inactive toward α-substituted vinylarenes even at high catalyst loading (5 mol %). NNN-Mn (NNN = 2,2′:6′,2″-terpyridine) pincer catalyzed hydroboration of vinylstyrene and aliphatic alkenes offered Markovnikov and anti-Markovnikov products.12 Despite the fact that ruthenium serves as an efficient catalyst in a assortment of organic transformations, ruthenium-catalyzed hydroboration of alkenes is limited to three reports, which suffer from competing hydrogenation of olefins, isomerization, and dehydrogenative borylation of olefins.13 In contrast to these precedents, herein we report the highly efficient and general ruthenium-catalyzed hydroboration of olefins that occurs under solvent-free conditions, leading to the exclusive formation of alkylboronate esters with anti-Markovnikov selectivity.

■

RESULTS AND DISCUSSION Recently, we reported that the readily available, simple dinuclear ruthenium complex [Ru(p-cymene)Cl2]2 (1) catalyzed highly efficient chemoselective hydroboration of carbonyl compounds,14 imines, and nitriles,15 which proceeded with the unprecedented monohydrido-bridged dinuclear ruthenium intermediate 16 [{(η 6 -p-cymene)RuCl} 2 (μ-H-μ-Cl)] (2). We have also developed the efficient regioselective 1,4-hydroboration of pyridine17 and direct multicomponent synthesis of Received: May 29, 2017 Revised: July 21, 2017

5950

DOI: 10.1021/acscatal.7b01750 ACS Catal. 2017, 7, 5950−5954

Research Article

ACS Catalysis

Scheme 1. Recent Advances in Catalytic Hydroboration of Olefins: Designed Base-Metal Catalysts vs a Simple Ruthenium Precursor

Table 1. Optimization of Olefin Hydroborationa

borasiloxanes from pinacolborane, silane, and water, catalyzed by mononuclear ruthenium complexes and 2.18 In a continuation of our interest in ruthenium-catalyzed hydroelementation reactions, we have investigated the hydroboration of olefins using [Ru(p-cymene)Cl2]2 (1). At the outset, a control experiment performed in the absence of catalyst confirmed that hydroelementation of alkenes is a catalytic process. When 1-heptene and pinacolborane were stirred at room temperature for 24 h, no reaction was observed (entry 1, Table 1). However, a similar experiment carried out in the presence of 1 as a precatalyst (0.1 mol %) provided quantitative conversion (>99%) of reactants (entry 2, Table 1). GC and NMR analysis of the reaction mixture and isolation and characterization of the product clearly established the formation of a single regioisomer with anti-Markovnikov selectivity. Lowering the catalyst loading to 0.05 mol % also provided >99% conversion (TON > 1980; >990 per Ru) in 24 h (entry 3, Table 1). Decreasing the catalyst loading further resulted in incomplete conversion of reactants (entry 4, Table 1).

entry

catalyst loading (mol %)

time (h)

conversion (%)b

1 2 3 4

nil 0.1 0.05 0.01

24 4 24 24

trace >99 >99 78

a

Conditions: 1-heptene (1 mmol), HBpin (1 mmol). bConversion was determined by GC.

Following the optimized experimental conditions, we subjected a wide range of alkenes to ruthenium-catalyzed hydroboration, which offered moderate to excellent yields of alkylboronate esters with anti-Markovnikov selectivity. Analysis of these reaction mixtures did not provide any evidence for the dehydrogenative borylation or formation of Markovnikov product. When styrene was reacted with pinacolborane, 5951

DOI: 10.1021/acscatal.7b01750 ACS Catal. 2017, 7, 5950−5954

Research Article

ACS Catalysis

This insensitivity to steric effects indicates the ability of the ruthenium center to accommodate the sterically hindered alkenes in the coordination sphere. However, sterically hindered alkenes were not amenable to hydroboration reactions by all Co catalysts, as the metal center is encumbered with pincer and other hindered ligand motifs.9b,11 Alkenes with diverse functional groups were well tolerated. Alkenylbenzenes and allyl- and vinylsilanes provided the exclusive anti-Markovnikov products 3k−o in moderate to excellent yields (Table 2). Acetal-, oxirane-, and ether-containing olefins also exhibited similar reactivity to provide the selective products 3p−r. Interestingly, alkenols can be subjected to this hydroboration protocol; while catalytic hydroboration occurred on the alkene, the hydroxy functional group was also borylated with liberation of dihydrogen in a noncatalytic process to provide the diboryl products 3s,t in excellent yields. Notably, sterically hindered 1,1-disubstituted alkenes such as α-methylstyrene and methylenecyclohexane can be subjected to the ruthenium-catalyzed hydroboration process, which provided the exclusive formation of products 3u,v in excellent yields. Similarly, cyclic alkenes were also amenable to this hydroboration protocol. Cyclohexylboronate (3w) and cyclooctylboronate (3x) esters were obtained in 97% and 73% isolated yields from the corresponding cyclic olefins, demonstrating the powerful prowess that this ruthenium-catalyzed hydroboration process offers. To understand the intermediates involved in this selective and efficient hydroboration, we turned to in situ 1H NMR monitoring of reactions. When the reaction of 1-heptene and pinacolborane with [Ru(p-cymene)Cl2]2 (1; 0.05 mol %) was monitored, 1H NMR indicated the immediate formation of the intermediate [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)] (2), as observed in the hydroboration of carbonyl compounds, nitriles, and imines.14,15 When isolated pure complex 2 (0.05 mol %) was used as a catalyst in the hydroboration, quantitative conversion of 1-heptene occurred in 24 h to selectively provide the single linear isomer of n-heptylboronate ester (Scheme 2).

Table 2. Ruthenium-Catalyzed Anti-Markovnikov Selective Hydroboration of Olefinsa

Scheme 2. Catalytic Hydroboration of 1-Heptene by the Isolated Intermediate [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)] (2)

a

Olefin (1 mmol), HBpin (1 mmol), and [Ru(p-cymene)Cl2]2 (1; 0.05 mol %) were stirred at room temperature for 24 h. Conversions were determined by GC and are given in parentheses. Yields correspond to isolated pure products. b2 mmol of HBpin was used (as the corresponding alkenol was the starting material).

The similar catalytic result obtained with 2 as catalyst in comparison to that of complex 1 further confirmed the involvement of intermediate 2 in the hydroboration of alkenes. Further, 1H NMR and mass spectral analysis of the stoichiometric reaction of 9-vinylanthracene, pinacolborane, and complex [Ru(p-cymene)Cl2]2 (1) indicated the presence of the monohydrido-bridged dinuclear intermediate [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)] (2) and mononuclear intermediate [Ru(pcymene)HCl] (2a; m/z 289 (M + 2H)+), respectively.15 However, repeated attempts made to observe the mononuclear intermediate 2a in 1H NMR of the reaction mixture were unsuccessful. Although more data are required, we propose the plausible reaction mechanism for the ruthenium-catalyzed hydroboration of alkenes as delineated in Scheme 3. The stoichiometric reaction of 2 with pinacolborane results in the formation of mononuclear intermediates 2a,b. Reaction with pinacolborane converts the ruthenium dichloride intermediate 2b into 2a, which was inferred from the presence of ClBpin (11B NMR, δ 27.9 ppm) in the reaction mixture. Further

quantitative conversion was observed and the corresponding phenethylboronate 3a was isolated in 98% yield (Table 2). Styrenes with electron-donating substituents (4-methyl and 4-methoxy) offered 90% conversion, and the corresponding boronate esters (3b,c) were isolated in good yields. However, highly substituted pentafluorostyrene provided only 73% conversion. Vinylanthracene resulted in 98% conversion, and the corresponding boronate ester was isolated in 95% yield. Linear aliphatic alkenes such as 1-heptene and 1-decene provided quantitative conversions. When allylcyclopentane and allylcyclohexane were subjected to catalysis, the corresponding linear alkyl boronates 3h,i were isolated in 91% yields. Notably, tert-butylethylene was amenable to ruthenium-catalyzed hydroboration, which provided the product 3j in 87% yield. 5952

DOI: 10.1021/acscatal.7b01750 ACS Catal. 2017, 7, 5950−5954

Research Article

ACS Catalysis Scheme 3. Proposed Mechanism for the RutheniumCatalyzed Hydroboration of Olefins

Scheme 4. Catalytic Hydroboration of 1-Heptene Using Mononuclear Ru Complexes

the corresponding product, heptylboronate ester, in 82% and 60% yields, respectively (Scheme 4). This experimental evidence strongly indicates the involvement of mononuclear ruthenium species in the catalytic hydroboration of olefins.

■

CONCLUSION In summary, we have developed a highly efficient Ru-catalyzed hydroboration of olefins that provided exclusively the antiMarkovnikov organoboronate ester in all substrates used. The complete hydroboration process can be accomplished in a few hours by using 0.1 mol % of [Ru(p-cymene)Cl2]2 (1), whereas conducting the experiments with 0.05 mol % of 1 for 24 h allowed us to double the efficiency of the catalytic systems and a TON of >1980 (>990 per Ru) was achieved. The present catalytic hydroboration method works efficiently on sterically hindered and electronically divergent olefins. Mechanistic studies confirmed the involvement of the intermediate [{(η6p-cymene)RuCl}2(μ-H-μ-Cl)] (2). Further splitting of 2 to mononuclear species provides catalytically active ruthenium intermediates.14−16 The catalytic cycle involving 1,3-hydride transfer leading to the regioselective 1,2-insertion of olefins, oxidative addition of borane, and reductive elimination of primary alkylboronate esters from a Ru(IV) intermediate is proposed.

■

reaction of 2a with pinacolborane in the presence of olefins generates the active intermediate I. 1,3-Hydride transfer occurs on I, leading to the regioselective 1,2-insertion reaction on olefins to provide primary alkyl intermediate II. A β-hydride elimination process on II can regenerate the alkene complex I. The absence of Markovnikov product resulting from the 2,1-insertion can be attributed to steric factors and this equilibrium, which causes the ruthenium to insert into the less sterically hindered carbon on monosubstituted or 1,1-disubstituted olefins. However, unlike the designed base-metal catalysts, the ruthenium center in half-sandwich type intermediate I possesses enough of a coordination sphere to accommodate the coordination of sterically hindered olefins, as excellent yields and turnovers were observed with such substrates (Table 2). The ability of the ruthenium center to sterically discriminate the monosubstituted olefins as well as to accommodate the sterically crowded olefins is commendable. Oxidative addition of pinacolborane to II can lead to the formation of the diboryl ruthenium intermediate III,14 from which the reductive elimination of boryl and primary alkyl ligands furnishes the anti-Markovnikov organoboronate ester product and intermediate IV. Coordination of olefin to IV can regenerate the active intermediate I to complete one loop in the catalytic cycle. To further probe the involvement of the mononuclear ruthenium intermediates in the catalytic cycle, phosphine-ligated half-sandwich ruthenium complexes [Ru(p-cymene)Cl2(PCy3)] (3a) and [Ru(p-cymene)Cl2(PPh3)] (3b) were employed as catalysts17 in the hydroboration of 1-heptene, which provided

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.7b01750. Experimental procedures, spectral data, and 1H and 13C NMR spectra of the products (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail for C.G.: [email protected]. ORCID

Chidambaram Gunanathan: 0000-0002-9458-5198 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We thank the SERB New Delhi (EMR/2016/002517 and SR/S2/ RJN-64/2010), DAE, and NISER for financial support. S.K. thanks the DST for INSPIRE fellowship. V.K. thanks the SERB for a National Postdoctoral Fellowship. C.G. is a Ramanujan Fellow.

■

REFERENCES

(1) (a) Hartwig, J. F. Acc. Chem. Res. 2012, 45, 864−873. (b) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461−1473. (c) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169−196. (d) Morrill, C.; Grubbs, R. H. J. Org. Chem. 2003, 68, 6031−6034. (e) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417−1492. (f) Frisch, A.

5953

DOI: 10.1021/acscatal.7b01750 ACS Catal. 2017, 7, 5950−5954

Research Article

ACS Catalysis C.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674−688. (h) Crudden, C. M.; Edwards, D. Eur. J. Org. Chem. 2003, 2003, 4695−4712. (2) Hall, D. G. Boronic Acids: Preparation and Applications in Organic Synthesis and Medicine; Wiley-VCH: Weinheim, Germany, 2005. (3) Brown, H. C. Organic Synthesis via Organoboranes; Wiley Interscience: New York, 1975. (4) Männig, D.; Nöth, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 878− 879. (5) Zaidlewicz, M.; Wolan, A.; Budny, M. In Hydrometallation of C C and CC Bonds. Group 3, 2nd ed.; Knochel, P., Molander, G. A., Eds.; Elsevier: Amsterdam, 2014. (6) (a) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890−931. (b) Chen, H.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science 2000, 287, 1995−1997. (c) Shimada, S.; Batsanov, A. S.; Howard, J. A. K.; Marder, T. B. Angew. Chem., Int. Ed. 2001, 40, 2168−2171. (7) (a) Atack, T. C.; Cook, S. P. J. Am. Chem. Soc. 2016, 138, 6139− 6142. (b) Yang, C. T.; Zhang, Z. Q.; Tajuddin, H.; Wu, C. C.; Liang, J.; Liu, J. H.; Fu, Y.; Czyzewska, M.; Steel, P. G.; Marder, T. B.; Liu, L. Angew. Chem., Int. Ed. 2012, 51, 528−532. (8) (a) Wu, J. Y.; Moreau, B.; Ritter, T. J. Am. Chem. Soc. 2009, 131, 12915−12917. (b) Zhang, L.; Peng, D.; Leng, X.; Huang, Z. Angew. Chem., Int. Ed. 2013, 52, 3676−3680. (c) Tseng, K. N. T.; Kampf, K. W.; Szymczak, N. K. ACS Catal. 2015, 5, 411−415. (d) Obligacion, J. V.; Chirik, P. J. Org. Lett. 2013, 15, 2680−2683. (9) (a) Obligacion, J. V.; Chirik, P. J. J. Am. Chem. Soc. 2013, 135, 19107−19110. (b) Ibrahim, A. D.; Entsminger, S. W.; Fout, A. R. ACS Catal. 2017, 7, 3730−3734. (c) Ogawa, T.; Ruddy, A. J.; Sydora, O. L.; Stradiotto, M.; Turculet, L. Organometallics 2017, 36, 417−423. (10) (a) Chen, J.; Xi, T.; Ren, X.; Cheng, B.; Guo, J.; Lu, Z. Org. Chem. Front. 2014, 1, 1306−1309. (b) Zhang, L.; Zuo, Z.; Wang, X.; Huang, Z. J. Am. Chem. Soc. 2014, 136, 15501−15504. (11) Zhang, L.; Zuo, Z.; Leng, X.; Huang, Z. Angew. Chem., Int. Ed. 2014, 53, 2696−2700. (12) Zhang, G.; Zeng, H.; Wu, J.; Yin, Z.; Zheng, S.; Fettinger, J. C. Angew. Chem., Int. Ed. 2016, 55, 14369−14372. (13) (a) Burgess, K.; Jaspars, M. Organometallics 1993, 12, 4197− 4200. (b) Caballero, A.; Etienne, S. S. Organometallics 2007, 26, 1191− 1195. (c) Riddlestone, I. M.; McKay, D.; Gutmann, M. J.; Macgregor, S. A.; Mahon, M. F.; Sparkes, H. A.; Whittlesey, M. K. Organometallics 2016, 35, 1301−1312. (14) Kaithal, A.; Chatterjee, B.; Gunanathan, C. Org. Lett. 2015, 17, 4790−4793. (15) Kaithal, A.; Chatterjee, B.; Gunanathan, C. J. Org. Chem. 2016, 81, 11153−11161. (16) Chatterjee, B.; Gunanathan, C. Chem. Commun. 2014, 50, 888− 890. (17) Kaithal, A.; Chatterjee, B.; Gunanathan, C. Org. Lett. 2016, 18, 3402−3405. (18) Chatterjee, B.; Gunanathan, C. Chem. Commun. 2017, 53, 2515−2518.

5954

DOI: 10.1021/acscatal.7b01750 ACS Catal. 2017, 7, 5950−5954