B(C6F5)3-Catalyzed Highly Stereoselective Hydrogenation of

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

pubs.acs.org/OrgLett

B(C6F5)3‑Catalyzed Highly Stereoselective Hydrogenation of Unfunctionalized Tetrasubstituted Olefins Yun Dai,†,‡ Xiangqing Feng,*,†,‡ and Haifeng Du*,†,‡ †

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China ‡ University of Chinese Academy of Sciences, Beijing 100049, China

Downloaded via MACQUARIE UNIV on August 29, 2019 at 08:01:54 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: A metal-free hydrogenation of unfunctionalized tetrasubstituted olefins were successfully realized using a combination of B(C6F5)3 and Ph2NMe catalyst. The corresponding products were afforded in 58−98% yields with up to >99:1 cis/ trans selectivity.

T

complex and B(C6F5)3 adduct was developed by Ison’s group, and the catalyst could effectively catalyze the hydrogenation of monosubstituted olefins, geminal substituted olefins, and vicinal disubstituted olefins. The tetrasubstituted olefin tetramethylethylene was also suitable for this transformation and gave a 13% yield.8c In addition, Li, Wang, and co-workers reported an HB(C6F5)2-mediated hydroboration and σ-bond metathesis of mono-, di-, or trisubstituted olefins, and tetramethylethylene in 2013.8d To date, the metal-free hydrogenation of unfunctionalized tetrasubstituted olefins is still an unsolved problem and presents a great challenge. As part of our research interest in the FLP catalysis,9 the hydrogenation of several types of unsaturated compounds such as imines,10 N-heterocycles,11 naphthylamines,12 and alkynes13 has been successfully realized. On the basis of these results, we will further devote our efforts to the difficult and challenging hydrogenation of unfunctionalized tetrasubstituted olefins. Herein, we reported our preliminary results on the metal-free highly stereoselective hydrogenation of indenes and 1,2dihydronapthalenes. Initially, the hydrogenation of 2,3-dimethyl-1H-indene (1a) was examined using B(C6F5)314 (2a) (20 mol %) as a catalyst in CH2Cl2 at 100 °C for 24 h. Without Lewis base, the reaction could not carry out. With Ph3P (3a) and Ph3N (3b) as Lewis bases, the reduction product 4a was afforded in 16% and 79% conversion, respectively (Scheme 2). Because the amine−Lewis base exhibited significantly higher activity than the phosphine−Lewis base, a variety of amines were screened as Lewis bases as shown in Table 1. A series of diaryl- and dialkylamines 3c−j were attempted, and it was found that dialkylamines (3i and 3j) and the amines with larger steric hindrance (3d and 3f) led to lower reactivities (Table 1, entries 1−8). The reaction could not be conducted using N-methylaniline (3k) as a Lewis base (Table 1, entry 9). With N,N-dimethylaniline (3l), 50% conversion was achieved,

he catalytic hydrogenation of olefins is one of the most fundamental and important transformations in synthetic chemistry and has been widely applied in pharmaceuticals, agrochemicals, material chemistry, and chemical industries.1 Among the olefins, the unfunctionalized tetrasubstituted ones are undoubtedly the least reactive class of olefins, which may attribute to their steric hindrance and lack of the coordination heteroatoms.2 Transition-metal catalysts such as Ru,3 Rh,4 and Ir,5 have been predominant in catalytic hydrogenation and asymmetric hydrogenation of unfunctionalized olefins, and have made great progress. However, metal-free hydrogenation of these substrates is still in its infancy.6 The emergence and development of frustrated Lewis pairs chemistry7 provided a new opportunity for metal-free catalytic hydrogenation of unfunctionalized olefins. In 2013, Grimme and Stephan reported an Et2O·B(C6F5)3 FLP catalyst, which could activate H2 and catalyze the hydrogenation of 1,1-diphenylethylene and anthracene.8a In 2015, the hydrogenation of olefins was realized with a combination of electrophilic fluorophosphonium cation and diaryl amines or diaryl silylamines catalyst (Scheme 1).8b In 2016, an oxorhenium diamidopyridine Scheme 1. Frustrated Lewis Pairs Catalyzed Hydrogenation of Unfunctionalized Olefins

Received: July 19, 2019

© XXXX American Chemical Society

A

DOI: 10.1021/acs.orglett.9b02512 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

screened in the hydrogenation, accompanied by weakened Lewis acidity, and the reaction activity gradually decreased. B(C6F5)3 (2a) gave a quantitative conversion, but B(pHC6F4)3 (2b) gave a much lower conversion. With B(2,4,6F3-C6H2)3 (2c), there was no predicted product (Table 2,

Scheme 2. Initial Study on Hydrogenation of 2,3-Dimethyl1H-indene 1a

Table 2. Optimization of Reaction Conditionsa

Table 1. Evaluation of Lewis Base 3a entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14d 15e 16f

borane (x mol %) B(C6F5)3 (2a) (20 mol %) B(p-HC6F4)3 (2b) (20 mol %) B(2,4,6-F3−C6H2)3(2c) (20 mol %) 2a (20 mol %) 2a (20 mol %) 2a (20 mol %) 2a (20 mol %) 2a (20 mol %) 2a (20 mol %) 2a (20 mol %) 2a (10 mol %) 2a (10 mol %) 2a (10 mol %) 2a (10 mol %) 2a (10 mol %) 2a (10 mol %)

temp (°C)

time (h)

convb (%)

CH2Cl2

100

24

100

CH2Cl2

100

24

61

CH2Cl2

100

24

nrc

CH2Cl2 CHCl3 ClCH2CH2Cl BrCH2CH2Br Cl2CHCHCl2 toluene hexane CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2

60 60 60 60 60 60 60 60 100 120 120 120 120

5 5 5 5 5 5 5 24 24 24 24 24 24

100 33 3 nrc 85 10 nrc 57 80 100 70 83 100

solvent

a

All reactions were carried out with 1a (0.1 mmol), B(C6F5)3 (2a) (20 mol %), Ph2NMe (3m) (20 mol %), and H2 (40 bar) in solvent (0.5 mL) unless otherwise noted. bDetermined by crude 1H NMR. c No reaction. d1a (0.5 mmol) in CH2Cl2 (2.5 mL). e1a (0.5 mmol) in CH2Cl2 (1.0 mL). f1a (0.5 mmol) in CH2Cl2 (0.5 mL).

entries 1−3). The solvents influenced the reaction activity significantly, CH2Cl2 was the optimal one, and the hydrogenation product could be afforded in quantitative conversion at 60 °C for 5 h (Table 2, entries 4−10). Reducing the catalyst loading to 10 mol %, higher temperature was need to maintain the reactivity, and full conversion could be obtained at 120 °C (Table 2, entries 11−13). On a larger scale, it was found that a higher concentration gave a better reactivity (Table 2, entries 14−16). Under the optimal reaction conditions, we investigated the scope of the B(C6F5)3-Ph2NMe catalyzed hydrogenation of unfunctionalized tetrasubstituted olefins, and the results are summarized in Scheme 3. For five-membered ring substrates 1a−m, the reactions went well and gave satisfactory isolated yields and up to >99/1 cis/trans selectivity. 1,2-Dialkylsubstituted alkenes showed better reactivity but lower cis/ trans selectivity than the 1-alkyl-2-Ph or the 1-Ph-2-alkyl ones; the latter usually need a longer reaction time. The aromatic ring-substituted substrates 1n−p were also examined, and electron-withdrawing substituted compound 1p gave relatively poor reactivity and selectivity with 20 mol % catalyst in 150 °C for 48 h. For six-membered ring substrates 1q−t, lower yields and poor stereoselectivities were achieved. A 1 mmol scale hydrogenation of 2,3-dimethyl-1H-indene (1a) was further examined, and the compound 4a was afforded in 96% yield with 96/4 cis/trans selectivity (Scheme 4).

a All reactions were carried out with 1a (0.1 mmol), B(C6F5)3 (2a) (20 mol %), Lewis base 3 (20 mol %), and H2 (40 bar) in CH2Cl2 (0.5 mL) at 100 °C for 24 h unless otherwise noted. bDetermined by crude 1H NMR. c10 mol % Lewis base was used. dNo reaction. eThe reaction was performed for 5 h.

while N-methyl-N-phenylaniline (3m) could give completely conversion in 5 h (Table 1, entries 10−12). Subsequently, the alkyl group and the substituents on the aromatic rings on the N-alkyl-N-arylanilines were investigated, Ph2NMe (3m) was still proven to be the optimal Lewis base (Table 1, entries 12− 18). The conditions of metal-free hydrogenation of 2,3-dimethyl1H-indene (1a) were further examined. The boranes 2 were B

DOI: 10.1021/acs.orglett.9b02512 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

transfer from the hydridoborate moiety to liberate the hydrocarbon 4 and regenerate the B(C6F5)3 2a. In summary, we have demonstrated a metal-free hydrogenation of indenes and 1,2-dihydronapthalenes using a borane-amine FLP catalyst. The corresponding reductants were achieved in 58−98% yields with up to >99:1 cis/trans selectivity. Further work will be devoted to explore efficient chiral catalyst for the asymmetric versions and expand this methodology to other substrates.

Scheme 3. Hydrogenation of Unfunctionalized Tetrasubstituted Olefins 1

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b02512. Experimental procedures for metal-free hydrogenation, characterization of substrates and products, and NMR spectra (PDF)

■

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Xiangqing Feng: 0000-0003-1739-925X Haifeng Du: 0000-0003-0122-3735 Notes

The authors declare no competing financial interest.

■

a

48 h. bWith 20 mol % of B(C6F5)3 (2a) and Ph2NMe (3m). c150 °C. d36 h.

ACKNOWLEDGMENTS We are grateful for generous financial support from the National Natural Science Foundation of China (21871269 and 21521002).

Scheme 4. 1 Mmol Scale Hydrogenation of 1a

■

REFERENCES

(1) de Vries, J. G.; Elsevier, C. J. The Handbook of Homogeneous Hydrogenations; Wiley-VCH: Weinheim, 2007. (2) (a) Troutman, M. V.; Appella, D. H.; Buchwald, S. L. Asymmetric Hydrogenation of Unfunctionalized Tetrasubstituted Olefins with a Cationic Zirconocene Catalyst. J. Am. Chem. Soc. 1999, 121, 4916−4917. (b) Kraft, S.; Ryan, K.; Kargbo, R. B. Recent Advances in Asymmetric Hydrogenation of Tetrasubstituted Olefins. J. Am. Chem. Soc. 2017, 139, 11630−11641. (3) (a) Cui, X.; Burgess, K. Catalytic Homogeneous Asymmetric Hydrogenations of Largely Unfunctionalized Alkenes. Chem. Rev. 2005, 105, 3272−3296. (b) Sunada, Y.; Ogushi, H.; Yamamoto, T.; Uto, S.; Sawano, M.; Tahara, A.; Tanaka, H.; Shiota, Y.; Yoshizawa, K.; Nagashima, H. Disilaruthena- and Ferracyclic Complexes Containing Isocyanide Ligands as Effective Catalysts for Hydrogenation of Unfunctionalized Sterically Hindered Alkenes. J. Am. Chem. Soc. 2018, 140, 4119−4134. (4) (a) Co, T. T.; Kim, T.-J. Chiral (iminophosphoranyl) Ferrocenes: Highly Efficient Ligands for Rhodium- and IridiumCatalyzed Enantioselective Hydrogenation of Unfunctionalized Olefins. Chem. Commun. 2006, 3537−3539. (b) Wang, X.; Guram, A.; Caille, S.; Hu, J.; Preston, J. P.; Ronk, M.; Walker, S. Highly Enantioselective Hydrogenation of Styrenes Directed by 20-Hydroxyl Groups. Org. Lett. 2011, 13, 1881−1883. (c) Margarita, C.; Andersson, P. G. Evolution and Prospects of the Asymmetric Hydrogenation of Unfunctionalized Olefins. J. Am. Chem. Soc. 2017, 139, 1346−1356. (5) (a) Roseblade, S. J.; Pfaltz, A. Iridium-Catalyzed Asymmetric Hydrogenation of Olefins. Acc. Chem. Res. 2007, 40, 1402−1411.

The catalytic cycle was proposed as shown in Scheme 5.8a,b Initially, H2 was heterolytic split by the B(C6F5)3 and Ph2NMe FLP to generate a N−B zwitterion. This step is followed by proton transfer from the [N−H]+ unit to the alkene carbon and form the benzyl carbocation. Subsequently, hydride Scheme 5. Proposed Catalytic Cycle

C

DOI: 10.1021/acs.orglett.9b02512 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

of3,6-Diarylpyridazines. Dalton Trans. 2016, 45, 5945−5948. (f) Wang, W.; Feng, X.; Du, H. Borane-Catalyzed Metal-free Hydrogenation of 2,7-Disubstituted 1,8-Naphthyridines. Org. Biomol. Chem. 2016, 14, 6683−6686. (g) Liu, X.; Liu, T.; Meng, W.; Du, H. Highly Stereoselective Metal-Free Hydrogenations of Pyrrolo[1,2a]quinoxalines. Org. Lett. 2018, 20, 5653−5656. (12) Li, G.; Liu, Y.; Du, H. B(C6F5)3-Catalyzed Metal-free Hydrogenation of Naphthylamines. Org. Biomol. Chem. 2015, 13, 2875−2878. (13) Liu, Y.; Hu, L.; Chen, H.; Du, H. An Alkene-Promoted BoraneCatalyzed Highly Stereoselective Hydrogenation of Alkynes to Give Z- and E-Alkenes. Chem. - Eur. J. 2015, 21, 3495−3501. (14) (a) Massey, A. G.; Park, A. J. Perfluorophenyl Derivatives of the Elements: I. Tris(pentafluorophenyl)boron. J. Organomet. Chem. 1964, 2, 245−250. (b) Massey, A. G.; Park, A. J.; Stone, F. G. A. Tris (pentafluorophenyl) boron. Proc. Chem. Soc. 1963, 212.

(b) Woodmansee, D. H.; Pfaltz, A. Asymmetric hydrogenation of alkenes lackingcoordinating groups. Chem. Commun. 2011, 47, 7912− 7916. (c) Zhu, Y.; Burgess, K. Filling Gaps in Asymmetric HydrogenationMethods for Acyclic Stereocontrol: Application to Chirons for Polyketide-Derived Natural Products. Acc. Chem. Res. 2012, 45, 1623−1636. (d) Zhu, S.-F.; Zhou, Q.-L. Iridium-Catalyzed Asymmetric Hydrogenation of Unsaturated Carboxylic Acids. Acc. Chem. Res. 2017, 50, 988−1001. (6) (a) Haenel, M. W.; Narangerel, J.; Richter, U. B.; Rufinska, A. The First Liquefaction of High-Rank Bituminous Coals by Preceding Hydrogenation with Homogeneous Borane or Iodine Catalysts. Angew. Chem., Int. Ed. 2006, 45, 1061−1066. (b) Inés, B.; Palomas, D.; Holle, S.; Steinberg, S.; Nicasio, J. A.; Alcarazo, M. Metal-Free Hydrogenation of Electron-Poor Allenes and Alkenes. Angew. Chem., Int. Ed. 2012, 51, 12367−12369. (7) (a) Welch, G. C.; San Juan, R. R.; Masuda, J. D.; Stephan, D. W. Reversible, Metal-Free Hydrogen Activation. Science 2006, 314, 1124−1126. (b) Kenward, A. L.; Piers, W. E. Heterolytic H2 Activation by Nonmetals. Angew. Chem., Int. Ed. 2008, 47, 38−41. (c) Stephan, D. W.; Erker, G. Frustrated Lewis Pairs: Metal-free Hydrogen Activationand More. Angew. Chem., Int. Ed. 2010, 49, 46− 76. (d) Soós, T. Design of Frustrated Lewis Pair Catalysts for Metalfree and Selective Hydrogenation. Pure Appl. Chem. 2011, 83, 667− 675. (e) Erker, G. Frustrated Lewis Pairs: Some Recent Developments. Pure Appl. Chem. 2012, 84, 2203−2217. (f) Paradies, J. MetalFree Hydrogenation of Unsaturated Hydrocarbons Employing Molecular Hydrogen. Angew. Chem., Int. Ed. 2014, 53, 3552−3557. (g) Stephan, D. W.; Erker, G. Metal-Free Hydrogenation of Unsaturated Hydrocarbons Employing Molecular Hydrogen. Angew. Chem., Int. Ed. 2015, 54, 6400−6441. (h) Stephan, D. W. Frustrated Lewis Pairs. J. Am. Chem. Soc. 2015, 137, 10018−10032. (i) Stephan, D. W. Frustrated Lewis Pairs: From Concept to Catalysis. Acc. Chem. Res. 2015, 48, 306−316. (8) (a) Hounjet, L. J.; Bannwarth, C.; Garon, C. N.; Caputo, C. B.; Grimme, S.; Stephan, D. W. Combinations of Ethers and B(C6F5)3 Function as Hydrogenation Catalysts. Angew. Chem., Int. Ed. 2013, 52, 7492−7495. (b) vom Stein, T.; Peréz, M.; Dobrovetsky, R.; Winkelhaus, D.; Caputo, C. B.; Stephan, D. W. Electrophilic Fluorophosphonium Cations in Frustrated Lewis Pair Hydrogen Activation and Catalytic Hydrogenation of Olefins. Angew. Chem., Int. Ed. 2015, 54, 10178−10182. (c) Lambic, N. S.; Sommer, R. D.; Ison, E. A. Transition-Metal Oxos as the Lewis Basic Component of Frustrated Lewis Pairs. J. Am. Chem. Soc. 2016, 138, 4832−4842. (d) Wang, Y.; Chen, W.; Lu, Z.; Li, Z. H.; Wang, H. Metal-Free HB(C6F5)2-Catalyzed Hydrogenation of UnfunctionalizedOlefins and Mechanism Study of Borane-Mediated σ-Bond Metathesis. Angew. Chem., Int. Ed. 2013, 52, 7496−7499. (9) (a) Liu, Y.; Du, H. Frustrated Lewis Pair Catalyzed Asymmetric Hydrogenation. Huaxue Xuebao 2014, 72, 771−777. (b) Feng, X.; Du, H. Metal-free Asymmetric Hydrogenation and Hydrosilylation Catalyzedby Frustrated Lewis Pairs. Tetrahedron Lett. 2014, 55, 6959−6964. (c) Meng, W.; Feng, X.; Du, H. Frustrated Lewis Pairs Catalyzed Asymmetric Metal-Free Hydrogenations and Hydrosilylations. Acc. Chem. Res. 2018, 51, 191−201. (10) (a) Liu, Y.; Du, H. Chiral Dienes as “Ligands” for BoraneCatalyzed Metal-Free Asymmetric Hydrogenation of Imines. J. Am. Chem. Soc. 2013, 135, 6810−6813. (b) Zhu, X.; Du, H. A Highly Stereoselective Metal-Free Hydrogenation of Diimines forthe Synthesis of Cis-Vicinal Diamines. Org. Lett. 2015, 17, 3106−3109. (11) (a) Liu, Y.; Du, H. Metal-Free Borane-Catalyzed Highly Stereoselective Hydrogenationof Pyridines. J. Am. Chem. Soc. 2013, 135, 12968−12971. (b) Zhang, Z.; Du, H. A Highly cis-Selective and Enantioselective Metal-Free Hydrogenationof 2,3-Disubstituted Quinoxalines. Angew. Chem., Int. Ed. 2015, 54, 623−626. (c) Zhang, Z.; Du, H. Cis-Selective and Highly Enantioselective Hydrogenation of 2,3,4-Trisubstituted Quinolines. Org. Lett. 2015, 17, 2816−2819. (d) Zhang, Z.; Du, H. Enantioselective Metal-Free Hydrogenations of Disubstituted Quinolines. Org. Lett. 2015, 17, 6266−6269. (e) Wang, W.; Meng, W.; Du, H. B(C6F5)3-Catalyzed Metal-free Hydrogenation D

DOI: 10.1021/acs.orglett.9b02512 Org. Lett. XXXX, XXX, XXX−XXX