Enantioselective Copper-Catalyzed Methylboration of Alkenes

3 days ago - We began our investigation by examining the three-component reaction using MeI as the Csp3-electrophile in the presence of chiral Cu(I)/S...
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Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Enantioselective Copper-Catalyzed Methylboration of Alkenes Bin Chen,†,‡,§ Peng Cao,§ Yang Liao,† Min Wang,† and Jian Liao*,†,‡ †

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People’s Republic of China and University of Chinese Academy of Sciences, Beijing 10049, People’s Republic of China ‡ College of Chemical Engineering, Sichuan University, Chengdu 610065, People’s Republic of China § College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610068, People’s Republic of China S Supporting Information *

ABSTRACT: An enantioselective Cu-catalyzed borylative crosscoupling reaction of alkenes, bis(pinacolato)diboron (B2(pin)2), and methyl iodide is reported. Alkenes including styrenes, βsubstituted styrenes, and challenging aliphatic olefins were smoothly transferred to the desired methylboration products with excellent diastereoselectivities (dr up to >99:1) and enantioselectivities (er up to 99:1). The utility of this process was demonstrated by the synthesis of naproxen and formal synthesis of two natural products.

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smoothly transferred to the desired methylboration products with excellent diastereoselectivities (dr up to >99:1) and enantioselectivities (er up to 99:1). This process provides an efficient and valuable option for the synthesis of the important chiral methyl containing frameworks, which are frequently encountered in many bioactive compounds (Figure 1).12 The utility of the products obtained by this method is demonstrated by their straightforward elaboration to commercial drugs and natural products.

ransition-metal catalyzed borylative coupling reactions have been recognized as a significant approach to access organoboron compounds.1 Among them, the Cu-catalyzed three-component carboboration of unsaturated hydrocarbons with C-electrophiles has received a tremendous amount of interest recently.2 The process generally involves the Cu−B addition across the C−C unsaturated bond and subsequent cross-coupling with C-electrophiles. This chemistry represents a versatile and straightforward method to access functionalized organoboron compounds, owing to the availability of substrates as well as the diversity of carbon electrophiles. To date, an array of electrophiles, such as aldehydes and ketones,3 imines,4 aryl halides,5 unsaturated carbonyls,6 allyl electrophiles,7 and so on,8 have been extensively studied and successfully introduced in the enantioselective carboboration of alkenes,3a,4d,5f,g,7c,e,g,h,8e,f alkynes,6a allenes,3b,4b,6c,7a 1,2-enynes,3c or dienes.4c,5i,6b At the same time, Cu-catalyzed alkylboration9 with Csp3 electrophilic reagents (i.e., alkyl halides) have been elegantly disclosed by Ito,9a−c,e,h,l,n Tortosa,9d Yoshida,9f,k Fu,9g,j and Kanai9i recently. However, intermolecular, enantioselective alkylboration remains challenging,9a,b and a reaction that introduces a singularly important methyl substituent has not been realized. The challenge inherent to intermolecular enantioselective alkylboration of alkenes involves the intermolecular Csp3−Csp3 coupling between a stereochemically defined alkylcuprate and an inactivated alkyl halide. The enantiomeric purity of a Cualkyl intermediate might erode if trapped slowly by a less reactive electrophile.10,7g A potential solution may rely on the identification of a suitable chiral ligand that promotes the Cu− B addition to a C−C double bond with high facial selectivity and accelerates the alkyl−alkyl coupling with high stereospecificity. Herein, we developed an enantioselective coppercatalyzed methylboration of alkenes utilizing chiral sulfoxide phosphine ligand developed in our own group or the commercial quinoxP* ligand.11 Alkenes including styrenes, βsubstituted styrenes, and challenging aliphatic olefins were © XXXX American Chemical Society

Figure 1. Selected chiral methyl containing bioactive molecules.

We began our investigation by examining the threecomponent reaction using MeI as the Csp3-electrophile in the presence of chiral Cu(I)/SOP complexes5g,7c,13 (Table 1). With 10 mol % CuCl, 12 mol % of (R)-sulfoxide-(diisopropyl)phosphine (L1), and 1.5 equiv of MeOK, the reaction of Received: January 9, 2018

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DOI: 10.1021/acs.orglett.7b03860 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Table 1. Conditions Optimizationa

Scheme 1. Scope of Styrenesa

entry

ligand

RX

yield (%)b (2a/2a′)

2a, erc

1 2 3 4 5 6 7 8 9 10 11 12e

L1 L1 L1 L1 L2 L3 L4 L5 L6 L7 L8 L4

CH3I BnBr CH3OMs CH3OTs CH3I CH3I CH3I CH3I CH3I CH3I CH3I CH3I

96:trace 56:23 trace:45 12:56 92:7 93:6 97(94d):trace 78:3 35:6 86:13 24:14 97d:trace

94.5:5.5 racemic n.d. racemic 86:14 95:5 97:3 27:73 96:4 11:89 39:61 95.5:4.5

a Conditions: 1a (0.2 mmol), RX (0.3 mmol), B2(pin)2 (0.3 mmol), CuCl (10 mol %), ligand (12 mol %), MeOK (0.3 mmol), THF (1.5 mL) at 25 °C for 12 h. bDetermined by crude 1H NMR spectroscopy. c Determined by chiral HPLC analysis. dIsolated yield. ePerformed in 10 mmol scale.

styrene 1a, B2(pin)2, and methyl iodide proceeded smoothly at room temperature in tetrahydrofuran (THF). The desired methylboration adduct 2a was released in high NMR yield (96%) with good enantioselectivity (er = 94.5:5.5) (Table 1, entry 1). The stereochemistry of 2a was determined by comparison of its optical rotation with literature.14 Intriguingly, the use of other Csp3-electrophiles such as BnBr or MeOTs afforded the corresponding products in almost racemic form (Table 1, entries 2 and 4). The evaluation of ligands demonstrated that the SOP L4 slightly improved the yield and er (yield = 97% by NMR and er = 97:3) (Table 1, entry 7). All tested commercially available ligands in this reaction did not show better results. For instance, excellent enantioselectivity (er = 96:4) was promoted by (R,R)-Ph-BPE, but the reactivity and chemoselectivity were very poor. (R)-Binap and (S,S)-Me-Duphos showed good activities and chemoselectivities but low er values, and (R,R)-quinoxP* generated a very poor result in this process (Table 1, entries 8− 11). Other reaction parameters, such as base, solvent, and copper salt, were also systematically screened to establish the optimal conditions (for details, see Supporting Information (SI)). To demonstrate the scalability of this transformation, the reaction was performed in 10 mmol scale (1.04 g of 1a) (Table 1, entry 12) and a high yield (97%) and enantioselectivity (er = 95.5:4.5) were obtained. In addition, other diboron reagents such as bis(2,4-dimethylpentane-2,4-glycolato)diboron, also worked well in this system, as a 90% yield and 95:5 er were obtained (for analysis data, see SI). Under the optimized conditions, we then explored the substrate scope of this copper-catalyzed methylboration process (Scheme 1). Styrenes were first tested, and a broad range of substrates bearing various functional groups (alkyl, aryl, halogens, and ethers) at different positions were well-tolerated and effectively converted to the corresponding threecomponent products 2 in good yields (85−95% isolated yields). The electronic nature of styrenes has negligible effect on the reactivity but influences the enantioselectivity. Electronrich or -neutral styrenes with alkoxyl, alkyl, or aryl groups gave products with generally high er values (92:8−98:2). Notably,

a Conditions: 1 (0.2 mmol), CH3I or CD3I (0.3 mmol), B2(pin)2 (0.3 mmol), CuCl (10 mol %), L4 (12 mol %), MeOK (0.3 mmol), THF (1.5 mL) at 25 °C for 12 h. bIsolated yield. cDetermined by chiral HPLC analysis.

3,4-OMe styrene, which is inert in the allylboration,7c is quite reactive in the methylboration transformation to afford 2v in 88% yield and 94:6 er. Styrenes with a halide at the ortho- (2d and 2e) or para-position (2m−o) of the aryl ring also gave good er values, but the enantioselectivity was eroded when styrene bears a meta-Cl or -Br substituent (2h and 2i). Particularly, p-CF3 or CN substituted styrene afforded 2p (er = 63:37) and 2q (er = 50:50) with a disappointing er, probably due to the loss of enantiomeric purity in the C−C crosscoupling process. The successful late-stage modification of a steroid derivative (2x, 95% yield, dr = 97.5:2.5) also proved the generality of this transformation. In addition, a deuterated methyl reagent, CD3I, was successfully employed in the reaction and the desired CD3-containing products (2a-D and 2y-D) were achieved with satisfactory results. These products may show utility in the preparation of the deuterated drugs. We next set out to examine other alkenes, such as βsubstituted styrenes and inactive aliphatic olefins. However, sulfoxide phosphine (SOP) does not work for these alkenes. To our delight, (R,R)-quinoxP*, which was the inefficient ligand for vinylarene substrates, successfully promoted the methylboration process here. (For conditions optimization, see SI. The products were characterized by an oxidation procedure to convert Bpin to hydroxyl group.) For example, β-methyl or phenyl substituted styrenes and cinnamyl methyl ether were effectively transformed to the single syn-addition products with excellent diastereoselectivities (dr >99:1) and enantioselectivities (er = 93.5:6.5−99:1) (4a−e) (Scheme 2). Importantly, product 4e, a diastereomer of 4a, was accessed from Z-βmethylstyrene with excellent dr and er (4a vs 4e).15 The method thus allows for stereospecific synthesis of enantioenriched secondary alcohols bearing vicinal stereogenic tertiary B

DOI: 10.1021/acs.orglett.7b03860 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Scheme 2. Scope of β-Substituted Styrenes and Aliphatic Olefinsa

C−C double bond of aliphatic olefins with high facial selectivity. To demonstrate the applicability of this process, we prepared naproxen, a marketed anti-inflammatory drug, in gram scale. The synthesis started from 7-methoxy-2-vinylnaphthalene 1y. Under our standard methylboration conditions, compound 5 was obtained with a 95% yield and 97:3 er. Then, through a simple iron-catalyzed oxidation reaction developed by Ma,16 (S)-naproxen was achieved in 90% yield and 97:3 er. Similarly, after inserting a methylene moiety between the C−B bond of product 2k, and conducting two oxidation procedures, the key intermediate 7, which had been used in the synthesis of natural products (R)-ar-turmerone17 and 8-deoxyanisatin,18 was obtained with a high yield and high er (Scheme 3). In summary, we have developed the first enantioselective copper-catalyzed alkylboration of alkenes utilizing SOP or quinoxP* as a ligand. Methyl iodide was demonstrated to couple with the enantiomerically enriched Cu-alkyl intermediate in high stereospecificity. More importantly, this process provides an efficient platform and valuable option for the synthesis of the important chiral methyl containing frameworks from simple alkenes.

a

Conditions: 3 (0.2 mmol), CH3I or CD3I (0.3 mmol), B2(pin)2 (0.3 mmol), CuCl (10 mol %), (R,R)-quinoxP* (12 mol %), MeOK (0.3 mmol), THF (1.5 mL) at 25 °C for 12 h. bIsolated yield. cDetermined by crude 1H NMR spectroscopy. dDetermined by chiral HPLC analysis.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b03860. Experimental details and analytical data (NMR, HPLC, ESI-HRMS) (PDF)

carbon centers from either E- or Z-styrene derivatives. 1,2Dihydronaphthalene also worked well in this process to give 1methyl-1,2,3,4-tetrahydronaphthalen-2-ol (4f), (70% yield, dr >99:1 and er = 98:2).

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Scheme 3. Application of Enantioselective Methylboration Strategy

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Jian Liao: 0000-0001-8033-6521 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the NSFC (Nos. 21472184, 21572218, and 21402186) and Sichuan Sci&Tech Department (2016JZ0022) for financial support.

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REFERENCES

(1) A recent review: Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B. Chem. Rev. 2016, 116, 9091. (2) Reviews: (a) Shimizu, Y.; Kanai, M. Tetrahedron Lett. 2014, 55, 3727. (b) Semba, K.; Fujihara, T.; Terao, J.; Tsuji, Y. Tetrahedron 2015, 71, 2183. (c) Yoshida, H. ACS Catal. 2016, 6, 1799. (3) For selected examples, see: (a) Burns, A. R.; Gonzalez, J. S.; Lam, H. W. Angew. Chem., Int. Ed. 2012, 51, 10827. (b) Meng, F.; Jang, H.; Jung, B.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2013, 52, 5046. (c) Meng, F.; Haeffner, F.; Hoveyda, A. H. J. Am. Chem. Soc. 2014, 136, 11304. (4) For selected examples, see: (a) Rae, J.; Yeung, K.; McDouall, J. J. W.; Procter, D. J. Angew. Chem., Int. Ed. 2016, 55, 1102. (b) Yeung, K.; Ruscoe, R. E.; Rae, J.; Pulis, A. P.; Procter, D. J. Angew. Chem., Int. Ed. 2016, 55, 11912. (c) Jiang, L.; Cao, P.; Wang, M.; Chen, B.; Wang, B.; Liao, J. Angew. Chem., Int. Ed. 2016, 55, 13854. (d) Smith, J. J.; Best, D.; Lam, H. W. Chem. Commun. 2016, 52, 3770.

Furthermore, the reactivity of aliphatic olefins was evaluated in this catalysis. (R,R)-QuinoxP* is again the suitable ligand in terms of the reactivity and selectivity. An array of α-olefins, bearing a heteroatom or phenyl group at the end, are quite reactive to give anti-Markovnikov methylboration products with good yields and enantioselectivities (4g−4j). This also, for the first time, proves the efficient Cu−B(pin) addition to the C

DOI: 10.1021/acs.orglett.7b03860 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters

(14) Zhang, L.; Zuo, Z.; Wan, X.; Huang, Z. J. Am. Chem. Soc. 2014, 136, 15501. (15) The absolute configration was determined by the comparison of optical rotation with literature: Vitale, P.; Perna, F. M.; Perrone, M. G.; Scilimati, A. Tetrahedron: Asymmetry 2011, 22, 1985. (16) Jiang, X.; Zhang, J.; Ma, S. J. Am. Chem. Soc. 2016, 138, 8344. (17) Yan, Q.; Kong, D.; Li, M.; Hou, G.; Zi, G. J. Am. Chem. Soc. 2015, 137, 10177. (18) Loh, T.-P.; Hu, Q.-Y. Org. Lett. 2001, 3, 279.

(5) For selected examples, see: (a) Zhou, Y.; You, W.; Smith, K. B.; Brown, M. K. Angew. Chem., Int. Ed. 2014, 53, 3475. (b) Semba, K.; Nakao, Y. J. Am. Chem. Soc. 2014, 136, 7567. (c) Smith, K. B.; Logan, K. M.; You, W.; Brown, M. K. Chem. - Eur. J. 2014, 20, 12032. (d) Logan, K. M.; Smith, K. B.; Brown, M. K. Angew. Chem., Int. Ed. 2015, 54, 5228. (e) Semba, K.; Ohtagaki, Y.; Nakao, Y. Org. Lett. 2016, 18, 3956. (f) Logan, K. M.; Brown, M. K. Angew. Chem., Int. Ed. 2017, 56, 851. (g) Chen, B.; Cao, P.; Yin, X.; Liao, Y.; Jiang, L.; Ye, J.; Wang, M.; Liao, J. ACS Catal. 2017, 7, 2425. (h) Smith, K. B.; Brown, M. K. J. Am. Chem. Soc. 2017, 139, 7721. (i) Sardini, S. R.; Brown, M. K. J. Am. Chem. Soc. 2017, 139, 9823. (6) For selected examples, see: (a) Liu, P.; Fukui, Y.; Tian, P.; He, Z.T.; Sun, C.- Y.; Wu, N.- Y.; Lin, G.- Q. J. Am. Chem. Soc. 2013, 135, 11700. (b) Li, X.; Meng, F.; Torker, S.; Shi, Y.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2016, 55, 9997. (c) Meng, F.; Li, X.; Torker, S.; Shi, Y.; Shen, X.; Hoveyda, A. H. Nature 2016, 537, 387. (7) For selected examples, see: (a) Meng, F.; McGrath, K. P.; Hoveyda, A. H. Nature 2014, 513, 367. (b) Semba, K.; Bessho, N.; Fujihara, T.; Terao, J.; Tsuji, Y. Angew. Chem., Int. Ed. 2014, 53, 9007. (c) Jia, T.; Cao, P.; Wang, B.; Lou, Y.; Yin, X.; Wang, M.; Liao, J. J. Am. Chem. Soc. 2015, 137, 13760. (d) Bin, H.- Y.; Wei, X.; Zi, J.; Zuo, Y.-J.; Wang, T.-C.; Zhong, C.-M. ACS Catal. 2015, 5, 6670. (e) Radomkit, S.; Liu, Z.; Closs, A.; Mikus, M. S.; Hoveyda, A. H. Tetrahedron 2017, 73, 5011. (f) Mateos, J.; Rivera-Chao, E.; Fañanás-Mastral, M. ACS Catal. 2017, 7, 5340. (g) Lee, J.; Radomkit, S.; Torker, S.; del Pozo, J.; Hoveyda, A. H. Nat. Chem. 2017, 10, 99. (h) Kim, N.; Han, J. T.; Ryu, D. H.; Yun, J. Org. Lett. 2017, 19, 6144. (8) For selected examples, see: (a) Zhang, L.; Cheng, J.; Carry, B.; Hou, Z. J. Am. Chem. Soc. 2012, 134, 14314. (b) Zhao, W.; Montgomery, J. J. Am. Chem. Soc. 2016, 138, 9763. (c) Butcher, T. W.; McClain, E. J.; Hamilton, T. G.; Perrone, T. M.; Kroner, K. M.; Donohoe, G. C.; Akhmedov, N. G.; Petersen, J. L.; Popp, B. V. Org. Lett. 2016, 18, 6428. (d) Fujihara, T.; Sawada, A.; Yamaguchi, T.; Tani, Y.; Terao, J.; Tsuji, Y. Angew. Chem., Int. Ed. 2017, 56, 1539. (e) Huang, Y.; Smith, K. B.; Brown, M. K. Angew. Chem., Int. Ed. 2017, 56, 13314. (f) Gong, T.-J.; Yu, S.-H.; Li, K.; Su, W.; Lu, X.; Xiao, B.; Fu, Y. Chem. - Asian J. 2017, 12, 2884. (9) For selected examples, see: (a) Ito, H.; Kosaka, Y.; Nonoyama, K.; Sasaki, Y.; Sawamura, M. Angew. Chem., Int. Ed. 2008, 47, 7424. (b) Ito, H.; Toyoda, T.; Sawamura, M. J. Am. Chem. Soc. 2010, 132, 5990. (c) Zhong, C.; Kunii, S.; Kosaka, Y.; Sawamura, M.; Ito, H. J. Am. Chem. Soc. 2010, 132, 11440. (d) Alfaro, R.; Parra, A.; Aleman, J.; Ruano, J. L. G. R.; Tortosa, M. J. Am. Chem. Soc. 2012, 134, 15165. (e) Kubota, K.; Yamamoto, E.; Ito, H. J. Am. Chem. Soc. 2013, 135, 2635. (f) Yoshida, H.; Kageyuki, I.; Takaki, K. Org. Lett. 2013, 15, 952. (g) Su, W.; Gong, T.; Lu, X.; Xu, M.; Yu, C.; Xu, Z.; Yu, H.; Xiao, B.; Fu, Y. Angew. Chem., Int. Ed. 2015, 54, 12957. (h) Kubota, K.; Iwamoto, H.; Yamamoto, E.; Ito, H. Org. Lett. 2015, 17, 620. (i) Itoh, T.; Shimizu, Y.; Kanai, M. J. Am. Chem. Soc. 2016, 138, 7528. (j) Su, W.; Gong, T.-J.; Zhang, Q.; Zhang, Q.; Xiao, B.; Fu, Y. ACS Catal. 2016, 6, 6417. (k) Kageyuki, I.; Osaka, I.; Takaki, K.; Yoshida, H. Org. Lett. 2017, 19, 830. (l) Iwamoto, H.; Akiyama, S.; Hayama, K.; Ito, H. Org. Lett. 2017, 19, 2614. (m) Mun, B.; Kim, S.; Yoon, H.; Kim, K. H.; Lee, Y. J. Org. Chem. 2017, 82, 6349. (n) Iwamoto, H.; Ozawa, Y.; Kubota, K.; Ito, H. J. Org. Chem. 2017, 82, 10563. (10) Gribble, M. W.; Pirnot, M. T.; Bandar, J. S.; Liu, R. Y.; Buchwald, S. L. J. Am. Chem. Soc. 2017, 139, 2192. (11) Imamoto, T.; Sugita, K.; Yoshida, K. J. Am. Chem. Soc. 2005, 127, 11934. (12) For reviews, see: (a) Barreiro, E. J.; Kummerle, A. E.; Fraga, C. A. M. Chem. Rev. 2011, 111, 5215. (b) Schonherr, H.; Cernak, T. Angew. Chem., Int. Ed. 2013, 52, 12256. (13) (a) Lou, Y.; Cao, P.; Jia, T.; Zhang, Y.; Wang, M.; Liao, J. Angew. Chem., Int. Ed. 2015, 54, 12134. (b) Jia, T.; Cao, P.; Wang, D.; Lou, Y.; Liao, J. Chem. - Eur. J. 2015, 21, 4918. (c) Wang, D.; Cao, P.; Wang, B.; Jia, T.; Lou, Y.; Wang, M.; Liao, J. Org. Lett. 2015, 17, 2420. (d) Zhang, Y.; Wang, M.; Cao, P.; Liao, J. Huaxue Xuebao 2017, 75, 794. D

DOI: 10.1021/acs.orglett.7b03860 Org. Lett. XXXX, XXX, XXX−XXX