Asymmetric Cu(I)-Catalyzed Conjugate Borylation of α,β-Unsaturated Acyl Silanes

Abstract

We report the development of a Cu(I)-catalyzed conjugate borylation of α,β-unsaturated acyl silanes using bis(pinacoloto)diboron. Racemic borylations of β-aryl- and β-alkyl-substituted silyl enones were achieved using ligand-free conditions to access β-borylated acyl silanes in up to 97% yield. Josiphos enabled the synthesis of enantioenriched boronic esters in up to 58% yield and 94% ee. The racemic reaction was demonstrated on 5.0 mmol scale and isolation of the boronic esters was achieved using simple filtration and normal-phase chromatography. This work supplements known methods to access boronic esters from electron-deficient olefins using Cu(I) catalysis.

Key words

conjugate borylation - α,β-unsaturated acyl silanes - asymmetric borylation - copper catalysis - organoboronic esters

Publication History

Received: 15 September 2023

Accepted after revision: 18 October 2023

Article published online:
21 November 2023

• References and Notes

• 1 Fyfe JW. B, Watson AJ. B. Chem 2017; 3: 31
• 2a Calow AD. J, Whiting A. Org. Biomol. Chem. 2012; 10: 5485
• 2b Hu J, Ferger M, Shi Z, Marder TB. Chem. Soc. Rev. 2021; 50: 13129
• 2c Alam S, Karim R, Khan A, Pal AK, Maruani A. Eur. J. Org. Chem. 2021; 6115
• 3a Mun S, Lee J.-E, Yun J. Org. Lett. 2006; 8: 4887
• 3b Lee J.-E, Yun J. Angew. Chem. Int. Ed. 2008; 47: 145
• 3c O’Brien JM, Lee K, Hoveyda AH. J. Am. Chem. Soc. 2010; 132: 10630
• 3d Lee JC. H, McDonald R, Hall DG. Nat. Chem. 2011; 3: 894
• 3e He Z.-T, Zhao Y.-S, Tian P, Wang C.-C, Dong H.-Q, Lin G.-Q. Org. Lett. 2014; 16: 1426
• 3f Niu Z, Chen J, Chen Z, Ma M, Song C, Ma Y. J. Org. Chem. 2015; 80: 602
• 3g Jana A, Trzybiński D, Woźniak K, Grela K. Chem. Eur. J. 2018; 24: 891
• 3h Miwa Y, Kamimura T, Sato K, Shishido D, Yoshida K. J. Org. Chem. 2019; 84: 14291
• 4a Ito H, Yamanaka H, Tateiwa J, Hosomi A. Tetrahedron Lett. 2000; 41: 6821
• 4b Chen I.-H, Yin L, Itano W, Kanai M, Shibasaki M. J. Am. Chem. Soc. 2009; 131: 11664
• 4c Sim H.-S, Feng X, Yun J. Chem. Eur. J. 2009; 15: 1939
• 4d Xie J.-B, Lin S, Luo J, Wu J, Winn TR, Li G. Org. Chem. Front. 2015; 2: 42
• 4e Jiang Q, Guo T, Yu Z. ChemCatChem 2015; 7: 660
• 4f Jiang Q, Guo T, Yu Z. J. Org. Chem. 2017; 82: 1951
• 4g Tsutsumi R, Taguchi R, Yamanaka M. ChemCatChem 2022; 14: e202101278
• 4h Qian Y.-S, Wang Z.-L, Jiang B, Xiao Z.-Y, Xu Y.-H. Org. Lett. 2023; 25: 3364
• 5a Chea H, Sim H.-S, Yun J. Adv. Synth. Catal. 2009; 351: 855
• 5b Sandrock DL, Jean-Gérard L, Chen C, Dreher SD, Molander GA. J. Am. Chem. Soc. 2010; 132: 17108
• 5c Zhao L, Ma Y, Duan W, He F, Chen J, Song C. Org. Lett. 2012; 14: 5780
• 5d Molander GA, Wisniewski SR, Hosseini-Sarvari M. Adv. Synth. Catal. 2013; 355: 3037
• 6 Moure AL, Gómez ArrayásR, Carretero JC. Chem. Commun. 2011; 47: 6701
• 7 Kim J, Lee H, Yun J. Tetrahedron 2019; 75: 4250
• 8 Hornillos V, Vila C, Otten E, Feringa BL. Angew. Chem. Int. Ed. 2015; 54: 7867
• 9a Brook AG. Acc. Chem. Res. 1974; 7: 77
• 9b Zhang H.-J, Priebbenow DL, Bolm C. Chem. Soc. Rev. 2013; 42: 8540
• 9c Hong WP, Lim HN, Shin I. Org. Chem. Front. 2023; 10: 819
• 10 Parra A, Amenós L, Guisán-Ceinos M, López A, García Ruano JL, Tortosa M. J. Am. Chem. Soc. 2014; 136: 15833
• 11 Kim C, Roh B, Lee HG. Chem. Sci. 2021; 12: 3668
• 12 Nagy A, Collard L, Indukuri K, Leyssens T, Riant O. Chem. Eur. J. 2019; 25: 8705
• 13 General Procedure A for Racemic Conjugate BorylationsA flame-dried 8 mL screw top vial equipped with a stir bar was charged with CuCl (0.01 mmol, 5.0 mol%), LiOt-Bu (0.2 mmol, 1.0 equiv), and then sealed with a rubber septum and electrical tape. The vial was backfilled three times with argon, THF (0.30 mL) was added, and the yellow/lime green suspension was stirred at room temperature for 30 min. B₂pin₂ (0.24 mmol, 1.2 equiv) in THF (0.15 mL) was added, and the resulting black solution was stirred for 10 min at room temperature. A solution of acyl silane 1a (0.2 mmol, 1.0 equiv) and MeOH (0.6 mmol, 3.0 equiv) in THF (0.22 mL) was then added, and the reaction was stirred for 1 h. The reaction was then diluted with 1 mL of Et₂O and passed through a short plug of Celite. The filtrate was then concentrated in vacuo and purified by silica gel column chromatography using 6% EtOAc–hexanes, affording the desired boronic ester 2a. Data for Representative Compound 2aColorless oil that solidifies in the freezer to an off-white waxy solid; R_f = 0.29 (10% EtOAc–hexanes). ¹H NMR (500 MHz, CDCl₃): δ = 7.11–7.08 (m, 2 H), 7.07–7.03 (m, 2 H), 3.16 (dd, J = 18.8, 10.9 Hz, 1 H), 3.00 (dd, J = 18.8, 4.8 Hz, 1 H), 2.55 (dd, J = 10.9, 4.8 Hz, 1 H), 2.29 (d, J = 0.6 Hz, 3 H), 1.24–1.21 (m, 6 H), 1.14 (s, 6 H), 0.18 (s, 9 H). ¹³C NMR (126 MHz, CDCl₃): δ = 246.9, 139.2, 134.7, 129.1, 128.1, 83.2, 53.5, 24.6, 24.5, 20.9, –3.3. ¹¹B NMR (160 MHz, CDCl₃): δ = 33.5. ²⁹Si NMR (99 MHz, CDCl₃): δ = –10.7. HRMS (DART): m/z calcd for C₁₉H₃₁BO₃Si [M + H]⁺: 347.2208; found: 347.2208.
• 14 General Procedure B for Asymmetric Conjugate Borylations To a flame-dried 8 mL screw top vial equipped with a magnetic stir bar was added Cu(MeCN)₄ClO₄ (0.02 mmol, 10 mol%) and Josiphos SL-J001-1 (0.024 mmol, 12 mol%), the vial was sealed with a rubber septum and electrical tape and backfilled three times with argon. THF sparged with argon (0.3 mL) was added, and the mixture was stirred for 30 min at room temperature. Solvent was then removed in vacuo and dried on high vacuum for 15 min. B₂pin₂ (0.3 mmol, 1.5 equiv) in THF (0.2 mL) was added, and the solution was stirred for 10 min. A suspension of LiOt-Bu (0.1 mmol, 50 mol%) in THF (0.25 mL) was added, and the black solution was stirred for an additional 10 min at room temperature. The mixture was cooled to –78 °C with a cryostat, and acyl silane 1a (0.2 mmol, 1.0 equiv) with MeOH (0.6 mmol, 3.0 equiv) in THF (0.22 mL) was added dropwise. The reaction was warmed to –50 °C over 2 h and then stirred at temperature for 18 h. The reaction was diluted with 1 mL Et₂O at –78 °C, warmed to room temperature, filtered through a short plug of Celite, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography (5–7% EtOAc–hexanes) to afford 3a in 58% yield.