Synlett 2024; 35(08): 895-898
DOI: 10.1055/s-0043-1763621
cluster
Special Issue dedicated to Keith Fagnou

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

Anthony F. Palermo
,
Bianca Imbriaco
,
Samantha C. Chan
,
Brian A. Doan
,
We thank the Natural Sciences and Engineering Research Council of Canada (Discovery Grants and Canada Research Chair programs; RGPIN-2021-03533), the Canada Foundation for Innovation (Project No. 35261), the Government of Ontario (Ontario Research Foundation, Early Research Award), and the University of Toronto for generous financial support of this work. We also acknowledge the Canada Foundation for Innovation (Project No. 19119) and the Ontario Research Foundation for funding the Centre for Spectroscopic Investigation of Complex Organic Molecules and Polymers. A.F.P. and S.C.C. thank the NSERC for a graduate scholarship and an undergraduate research award (PGS D, NSERC USRA).


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.

Supporting Information



Publication History

Received: 15 September 2023

Accepted after revision: 18 October 2023

Article published online:
21 November 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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  • 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; Rf = 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.