CC BY-ND-NC 4.0 · Synlett 2019; 30(04): 449-453
DOI: 10.1055/s-0037-1610389
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Complex Boron-Containing Molecules through a 1,2-Metalate Rearrangement/anti-S N 2′ Elimination/Cycloaddition Reaction Sequence

Chloe Tillin
,
Raphael Bigler
,
Renata Calo-Lapido
,
Beatrice S. L. Collins
,
Adam Noble
,
School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK   Email: v.aggarwal@bristol.ac.uk
› Author Affiliations
This work was financially supported by the EPSRC (EP/I038071/1), H2020 ERC (670668), and the University of Bristol. R.B. thanks the Swiss National Science Foundation fellowship program (P2EZP2_165268). R.C.L. was funded by Xunta de Galicia and European Social Fund.
Further Information

Publication History

Received: 30 September 2018

Accepted after revision: 25 October 2018

Publication Date:
20 November 2018 (eFirst)

  

Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue

Abstract

The three-component coupling of benzylamines, boronic esters, and 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione (PTAD) is reported. The boronate complex formed from an ortho-lithiated benzylamine and a boronic ester undergoes a stereospecific 1,2-metalate rearrangement/anti-S N 2′ elimination in the presence of an N-activator to provide a dearomatized tertiary boronic ester. Interception of this dearomatized intermediate with a dienophile leads to stereopredictable cycloaddition reactions to generate highly complex three-dimensional boron-containing molecular structures. When enantioenriched α-methyl-substituted benzylamines are employed, the corresponding cycloaddition adducts are formed with excellent enantiospecificities.

Supporting Information

 
  • References and Notes

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  • 13 (±)-(5S,8R,11S)-11-Cyclohexyl-10-methylene-2-phenyl-11-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,8-dihydro-1H-5,8-ethano[1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dione (3aa) Typical ProcedureBoronic ester 2a (500 μmol) was added to the ortho-lithiated benzylamine Li–1a (525 μmol, 1.05 equiv; prepared from 1a) in THF (2 mL) at –78 °C, and the solution was stirred at –78 °C for 15 min, after which the cooling bath was removed, and the mixture was stirred for a further 15 min. ClCO2CMe2CCl3 (132.0 mg, 550 μmol, 1.10 equiv) was added at –78 °C, and the solution was stirred for 15 min at –78 °C, after which the cooling bath was removed and the mixture was stirred for a further 5 min. PTAD (96.3 mg, 550 μmol, 1.10 equiv) was added, and the solution was stirred for 1 h at r.t. CHCl3 (50 mL) was added and the solution was washed with H2O (25 mL) and sat. aq NaCl (25 mL), then dried (MgSO4), filtered, and concentrated under reduced pressure. Purification by flash column chromatography [silica gel. EtOAc–pentane (15:85)] gave a white solid; yield: 121 mg (50%), dr = 17:1; mp 86 °C, Rf  = 0.47 (EtOAc–pentane, 15:85).IR (liquid film): 2927, 1771, 1710, 1397, 1138, 908, 727, 644 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.48–7.36 (m, 4 H, Ar-H), 7.34–7.28 (m, 1 H, Ar-H), 6.50 (ddd, 3 J H,H′ = 7.7, 5.5 Hz, 4 J H,H′ = 1.8 Hz, 1 H, =CH), 6.43 (ddd, 3 J H,H′ = 7.7, 5.4 Hz, 4 J H,H′ = 1.7 Hz, 1 H, =CH), 5.39 (s, 1 H, =CHH), 5.26–5.21 [m, 2 H, =CHH (1 H) + CHN (1 H)], 5.11 (dd, 3 J H,H′ = 5.5 Hz, 4 J H,H′ = 1.7 Hz, 1 H, CHN), 2.08–2.00 (m, 1 H, CHH), 1.79–1.61 (m, 4 H, CHH), 1.26 [s, 6 H, CH 3 (pin)], 1.24 [s, 6 H, CH 3 (pin)], 1.23–1.02 [m, 6 H, CH (1 H) + CHH (5 H)]. 13C{1H} NMR (101 MHz, CDCl3): δ = 155.8 (CO), 155.3 (CO), 142.9 (=C), 131.8 (arom.), 129.9 (=CH), 129.0 (2 C, arom.), 128.6 (=CH), 128.0 (arom.), 125.4 (2C, arom.), 113.9 (=CH 2), 84.2 [2 C, OC(CH3)2], 59.0 (CHN), 57.0 (CHN), 44.4 (CH), 31.0 (CH 2), 29.8 (CH 2), 27.3 (CH 2), 27.1 (CH 2), 26.4 (CH 2), 25.1 [2 C, CH3 (pin)], 24.4 [2 C, CH3 (pin)]. Carbons attached to boron were not observed due to quadrupolar relaxation. 11B{1H} NMR (128 MHz, CDCl3): δ = 33.5 (br s). HRMS (ESI): m/z [M + Na]+ calcd for C27H34BN3NaO4: 498.2535; found: 498.2554.