A novel and highly regioselective Cr-mediated route to functionalised quinone boronic ester derivatives

Abstract

A novel and highly regioselective route to quinone boronic ester derivatives has been developed using a Fischer carbene mediated benzannulation process.

References

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8. Alkynylboronates are readily hydrolysed to the parent alkyne in the presence of protic reagents, (ref. 6), it is therefore plausible that the phenolic benzannulated product mediates alkyne protodeboronation. Indeed, hex-1-yne was recovered in the volatile material isolated from the reaction mixture in Table1, entry 1.
9. Crystal data for 3: C₂₁H₂₉BO₄, M= 356.25, triclinic, a= 9.4916(6), b= 11.1685(8), c= 18.9638(13)Å, α= 90.1890(10), β= 91.2770(10), γ= 92.5080(10)°, U= 2007.9(2)ų, Z= 4, D_c= 1.179 g cm^–3, space group P1̄(no. 2), T= 150 K, Mo-Kα radiation (λ= 0.71073 Å), µ(Mo-Kα)= 0.079 mm^–1, F(000)= 768. Data were collected in the range 1.83 < θ < 28.36 °, 5420 independent reflections (R_int= 0.0549), final R= 0.0778, with allowance for the thermal anisotropy of all non-hydrogen atoms. For 6: C₂₁H₂₉BO₄, M= 356.25, monoclinic, a= 8.845(2), b= 19.493(5), c= 12.055(3)Å, β= 103.804(6)°, U= 2018.5(10)ų, Z= 4, D_c= 1.172 g cm^–3, space group P 2₁/n(a non-standard setting of P2₁/c, no. 14), T= 150 K, Mo-Kα radiation (λ= 0.71073 Å), µ(Mo-Kα)= 0.079 mm^–1, F(000)= 768. Data were collected in the range 2.03 < θ < 28.31 °, 1895 independent reflections (R_in= 0.0932), final R= 0.0618, with allowance for the thermal anisotropy of all non-hydrogen atoms. CCDC 182/1418.
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13. The rigorous establishment of compounds 11 and 16 is ongoing but at present is assumed to follow the same insertion patterns as outlined in Scheme 4.
14. The A value of the alkynyl substituent can often serve as a useful guide to predicting regioselectivity (ref. 10). In this context, studies are underway to determine the A value of a range of boronic ester moieties and will be the subject of a future disclosure.
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17. Typical experimental procedure as exemplified by benzannulation of complex 1 and alkyne 2(Scheme 2): to a solution of 1(102 mg, 0.327 mmol) in THF (6.4 ml) was added alkyne 2(204 mg, 0.980 mmol)via syringe under nitrogen. The reaction mixture was stirred at 45 °C for 14 h and concentrated by rotary evaporation. Purification of the resulting residue by silica gel chromatography provided hydroquinone 4(ref. 18)(11 mg, 15%) and boronate ester 3(85 mg, 73%) which could be crystallised from hexanes to provide an amber solid, mp 116–116.5 °C.; δ_H(250 MHz, CDCl₃)0.96 (3H, t, J 7.3, CH₃CH₂), 1.42 (12H, s, CH₃), 1.47–1.72 (4H, m, CH₂CH₂CH₃), 2.73 (2H, app t, J 7.9, C=CCH₂), 3.91 (3H, s, CH₃O), 4.93 (1H, br s, OH), 7.39–7.53 (2H, m, Ar-H) 7.95–8.03 (1H, m, Ar-H), 8.05–8.13 (1H, m, Ar-H); δ_C(62.9 MHz, CDCl₃) 14.1, 24.7, 24.9, 30.2, 33.0, 63.5, 84.0, 121.6, 122.0, 124.3, 125.2, 125.9, 126.6, 144.4, 153.9; V_max/cm^–1 3445 (br), 2991 (m), 2977 (m), 1662 (m), 1142 (s)(calc. for C₂₁H₂₉BO₄:C, 70.80; H, 8.20. Found: C, 70.67; H, 8.36%).
18. ¹³C and ¹H spectra of 4 were identical to an authentic sample prepared from hex-l-yne: A. Yamashita, S. Ayako, R. G. Schaub, M. K. Bach, G. J. White and A. Toy, J. Med. Chem., 1990, 33, 775.