Synlett 2017; 28(14): 1733-1737
DOI: 10.1055/s-0036-1588494
cluster
© Georg Thieme Verlag Stuttgart · New York

Bromine-Radical-Mediated Synthesis of β-Functionalized β,γ- and δ,ε-Unsaturated Ketones via C–H Functionalization of Aldehydes

Takashi Kippo
a  Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan   Email: ryu@c.s.osakafu-u.ac.jp
,
Yuki Kimura
a  Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan   Email: ryu@c.s.osakafu-u.ac.jp
,
Mitsuhiro Ueda
a  Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan   Email: ryu@c.s.osakafu-u.ac.jp
,
Takahide Fukuyama
a  Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan   Email: ryu@c.s.osakafu-u.ac.jp
,
Ilhyong Ryu*
a  Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan   Email: ryu@c.s.osakafu-u.ac.jp
b  Department of Applied Chemistry, National Chiao Tung University, Hsinchu 30010, Taiwan
› Author Affiliations
This work has been supported by a Grant-in-Aid for Scientific Research from the MEXT (no. 15H05850). T.K. acknowledges the Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists.
Further Information

Publication History

Received: 26 April 2017

Accepted after revision: 15 June 2017

Publication Date:
29 June 2017 (online)


Published as part of the ISHC Conference Special Section

Abstract

The bromine-radical-mediated allylation reaction of aldehydes was studied. In the presence of V-65 as radical initiator, the reaction of aldehydes with allyl bromides gave β,γ-unsaturated ketones in good yields (13 examples, 45–84%). The reaction is triggered by hydrogen abstraction from the aldehyde by bromine radical to form an acyl radical, which undergoes an SH2′-type addition–elimination reaction with allyl bromides to give coupling products with liberation of bromine radical. Three-component coupling reactions comprising aldehydes, electron-deficient alkenes, and methallyl bromide also proceeded to give δ,ε-unsaturated ketones.

Supporting Information

 
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  • 14 General Procedure for the Synthesis of 3 To a 20 mL two-necked round-bottom flask attached with a reflux condenser were added V-65 (25 mg, 0.1 mmol) and K2CO3 (138 mg, 1.0 mmol), and this flask was purged with argon. Then, 1-nonanal (1a, 71 mg, 0.5 mmol), methyl 2-(bromomethyl)acrylate (2a, 269 mg, 1.5 mmol), and degassed benzene (5 mL) were added. The mixture was stirred at 60 °C for 1 h. The reaction mixture was filtered through a short plug of Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on SiO2 (hexane/EtOAc = 1:0 to 30:1) and preparative HPLC (chloroform) to give methyl 2-methylene-4-oxododecanoate (3b, 101 mg, 84%). Colorless oil; Rf = 0.55 (hexane/EtOAc = 5:1). 1H NMR (500 MHz, CDCl3): δ = 0.87 (t, J = 6.9 Hz, 3 H), 1.20–1.33 (m, 10 H), 1.55–1.65 (m, 2 H), 2.47 (t, J = 7.4 Hz, 2 H), 3.40 (s, 2 H), 3.74 (s, 3 H), 5.63 (s, 1 H), 6.33 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 14.02, 22.58, 23.67, 29.10, 29.30, 31.76, 42.63, 45.63, 52.00, 128.53, 134.25, 166.78, 207.42. IR (neat): 2953, 2926, 2855, 1720, 1638 cm–1. MS (EI): m/z (relative intensity): 240 (12) [M]+, 209 (5) [M – OMe]+, 141 (100), 82 (14), 71 (25), 57 (26), 55 (11). HRMS (EI): m/z calcd for C14H23O3 [M]+: 240.1725; found: 240.1725.
  • 15 General Procedure for the Synthesis of 5 To a 20 mL two-necked round-bottom flask attached with a reflux condenser were added AIBN (16 mg, 0.1 mmol) and K2CO3 (138 mg, 1.0 mmol), and this flask was purged with argon. Then, 1-nonanal (1a, 71 mg, 0.5 mmol), acrylonitrile (4a, 53 mg, 1.0 mmol), methallyl bromide (2e, 203 mg, 1.5 mmol), and degassed benzene (5 mL) were added. The mixture was stirred at 80 °C for 4 h. The reaction mixture was filtered through a short plug of Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on SiO2 (hexane/EtOAc = 1:0 to 30:1) and preparative HPLC (CHCl3) to give 2-(2-methylallyl)-4-oxododecanenitrile (5a, 71.1 mg, 57%). Compound 5a is known in literature, and all spectral data matched that reported.6b