Formation of Seven-Membered Rings by Ring-Closing Metathesis of Vinyl Bromides
Vachiraporn Ajavakom∗
a
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand
,
Potchanee Pandokrak
a
Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand
,
Sofia S. Salim
b
School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
,
Gamal A. I. Moustafa
b
School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
,
Richard K. Bellingham
c
Synthetic Chemistry Department, Chemical Development, GlaxoSmithKline Pharmaceuticals, Old Powder Mills, Tonbridge, Kent, TN11 9AN, UK
,
Joseph T. Hill-Cousins
b
School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
,
Anawat Ajavakom
d
Nanotec-CU Center of Excellence on Food and Agriculture, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
,
Richard C. D. Brown∗
b
School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
› Author AffiliationsThe authors acknowledge EPSRC and GlaxoSmithKline for a CASE award (S.S.S.), the Royal Society for a University Research Fellowship (R.C.D.B.), and the European Regional Development Fund (ERDF) for funding the AI-Chem project through the INTERREG IVa program 4061. This work was also supported by the Center of Excellence for Innovation in Chemistry (PERCH-CIC).
A Grubbs II catalyst mediated ring-closing metathesis (RCM) of monobrominated dienes is reported to proceed in moderate to good yields (40–80%) where the linking chain contains five atoms, leading to carbocyclic and heterocyclic seven-membered bromoolefins. Notably, RCM to form five-, six-, or eight-membered bromoolefins was unsuccessful, with the exception of one example where RCM afforded diethyl 3-bromocyclohex-3-ene-1,1-dicarboxylate. In this case, a bromomethyl-substituted cyclohexene was obtained as a byproduct. The utility of selected bromoolefin RCM products was demonstrated through their participation in Suzuki–Miyaura reactions. Vinylic halide exchange (Br → Cl) was noted as a side reaction under RCM conditions.
192,7-Dibenzyl-4-bromo-2,3,6,7-tetrahydro-1,2,7-thiadiazepine 1,1-Dioxide (2a); Typical Procedure A solution of GII (6.0 mg, 7.0 μmol) in benzene (2 mL) was added to a solution of compound 1a (31.2 mg, 0.07 mmol) in benzene (5 mL), and the mixture was stirred and degassed for 30 s then refluxed for 18 h. A second portion of the GII (3.0 mg, 3.5 μmol) dissolved in benzene (1 mL) was then added and heating was continued for 18 h. The solution was then concentrated under reduced pressure to afford the crude product as a black oil. Purification by column chromatography [silica gel, EtOAc/hexane (2:98)] gave a white solid; yield: 26 mg (90%); mp 106–108 °C. IR (ATR): 3030, 2919, 1507, 1456, 1359 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.40–7.24 (m, 10 H), 6.24 (t, J = 5.7 Hz, 1 H), 4.52 (s, 2 H), 4.45 (s, 2 H), 4.03 (s, 2 H), 3.60 (d, J = 5.7 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 135.6 (C), 135.3 (C), 130.5 (CH), 128.8 (CH), 128.7 (CH), 128.6 (CH), 128.3 (CH), 128.2 (CH), 122.7 (C), 52.4 (CH2), 52.1 (CH2), 44.1 (CH2). LRMS (ES+, MeCN): m/z (%): 431 (100) and 429 (100) [M + Na]+. HRMS (ES+): m/z [M + Na]+ calcd for C18H1979BrN2NaO2S: 429.0242; found: 429.0239.
