Construction of protected hydroxylated pyrrolidines using nitrogen-centered radical cyclizations

Huimin Zhai, Maria Zlotorzynska, Glenn Sammis
2009 Chemical Communications  
General Methods All reactions were performed under a nitrogen atmosphere in flame-dried glassware. Tetrahydrofuran, diethyl ether, dichloromethane and benzene were purified by MBRAUN MB-SPS solvent purification system. Thin layer chromatography (TLC) was performed on Whatman Partisil K6F UV 254 pre-coated TLC plates. Chromatographic separations were effected over Fluka 60 silica gel. Triethylamine washed silica gel has been stirred with triethylamine prior to packing. All chemicals were
more » ... d from commercial sources and used as received. Azidecontaining silyl enol ethers, such as azides 7, 13, 16, 19, 20 and 25, are bench-stable for at least 2 weeks. Instrumentation A KD-Scientific KDS100 syringe pump was used for all slow additions. Melting points were performed using a Mel-Temp II apparatus (Lab devices USA) and are uncorrected. Optical rotations were recorded using a Perkin-Elmer 241 ML Polarimeter. Infrared (IR) spectra were obtained using a Thermo Nicolet 4700 FT-IR spectrometer. Proton nuclear magnetic resonance ( 1 H NMR) spectra were recorded in deuterochloroform using a Bruker AV-300 or AV-400 spectrometer. Carbon nuclear magnetic resonance ( 13 C NMR) spectra were recorded in deuterochloroform using a Bruker AV-300 or AV-400 spectrometer. Chemical shifts are reported in parts per million (ppm) and are referenced to the centerline of deuterochloroform (7.27 ppm 1 H NMR; 77.0 ppm 13 C NMR). Low resolution mass spectra (LRMS) and high resolution mass spectra (HRMS) were recorded on either a Bruker Esquire-LC spectrometer (for LRMS) or a Waters/Micromass LCT spectrometer (for HRMS). Supplementary Material (ESI) for Chemical Communications This journal is Syntheses of silyl enol ether 7 TsO OTBS N 3 OTBS 7 NaN 3 DMF, 50 °C (Z)-tert-butyl-dimethyl-silanoxy-5-azido-pent-1-ene (7): To a solution of tosylate 1 (1.381 g, 3.73 mmol) in DMF (20 mL) was added sodium azide (533 mg, 7.5 mmol). The mixture was heated at 50 °C for 10 h, then taken up in EtOAc (40 mL). The mixture was then washed with water (2x15 mL), brine (15 mL), dried over Na 2 SO 4 , filtrated and concentrated by rotary evaporation to provide a yellow oil. Purification by flash chromatography (hexanes) gave 749 mg (83%) of azide 7 (Z/E = 88:12) 2 as a clear oil. HRMS-ESI (m/z) [M+Na] + calcd for C 11 H 23 N 3 ONaSi: 264.1508. Found: 264.1514. Cyclization to form pyrrolidine 9 H N OTBS 9 N 3 OTBS 7 Bu 3 SnH, AIB N C 6 H 6 , 80 °C 2-(tert-Butyl-dimethyl-silanyloxymethyl)-pyrrolidine (9): A solution of silyl enol ether 7 (301 mg, 1.27 mmol) Bu 3 SnH (438 mg, 1.5 mmol), AIBN (27 mg, 0.15 mmol) in degassed benzene 3 (40 mL) was heated to 80 °C and stirred for 10 h, and the solution was allowed to cool to room temperature and the solvent was removed by rotary evaporation. Purification by flash chromatography (1% methanol in EtOAc) afforded 206 mg (75%) of pyrrolidine 9 as a yellow oil.
doi:10.1039/b914757h pmid:19774246 fatcat:iageybnxv5bxpgbm5dn7w3f3ne