Lecture 11

Lecture 11 - Alcohol Protecting Groups O OTBS O O O O O TMS...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Alcohol Protecting Groups O OTBS O O O O O TMS O NH O OPMB O MeO OAc Me OAc PMBO OPMB O Me OPMB OMe O OTBS OBz BzO OBz OAc OBz OAc TBSO Me H OTBS Me OTBS Me PMBO OPMB O H OPMB TBSO OTBS O Me O OPMB OPMB O OTBS OTBS OTBS TBSO OTBS Me OTBS OH OTBS OTBS OTBS OTBS TBSO OTBS OTBS Greene & Wuts, "Protective Groups in Organic Synthesis", Chapter 2 . Silicon Protecting Groups Silicon Protecting Groups Bonding Considerations: Carbon vs Silicon Average Bond dissociation eneregies (Kcal/mol) CC 83 CSi 76 CH 83 SiH 76 CO 86 SiO 108 CF 116 SiF 135 Average Bond Lengths () CC 1.54 CSi 1.87 CO 1.43 SiO 1.66 Group IV Electronegativities (Pauling) Carbon 2.55 Silicon 1.90 Germanium 2.01 Tin 1.96 Lead 2.33 Silicon Protecting Groups Silicon Protecting Groups Unlike carbon, substitution at silicon proceeds through a hypervalent silicon species: Me Me Si O Me R F Me F Si O Me R Me O R + Me Me Si F Me OSiMe3 KOCMe3 THF 20 2h O K Me3SiOCMe3 Duhamel et al. J. Org. Chem. 1996, 61, 2232 OSiMe3 MeLi THF O Li Me3SiMe Stork et al. JACS. 1968, 90, 4462, 4464 Silicon Protecting Groups Silicon Protecting Groups Substitution (deprotection) under basic conditions: Me Me Si O Me R Nu Me Me Nu Si O Me R O R + Me Me Si Nu Me Substitution (deprotection) under acidic conditions: Me Me Si O Me R HX Me Me H Si O Me R Nu H Me Nu Si O Me R Me OH R + Me Me Si Nu Me Silicon Protecting Groups Silicon Protecting Groups Silyl Ethers: Me Me Si OR Me trimethylsilyl (TMS) Et Et Si OR Et triethylsilyl (TES) Me t-Bu Si OR Me tert-butyldimethylsilyl (TBS or TBDMS) t-Bu Ph t-Bu Si O R' i-Pr i-Pr Si OR t-Bu Si OR Ph O R i-Pr triisopropylsilyl (TIPS) n tert-butyldiphenylsilyl (TBDPS) di-tert-butyldimethylsilylene (DTBS) Formation: R OH R3Si-Cl, imidazole DMF, R.T. R OSiR3 Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190. 2 equiv of imidazole are required relative to R3SiCl. R OH R3Si-OTf, 2,6-lutidine CH2Cl2, 0 C R OSiR3 Corey, E. J. et al., Tetrahedron Lett. 1981, 22, 3455. Silicon Protecting Groups Silicon Protecting Groups Relative stabilities: TES ~102 times more stable to acidic hydrolysis than TMS TBS ~104 times more stable to acidic hydrolysis than TMS Acidic Deprotection: Basic Deprotection: Me OSiR3 1% HCl in EtOH 22.5 C SiR3 TBS TIPS TBDPS Half-life < 1 min 18 min 244 min Me OH Me OSiR3 5% NaOH in EtOH 90 C SiR3 TBS TIPS TBDPS Half-life 1h 14 h <4h Me OH OSiR3 2 equiv TBAF THF, 22.5 C SiR3 TBS TIPS Half-life 76 min 137 min OH Cunico, R. F.; Bedell, L. J. Org. Chem. 1980, 45, 4797-4798. Silicon Protecting Groups Silicon Protecting Groups OH Me Me Me OH TBDPSCl, imidazole DMF, RT 95% OH Me Me Me OTBDPS Me Me O MeO OH OH Me OTIPS TESCl, DMAP CH2Cl2, 0 C 77% O MeO OTESOH Me OTIPS Evans et al.JACS 1999, 121, 7540-7552. HO SO2Ph TBSCl, imid. DMF, RT 80% HO SO2Ph HO TBSO Donaldson, R. E.; Fuchs, P. L. J. Am. Chem. Soc. 1981, 103, 2108. ROH Protecting Groups-2 Alcohol Protecting Groups Selective Deprotection: Me TMSO Me O OTMS Me OMe Me Me K2CO3 MeOH 100% Me OMe O Calter, M. A. Ph. D. Thesis, Harvard University, 1993 Me OMe O TMSO Me O OH Me OMe Me OTBS O (NCCH2CH2O)2P O Me Me O O PivO OMe OH O (NCCH2CH2O)2P HFpyr, pyridine THF 94% Me OTBS JACS 1992, 114, 9434 Evans, Gage, Leighton O Me Me O O Me OTBS PivO OMe Alternative Alcohol Protecting Groups Other Alcohol Protecting Groups R OH conditions R O Formation: 1. R OH 1. NaH, DMF, 0 C 2. BnBr NH R OBn 2. R OH Ph O CCl3 cat. TfOH R OBn Iversen, T.; Bundle, K. R. J. Chem. Soc., Chem. Commun. 1981, 1240. 3. R OH 1. (Bu3Sn)2O, PhMe, 2. BnBr, N-methylimidazole R OBn Cruzado, C.; Bernabe, M.; Martin-Lomas, M. J. Org. Chem. 1989, 54, 465. Review: David, S.; Hanessian, S. Tetrahedron, 1985, 41, 643-663. 4. R OH Ag2O, BnBr DMF R OBn Van Hijfte, L.; Little, R. D. J. Org. Chem. 1985, 50, 3940. Alcohol Alternative AlcoholProtecting Groups Groups Protecting Removal: 1. Hydrogenation R OBn 10% Pd on C, H2 EtOH/EtOAc/AcOH R OH 2. Transfer Hydrogenation R OBn 10% Pd on C Hydrogen Source Ref. R OH Hydrogen Source Cyclohexene Cyclohexadiene HCO2H Synthesis 1981, 396. J. Org. Chem. 1978, 43, 4194. J. Org. Chem. 1979, 44, 3442. Tetrahedron Lett. 1986, 27, 2497 i-PrOH 3. Lewis Acids R OBn R OH Reagents BF3OEt2, EtSH 1. BCl3, -78 C to 0 C. 2. MeOH, -78 C. TMSBr, C6H5SMe Ref. Tetrahedron Lett. 1989, 30, 5713. J. Am. Chem. Soc. 1989, 111, 1923. Chem. Pharm. Bull. 1987, 35, 3880. Alternative Alcohol Protecting Groups Alcohol Protecting Groups Selective Benzylation: Br Me Br Me NaH, BnBr H OH OH DMF, -70 C 97% OH H OBn Fukuzawa, A. et al. Tetrahedron Lett. 1987, 28, 4303. O HO OH O O 1. (Bu3Sn)2O, PhMe, OH 2. BnBr, N-methylimidazole 92% BnO OH O OBn Cruzado, C.; Bernabe, M.; Martin-Lomas, M. J. Org. Chem. 1989, 54, 465. ...
View Full Document

{[ snackBarMessage ]}

Ask a homework question - tutors are online