D. A. Evans Introduction to Organosilicon Chemistry Chem 206 http://www.courses.fasharvardedu/-chem206/ Problems to Contemplate Chemistry 206 Advanced Organic Chemistry Lecture number 33 TBSO OH OTBS KHMDS THF,-78℃c Introduction to Organosilicon Chemistry icon Bonding Considerations Calter, M. A Ph. D Thesis, Harvard University, 1993 Silicon-Proton Analogy C=0 Addition of organosilanes Sigmatropic Rearrangements of Organosilanes The C=o addition illustrated in eq 1 proceeds while the carbon analogue (eq 2) does not. Explain I Anionic(Brook) Rearrangement I Peterson olefination reaction OTMS I Survey of Silicon(and related) Protecting Groups RO-P Reading Assignment for this Lecture RO OR Carey& Sundberg, Advanced Organic Chemistry, 4th Ed. Part B Chapter 9, " C-C Bond Forming Rxns of Boron, Silicon& Tin", 595 OMe Fleming, I; Barbero, A Walter, D "Stereochemical control in using silicon-containing compounds. "Chem. Rev. 1997, 97, 20 Moser, W.H. The brook Rearrangement in Tandem Bond Formation e, C. E: Panek, J.S. selective reactions of chiral allyl- and bonds"chem.Rev.195,95,1293-1316 Provide a mechanism for the indicated transformation Ager, D J. "The Peterson olefination reaction "Org. Reactions 1990, 38, 1-224 Colvin, E. "Silicon in Organic Synthesis " Butterworths, 1981 人 Bois, et al. "Silicon Tethered reactions"Chem. Rev 1995 95. 1253-1277. Matthew d shair Wednesda December 11. 2002 Takeda, Org. Let, 2000, 2, 903-1905
D. A. Evans Chem 206 Matthew D. Shair Wednesday, December 11, 2002 http://www.courses.fas.harvard.edu/~chem206/ Reading Assignment for this Lecture: Introduction to Organosilicon Chemistry Chemistry 206 Advanced Organic Chemistry Lecture Number 33 Introduction to Organosilicon Chemistry ■ Silicon Bonding Considerations ■ The Silicon–Proton Analogy ■ C=O Addition of Organosilanes ■ Sigmatropic Rearrangements of Organosilanes ■ Anionic (Brook) Rearrangements ■ Peterson Olefination Reaction ■ Survey of Silicon (and related) Protecting Groups Masse, C. E.; Panek, J. S. "Diastereoselective reactions of chiral allyl- and allenylsilanes with activated C-X pi-bonds." Chem. Rev. 1995, 95, 1293-1316. Ager, D. J. "The Peterson olefination reaction." Org. Reactions 1990, 38, 1-224 Fleming, I.; Barbero, A.; Walter, D. "Stereochemical control in organic synthesis using silicon-containing compounds." Chem. Rev. 1997, 97, 2063-2192. (Web) Moser, W. H. "The Brook Rearrangement in Tandem Bond Formation Strategies," Tetrahedron 2001, 57, 2065-2084 (handout) Colvin, E. "Silicon in Organic Synthesis," Butterworths, 1981 KHMDS THF, -78 °C Calter, M. A. Ph. D. Thesis, Harvard University, 1993. 94% Bu3Sn Bu3Sn OMe TBSO Me OH OMe OH OTBS Explain what drives this rearrangement. TBS = Si Me Me CMe3 O TMS RO P OR R P O O RO OR SiR3 R P OTMS O RO OR The C=O addition illustrated in eq 1 proceeds while the carbon analogue (eq 2) does not. Explain (1) R H O O Me RO P OR R P O O RO OR Me R P OMe O RO OR (2) Me OLi Me3Si O X Me H H O OSiMe3 X Takeda, Org. Lett, 2000, 2, 903-1905 Provide a mechanism for the indicated transformation Problems to Contemplate Bois, et al. "SiliconTethered Reactions" Chem. Rev. 1995, 95, 1253-1277. (Handout) Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part B Chapter 9, " C–C Bond Forming Rxns of Boron, Silicon & Tin", 595– 680
D. A. Evans Bonding considerations: Carbon vs Silicon Chem 206 Bonding Considerations: Carbon vs Silicon Hypervalent 5-Coordinate Silicon Compounds Average Bond dissociation energies(Kcal/mol) Akiba, " Chemistry of hypervalent Compounds"Wiley-VCH, Chapters 4-5, 1999 C-c C-Si Si-si C-F Si-F Penta-coordinate silicates are commonly observed MesiA nEta Ph3 SiF2 verage Bond Lengths(A) C-H Si-H C-c C-Si C-o Si-c Nucleophilic substitution at Silicon 1541.871431.66 10 F-SiMe ○→ better thai Me3 SHOCMe3 C-SP Duhamel et al. J. Org. Chem. 1996, 61, 2232 gC-c H3C-CH3 BDE= 83 kca/mol H3C-SiH3 BDE -76 kcal/mol OSiMe3 Bond length=1.534A Bond length =1.87A HF This trend is even more dramatic with pi-bonds Stork et al. JACS. 1968. 90. 4462 4464 TC-C= 65 kcal/mol C-Si= 36 kcal/mol I Si-Si= 23 kcal/mol i Thermal Rearrangements One may readily access divalent intermediates Group /V Electronegativities(Pauling CH2 H,C=Cl Carbon Silicon Germanium Tin Lead Me 255 190 201 196233 +2 Oxidation state becones increasingly more stable
D. A. Evans Bonding Considerations: Carbon vs Silicon Chem 206 Bonding Considerations: Carbon vs Silicon C–C C–Si 83 76 Si–Si 53 C–O Si–O 86 108 C–H Si–H 83 76 C–F Si–F 116 135 Average Bond dissociation eneregies (Kcal/mol) C–C C–Si 1.54 1.87 C–O Si–O 1.43 1.66 Average Bond Lengths (Å) p C–C = 65 kcal/mol p C–Si = 36 kcal/mol p Si–Si = 23 kcal/mol This trend is even more dramatic with pi-bonds: s* C–Si s* C–C s C–Si s C–C Bond length = 1.87 Å Bond length = 1.534 Å H3C–SiH3 BDE ~ 76 kcal/mol H3C–CH3 BDE = 83 kcal/mol better than Group IV Electronegativities (Pauling) Carbon Silicon Germanium Tin Lead 2.55 1.90 2.01 1.96 2.33 +2 Oxidation state becones increasingly more stable C Si d– d+ Hypervalent 5-Coordinate Silicon Compounds Akiba, "Chemistry of hypervalent Compounds" Wiley-VCH, Chapters 4-5, 1999 Penta-coordinate silicates are commonly observed Nucleophilic substitution at Silicon F F–SiMe3 + OSiMe3 KOCMe3 O K Me3Si–OCMe3 Duhamel et al. J. Org. Chem. 1996, 61, 2232 OSiMe3 MeLi O Li Me3Si–Me Stork et al. JACS. 1968, 90, 4462, 4464 THF THF –20 ° 2h Thermal Rearrangements One may readily access divalent intermediates Si Me Me Si CH2 Me Me H2C CH2 thermolysis H Si Me Me thermolysis Si Me Me Si Me Me H Colvin, pp 7-9 C-SP3 Si-SP3 C-SP3 C-SP3 C C C C C Si C Si MeSiF4 NEt4 Ph3SiF2 NR4 RO–SiMe3 RO
K Scheidt D. A. Evans Hypervalent Silicon Ate-Complexes Chem 206 1689A CF Inorg Chem. 1984, 23, 13 J.Am. Chem. Soc.1987,109,476 2.198A 1668A 1604A 2.104A 1597A J Organomet Chem. 1981, 221, 137 Acta Crystallogr. Sect. C 1984, 40,476
K. Scheidt, D. A. Evans Hypervalent Silicon Ate-Complexes Chem 206 1.689 Å 1.647 Å Inorg. Chem. 1984, 23, 1378 J. Am. Chem.Soc. 1987, 109, 476 Si Ph Ph O F3C CF3 F F Si Ph Ph F CF3 F S(NMe2 )3 J. Organomet.Chem. 1981, 221, 137. F Si F Ph F F 1.668 Å 1.604 Å 1.597 Å Acta Crystallogr. Sect. C 1984, 40, 476 Cl Me O 2.104 Å 2.198 Å
D. A. Evans Bonding considerations: Carbon vs Silicon Chem 206 Carbonyl addition Reactions The prospect of catalysis was investigated 1970 DAE Objective: Develop a reagent that will transform aldehydes into protected cyanohydrins in one step Me3Si-CN 1-5 min OSiMe3 reaction was instaneous and quantitative OSiR3 1-5 min i Principle established that normally inaccessible cyanohydrin derivatives G=carbanion-stabilizing FG Carbonyl Anion Equivalent may now be accessed TMSO CN >95% yield R3Si-G Candidates Carbonyl Adducts only 1, 2-addition OSiR3 95%ye R,Si-CN with Truesdale, Carroll, Chem Commun. 1973, 55: J. Org. Chem. 1974, 39, 914 Tetrahedron Lett 1973, 4929(first discussion of Nu catalysis) OSiR R3Si-OSO,Ar R- The Silicon Advantage From the preceding case, it is clear that AHs is more exothermic than AHH R3Si-OPR R-tPOR2 X XcN一 Hsi>AH Thermalc=o addition of mscn is not a clean reaction Nucleophilic Catalysis e3SI-CN OSiMe ato:65:35
D. A. Evans Bonding Considerations: Carbon vs Silicon Chem 206 Carbonyl addition Reactions 1970 DAE Objective: Develop a reagent that will transform aldehydes into protected cyanohydrins in one step R H O SiR3 G + R G OSiR3 H R G OSiR3 Li R3Si G Candidates Carbonyl Adducts R3Si CN R CN OSiR3 H R3Si OSO2Ar R SO2Ar OSiR3 H R3Si OPR2 R POR2 OSiR3 H G = carbanion-stabilizing FG Carbonyl Anion Equivalent Thermal C=O addition of TMSCN is not a clean reaction + Me3Si CN C5H11 H OSiMe3 CN 50 C° Me H O C4H9 H OSiMe3 + ratio: 65:35 2-5 hr The prospect of catalysis was investigated C5H11 H OSiMe3 CN 1-5 min ZnI2 reaction was instaneous and quantiltative 1-5 min CN– Principle established that normally inaccessible cyanohydrin derivatives may now be accessed Me Me Me OTMS CN >95% yield (ZnI2 catalysis) Me Me TMSO Me CN 92% yield only 1,2-addition (ZnI2 catalysis) O TMSO CN >95% yield only 1,2-addition (CN– catalysis) with Truesdale, Carroll, Chem Commun. 1973, 55; J. Org. Chem.. 1974, 39, 914 Tetrahedron Lett 1973, 4929 (first discussion of Nu catalysis) + Me3Si CN Me H O "The Silicon Advantage" R R O + X CN R R O–X CN DHSi > DHH From the preceding case, it is clear that DHSi is more exothermic than DHH R R O Nucleophilic Catalysis C N R R O CN Me3Si CN R R OTMS CN C N + LiNR2
D. A. Evans Carbonyl Addition Reactions-2 Chem 206 Explain the following observations The Proton-Silicon Correlation +○c三N 1-4 addition with their proton counterparts but with an attendant greater exothermicity i Organosilanes undergo a range of thermal rearrangements processes in direct analogy with their proton counterparts TMSCN 1-2 addition k(S=106K(H TMSO CN A J. Ashe Ill. JACS 1970. 92. 1233 OSiMe. heat c Colvin, pp 37-8 th Truesdale Grimm, Nesbitt, JAcs1975,97,3229 JAcS1977.99.5009 OTMS Si transfer is intramolecular etal,JAcS1974.96,4283 Non-catalyzed processes may also occur if a proper geometry for atom transfer can be achieved oc1976.41 Me3Sc式N→-CN-SMe3 MS Organosilicon hydrides undergo transition metal catalyzed hydrosilylation processes in direct analogy with normal hydrogenation reactions H RO-P RO OR H-SIRa Me H-H Me 8/-8~m RhO catalysis Rh(o catalysis Hydrosilylation of C-C Bonds". T. Hayashi In Comprehensive Asymmetric Catalysis, Jacobsen, E.N. Pfaltz, A and Yamamoto, H Editors; Springer Verlag eidelberg, 1999; Vol L, 319-332
D. A. Evans Carbonyl Addition Reactions-2 Chem 206 Explain the following observations O O + C N OH OH CN THF/H2O O TMSO CN TMSCN O O + benzene C N 1-4 addition 1-2 addition R1 R2 OSiMe3 SR RS– ZnI2 R1 R2 SR SR with Truesdale, Grimm, Nesbitt, JACS 1975, 97, 3229 JACS 1977, 99, 5009 Me3Si SR R1 R2 O + Me3Si OEt O N2 R H O CN– or F– OEt O N2 R OTMS 1-5 min with Truesdale, Grimm JOC 1976, 41, 3335 R H O O TMS RO P OR + R P O O RO OR SiR3 R P OTMS O RO OR with Hurst, Takacs JACS 1978, 100, 3467 Non-catalyzed processes may also occur if a proper geometry for atom transfer can be achieved R O P O R OR TMSO RO R OTMS P O RO RO "The Proton–Silicon Correlation" ■ Organosilanes undergo carbonyl addition processes in direct analogy with their proton counterparts but with an attendant greater exothermicity. ■ Organosilanes undergo a range of thermal rearrangements processes in direct analogy with their proton counterparts. X H X H k(Si) =10+6 K(H) A. J. Ashe III, JACS 1970. 92, 1233 O O Me3Si O Me MeMe Me C O O SiMe3 O Me Me Me Me heat Colvin, pp 37-8 ■ Organosilicon hydrides undergo transition metal catalyzed hydrosilylation processes in direct analogy with normal hydrogenation reactions R N O SiR3 SiR3 R N O SiR3 SiR3 Yoder et al., JACS 1974. 96, 4283 DG* 15-22kcal/mol Si transfer is intramolecular Me3Si C N C N SiMe3 rt H–SiR3 H–H R Me R Me H R Me SiR3 Rh(I) catalysis Rh(I) catalysis "Hydrosilylation of C–C Bonds". T. Hayashi In Comprehensive Asymmetric Catalysis, Jacobsen, E. N.; Pfaltz, A.; and Yamamoto, H. Editors; Springer Verlag: Heidelberg, 1999; Vol I, 319-332