11antiperiplanar vs. synclinal transition state: S. E. Denmark, Helv. Chim. Acta1983, 66, 1655; J. Am. Chem. Soc. 1987, 109, 2512; Tetrahedron 1989, 45,1053.→ the LA influences the properties of the reaction taking place from thesynclinal and antiperiplanar arrangements, with the former in general beingthe more important:P. Wipf - Chem 2320114/3/200612Related: Prins reactionLA = H+ is inappropriate. Why?P. Wipf - Chem 2320124/3/200613• Reactions of Allyl- and Crotylsilanes• Tetraorganosilanes• Electrophiles• Regiochemistry• Selected synthetic applications1970Chain Extension of Organosilanes1980Golden Age of Allylsilanes / Propargylsilanes / Vinylsilanes1990Asymmetric Applications2000Activation/Generalization of ScopeMechanismsβ effectAllylsilanesVinylsilanesβ effectP. Wipf - Chem 2320134/3/200614ReactivitiesActivation of allylsilaneActivation of electrophile2 (3) basic activation methods:Lewis base catalysis Lewis acid catalysisReactivitiesAllylsilanes are not reactive enough for direct additionsOrganocatalysisP. Wipf - Chem 2320144/3/200615Nucleophilic - Lewis Base CatalysisFluoride coordinationAdvantage : - fluoride anion is catalyticDisadvantage : - control of reactive intermediate formation is difficult - isomerization of allylic silane is possible - can lead to α−attackP. Wipf - Chem 2320154/3/200616Lewis Acid CatalysisRational selection of Lewis acid is difficultGenerally accepted order of reactivity:Advantage: - allylsilane is not affectedDisadvantage: - (super)stoichiometric quantities - limited functional group tolerancemono- andbidentateSakurai-Hosomi ReactionP. Wipf - Chem 2320164/3/200617Stereochemistryanti-SE’ :Attack trajectory of electrophile is determined by - steric effects (vs Si) - electronic effects (antiperiplanar to C-Si bond)Ground state control; A1,3 strain is minimizedchiral allylsilanes react antarafacially (JACS 1982, 104, 4963):P. Wipf - Chem 2320174/3/2006181,5-acyclic stereocontrol (E. J. Thomas, JCS PT1 1995, 2477; CC 1995,657; THA 1995, 6, 2575):Asymmetric Induction3 Possibilities for Stereocontrol:Effect of allylic carbon:Chiral Si-substituent:Chiral silicon atom:40-95% ee0-50% eeAll. 50-99%eeCrot. 80-99% eeP. Wipf - Chem 2320184/3/200619 with α-chiral aldehydes:improved selectivity with α-ether substituents: Danishefsky, TH 1986, 42, 2809.Double diastereodifferentiation: THL 1984, 25, 4371; Ann. Chem. 1989, 884:intramolecular attack (TH 1981, 37, 4069):P. Wipf - Chem 2320194/3/200620Acetals & AllylsilanesIs attack on acetals SN2 or SN1 ?SN2SN1Yamamoto,Y.;Nishii,S.;YamaJd.a J,.A m.Chem.Soc. 1986, 7116.Denmark, S. E.; Weber, E. J. J. Am. Chem. Soc. 1984,1106,7970.Hint (?):Allylsilanes & EnonesIn general, unsubstituted allylsilane addition to enones is electronicallycontrolled, not sterically.(E)- 11 : 1(Z)- 3 : 181%Blumenkopf, T. A.; Heathcock, C. H. J. Am. Chem. Soc. 1983, 2354.Tokoroyama, Y.; Pan, L. R. Tetrahedron Lett. 1989, 197.Complementary to Kharash Grignard:(E)-Crotylsilanes give higher d.e.’s:73%13 : 1>10 : 1P. Wipf - Chem 2320204/3/200621Majetich, G.; Defauw, J.; Ringold, C. J. Org. Chem. 1988, 50.Majetich, G.; Song, J. S.; Ringold, C.; Nemeth, G. A.; Newton, M. G. J. Org. Chem. 1991, 3973.Allylsilanes & IminesAllylation of imines in the presence of Lewis acids leads to polymerization60-84%Allylation of imines under basic conditions is possible with pentavalent silicatesR < i-Prd.e. = < 33%Kira, M.; Hino, T.; Sakurai, H. Chem. Lett. 1991, 277.P. Wipf - Chem 2320214/3/20062293 : 785 : 15Yamamoto, Y.; Nakada, T.; Nemoto, H. J. Am. Chem. Soc. 1992, 121.He, F.; Bo, Y.; Altom, J. D.; Corey, E. J. "Enantioselective totalsynthesis of aspidophytine." J. Am. Chem. Soc. 1999, 121,6771-6772.P. Wipf - Chem 2320224/3/200623P. Wipf - Chem 2320234/3/200624Key Cyclization Mechanism:P. Wipf - Chem 2320244/3/200625Reactions with sugar acetals and ketals (Kishi, JACS 1982, 104, 4976):Carba-Ferrier (Danishefsky, JACS 1987, 109, 8117)P. Wipf - Chem 2320254/3/200626III. anti-selective irrespective of olefin geometry (Ti, Cr, Zr,In, Zn).Heathcock-Hiyama (1978):The principal difference between type I and type III crotyl organometallics is thelack of configurational integrity of type III species.P. Wipf - Chem 2320264/3/200627Chromium- Cintus, P. Synthesis 1992, 248.- Wessjohann, L. A., "Recent advances in chromium(II)- andchromium(III)-mediated organic synthesis." Synthesis 1999, 1.- Fürstner, A., "Carbon-carbon bond formations involvingorganochromium(III) reagents." Chem. Rev. 1999, 99, 991.Nozaki-Takai-Hiyama-Kishi reaction:Kishi: 0.1 - 1% of Ni(II) is beneficial:P. Wipf - Chem 2320274/3/200628the functional group compatibility of this reagent is excellent:W.C. Still, JOC 1983, 48, 4785. Asperdiol.Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A., "The firstcatalytic enantioselective Nozaki-Hiyama reaction." Angew. Chem. Int. Ed.1999, 38, 3357-3359.P. Wipf - Chem 2320284/3/200629other type III:Ti, Zn, Sb, Bi,In, Mn, ZrChem Lett. 1983, 219:Wipf, P.; Kendall, C., "Tandem zirconocene homologation – aldimineaddition." Org. Lett. 2001, 3, 2773-2776. Hydrozirconation of internal andterminal alkynes followed by in situ transmetalation to dimethylzinc andtreatment with diiodomethane leads to chain extended allylicorganometallics. Addition to N-phosphinoyl or N-sulfonyl aldiminesprovides homoallylic amines in 48-87% yield and 3:2 to >20:1diastereomeric ratios favoring anti-products.P. Wipf - Chem 2320294/3/200630Chiral Allyl Transfer ReagentsSelectivities are for PhCHOChiral Allyl Transfer ReagentsSelectivities are for PhCHOP. Wipf - Chem 2320304/3/200631Williams, D. R.; Brooks, D.A.; Berliner, M. A., "Totalsynthesis of (-)-hennoxazole A." J. Am.Chem. Soc. 1999, 121,4924.P. Wipf - Chem 2320314/3/200632Carreira: Angew. Chem. Int. Ed. Engl. 1996, 35, 2363.Taylor, R. E.; Haley, J. D. Tetrahedron Lett. 1997, 38, 2061 (using the Keckprotocol: Keck, G. E.; Geraci, L. S. Tetrahedron Lett. 1993, 34, 7827).P. Wipf - Chem 2320324/3/200633Double Diastereodifferentiationmatched:(S)-1 + (S,S)-A: 1 : 200includes 1:2 selectivity→ inherent selectivity of chiral reagent is 1 : 100mismatched:(S)-1 + (R,R)-A: 100 : 1 reagent selectvity 1 : 2 substrate selectivity 50 : 1 theoretical resulting selectivity100 : 2 experimentalP. Wipf - Chem
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