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antiperiplanar 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:
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• Reactions of Allyl- and Crotylsilanes
• Tetraorganosilanes
• Electrophiles
• Regiochemistry
• Selected synthetic applications
1970 Chain Extension of Organosilanes
1980 Golden Age of Allylsilanes / Propargylsilanes / Vinylsilanes
1990 Asymmetric Applications
2000 Activation/Generalization of Scope
Mechanisms
β effect
Allylsilanes
Vinylsilanes
β effect
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Reactivities
Activation of allylsilane Activation of electrophile
2 (3) basic activation methods:
Lewis base catalysis Lewis acid catalysis
Reactivities
Allylsilanes are not reactive enough for direct additions
Organocatalysis
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Nucleophilic - Lewis Base Catalysis
Fluoride coordination
Advantage : - fluoride anion is catalytic
Disadvantage : - control of reactive intermediate formation is difficult - isomerization of allylic silane is possible - can lead to α−attack
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Lewis Acid Catalysis
Rational selection of Lewis acid is difficult
Generally accepted order of reactivity:
Advantage: - allylsilane is not affected
Disadvantage: - (super)stoichiometric quantities - limited functional group tolerance
mono- andbidentate
Sakurai-Hosomi Reaction
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Stereochemistry
anti-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 minimized
chiral allylsilanes react antarafacially (JACS 1982, 104, 4963):
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1,5-acyclic stereocontrol (E. J. Thomas, JCS PT1 1995, 2477; CC 1995,657; THA 1995, 6, 2575):
Asymmetric Induction
3 Possibilities for Stereocontrol:
Effect of allylic carbon:
Chiral Si-substituent:
Chiral silicon atom:
40-95% ee
0-50% ee
All. 50-99%eeCrot. 80-99% ee
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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):
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Acetals & Allylsilanes
Is attack on acetals SN2 or SN1 ?
SN2 SN1
Yamamoto,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 : 1
81%
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 : 1
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Majetich, 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 & Imines
Allylation of imines in the presence of Lewis acids leads to polymerization
60-84%
Allylation of imines under basic conditions is possible with pentavalent silicates
R < i-Prd.e. = < 33%
Kira, M.; Hino, T.; Sakurai, H. Chem. Lett. 1991, 277.
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93 : 785 : 15
Yamamoto, 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.
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Reactions with sugar acetals and ketals (Kishi, JACS 1982, 104, 4976):
Carba-Ferrier (Danishefsky, JACS 1987, 109, 8117)
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III. 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.
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Chromium
- 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:
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the 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.
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other type III:Ti, Zn, Sb, Bi,In, Mn, Zr
Chem 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.
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Chiral Allyl Transfer Reagents
Selectivities are for PhCHO
Chiral Allyl Transfer Reagents
Selectivities are for PhCHO
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Williams, D. R.; Brooks, D.A.; Berliner, M. A., "Totalsynthesis of (-)-hennoxazole A." J. Am.Chem. Soc. 1999, 121,4924.
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Carreira: 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).
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Double Diastereodifferentiation
matched:(S)-1 + (S,S)-A: 1 : 200
includes 1:2 selectivity
→ inherent selectivity of chiral reagent is 1 : 100
mismatched:(S)-1 + (R,R)-A: 100 : 1 reagent selectvity
1 : 2 substrate selectivity 50 : 1 theoretical resulting selectivity100 : 2 experimental
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