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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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Related: Prins reaction

LA = H+ is inappropriate. Why?

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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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Key Cyclization Mechanism:

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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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