A Stereochemical Model for Merged 1,2- and 1,3-Asymmetric Induction in Diastereoselective Mukaiyama Aldol Addition Reactions and Related Processes
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- 作者：David A. Evans ; Michael J. Dart ; Joseph L. Duffy ; and Michael G. Yang
- 刊名：Journal of the American Chemical Society
- 出版年：1996
- 出版时间：May 8, 1996
- 年：1996
- 卷：118
- 期：18
- 页码：4322 - 4343
- 全文大小：853K
- 年卷期：v.118,no.18(May 8, 1996)
- ISSN：1520-5126
文摘
A systematic investigation of the direction and degreeof stereoselectivity in aldol addition reactions ispresented involving achiral unsubstituted metal enolate and enolsilanenucleophiles and chiral aldehydes. TheBF3·OEt2mediated Mukaiyama aldol reaction with 
-unsubstituted, 
-alkoxyaldehydes afforded good levels of 1,3-antiinductionin the absence of internal aldehyde chelation. The level of1,3-induction was found to be primarily dependent onthe electrostatic nature of the aldehyde -substituent. Arevised model for 1,3-asymmetric induction is presented toaccount for these results based primarily on minimization of internalelectrostatic and steric repulsion between thealdehyde carbonyl moiety and the -substituents. A fullconformational analysis, corroborated by semiempirical(AM1) calculations, is presented to support the proposed model.The merged impact of and aldehydesubstituentswas also systematically investigated, and an integrated 1,2- and1,3-asymmetric induction model is proposed thatincorporates the salient features of the Felkin-Anh and revised1,3-model. In accordance with this integrated model,uniformly high levels of Felkin, 1,3-anti diastereofacialselectivity are observed in Mukaiyama aldol reactions withanti substituted -methyl--alkoxy aldehydes, whichcontain stereocontrol elements that are in astereoreinforcingrelationship. In contrast, variable levels of aldehyde facialinduction were observed in the corresponding reactionswith syn substituted aldehyde substrates, which containstereocontrol elements in a non-reinforcing relationship.The direction of aldehyde facial induction in Mukaiyama aldoladditions to the syn substituted aldehydes wasfoundto be primarily dependent on the size of the enolsilane, with the firstknown examples of anti-Felkin selectiveMukaiyama aldol reactions observed under conditions known to precludechelation for the addition of the enolsilaneof acetone. We conclude that dominant 1,2-stereoinduction will befound in those reactions proceeding with thereactants in an antiperiplanar relationship, favored bysterically encumbered enolsilane substituents, whiledominant1,3-stereoinduction will be manifest from a synclinaltransition state, preferred for less bulky enolsilanesubstituents.By inspection, the synclinal transition state may bedestabilized by an increase in the steric bulk of the Lewisacid,and in accordance with this prediction the trityl perchlorate mediatedenolsilane addition resulted in a dramaticreversal of facial selectivity relative to theBF3·OEt2 mediated reaction. Thesetrends were also documented in themechanistically related addition of allylstannanes to antiand syn disubstituted chiral aldehydes.
-unsubstituted, -alkoxyaldehydes afforded good levels of 1,3-antiinductionin the absence of internal aldehyde chelation. The level of1,3-induction was found to be primarily dependent onthe electrostatic nature of the aldehyde -substituent. Arevised model for 1,3-asymmetric induction is presented toaccount for these results based primarily on minimization of internalelectrostatic and steric repulsion between thealdehyde carbonyl moiety and the -substituents. A fullconformational analysis, corroborated by semiempirical(AM1) calculations, is presented to support the proposed model.The merged impact of and aldehydesubstituentswas also systematically investigated, and an integrated 1,2- and1,3-asymmetric induction model is proposed thatincorporates the salient features of the Felkin-Anh and revised1,3-model. In accordance with this integrated model,uniformly high levels of Felkin, 1,3-anti diastereofacialselectivity are observed in Mukaiyama aldol reactions withanti substituted -methyl--alkoxy aldehydes, whichcontain stereocontrol elements that are in astereoreinforcingrelationship. In contrast, variable levels of aldehyde facialinduction were observed in the corresponding reactionswith syn substituted aldehyde substrates, which containstereocontrol elements in a non-reinforcing relationship.The direction of aldehyde facial induction in Mukaiyama aldoladditions to the syn substituted aldehydes wasfoundto be primarily dependent on the size of the enolsilane, with the firstknown examples of anti-Felkin selectiveMukaiyama aldol reactions observed under conditions known to precludechelation for the addition of the enolsilaneof acetone. We conclude that dominant 1,2-stereoinduction will befound in those reactions proceeding with thereactants in an antiperiplanar relationship, favored bysterically encumbered enolsilane substituents, whiledominant1,3-stereoinduction will be manifest from a synclinaltransition state, preferred for less bulky enolsilanesubstituents.By inspection, the synclinal transition state may bedestabilized by an increase in the steric bulk of the Lewisacid,and in accordance with this prediction the trityl perchlorate mediatedenolsilane addition resulted in a dramaticreversal of facial selectivity relative to theBF3·OEt2 mediated reaction. Thesetrends were also documented in themechanistically related addition of allylstannanes to antiand syn disubstituted chiral aldehydes.