The concept of the complex-induced proximity effect (CIPE) in deprotonations is helpful in elucidating the mechanisms involved in carbanion chemistry and in planning organic syntheses. In this Review, the consequences of complexation of organolithium bases to functional groups of the substrates before the proton-transfer step are discussed. Experimental data from kinetic measurements and isotope-labeling experiments as well as the results of calculations in many cases point to a prelithiation complex as a reaction intermediate. Some examples from natural products synthesis illustrate how this concept can be used to obtain intermediates in a regio- or stereoselective manner. Of particular interest is the functionalization of positions that are remote from the coordination group.

Das Konzept des Komplex‐induzierten Näherungseffekts (complex induced proximity effect, CIPE) bei Deprotonierungen ist hilfreich bei der Aufklärung von Mechanismen in der Carbanionenchemie und bei der Planung organischer Synthesen. Im vorliegenden Aufsatz werden die Konsequenzen der Komplexierung von Organolithiumbasen an funktionellen Gruppen der Substrate vor dem Protonenübertragungsschritt diskutiert. Dabei zeigt sich, dass die experimentellen Daten aus kinetischen Messungen und Isotopenmarkierungsexperimenten ebenso wie die Ergebnisse von Rechnungen in vielen Fällen auf einen Prälithiierungskomplex als Reaktionsintermediat hinweisen. Einige Beispiele aus der Naturstoffsynthese verdeutlichen, wie mithilfe dieses Konzepts Zwischenstufen gezielt regio‐ oder stereoselektiv erhalten werden können. Von besonderem Interesse sind dabei Funktionalisierungen an Positionen, die von der koordinierenden Gruppe vermeintlich weit entfernt sind.

[reaction: see text](-)-Sparteine-mediated lithiation/transmetalation/substitution of N-Boc allylic amines provides anti-configured homoaldol precursors in yields of 38-85% and enantiomeric ratios of 83:17-99:1. Subsequent O-protection and hydrolysis allows access to O-protected homoaldol adducts in good yields. The absolute configurations of the homoaldol products have been assigned by calculation of optical rotations and by X-ray crystallography of derivatives. A stereochemical course of reaction for the lithiation/transmetalation/substitution sequence is proposed.

Organic chemistryOrganic chemistry Z 0200 Beyond Thermodynamic Acidity: A Perspective on the Complex-Induced Proximity Effect (CIPE) in Deprotonation Reactions-[106 refs.]. -(WHISLER, M. C.; MACNEIL, S.; SNIECKUS*, V.; BEAK*, P.; Angew.

Lithiation of N-(Boc)-N-(p-methoxyphenyl) allylic amines in the presence of (-)-sparteine provides asymmetric homoenolate equivalents which react with electrophiles to provide highly enantioenriched enecarbamates. Acidic hydrolysis of the enecarbamates can provide the corresponding beta-substituted aldehydes. A synthetic sequence that involves a stereocontrolled intramolecular nitrone-olefin dipolar cycloaddition has been developed for the preparation of enantioenriched 2-formyl-4-phenyl-1-aminocyclopentanes from one beta-allyl-substituted aldehyde. Further manipulations allow access to an enantioenriched beta-lactam. In another synthetic sequence, transmetalation of the lithiated intermediates and reactions with aldehyde electrophiles can be controlled to afford highly enantioenriched anti homoaldol products. Use of an anti aldehyde homoaldol product as the chiral electrophile in an iterative reaction provides a double homoaldol product containing four stereogenic centers with high diastereoselectivity and enantioselectivity. Reaction pathways are proposed to account for the observed products.