Presentation on theme: "Special Topic 27/02/09 Anne Fournier"— Presentation transcript:
1 Special Topic 27/02/09 Anne Fournier Umpolung reactivitySpecial Topic 27/02/09Anne Fournier
2 The synthetic problemX = halogen, O, Nd = donor (-)a = acceptor (+)Heteroatoms impose an alternating acceptor and donor reactivity patternAn odd number of carbons between functional groupsAn even number of carbons between functional groups
3 Definition« usual » reactivity:C2n= donor, C2n+1= acceptorUmpolung reactivity:C2n= acceptor, C2n+1= donorUmpolung is any process by which donor and acceptor reactivity of an atom are interchanged (reversal in polarity).Reactivity enables us to construct new bonds which are difficult to construct or cannot be achieved by « usual » reactivity, particulary the construction of 1,2 or 1,4-difunctionality.Seebach ACIEE 1979, 239
4 Carbonyl UmpolungPatterns of Carbonyl Reactivity
6 Carbonyl Umpolung Masked Acyl Anion Equivalents 1a. Benzoin Condensation:Cyanide ion Catalyzed AdditionMust use aromatic or heteroaromatic aldehydes; aliphatic aldehydes tend to undergo an aldol condensationCannot selectivity cross couple of two different aldehydesLapworth JACS 1903, 995.
7 Carbonyl Umpolung Masked Acyl Anion Equivalents 1b. Cyanide ion Catalyzed Cross Silyl-Benzoin ReactionKinetic control, regiosepecific, (but need to make acyl silane), lower yields often result from aliphatic aldehydes (improvement with La(CN)3 catalyst)[1,2]-BrookRearrangementJohnson JACS 2005, 1833
8 Carbonyl Umpolung Masked Acyl Anion Equivalents 2. N-Heterocyclic Carbenes Catalyzed Acyloin FormationEffective for aliphatic and (hetero)aromatic aldehydesApplicable to acylsilanes(a) Breslow JACS 1958,3719.(b) Enders Acc. Chem. Res. 2004, 534.
21 Carbonyl Umpolung Homoenolate Equivalents 1. The Tautomerism Problem Enolates• tautomerism is generally not a problembecause oxyanionic tautomer still acts ascarbon nucleophileHomoenolates• tautomerism is a much larger problembecause it is often irreversible andoxyanioic tautomer rarely acts as a