One-Pot Asymmetric Conjugate Addition−Trapping of Zinc Enolates by Activated Electrophiles

Abstract

The copper-catalyzed asymmetric conjugate addition of dialkyl zinc leads to homochiral zinc enolates. These intermediates were trapped in situ with activated allylic electrophiles, without the need of additional palladium catalysis. High trans selectivity (85/15 to 100/0) and excellent enantioselectivities (up to 99%) could be attained. The functionalized nature of the electrophiles makes the new synthons potential candidates for further elaboration.

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…[140] Nach ersten Arbeiten über eine sequenzielle Cu-katalysierte konjugierte Addition/Pd-katalysierte Allylierung, [141] wurde über das direkte Abfangen der Zinkenolate 34 mit aktivierten allylischen Elektrophilen berichtet (Schema 11). [142] Mit dem Biphenol-Phosphoramidit-Liganden L17 und [Cu(TC)] (TC = Thiophencarboxylat) als Katalysator konnten die a,b-disubstituierten Cyclohexanone und Cycloheptanone 35 mit Ausbeuten bis 80 % und ausgezeichneten ee-Werten (bis 99 %) erhalten werden. Das trans/cis-Verhältnis von 35 war in den meisten Fällen hoch, wobei das trans-Produkt überwog.…”

Addition Reactions: Polar Addition

“…227 The new tridentate aminohydroxyphosphine ligand (178) has been developed for the copper-catalysed asymmetric conjugate addition of organozinc reagents to acyclic ee α,β-unsaturated carbonyl compounds R 1 CH=CHCO 2 R 2 ; the addition is characterized by high enantioselectivity (≤98% ee). Theoretical analysis suggests that the C-C bond formation takes place through a highly ordered transition state by the coordination of the phosphorus and nitrogen atoms to the copper(III) and zinc(II) atoms, respectively, and of the oxygen anion to both the metal centers.…”

“…This is the first case of a highly enantioselective base-catalysed anthrone ee Diels-Alder reaction. 263 A nucleophilic addition of bis(TMS) ketene acetals to pyridines (223), aided by acylation of the pyridine nitrogen with methyl chloroformate, has been reported to produce the 1,4-adduct (224 Triphenylphosphine was employed as a nucleophilic catalyst for the umpolung addition of azoles (225) to the electron-deficient allenes (226; R 1 = H, R 2 = OEt, R 3 = H, Et) to afford the addition products (227). This organocatalytic methodology has been extended to addition-cyclization reactions between electron-deficient allenes or alkynes and pyrrole-2-carboxaldehyde in the presence of a catalytic amount of tributylphosphine, giving the substituted indolizine-7-carboxylates (228; R 2 = OEt, Me; R 3 = H, Et THF at room temperature to produce substituted phenylallenes (231).…”

Carbanions and Electrophilic Aliphatic Substitution

“…28 These intermediates have been trapped in situ with activated allylic electrophiles, without the need for additional palladium catalysis (Scheme 3). High trans selectivity (85:15 to 100:0) and excellent enantioselectivities (up to 99%) de have been reported.…”