Effect of Multinuclear Copper/Aluminum Complexes in Highly Asymmetric Conjugate Addition of Trimethylaluminum to Acyclic Enones

Abstract

Al and friends: asymmetric conjugate addition of Me(3)Al to β,β-disubstituted α,β-unsaturated ketones in the presence copper and L1 leads to a highly efficient construction of an all-carbon-substituted chiral quaternary center. This result is the first example of an asymmetric conjugate addition of Me(3)Al to acyclic enones to give a chiral quaternary carbon center with excellent yield and enantioselectivity under mild reaction conditions.

Development of Neighboring Electrophilic Activation of Active Center in Catalytic Reactions via Organometallic Intermediates

“…The present Cu/Al-complex can catalyze the asymmetric conjugate addition reaction of organoaluminum reagents to enones and acrylamide derivatives (Scheme 22, Figure 13). 25 Acrylamide derivatives are synthetic intermediates for the synthesis of natural products (Scheme 23). Furthermore, the first example of the asymmetric conjugate addition to acyclic tri-substituted enones successfully created a chiral quaternary stereogenic center (Scheme 24, Figure 14).…”

Enantioselective Catalytic Reactions with N-Acyliden Penta-atomic Aza-heterocycles. Heterocycles as Masked Bricks To Build Chiral Scaffolds

“…45 The asymmetric conjugate addition of Me 3 intensity makes it useful in all areas of perfumery. In comparison with the racemate, the (S)-enantiomer has a more green, less watery, and more powerful fragrance.…”

“…In comparison with the racemate, the (S)-enantiomer has a more green, less watery, and more powerful fragrance. 45 Analogously, but starting from (E)-3-p-tolyl-1-(1H-pyrrol-1-yl)prop-2-en-1-one (1b) and using [(R)-IIe/Cu(OTf) 2 ] as catalyst, the Michael adduct (S)-79 was obtained with excellent ee. By using the protocol illustrated above, followed by the nucleophilic addition of a Grignard reagent and the MnO 2 -mediated oxidation, (+)-ar-turmerone [(S)-80], a potent antivenom against snake bites, was obtained with 96% ee.…”

“…By using the protocol illustrated above, followed by the nucleophilic addition of a Grignard reagent and the MnO 2 -mediated oxidation, (+)-ar-turmerone [(S)-80], a potent antivenom against snake bites, was obtained with 96% ee. 45 Whereas the enantioselective methylations of 1au and 1b, catalyzed by [(R)-II/Cu(OTf) 2 ], afford products whose stereochemistry is consistent with a β-Si face approach of the nucleophile to the coordinated substrate, the Cu(II) complex of ligand (S)-p-spinol-phos (S)-XVII induces an opposite enantioselectivity. A nice example is the addition of Me 3 Al to the β-Re face of (E)-3-(5-methoxybenzofuran-2-yl)-1-(1H-pyrrol-1-yl)prop-2-en-1-one (1av) to give (R)-81.…”

Enantioselective Synthesis of Quaternary Carbon Stereogenic Centers through Copper‐Catalyzed Conjugate Additions of Aryl‐ and Alkylaluminum Reagents to Acyclic Trisubstituted Enones

“…Enantioselective synthesis of 6 c, a product that contains two functionalizable and differentiable carbonyl groups, illustrates that addition to the site b to the ketone unit, versus to the carboxylic ester, is exclusive in spite of formation of a more hindered quaternary carbon stereogenic center. Representative reactions with Me 3 Al are shown in Scheme 3 as well; [9] (R)-5 a and (R)-5 d are obtained in 77 % and 95 % yield and > 99:1 and 97:3 e.r., respectively. Enantioselective synthesis of isobutyl-substituted ketone 7, generated in 82 % yield and 98:2 e.r., shows that the NHC-Cu-catalyzed protocol can be extended to ECA with (iBu) 3 Al, another commercially available organoaluminum species the ECA of which has not been reported with trisubstituted acyclic enones.…”