Copper‐Catalyzed Enantioselective Intramolecular Conjugate Addition/Trapping Reactions: Synthesis of Cyclic Compounds with Multichiral Centers

Abstract

The Cu-catalyzed enantioselective conjugate addition of dialkylzinc to bis-alpha,beta-unsaturated carbonyl compounds followed by the intramolecular trapping of the zinc enolate in the presence of chiral phosphoramidite ligands was investigated. Cyclic and heterocyclic compounds with multichiral centers were formed as a mixture of two diastereomers with excellent diastereoselectivities (up to 99:1) and enantioselectivities (up to 94 % ee, ee=enantiomeric excess). The stereochemistry was determined to be trans,trans for the major products and trans,cis for the minor products. The absolute configuration of the cyclic compounds was assigned by comparison with the analogous adduct derived from trans-3-nonen-2-one and Et(2)Zn or the adduct obtained through conjugate addition of Me(2)Zn to trans-1-phenyl-non-2-en-1-one. Further transformation of these cyclic products into more complex compounds is under investigation in our laboratory.

Phosphoramidites: Privileged Ligands in Asymmetric Catalysis

“…A related tandem copper/phosphoramiditecatalyzed conjugate addition with subsequent ring closure was also reported (Scheme 12). [146,147] The linear bis-a,b-unsaturated compound 36 was subjected to conjugate addition of diethylzinc, and the intermediate zinc enolate was trapped by an intramolecular Michael reaction, which resulted in trisubstituted cyclohexane 37 in excellent yield (99 %), high diastereoselectivity, and very good enantioselectivity. The outcome of this reaction with respect to the diastereo-and enantioselectivity is strongly dependent on the phosphoramidite ligand applied.…”

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…[146,147] [111][112][113] Zu diesen Liganden gehören Derivate von Octahydro-BINOL L3, [150] TADDOLen L4, [137,151] 8,8'-verknüpften Binaphtholen L9 [152] und Spirobiindandiolen L11, [153,154] die Phosphoramidite von Zuckerphosphiten L12 [155] und 9,9'-Spirobixanthenderivate L10 [156] (Abbildung 2). Allerdings erreichten nur wenige dieser neu entwickelten Liganden in der Cu-katalysierten konjugierten Addition von Dialkylzinkreagentien an Enone die Ausbeuten und Enantioselektivitäten, die mit den früher beschriebenen Phosphoramiditen [31,32,63,112,127] (siehe Abbil- Auch die flexiblen Biphenol-Phosphoramidite L16 (siehe Abbildung 5) mit sterisch anspruchsvollen Substituenten an der Aminogruppe wurden als Liganden in der konjugierten Addition an Nitroalkene untersucht.…”

Renoprotective effect of Tanshinone IIA, an active component of Salvia miltiorrhiza, on rats with chronic kidney disease

“…Among these reactions, are enantioselective copper‐catalyzed domino reactions initiated by conjugate additions. A recent example was reported by Alexakis et al., involving the Cu‐catalyzed enantioselective conjugate addition of dialkylzinc to bis‐α,β‐unsaturated carbonyl compounds 17a – c , followed by the intramolecular trapping of the intermediate zinc enolate through a second intramolecular conjugate addition in the presence of chiral phosphoramidite ligands 19 and 20 26. This domino Michael–Michael process afforded the corresponding chiral cyclic and heterocyclic products 18a – d having three stereocenters as mixtures of two diastereomers with moderate to high diastereoselectivities of up to >98% de , and enantioselectivities of up to 94% ee , as shown in Scheme .…”