First Tandem Asymmetric Conjugate Addition of Alkenyl Nucleophiles and Silyl Trapping of the Intermediate Enolates

• Published in: Advanced synthesis & catalysis Vol. 355; no. 13; pp. 2651 - 2658
• Main Authors: Westmeier, Johannes, Pfaff, Christopher, Siewert, Jürgen, von Zezschwitz, Paultheo
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16.09.2013; WILEY‐VCH Verlag; Wiley
• Subjects: asymmetric catalysis; Asymmetry; Chemistry; Chemistry, Applied; Chemistry, Organic; Chlorides; conjugate addition; Conjugates; enones; Ethers; Nucleophiles; Physical Sciences; rhodium; Science & Technology; Synthesis; Trapping; Zirconium; ENANTIOSELECTIVE SYNTHESIS; ALDOL REACTIONS; asymmetric catalysis; conjugate addition; enones; STREPTOMYCES SP; RHODIUM-CATALYZED 1,4-ADDITION; KINETIC RESOLUTION; DIENE LIGANDS; SPIRODIONIC ACID; zirconium; PHOSPHINE-PHOSPHITE LIGANDS; GRIGNARD-REAGENTS; rhodium
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201300524

The tandem asymmetric conjugate addition of alkyl or aryl groups to enones and subsequent silyl trapping has already been achieved and yields valuable silyl enol ethers. Herein, the first method for the respective addition of alkenyl groups is reported, which is based on a rhodium(I)‐catalyzed addition of readily available alkenylzirconocenes. As prerequisite for silyl trapping, the initially formed enolates have to be transmetalated from zirconium to lithium by treatment with methyllithium prior to addition of the silyl chloride. Starting from 5‐ to 7‐membered cycloalkenones, the respective silyl enol ethers were obtained in excellent yields and ≥93% ee; an acyclic substrate furnished a moderate enantioselectivity. Besides trimethylsilyl chloride, the silylation was also performed with tert‐butyldimethylsilyl chloride, and the synthetic scope was evaluated by employing five different alkenyl groups. Moreover, the mechanism of this sequence was elucidated by 1H NMR studies, and the efficiency of catalyst control was exemplified by synthesis of a cis‐3,5‐disubstituted cyclohexanone which, due to strong substrate control, cannot be obtained by copper‐catalyzed conjugate addition.