Multicenter Strategy for the Development of Catalytic Enantioselective Nucleophilic Alkylation of Ketones: Me2Zn Addition to α-Ketoesters

✍ Scribed by Ken Funabashi; Markus Jachmann; Motomu Kanai; Masakatsu Shibasaki

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 141 KB
• Volume: 115
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/ange.200351650

✦ Synopsis

The catalytic construction of stereogenic tetrasubstituted carbon centers through the addition of carbon nucleophiles to ketones or ketoimines is very challenging, partly because of the lower reactivity of these substrates relative to aldehydes and aldoimines. [1] This task requires strong activation of the substrate and/or the nucleophile by an asymmetric catalyst. We developed Lewis acid-Lewis base two-center asymmetric catalysts (titanium and lanthanide complexes of 1) that promote the cyanosilylation of ketones and ketoimines with broad substrate generality. [2] The fundamental concept for the catalyst design was that the Lewis acid metal and the Lewis base (the phosphane oxide) activate both the substrate and the nucleophile (TMSCN) simultaneously at defined positions in the transition state. A logical extension of this concept is to target the diorganozinc addition to ketones, [3] because both Lewis acid activation of the substrate and Lewis base activation of the reagent are required to promote the reaction. [4] We report herein our initial investigations toward this goal: the catalytic enantioselective addition of Me 2 Zn to a-ketoesters. Our newly designed catalyst 2, which