Catalytic Asymmetric 1,4-Addition Reactions Using α,β-Unsaturated N-Acylpyrroles as Highly Reactive Monodentate α,β-Unsaturated Ester Surrogates

• Published in: Journal of the American Chemical Society 2004-06, Vol.126 (24), p.7559-7570
• Main Authors: Matsunaga, Shigeki, Kinoshita, Tomofumi, Okada, Shigemitsu, Harada, Shinji, Shibasaki, Masakatsu
• Format: Article
• Language: English
• Subjects: Catalysis; Chemical reactivity; Chemistry; Epoxy Compounds - chemical synthesis; Epoxy Compounds - chemistry; Esters - chemical synthesis; Esters - chemistry; Exact sciences and technology; Molecular Structure; Organic chemistry; Pyrroles - chemical synthesis; Pyrroles - chemistry; Reactivity and mechanisms
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0485917

Synthesis and application of α,β-unsaturated N-acylpyrroles as highly reactive, monodentate ester surrogates in the catalytic asymmetric epoxidation and Michael reactions are described. α,β-Unsaturated N-acylpyrroles with various functional groups were synthesized by the Wittig reaction using ylide 2. A Sm(O-i-Pr)3/H8-BINOL complex was the most effective catalyst for the epoxidation to afford pyrrolyl epoxides in up to 100% yield and >99% ee. Catalyst loading was successfully reduced to as little as 0.02 mol % (substrate/catalyst = 5000). The high turnover frequency and high volumetric productivity of the present reaction are also noteworthy. In addition, a sequential Wittig olefination−catalytic asymmetric epoxidation reaction was developed, providing efficient one-pot access to optically active epoxides from various aldehydes in high yield and ee (96→99%). In a direct catalytic asymmetric Michael reaction of hydroxyketone promoted by the Et2Zn/linked-BINOL complex, Michael adducts were obtained in good yield (74−97%), dr (69/31−95/5), and ee (73−95%). This represents the first direct catalytic asymmetric Michael reaction of unmodified ketone to an α,β-unsaturated carboxylic acid derivative. The properties of α,β-unsaturated N-acylpyrrole are also discussed. Finally, the utility of the N-acylpyrrole unit for further transformations is demonstrated.