Mr. Jian Zhou
Despite the universal existence of chiral 1,4-diamines in bioactive molecules and their omnipresent application in asymmetric catalysis, the catalytic and asymmetric synthesis of such structure from readily accessible substrates remains a long-standing challenging.1 Here we develop a Cu-catalyzed asymmetric cascade hydroamination protocol to construct a wide range of chiral 1,4-diamine derivatives in high yields and excellent ees (up to 95% yield and up to ＞99% ee). The further improvement of 1,4-diamine structure complexity is achieved by using two hydroxylamine esters containing different functionalized amino group. These desired products can be easily transformed into chiral 1,4-diamine and chiral NH2-Terfenadine. Mechanistic study demonstrated that this reaction proceeds through hydroamination ring opening and cascade hydroamination sequence.
- V. R. Fernandez de la Pradilla, A.; Garcia, A. Flores. Chem. Rev. 2005, 105, 3167-3196.
- A. Noble, J. C. Anderson. Chem. Rev. 2013, 113, 2887-2939.