Stereoselective Synthesis of Trisubstituted Alkenes through Sequential Iron-Catalyzed Reductive anti-Carbozincation of Terminal Alkynes and Base-Metal-Catalyzed Negishi Cross-Coupling

• Published in: Chemistry : a European journal 2015-12, Vol.21 (50), p.18439-18444
• Main Authors: Cheung, Chi Wai, Hu, Xile
• Format: Article
• Language: English
• Subjects: Alkenes; Alkynes; carbozincation; catalysis; Chemistry; Cross coupling; Iodides; iron; Joining; Nickel; olefin synthesis; stereoselective; Synthesis; Terminals
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201504049

The stereoselective synthesis of trisubstituted alkenes is challenging. Here, we show that an iron‐catalyzed anti‐selective carbozincation of terminal alkynes can be combined with a base‐metal‐catalyzed cross‐coupling to prepare trisubstituted alkenes in a one‐pot reaction and with high regio‐ and stereocontrol. Cu‐, Ni‐, and Co‐based catalytic systems are developed for the coupling of sp‐, sp2‐, and sp3‐hybridized carbon electrophiles, respectively. The method encompasses a large substrate scope, as various alkynyl, aryl, alkenyl, acyl, and alkyl halides are suitable coupling partners. Compared with conventional carbometalation reactions of alkynes, the current method avoids pre‐made organometallic reagents and has a distinct stereoselectivity. One‐pot reaction: A wide range of trisubstituted olefins can be stereoselectively prepared by a sequential iron‐catalyzed anti‐carbozincation of terminal arylalkynes with alkyl iodides followed by copper‐, nickel‐, and cobalt‐catalyzed cross‐couplings with various sp‐, sp2‐, and sp3‐carbon electrophiles, respectively (see scheme; DMA=dimethylacetamide, bipy=2,2‐bipyridine, cod=1,5‐cyclooctadiene, TMEDA=N,N,N′,N′‐tetramethylethylenediamine).