Palladium-catalyzed cross-coupling reactions and electrocyclizations—efficient combinations for new cascade reactions

• Published in: Journal of organometallic chemistry Vol. 687; no. 2; pp. 249 - 255
• Main Authors: de Meijere, Armin, Schelper, Michael, Knoke, Mario, Yucel, Baris, Sünnemann, Hans Wolf, Scheurich, René Peter, Arve, Lars
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 07.12.2003
• Subjects: Cascade reactions; Combinatorial chemistry; Cross coupling; Palladium catalysis; Small rings; Combinatorial chemistry; Cross coupling; Palladium catalysis; Cascade reactions; Small rings
• ISSN: 0022-328X; 1872-8561
• DOI: 10.1016/j.jorganchem.2003.07.007

Palladium-catalyzed cross-coupling reactions and electrocyclic transformations as well as cycloadditions can efficiently be combined in one-pot sequences to build up complex molecules from simple precursors. 1,3-Dicyclopropyl-1,2-propadiene ( 1) could be coupled to various aryl halides, and the 1,3,5-hexatrienes resulting after rearrangement were trapped with different dienophiles. Further exploration of the highly reactive building block bicyclopropylidene ( 8) demonstrates the combinatorial potential of the two reaction modes in terms of two different three-component reactions, and even a novel four-component reaction was readily developed. Additional increase of complexity was gained by combining an intramolecular Heck reaction with consecutive trapping by 8, which can be carried out with or without 6π-electrocyclization. Finally a Stille–Heck-coupling sequence of substituted 2-bromocycloalkenyl triflates with functionally substituted alkenylstannanes and acrylic esters led to highly substituted 1,3,5-hexatrienes, which smoothly underwent 6π-electrocyclization at elevated temperatures to yield bi- and tricyclic skeletons. With this methodology at hand, a new versatile access to steroid-analogues with a diene moiety in the B ring and a functionality at C-7 was developed. Palladium-catalyzed cross-coupling reactions can be efficiently combined with subsequent thermal reactions (such as 6π-electrocyclizations and Diels–Alder reactions) to build up complex molecules from rather simple precursors in single or two step operations. With the appropriate building blocks at hand, products range from oligosubstituted spiro[2.5]octene derivatives over spirocyclopropanated oligocycles to novel steroid analogues.