Stereoselective Domino Heck‐Suzuki Reactions

Abstract

Palladium catalysis enables efficient and versatile domino reactions that are initiated by an intramolecular Mizoroki‐Heck reaction and then terminated by a Suzuki‐Miyaura coupling. The stereochemistry of this cascade is concerned under three aspects: Firstly, as stereoselective formation of carbon−carbon‐double bonds, when the initial carbometalation occurs at an alkyne moiety. Secondly as diastereoselective and thirdly enantioselective formation of stereogenic carbon centers when the intramolecular Heck step is directed to an alkene moiety. Valuable protocols lead to – otherwise not easily accomplished – stereo control in the formation of tri‐ and tetra‐substituted double bonds according to the first conception. The diastereoselective versions permit the formation of multiple stereocenters in mono‐ and polycycles. Enantioselective protocols were developed only recently. The fact that the newly created stereocenters are highly‐substituted, tertiary or quaternary ones, makes the methods that are presented in this review useful and versatile tools in synthesis.

Gold‐Catalyzed 1,2‐Dicarbofunctionalization of Alkynes with Organohalides**

“…In the past decade, gold catalysis has emerged as an excellent tool for the functionalization of alkynes [10] . Interestingly, in contrast to the prevalent inner sphere mechanisms observed in Pd, Ni or Cu catalysis, [6,7] gold complexes preferably follow an oxidation/π‐activation mechanism which has indeed emerged as an attractive alternative for the development of anti ‐selective 1,2‐difunctionalization of alkynes [11] . However, the arduous oxidative addition of Au(I)‐center to various carbon‐halogen bonds [12] and the facile rate of Au(I)‐catalyzed hydrofunctionalization reactions of alkynes, [13] has for long forbidden the use of organohalides for the development of 1,2‐difunctionalization of alkynes [14] .…”

“…Mechanistically, these reactions follow a carbometallation/migratory insertion pathway to sponsor a syn‐ vinyl‐metal intermediate ( Int A ) which after cross‐coupling with respective coupling partner affords the 1,2‐dicarbofunctionalization products. While this mechanistic pathway has remarkably advanced the development of highly general syn ‐selective 1,2‐dicarbofunctionalization, [6,7] reports on anti ‐selective 1,2‐dicarbofunctionalization of internal alkynes still remain highly sporadic [8] . This is mainly due to the need of bulky ligands, ortho ‐substituted iodoarenes or specialized substrates that are necessary to enable the cis‐trans isomerization [9] of the Int A , prior to the cross‐coupling step.…”

Palladium-Catalyzed Heck/Suzuki Tandem Reaction of (Z)-1-Iodo-1,6-dienes and Organoboronic Acids

“…This technique represents a potent strategy for the construction of useful carbo- and heterocyclic skeletons . Among them, the Heck/Suzuki tandem process, a fascinating approach for the construction of two C–C bonds in one pot, developed by Grigg’s group, has been widely applied to rapidly manufacture complex molecules bearing all-carbon quaternary centers . For instance, Pd- or Ni-catalyzed racemic and asymmetric versions of this domino reaction for the construction of all-carbon quaternary carbon centers have been well-developed by Zhang and co-workers, Kong and co-workers, Jia and co-workers, and others .…”