Construction of Quaternary Stereocenters by Palladium‐Catalyzed Carbopalladation‐Initiated Cascade Reactions

Abstract

The enantioselective synthesis of molecules containing quaternary stereocenters is a field of intense research interest and development. Among the known organic transformations, carbopalladation‐initiated domino transformations constitutes a general method for the construction of compounds containing cyclic or spiro quaternary stereocenters. In this Minireview, recent achievements in palladium‐catalyzed domino Heck/C−H functionalizations and developments in enantioselective carbopalladation‐initiated domino processes are summarized.

Palladium‐Catalyzed C—C Bond Activation/Suzuki Reaction of Methylenecyclobutanes

“…Intramolecular carbopalladation‐initiated domino processes of arylhalide‐tethered alkenes are powerful tools for the construction of structurally diverse cyclic molecules. [ 10 ] We anticipate that arylhalide‐tethered MCBs would undergo intramolecular carbopalladation and subsequent β‐carbon elimination to form alkylpalladium species, thus establishing a palladium‐catalyzed C—C bond activation manner of MCBs. The transient alkylpalladium intermediate would be trapped by coupling reagents to form a new C—C bond, [ 11 ] thus forming multisubstituted indanes.…”

Stereoselective 1,2-Dicarbofunctionalization of Trisubstituted Alkenes by Palladium-Catalyzed Heck/Suzuki or Heck/Sonogashira Domino Sequence

“…[1][2][3] In this regard, the transition-metal-catalyzed olefin difunctionalization achieved by intercepting Heck alkyl-metal intermediates provides a powerful and straightforward method. [4][5][6][7][8][9][10][11][12] By employing versatile carbon-based trapping agents to capture the alkyl-metal species derived from intramolecular carbometalation, tremendous transformations have been achieved and show their efficiency in the synthesis of cyclic molecules. [4][5][6][7][8][9][10][11][12] Nevertheless, compared with advances in racemic reactions, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] the development of enantioselective olefin dicarbofunctionalization has met with limited success.…”

Palladium-Catalyzed Asymmetric Domino Heck/Carbocyclization/Suzuki Reaction: A Dearomatization of Nonactivated Naphthalenes

“…Palladium (Pd)-catalyzed asymmetric domino Heck reaction is one of the most powerful methods for the construction of quaternary stereocenters. 26,27 Through trapping of the in situ generated alkyl-PdX intermediate, various enantioselective domino reactions, including Heck tandem coupling with azoles, 28,29…”