Construction of Bridged Polycyclic Skeletons via Transition‐Metal Catalyzed Carbon–Carbon Bond‐Forming Reactions

Abstract

Transition-metal catalysis has become one of most important methods for constructingm olecules with diverse architectures.B ridgedp olycyclic skeletons are often considered one of mostchallenging structures in organic synthesis. This Minireview summarizes the recent progress on synthesis of bridged polycyclic skeletons by transition-metal-catalyzed carbon-carbon bond-formingr eaction. Four main ring-forming strategies including connection via olefin or carbonyl functionality,e nolate intermediacy,C ÀHf unctionality,a nd aryl functionality are detaileda nd some effective methods are discussed with particular emphasis on reaction design and mechanism. Figure 1. Selectedexamples of bridged polycyclic natural products.

Construction of a Bicyclo[2.2.2]octene Skeleton via a Visible-Light-Mediated Radical Cascade Reaction of Amino Acid Derivatives with N-(2-Phenyl)benzoyl Groups

“…Bridged polycyclic ring systems are widely distributed in natural products and biologically active molecules. Such systems can give more effective and selective binding to target proteins than that achieved with simple flat polycycles . In medicinal chemistry, these scaffolds have attracted attention as three-dimensional (3D) drug templates and can contribute to decreasing the number of aromatic rings (#ArRNG) and increasing the fraction of sp 3 -hybridized carbons (Fsp 3 ).…”

“…In medicinal chemistry, these scaffolds have attracted attention as three-dimensional (3D) drug templates and can contribute to decreasing the number of aromatic rings (#ArRNG) and increasing the fraction of sp 3 -hybridized carbons (Fsp 3 ). These are important parameters associated with “drug-like” molecules. − In this context, considerable efforts have been made to develop efficient strategies for the construction of various bridged polycyclic ring systems, leading to several remarkable methodologies, such as intramolecular cycloadditions, − transition-metal-catalyzed reactions, polyene cyclizations, or dearomatization reactions. − Among these, dearomatization reactions are particularly useful, because they can rapidly convert readily available aromatic compounds with planar structures to complex 3D molecules. However, achieving efficient processes requires harsh reaction conditions to overcome the resonance stability of the aromatic ring.…”

Enantioselective Construction of Sila-bicyclo[3.2.1] Scaffolds Bearing Both Carbon- and Silicon-Stereocenters

“…Recent developments in asymmetric transition-metal catalysis have brought a multitude of creative ring-forming protocols toward enantioselective construction of bridged bicyclic skeletons . Among these, asymmetric Heck-type cyclizations have been well documented to be a universal tool for the enantioselective construction of a variety of structurally complex bridged polycyclic rings .…”

“…Recent developments in asymmetric transition-metal catalysis have brought a multitude of creative ring-forming protocols toward enantioselective construction of bridged bicyclic skeletons. 4 Among these, asymmetric Heck-type cyclizations 5 have been well documented to be a universal tool for the enantioselective construction of a variety of structurally complex bridged polycyclic rings. 6 We wondered whether asymmetric Heck-type reaction could also be highefficiently employed as central strategic step for highly enantioselective synthesis of a wide variety of bridged bicyclic silicon scaffolds with simultaneous formation of carbon and silicon-stereocenters.…”

Novel strategies for C-C/X bond formation

“…1-3 C-C bond forming reactions are not only central in the synthesis of many bioactive compounds but also important in the production of various chemical feedstocks used in pharmaceutical and plastic production. 4,5 Although there is an ever-growing number of methods available for carboncarbon bond formation, [6][7][8][9][10][11][12] more are needed. While several reactions can construct C-C bonds, only a few have proven robust.…”