Generation of Heteroatom Stereocenters by Enantioselective C–H Functionalization

Abstract

C-H Functionalization has been established as an efficient way to generate molecular complexity. The formation of stereogenic carbon atoms by asymmetric C-H functionalization has seen tremendous progress over the last decade. More recently, the direct catalytic modification of C-H bonds has been powerfully applied to the formation of non-carbon stereogenic centers, which constitute a key design element of biologically active molecules and chiral ligands for asymmetric catalysis. This area was opened by a seminal report describing enantioselective C-H functionalization for the formation of a silicon stereocenter. It rapidly expanded with advances in the enantioselective formation of phosphorus(V) centers. Moreover, enantioselective routes to chiral sulfur atoms in the oxidation state IV (sulfoxides) and VI (sulfoximines) have been disclosed. Herein, we discuss methods of using selective functionalization of C-H bonds to generate a remote heteroatom stereogenic center via an inner-sphere C-H activation mechanism.

Enantioselective Catalytic C-H Amidations: An Highlight

“…Interestingly, in the presence of Rh or Co catalysts no reaction was observed revealing the unique reactivity of the Ir catalyst in these reactions. Beyond the control of planar chirality, He and coworkers have also described an elegant enantioselective synthesis of chiral sulfoxides through the desymetrization of an enantiotopic sulfoxide group [66,67]. In this transformation, the achiral starting sulfoxide plays the role of the directing group.…”

“…Beyond the control of planar chirality, He and coworkers have also described an elegant enantioselective synthesis of chiral sulfoxides through the desymetrization of an enantiotopic sulfoxide group [66,67]. In this transformation, the achiral starting sulfoxide plays the role of the directing group.…”

Enantioselective “organocatalysis in disguise” by the ligand sphere of chiral metal-templated complexes

“…[49][50][51][52][53] A small amount of a chiral metal complex (in most cases around 1 mol%) can provide a great number of enantioselective transformations leading to stereocentres at carbon, nitrogen, sulphur, silicon and other atoms. [54][55][56][57] Although purely organic natural asymmetric catalysts, i.e. enzymes and chiral alkaloids, [58][59][60][61][62][63] have been very well known for a long time, the elaboration of asymmetric, artificial, organic non-metal catalysis began in the early 2000s after breakthrough studies on thiourea derivative and proline catalysis.…”

Sulfur stereogenic centers in transition-metal-catalyzed asymmetric C–H functionalization: generation and utilization

“…[1][2][3][4][5][6][7] By viewing C-H bond as "ubiquitous functionality", synthetic chemists open a new chapter in organic synthesis, that has revolutionised the rules for assembling molecules. In particular, new catalytic transformations based on enantioselective functionalization of C−H bonds have attracted considerable attention, [8][9][10][11][12] given the paramount importance of chirality in organic molecules and growing demand for enantiopure compounds in chemical and pharmaceutical industries. Although asymmetric C−H functionalization is still in its infancy, the recent developed chiral directing groups (cDGs) and chiral ligands have armed this promising methodology to streamline the synthesis of various chiral molecules in an atom-and stepeconomical manner.…”