Catalyst Control over Twofold and Higher-Order Stereogenicity by Atroposelective Arene Formation

Organocatalytic Enantioselective Construction of Conformationally Stable C(sp2)–C(sp3) Atropisomers

“…Archetypal synthetic scaffolds displaying restricted rotation around a C­(sp 2 )–C­(sp 3 ) single bond, among which only a few chiral compounds exist (Figure b), include encumbered naphthyl dialkyl carbinols, 9-arylfluorenes, and aryltriptycenes. Many of these examples do not possess a center of asymmetry and are therefore achiral molecules that can be isolated as a pair of conformational diastereomers due to the sole presence of a C­(sp 2 )–C­(sp 3 ) stereogenic axis. − Chiral C­(sp 2 )–C­(sp 3 ) atropisomers exhibiting axial chirality can be achieved if the axis displays a six-fold stereogenicity. − Recently, Sparr et al disclosed an elegant methodology targeting the asymmetric preparation of aryltriptycenes in which either the antiperiplanar ( ap ) or the clinal ( c ) stereoisomers could be synthesized by careful selection of the ligand structure (Figure c) . Alternatively, the introduction of stereogenic centers results in the formation of chiral C­(sp 2 )–C­(sp 3 ) atropisomers.…”

Synthesis of Atropisomeric Two‐Axis Systems by the Catalyst‐Controlled syn‐ and anti‐Selective Arene‐Forming Aldol Condensation

“…Together with their enantiomers, these diastereomers represent topologically well‐defined scaffolds with pertinent emerging applications [17–21] . Our group previously developed an iterative strategy to prepare atropisomeric multiaxis systems by a stepwise catalyst‐controlled stereodivergent approach [22, 23] . Encouraged by the efficient creation of stereochemical complexity by the simultaneous control over two stereocenters, we hence considered if the configuration of both stereogenic axis can be controlled simultaneously in a single catalytic step.…”

“…[17][18][19][20][21] Our group previously developed an iterative strategy to prepare atropisomeric multiaxis systems by a stepwise catalyst-controlled stereodivergent approach. [22,23] Encouraged by the efficient creation of stereochemical complexity by the simultaneous control over two stereocenters, we hence considered if the configuration of both stereogenic axis can be controlled simultaneously in a single catalytic step. The prospects of this notion were suitably underscored in the retrosynthetic analysis, in which the polyketide pattern of teraryls [24] indicated that two ortho positioned stereogenic axes are established concurrently in the assembly of the inner β-naphthol ring from simple diketo substrates by means of an arene-forming aldol condensation (Figure 1D).…”

The Catalytic Formation of Atropisomers and Stereocenters via Asymmetric Suzuki–Miyaura Couplings

“…In atropisomers, the steric strain or other contributors, such as ortho substituents, create a high rotational barrier, allowing the isolation of individual conformers. Notably, axial chirality is a critical element in many natural products, biologically active compounds (Ancistrotectoriline A, Gossypol or Steganacin), privileged chiral ligands (BINAP and BINOL derivatives), and many compounds for the area of material science (Scheme A). − To prepare atropisomers, several strategies have been documented in the literature, including the construction of aromatic rings by cycloaddition or chirality transfer, cross-coupling between two aryl units to build a stereogenic axis, and functionalization of prochiral or racemic biaryls (Scheme B). − Enzymatic, organo-, or transition-metal catalysts have been employed to accomplish this goal. − Among these methods, transition-metal catalyzed cross-couplings of two aryl units, particularly the asymmetric SM coupling, represents a straightforward synthetic strategy (Scheme C).…”