Axially Chiral Dibenzazepinones by a Palladium(0)‐Catalyzed Atropo‐enantioselective C−H Arylation

Abstract

Atropo-enantioselective C-H functionalization reactions are largely limited to the dynamic kinetic resolution of biaryl substrates through the introduction of steric bulk proximal to the axis of chirality. Reported herein is a highly atropo-enantioselective palladium(0)-catalyzed methodology that forges the axis of chirality during the C-H functionalization process, enabling the synthesis of axially chiral dibenzazepinones. Computational investigations support experimentally determined racemization barriers, while also indicating C-H functionalization proceeds by an enantio-determining CMD to yield configurationally stable eight-membered palladacycles.

Axially Chiral Dibenzazepinones by a Palladium(0)‐Catalyzed Atropo‐enantioselective C−H Arylation

“…In this case,the reaction could be conducted on gram-scale,a llowing ar eduction in palladium, ligand, and acid loading, while still maintaining ah igh yield and enantioselectivity (88 %, 97:3 e.r.,1.21 gisolated). Moreover, the absolute configuration of the biaryl axis present in 2l was confirmed through single-crystal X-ray analysis,and found to be S. [18] In the interest of accessing more structurally diverse dibenzazepinones,w ee xplored the effect of reducing the number of equivalent phenyl substituents in our cyclization precursors.T he dibenzazepinone 2m,d erived from the corresponding diphenyl derivative,w as accessed as as ingle diastereoisomer in 96 %yield and 98:2 e.r. In comparison, the synthesis of the dimethyl derivative 2n required 90 8 8Cf or cyclization, resulting in significant racemization.…”

In Situ Generation of Ruthenium Carbonyl Phosphine Complexes as a Versatile Method for the Development of Enantioselective C−O Bond Arylation

“…After having established the in situ generation method of the ruthenium catalysts described above, therefore, we explored the asymmetric C−O arylation of axially chiral biaryl compounds using optically active phosphine ligands . There have been only a few methods reported for catalytic atropo‐enantioselective biaryl synthesis by cross‐coupling of arenes through cleavage of inert C−H or C−O [13] bonds, and further developments of these reactions are still desired.…”

“…pounds using optically active phosphine ligands. [10] There have been only af ew methods reported for catalytic atropo-enantioselective biaryl synthesis by cross-coupling of arenes throughc leavage of inert CÀH [11,12] or CÀO [13] bonds,a nd further developmentso ft heser eactions are still desired. The reaction of 1'-methoxy-2'-acetonaphthone (6a)a nd 1naphthylboronates 7 was first examined in the presence of 10 mol %o f5 and (R)-MOP (L1)i nt oluene at 100 8Cf or 24 h and 1,1'-binaphthyl derivative 8aa was obtained in 49 %y ield and with 46 % ee ( Table 2, entry 1).…”

Challenging Atroposelective C–H Arylation

“…A few months later, an efficient protocol for intramolecular enantioselective C-H arylation was reported by Cramer and co-workers, 18 targeting the synthesis of original atropisomeric benzazepinones (Scheme 5). Benzazepinones are an interesting class of natural products.…”