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

Abstract

Atropo-enantioselective C À Hf unctionalization reactions are largely limited to the dynamic kinetic resolution of biaryl substrates through the introduction of steric bulk proximalt ot he axis of chirality.R eported herein is ah ighly atropo-enantioselective palladium(0)-catalyzed methodology that forges the axis of chirality during the C À Hf unctionalization process,e nabling the synthesis of axially chiral dibenzazepinones.C omputational investigations support experimentally determined racemization barriers,w hile also indicating CÀHf unctionalization proceeds by an enantio-determining CMD to yield configurationally stable eight-membered palladacycles.

Atroposelective Synthesis of Axially Chiral Styrenes via an Asymmetric C–H Functionalization Strategy

“…Although asymmetric CÀH functionalization has emerged as a powerful synthetic tool for the rapid generation of axially chiral biaryl skeletons, 11,14,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] construction of axially chiral styrenes bearing an open-chained alkene with more flexibility via catalytic asymmetric CÀH functionalization remains elusive. At least two main difficulties needed to be addressed: first, the reaction has to be conducted under mild conditions in order to preserve enantiomeric purity of the resulting products because of the relatively lower conformational stability.…”

Rhodium‐Catalyzed Atroposelective Construction of Indoles via C−H Bond Activation

“…Additionally, scale-up synthesis of 3 (1 mmol) was successful, with essentially no deterioration of enantioselectivity. Comparable efficiency and enantioselectivity (84-93 % ee) were also realized for a series of meta-substituted alkynes (11)(12)(13)(14). While ortho-substituted alkynes generally exhibited poor efficiency due to steric effect, presence of ortho F groups in the alkyne was tolerated (15).…”

“…Our CÀH activation approach to access axially chiral biindolyls [9] prompted us to take full advantage of CÀH activation for construction of axially chiral biaryls. Two substrategies are followed, namely, de novo construction of a new chiral axis and dynamic kinetic transformation based on an existing axis, [11] with the latter being dominant. Nevertheless, most dynamic kinetic transformations convert an ortho CÀH bond to a terminal group.…”

A C-H Activation-Based Enantioselective Synthesis of Lower Carbo[n]helicenes (n = 4-6)

“…Moreover, as this method enabled the access to scarcely reported configurationally stable carbo [4]helicenes, it led to an experimental comparative study of the photophysical and chiroptical properties of carbo [4], [5] and [6]helicenes, which revealed the high value of the dissymmetry factors of the smallest of these congeners. 26,27 warped molecules 28 (Het)…”