From Enantioenriched Donor‐Acceptor Cyclopropylcarbinols to Axially Chiral Arylnaphthalenes through Aryldihydronaphthalenes: Central‐to‐Axial Chirality Exchange

Abstract

Transformations of enantioenriched donor‐acceptor (D−A) cyclopropylcarbinols to enantioenriched 1‐arylnaphthalenes that bear an ortho‐substituent on a benzene ring provided a successful chirality‐exchange method with a high level of stereoinduction. A central chirality‐transfer step, i. e., a Lewis‐acid‐mediated ring‐opening cyclization of enantioenriched D‐A cyclopropylcarbinols (97 to >99 % ee), afforded 1‐aryl‐1,2‐dihydronaphthalenes with an ortho‐substituent (Me, Br, OMe, OBn, or OiPr) on the benzene ring with high enantioselectivity (97 to >99 % ee). The central‐to‐axial chirality‐exchange step, i. e., the dehydrogenation of the obtained enantioenriched 1‐aryl‐1,2‐dihydronaphthalenes using DDQ, furnished the axially chiral 1‐arylnaphthalenes with high enantioselectivity (90 to >99 % ee). Importantly, we developed a highly enantioselective synthesis of a 1‐arylnaphthalene with an ortho‐alkoxy group on the benzene ring. Moreover, we improved the chirality exchange to furnish a 1‐arylnaphthalene with an ortho‐alkoxy‐substituted benzene ring in high yield with high ee.

Enantioselective Synthesis of Atropisomers by Oxidative Aromatization with Central-to-Axial Conversion of Chirality

“…In 2022, Nishii and co-workers developed a seven-step procedure to synthetize the (aS)-atropisomers 123 from chiral cyclopropylcarbinols, implying central-to-axial chiral conversion ( Scheme 28 ) [ 148 ]. In this first step, the Hayashi-Jørgensen amino catalyst 103 promoted Wang’s asymmetric cyclopropanation between a cinnamaldehyde derivative 119 and dimethyl α-bromomalonate ( 120 ).…”

Recent advances in the catalytic asymmetric construction of atropisomers by central-to-axial chirality transfer

“…In this context, early reports mainly concentrated on the conversion of chiral substrates obtained from tedious procedures. [34][35][36][37][38][39] With the development of asymmetric catalysis, a variety of privileged atropisomers could be afforded from easily accessible substrates. The efficiency of central-toaxial chirality transfer, herein, was quantified using the enantiospecificity [es = (ee atropisomer /ee chiral precursor ) × 100%] values.…”

Strain-Released Hydrogenation of Donor-Acceptor Cyclopropane and Cyclobutane via Electrochemical Site Selective Carbonyl Reduction

“…23,26,32 Our lab has been working in the field of strain rings for a long and in the last few years, we have discovered a few electro-oxidative protocols for the activation of cyclopropanes. Ring-opening hydrogenation for DACs is known via the use of Pd-C/H2, 33,34 SmI2-ROH, 35,36 and Zn-AcOH-based systems 37 [Scheme 1(C)]. Such methodologies used harsh reaction conditions, which resulted in the over-reduction or hydrogenation at the multiple bonds.…”