Rhodium‐Catalyzed C−H Activation‐Based Construction of Axially and Centrally Chiral Indenes through Two Discrete Insertions

Abstract

Reported herein is asymmetric [3+ +2] annulation of arylnitrones with different classes of alkynes catalyzed by chiral rhodium(III) complexes,w ith the nitrone acting as an electrophilic directing group.T hree classes of chiral indenes/ indenones have been effectively constructed, depending on the nature of the substrates.T he coupling system features mild reaction conditions,excellent enantioselectivity,and high atomeconomy.I np articular,t he coupling of N-benzylnitrones and different classes of sterically hindered alkynes afforded CÀCor CÀNatropochiral pentatomic biaryls with aC-centered pointchirality in excellent enantio-and diastereoselectivity (45 examples,a verage 95.6 %e e). These chiral center and axis are disposed in adistal fashion and they are constructed via two distinct migratory insertions that are stereo-determining and are under catalyst control.Scheme 1. Formationo fmultiple chiral elements via CÀHfunctionalization (DG = directing group, SDS = stereo-determining step).

Twofold C−H Activation‐Based Enantio‐ and Diastereoselective C−H Arylation Using Diarylacetylenes as Rare Arylating Reagents

“…Having established the optimal reaction conditions, we next examined the scope of the arene substrates (Scheme 2). Symmetric diarylphosphinic amides bearing an electron-donating (Me, Et, t Bu, OEt, and OMe), -withdrawing (Ph and CF3), and halogen groups at the para position of the benzene ring were generally well tolerated, and the corresponding products (4)(5)(6)(7)(8)(9)(10)(11)(12)(13) were isolated in moderate to good yields and in 93.5:6.5 to 97.5:2.5 e.r. Arenes bearing meta alkyl and alkoxyl groups were also compatible (14)(15)(16)(17), and the C-H activation took place at the less hindered ortho C-H site in excellent enantioselectivity (95.5:4.5 to 97:3 e.r.).…”

“…[4] Our group also realized biaryl synthesis by alternative dynamic kinetic transformation of the coupling reagent (alkynes). [5] Direct arylation of arenes with concurrent generation of an axis seems a more straightforward protocol. In 2012 Yamaguchi and Itami applied naphthyl boronic acids as an arylating reagent in Pd-catalyzed arylation of thiophenes.…”

Rhodium‐Catalyzed C−H Activation‐Based Construction of Axially and Centrally Chiral Indenes through Two Discrete Insertions

“…The opposite (R)-configuration of the product 3 has been confirmed by X-ray crystallography. [22] Thes cope of this [3+ +2] annulation reaction has been investigated (Scheme 2). To our delight, nitrones bearing as eries of ortho electron-donating,-withdrawing,a nd bulky substituents all reacted in excellent enantioselectivity and good efficiency (4)(5)(6)(7)(8), which stayed contrast to limited compatibility of ortho groups in most CÀHactivation systems.…”

“…The N-benzyl group in the nitrone was been extendable to substituted ones, and the enantioselectivity was constantly excellent although the coupling efficiency varied (17)(18)(19)(20)(21). Thealkynes have been also varied to symmetrical (22)(23)(24)(25)(26)and non-symmetrical ( 27) diarylacetylenes.I na ddition, 1-phenyl-1-propyne also coupled in excellent regio-and enantioselectivity (28).…”

“…and isolated in > 20:1 d.r., and the absolute configuration of the product 62 was determined by X-ray crystallography. [22] Besides the 2-OTsg roup in the naphthalene ring, the 2-substituent was smoothly extended to OCbz, Ph, and CO 2 Me groups (66-68), and both 67 and 68 have been characterized by X-ray crystallography. [22] In contrast, changing the OTsg roup to OMs led to essentially no reaction.…”