A Stereodivergent–Convergent Chiral Induction Mode in Atroposelective Access to Biaryls via Rhodium-Catalyzed C–H Bond Activation

Abstract

Understanding the reaction mechanisms, particularly the chiral induction mode, is critical for the development of new asymmetric catalytic reactions. Rhodium(III)-catalyzed C–H activation en route to atroposelective [4 + 2] annulative coupling with α-diazo β-ketoesters has been realized, affording axially chiral phenanthrenes in good to excellent enantioselectivity. A combination of experimental and computational studies revealed a nontraditional stereodivergent–convergent chiral induction mode. The reaction proceeded with a rhodafluorene intermediate, followed by competitive, constructive, and stereodivergent migratory insertions of the two Rh–C(aryl) bonds into the carbene species to give β-ketoester intermediates. Then, the other Rh–C(aryl) bond migratorily inserts into the ketone carbonyl group. Following this stereodetermining carbonyl insertion, an ester-chelated rhodium(III) alkoxide species bearing two poorly controlled chiral centers and a well-controlled C(sp2)–C(sp3) chiral axis is generated. The final product is delivered via stereoconvergent elimination of a rhodium(III) species with retention of the well-controlled axial chirality and with loss of the central chirality.

Synthesis of 9,10‐Phenanthrenes via Rh(III)‐Catalyzed [4+2] Annulation of 2‐Biphenylboronic Acids with Diazo Compounds

“…According to the above results and related reports, [ 9,14‐17 ] the reaction mechanism is speculated as follows (Scheme 5). Firstly, an active Cp*RhX 2 is generated from the anion exchange between [Cp*RhCl 2 ] 2 and AgOAc.…”

“…Intermediate VI is then produced via nucleophilic addition of the rhodium center to the carbonyl group . [ 17 ] Finally, the target product 3aa is generated after protonation and intramolecular dehydration.…”

Rhodium-Catalyzed Asymmetric C–H Functionalization Reactions

“…245 Besides the widely used 1-diazonaphthoquinone derivatives, acceptor-acceptor diazo compounds 363 were employed in Rh(III)-catalyzed atroposelective C−H activation with biphenyl-2-boronic acid 362 by Li and co-workers. 247 With Rh-2k as the optimal catalyst, a wide array of axially chiral biphenyl compounds 364 could be afforded in up to 84% yield and 94% ee (Scheme 60). Further mechanistic study showed that forming an intermediate bearing a C(sp 2 )−C(sp 3 ) chiral axis is vital for enantioselective control.…”

Synthesis of Spirocyclohexadienones via Palladium-Catalyzed Dearomatization of Dibenzoxaborins

“…Recently, our research group has realized some annulation reactions initiated by transmetalation of arylboronic acid, demonstrating considerable efficiency in creating metal–carbon intermediates . Given the Lewis acidity and coordination ability of boron, which is easy to interact with oxygen, it is hypothesized that boron-containing substrates may promote dearomatization of 2-phenylphenol with the aid of the boron unit.…”