A Strategy for Synthesizing Axially Chiral Naphthyl‐Indoles: Catalytic Asymmetric Addition Reactions of Racemic Substrates

Abstract

An ew strategy for enantioselective synthesis of axially chiral naphthyl-indoles has been established through catalytic asymmetric addition reactions of racemic naphthylindoles with bulky electrophiles.Under chiral phosphoric acid catalysis,a zodicarboxylates and o-hydroxybenzyl alcohols served as bulky but reactive electrophiles that were attacked by C2-unsubstituted naphthyl-indoles,w hich underwent ad ynamic kinetic resolution to affordt wo series of axially chiral naphthyl-indoles in good yields (up to 98 %) and high enantioselectivities (up to 98:2 er).

Palladium‐Catalyzed Enantioselective Cacchi Reaction: Asymmetric Synthesis of Axially Chiral 2,3‐Disubstituted Indoles

“…Although enantioselectivity remained moderate, it did prove that the central chirality of a ligand could be transferred to the axial chirality of the N‐aryl indoles. Very recently, Li and co‐workers developed a chiral CpxRh III ‐catalyzed C−H activation/aminorhodation/reductive elimination cascade for the synthesis of enantioenriched indoles bearing a chiral indole C3‐aryl axis . To the best of our knowledge, an enantioselective version of the Cacchi reaction has yet to be developed.…”

Catalytic Asymmetric Construction of Axially Chiral Indole‐Based Frameworks: An Emerging Area

“…The Shi group utilized racemic arylindoles 32 as suitable substrates for asymmetric nucleophilic additions with bulky electrophiles such as azodicarboxylates 33 and o ‐hydroxybenzyl alcohols 35 in the presence of CPAs (Scheme 9 a). [29] The two reactions successfully underwent a DKR process to give two types of axially chiral arylindoles ( 34 and 36 ) in high yields with excellent stereoselectivities. Notably, arylindoles 36 have both axial and central chirality.…”

Organocatalytic Asymmetric Methodologies towards the Synthesis of Atropisomeric N-Heterocycles

“…In 2019, the Shi group 28,29 expanded the field of organocatalytic reactions towards atropisomeric indoles, by disclosing the possibility of engaging configurationally unstable substrates 28 (Scheme 7) or 33 (Scheme 8) in DKR processes. 6a,e,30 In this strategy, bulky groups were installed at C-2 of 3-arylindoles exploiting their nucleophilicity.…”

“…In the second report by the Shi group, 29 a similar process was developed for 3-naphthylindoles 33, reacting either with azodicarboxylates 36 or ortho-quinone methides derived from the acid-catalyzed dehydration of ortho-hydroxybenzyl alcohols 34 (Scheme 8). Reaction with the former resulted in the formation of products 37, displaying exclusive axial chirality, while the latter produced compounds 35 bearing a stereogenic axis and a contiguous stereocenter.…”