Unexpected regioselective carbon–hydrogen bond activation/cyclization of indolyl aldehydes or ketones with alkynes to benzo-fused oxindoles

Abstract

Rhodium-catalyzed carbon-hydrogen bond activation has attracted great interest in the construction of carbon-carbon and carbon-heteroatom bonds. In recent years, transition metal-mediated oxygen transposition through a 'dehydration-rehydration' process has been considered as a promising strategy towards oxygen-functionalized compounds. Here we describe an unexpected rhodium-catalyzed regioselective carbon-hydrogen bond activation/ cyclization of easily available indolyl aldehydes or ketones with alkynes to afford benzo-fused oxindoles, involving the sequential carbonyl-assisted carbon-hydrogen activation of the indole ring at the 4-position, [4 þ 2] cyclization, aromatization via dehydration, nucleophilic addition of water to iminium and oxidation. Isotopic labelling experiments disclose the occurrence of apparent oxygen transposition via dehydration-rehydration from the indolyl-3-carbonyl group to the 2-position of pyrrole to forge a new carbonyl bond. The tandem reaction has been used as the key step for the concise synthesis of priolines, a type of alkaloid isolated from the roots of Salvia prionitis.

Synthesis of Phenalenyl‐Fused Pyrylium Cations: Divergent C−H Activation/Annulation Reaction Sequence of Naphthalene Aldehydes with Alkynes

“…[17] Thus,i ti sr easonable to assume that the phenalenone derivative 6aa is not ad irect intermediate and that the double oxidative insertions of alkyne are not astep by step process.These observations also imply that the CÀHb ond activation initially occurred at the C8 position rather than the C2 position. We propose that the formation of 7aa could involve the sequential C8 À Ha ctivation/annulation/aromatization by dehydration/nucleophilic addition of water/oxidation (for details,s ee Scheme S1).…”

“…(1)]. Based on the above observations and the known reports [17,20] amechanism is proposed (Scheme 7; for detailed description from A to D,s ee Scheme S1). Based on the above observations and the known reports [17,20] amechanism is proposed (Scheme 7; for detailed description from A to D,s ee Scheme S1).…”

“…Unlike other directing groups,t he aldehyde-assisted CÀH activation examples are significantly underrepresented because of its weak chelation to metal ions,a nd almost all the successful cases are relevant to oxidative olefination. [17] Inspired by this work, we envisaged that the phenalenyl-fused pyrylium framework could be formed in one step by two [4+ +2] cyclizations of naphthalene aldehyde with two equivalents of alkyne through sequential C8 À Hand C2 À Hc leavage (Scheme 2). [17] Inspired by this work, we envisaged that the phenalenyl-fused pyrylium framework could be formed in one step by two [4+ +2] cyclizations of naphthalene aldehyde with two equivalents of alkyne through sequential C8 À Hand C2 À Hc leavage (Scheme 2).…”

Rhodium(III)‐Catalyzed Activation of CH Bonds and Subsequent Intermolecular Amidation at Room Temperature

“…[16] As the tert-butyl group has aconformational bias to favor of the formation of cyclometalated species, 1a was used to isolate rhodacycle intermediates.S urprisingly, 1a reacted stoichiometrically with [{RhCp*Cl 2 } 2 ]a nd AgSbF 6 to afford the neutral rhodium(III) complex 6 (Scheme 5a). (5)]. [17] It is notable that 6 could not be obtained without AgSbF 6 (Scheme 5b).…”

“…Although af ew rhodium-catalyzed functionalizations of reactive C sp 3 ÀHb onds,s uch as those which are acidic,adjacent to N, allylic,and benzylic have been reported recently, [3] thea ctivation of unreactive and remote C sp 3 À Hb onds with subsequent functionalization still remains unsolved. As part of our ongoing efforts in rhodium(III)-catalyzed C À Hactivation, [5] we herein illustrate as olution to this challenge through ar hodiumcatalyzed chelation-assisted amidation of unactivated C sp 3 ÀH bonds as ar epresentative example. As part of our ongoing efforts in rhodium(III)-catalyzed C À Hactivation, [5] we herein illustrate as olution to this challenge through ar hodiumcatalyzed chelation-assisted amidation of unactivated C sp 3 ÀH bonds as ar epresentative example.…”