Rhodium-Catalyzed Enantioselective Cyclization of 3-Allenyl-indoles: Access to Functionalized Tetrahydrocarbazoles

Abstract

Figure 1. Selected tetrahydrocarbazole (THC) natural products and structurally related alkaloids. Scheme 1. Transition-Metal Catalyzed Strategies for the Synthesis of Enantioenriched 1-Vinyltetra-hydrocarbazoles Letter pubs.acs.org/OrgLett

When Indoles Meet Allene and its Derivatives

“…The oxo-indole functionalization was observed after treatment with TFA (Scheme 24b, right). [60] Interestingly, Breit has recently reported the enantioselective reaction of related allenes 105 in the presence of rhodium catalysts to give the tetrahydrocarbazole core 107 via the formation of spirocycle intermediates 106 [61] that can also be trapped in situ with a reductant to give functionalized vinylic spiroindoles 108 (Scheme 24c). [62] Cationic gold species have promoted the dihydrocarbazole synthesis from compounds 109, in which indole and allene are separated by one carbon, unraveling a complex reaction mechanism where C3 vs. C2 indole nucleophilicity competes yielding a mixture of carbocyclization products 110 and rearrangement products 111 trough spirocyclic intermediates (112, Scheme 25a).…”

“…The oxo‐indole functionalization was observed after treatment with TFA (Scheme 24b, right). [ 60 ] Interestingly, Breit has recently reported the enantioselective reaction of related allenes 105 in the presence of rhodium catalysts to give the tetrahydrocarbazole core 107 via the formation of spirocycle intermediates 106 [ 61 ] that can also be trapped in situ with a reductant to give functionalized vinylic spiroindoles 108 (Scheme 24c). [ 62 ]…”

Total Synthesis of Allene-Containing Cyclic Tetrapeptide Pseudoxylallemycin C

“…1 Compared to their linear counterparts, cyclic peptides often possess enhanced target affinity and specificity, improved half-lives due to resistance to exo-and endopeptidases, and enhanced cell permeability. 1,2 By majority, these improved properties stem from the reduced conformational freedom of cyclic peptides and lack of carboxyl and amino termini. 1,2 These favourable attributes and their capacity to act on intracellular targets, unlike monoclonal antibodies, have resulted in cyclic peptides attracting significant attention as new therapeutic agents.…”

“…1,2 By majority, these improved properties stem from the reduced conformational freedom of cyclic peptides and lack of carboxyl and amino termini. 1,2 These favourable attributes and their capacity to act on intracellular targets, unlike monoclonal antibodies, have resulted in cyclic peptides attracting significant attention as new therapeutic agents. Importantly, several cyclic peptides such as vancomyin, cyclosporine A, daptomycin, integrilin, octreotide, plecanatide and linaclotide have been approved for clinical use.…”

“…however, pseudoxylallemycins B,C,D,F (2,3,4,6) that contain a rare allenyl modification to the phenol of tyrosine, have yet to be prepared by chemical synthesis. An attempt by Gunjal and Reddy 8 to prepare the bis-allenated pseudoyallemycin B (2) resulted in quantitative epimerisation, yielding solely 3-epipseudoxylallemycin B.…”