Rhodium‐Catalyzed Chemodivergent Regio‐ and Enantioselective Allylic Alkylation of Indoles

Abstract

The control of C3/N1 chemoselectivity in indole alkylation with the same electrophiles is still challenging. An Rh/bisoxazolinephosphane‐catalyzed chemodivergent regio‐ and enantioselective allylic alkylation of indoles was developed. Chiral C3‐ and N1‐allylindoles can be selectively obtained with high branched/linear ratio and up to 99 % ee by changing the counteranion of Rh, the allylic carbonate, the reaction temperature, and the ligand.

Enantioselective synthesis of N-alkylindoles enabled by nickel-catalyzed C-C coupling

“…In addition to aryl bromides, vinyl bromides were incorporated as well in this reaction, leading to structually diverse chiral Nallyl indoles 4a-4f in 35-60% yields with 73-95% ee values. Remarkably, this modular alkenylation complements previously established metal-catalyzed indole N-allylations in that di-and trisubstituted allylic products bearing aryl and alkyl groups are readily accessed 27,29,31,70,71 .…”

The Selective Nickel‐Catalyzed N‐Allylation of C3‐Unprotected Indoles under Mild and Clean Conditions

“…[19] It is noteworthy that a similar trend has been observed in the presence of transition metal catalysts such as palladium (with DMF and DMSO as solvents), [7a,c,20] iridium (DME) [5] and rhodium (CH 3 CN). [4] Considering the formation of the bis-allylated derivative, control experiments starting from Nallylated 3 a didn't lead to the formation of the 5 a product. [21] This latter compound is indeed solely formed from the Nallylation of 4 a and that clearly explains that high selectivities in N-allylation are accompanied with the formation of low amounts of the bis-allylated derivative even after prolonged reaction times.…”

“…Then, only few authors proposed a selective N-allylation of C3unprotected indoles. In this field, rhodium, [4] iridium, [5] platinum [6] and palladium [7] based catalysts have proven their efficiency and could be advantageous as the use of chiral ligands allows an access to asymmetric versions. In contrast, the proposed catalytic systems include generally the use of bases or additives to selectively produce the N-allylated product.…”

Ring Opening of Triflates Derived from Benzophospholan-3-one Oxides by Aryl Grignard Reagents as a Route to 2-Ethynylphenyl(diaryl)phosphine Oxides

“…The most explored methods here are Sonogashira coupling, 14 copper-free Sonogashira reactions, 15 and alkynylation reaction. 16 …”

“…All mentioned applications of alkynes benefit from the rapid development of the synthetic routes, enabling the incorporation of an ethynyl unit into the structure of nearly any organic molecule. The most explored methods here are Sonogashira coupling, copper-free Sonogashira reactions, and alkynylation reaction …”