Rh-catalyzed oxidative C2-alkenylation of indoles with alkynes: unexpected cleavage of directing group

Mn(I)-Catalyzed Mechanochemical C–H Bond Activation: C-2 Selective Alkenylation of Indoles

“…Indole is a ubiquitous heterocyclic scaffold among many biologically active natural products, pharmaceutical compounds, and functional materials. − Therefore, regioselective direct C–H bond functionalization , of the indole ring is a contemporary approach for the diversification of this highly important heterocyclic framework. − In addition to the nucleophilic N atom, the C-3 position of indole is the most suitable for various electrophilic substitution reactions. − Notably, few mechanochemical methods for selective C-3 functionalization are also reported. ,, However, the recent approach on the transition-metal-catalyzed directed C(2)–H functionalization has unraveled various methods for incorporation of aryl, ,− alkenyl, − alkynyl, − and alkyl − groups at the C-2 position of indole including few elegant methods under mechanochemical conditions. ,, In particular, the C-2 alkenylation of indoles is of special interest as a large variety of complex heterocycles can be generated utilizing the alkenyl functionality in different manners including pericyclic reactions, macrocyclizations, etc. − Moreover, C-2-alkenylated indoles are prevalent in natural products and medicinally important compounds. − Because of immense importance, a number of methods for C-2 alkenylation are developed in the solution phase. − ,−…”

Regioselective Direct C‐Alkenylation of Indoles

“…The reaction conditions tolerate different functional groups and the final products are obtained with high E stereoselectivity. In a related method, similar results can be obtained using [Cp*RhCl 2 ] 2 …”

“…The reaction conditions tolerate different functionalg roups and the final products are obtained with high E stereoselectivity.I narelated method, similar resultsc an be obtained using [Cp*RhCl 2 ] 2 . [116] As tereocomplementary procedure allowing a Z selectivity in the same process can be obtained using aR u II catalysti nt he presence of Cu(OAc) 2 (Scheme 50). [117] The reaction conditions also involve ac leavage of the N-carbamoyl moiety leadingt ot he unprotected indole derivative.…”

An entry to 2-(cyclobut-1-en-1-yl)-1H-indoles through a cyclobutenylation/deprotection cascade

“…A similar observation was reported for Kim's rhodium-catalysed directed C2-alkenylation, in which C3-substituted indoles also failed to deliver the desired products. 53 Moreover, we found that other cycloalkanones or acyclic ketones do not undergo the desired cycloalkenylation/deprotection cascade under these reaction conditions.…”

“…For example, deprotection strategies can limit functional group compatibility, as harsh reaction conditions are often required, or lead to dead ends in multi-step syntheses when the directing group proves to be non-removable. To avoid the aforementioned shortcomings, the development of one-pot C2-alkenylation/ directing group-removal cascades is highly desirable, and seminal studies by Kim, 52,53 Zeng, 54 Matsunaga, 55 and Zhao 56 have recently established the viability of this approach (Scheme 1a).…”