Regio‐ and Enantioselective Iridium‐Catalyzed N‐Allylation of Indoles and Related Azoles with Racemic Branched Alkyl‐Substituted Allylic Acetates

Abstract

Cyclometallated π‐allyliridium C,O‐benzoates modified with (S)‐tol‐BINAP, which are stable to air, water, and SiO2, catalyze highly enantioselective N‐allylations of indoles and related azoles. This reaction complements previously reported metal‐catalyzed indole allylations in that complete levels of N versus C3 and branched versus linear regioselectivity are observed.

Photochemical Asymmetric Nickel‐Catalyzed Acyl Cross‐Coupling

“…[15] However,i ti sad ifficult target as testified to by the paucity of asymmetric catalytic protocols available for the preparation of enantioenriched N-alkylated indoles. [16] We conducted our experiments in THF under irradiation by asingle high-power visible-light-emitting diode (LED, l max = 405 nm) with an irradiance of 75 mW cm À2 ,ascontrolled by an external power supply (full details of the illumination set-up are reported in the Supporting Information). By examining ar ange of reaction parameters,w ed etermined that NiCl 2 and the chiral box ligand L1 [17] can accomplish the enantioconvergent photochemical cross-coupling in good yield and high ee (3a formed in 65 %yield and 75 % ee;entry 1).…”

Enantioselective Catalytic Synthesis of N-alkylated Indoles

“…The indole moiety can be found in a wide range of natural products [3]. Therefore, some biologically active indoles contain a substituted α-chiral carbon center on the N1-position (Figure 1) [4][5][6][7]. The synthesis of enantioenriched indole derivatives is of great importance in organic chemistry.…”

“…Pd-catalyzed N-functionalization of indoles.Recently, Krische and co-workers demonstrated an efficient asymmetric intermolecular Tsuji-Trost-type indole N-allylation, where complete N-regioselectivity and regioselectivity towards branched products were achieved (Scheme 27, I)[6]. The reaction was smoothly catalyzed by cyclometallated p-allyliridium C,O-benzoates modified with (S)-tol-BINAP 132 under basic conditions.…”

Iridium‐Catalyzed Enantioselective Intermolecular Indole C2‐Allylation

“…Consistent with the innate reactivity of indoles, intermolecular asymmetric allylation of the C3‐position of indole is a well‐established process . The analogous N1‐allylation is relatively less well‐explored, although there exist various innovative methods for this recently developed by the groups of Hartwig, You, Krische and others . To the best of our knowledge, there are no methods capable of directly allylating indole at the C2‐position in an enantioselective, intermolecular fashion.…”