Ir-catalyzed intermolecular asymmetric allylic dearomatization reaction of indoles

Abstract

An Ir-catalyzed intermolecular asymmetric dearomatization reaction of substituted indoles with allylic alcohols has been realized to afford the corresponding indoline derivatives in 71-97% yield with up to 98% ee in the presence of the Lewis acid Fe(OTf) 2 . This methodology features the enantioselective construction of all-carbon quaternary stereogenic centers of prochiral nucleophiles and its utility has been demonstrated in the asymmetric total synthesis of (À)-debromoflustramine B.Scheme 1 Ir-catalyzed asymmetric allylic substitution reactions.

Copper‐Catalyzed Intermolecular Asymmetric Propargylic Dearomatization of Indoles

“…Thes ubstrate with a meta-substituent tends to give slightly lower yield and enantioselectivity (entry 8). Propargylic acetates bearing 1-naphthyl, 2-naphthyl, 2-furyl, and 2-thienyl groups were compatible with the transformation (entries [9][10][11][12]. Theh ighest ee value was obtained when the cinnamyl derivative 2m was used (98 % ee;e ntry 13).…”

“…[9] Recent elegant reports revealed that the copper allenylidene complexes are the key intermediates of the copper-catalyzed asymmetric propargylic substitution reactions. [11] Given our ongoing efforts towards the development of catalytic asymmetric dearomatization (CADA) reactions [12] and inspiration by recent rapid development of this field, [13] we envisioned that acopper-catalyzed asymmetric propargylic dearomatization of N-substituted tryptophol and tryptamine derivatives,i ncluding ap ropargylic substitution reaction and as ubsequent cyclization, would afford furoindolines and pyrroloindolines,r espectively (Scheme 1). [11] Given our ongoing efforts towards the development of catalytic asymmetric dearomatization (CADA) reactions [12] and inspiration by recent rapid development of this field, [13] we envisioned that acopper-catalyzed asymmetric propargylic dearomatization of N-substituted tryptophol and tryptamine derivatives,i ncluding ap ropargylic substitution reaction and as ubsequent cyclization, would afford furoindolines and pyrroloindolines,r espectively (Scheme 1).…”

“…After evaluation of several other commercially available chiral ligands (entries 2-7), the chiral tridentate PYBOX L5 was found to be optimal, thus providing 3aa in 58 %y ield and 58 % ee (entry 5). Propargylic acetates bearing 1-naphthyl, 2-naphthyl, 2-furyl, and 2-thienyl groups were compatible with the transformation (entries [9][10][11][12]. [14] By lowering the reaction temperature,t he diastereoselectivity and enantioselectivity were improved significantly at the expense of the yield at ap rolonged reaction time (entries 8-10).…”

“…[10] Despite these achievements,t he copper-catalyzed asymmetric propargylic substitution reaction with prochiral carbon nuleophiles remains rare.T oo ur knowledge,t he asymmetric propargylic dearomatization reaction has not been reported. [11] Given our ongoing efforts towards the development of catalytic asymmetric dearomatization (CADA) reactions [12] and inspiration by recent rapid development of this field, [13] we envisioned that acopper-catalyzed asymmetric propargylic dearomatization of N-substituted tryptophol and tryptamine derivatives,i ncluding ap ropargylic substitution reaction and as ubsequent cyclization, would afford furoindolines and pyrroloindolines,r espectively (Scheme 1). Herein, for the first time we report the copper-catalyzed intermolecular dearomatization of indoles through ap ropargylic substitution reaction.Our initial attempt was launched with the reaction of Nmethyl tryptophol (1a)w ith the propargylic acetate 2a in Figure 1.…”

Pd-catalyzed cascade allylic alkylation and dearomatization reactions of indoles with vinyloxirane

“…Recently, we have developed a Ru-catalyzed 9 intermolecular dearomatization of indoles with allylic alcohols via a cascade sequence including the allylic dearomatization/cyclization/allylic amination reaction. In addition, we realized an iridium-catalyzed 10 intermolecular allylic dearomatization reaction of substituted indoles using the Carreira ligand and Fe(OTf ) 2 as an additive.…”