Palladium(II)‐Catalyzed Efficient C‐3 Functionalization of Indoles with Benzylic and Allylic Alcohols under Co‐Catalyst, Acid, Base, Additive and External Ligand‐Free Conditions

Abstract

The bis(acetonitrile)palladium(II) chloride complex, PdCl2(MeCN)2, efficiently catalyzes the regioselective alkylation of indoles with various benzylic and allylic alcohols under moisture and air insensitive conditions. Notably the reaction does not require any other co‐catalyst, acid, base, additive, or external ligand.

σ–π Continuum in Indole–Palladium(II) Complexes

“…In contrast, the molecular structure of 4‐Me ( C ; Figure ) showed the σ/π(η 1 ‐C)‐intermediate‐mode, where d N−C2 (1.362(7) Å) and d C2−C3 (1.390(7) Å) in 4‐Me resembled that of the free N ‐methylindole than to that of the free N ‐methylindolium, reflecting the decrease of σ‐character and increase of π‐character. Against the previous assumption that σ(η 1 ‐C)‐mode is involved in a neutral indole–palladium complex, the coordination of indole or N ‐benzylindole in the neutral complex 5‐H or 5‐Bn was in the η 2 ‐mode ( F ; Figure ); that is, d Pd−C2 =2.416(8) Å, d Pd−C3 =2.155(7) Å for 5‐H ; d Pd−C2 =2.447(3) Å, d Pd−C3 =2.156(4) Å for 5‐Bn . Within the η 2 ‐mode, the indole ligands showed the σ/π‐intermediate‐character, where d N−C2 (1.344(4) Å) for 5‐Bn is longer than that in 3‐Me and shorter than that in 4‐Me (Scheme )…”

“…However, repeated evaporation from 1,2‐dichloroethane resulted in the shift of equilibrium to the indole–palladium adduct 4‐Me by removal of free CH 3 CN, yielding 4‐Me . The neutral Zeise‐dimer‐type complex of indole [Pd(indole)Cl 2 ] 2 ( 5‐H ) or of N ‐benzylindole [Pd( N ‐benzylindole)Cl 2 ] 2 ( 5‐Bn ) was isolated by treatment of PdCl 2 (CH 3 CN) 2 with the corresponding indole in CH 2 Cl 2 …”

Rapid Assembly of Functionalised Spirocyclic Indolines by Palladium‐Catalysed Dearomatising Diallylation of Indoles with Allyl Acetate

“…General procedure J: Synthesis of spirocyclic indolines (17) The corresponding substituted 3,3-diallyl-2-hydroxyindoline compound was added to a refluxing solution of first generation Grubbs' catalyst (15 mol %) in CH 2 Cl 2 (ca. 0.04 mol L À1 ) under argon.…”

“…Our synthetic plan involved the development of a Pd-catalysed allylation procedure to achieve regioselective introduc-tion of the allyl groups in a dearomatising reaction, to generate the desired isoindolinine. Whilst there is good precedent for the Pd-catalysed allylation of indoles with a range of allyl sources, [14][15][16][17][18] and even for the dearomatising allylation of 3substituted indoles with allyl carbonates, with allyl alcohols in combination with organoboranes [15] or by rearrangement of Nalloc protected indoles, [14,[19][20][21][22] the direct use of allyl acetate in such reactions has proved challenging to date. [23] Although highly activated allylic esters containing two conjugated aromatic rings can be successfully used in Pd-catalysed allylation reactions, [24] there is only a single report of the Pd-catalysed reaction of indole 1 a with allyl acetate 2, and the reaction was reported to produce a relatively complex mixture of N and C allylated products 3 a-6 a from which 3-allylindole 4 a was isolated in up to 54 % yield.…”

Additive-Free Pd-Catalyzed α-Allylation of Imine-Containing Heterocycles

“…3 Apart from CH-activated direct allylation of aromatic heterocycles, activation of C-sp 3 pronucleophiles for the formation of C–C bonds in classical allylic alkylations requires addition of bases or in situ generated bases or additives 4 and can only be circumvented in rare cases without additives. 5 …”