Synthesis of N‐Fused Tricyclic Indoles by a Tandem [1,2] Stevens‐Type Rearrangement/1,2‐Alkyl Migration of Metal‐Containing Ammonium Ylides

Abstract

We reported previously that novel metal-containing carbonyl or azomethine ylides could be generated by the nucleophilic attack of a carbonyl oxygen atom or imino nitrogen atom onto alkynes activated by electrophilic transition-metal complexes. The resulting species, which behave as both ylides ([3+2] cycloaddition) and carbene complexes (e.g. C À H insertion, 1,2-H or 1,2-alkyl shift), can be used as intermediates for the efficient preparation of synthetically useful, polycyclic compounds.[1] To expand the concept of metal-containing ylides, we have examined the generation and reaction of a newly designed metal-containing ammonium ylide, [2] which would enable concise access to a variety of polycyclic indoles with an N-fused ring. A recent report by Zhang and co-workers on a Pt-catalyzed reaction of N-(2-alkynylphenyl)lactams [3] prompted us to report our own approach, in which the main difference is the use of N-(2-alkynylphenyl)amines instead of lactams as the nucleophilic component. This transformation requires the use of [W(CO) 6 ] or [ReBr(CO) 5 ] as the alkynophilic reagent.The underlying strategy for the catalytic process described herein is depicted in Scheme 1: Upon the treatment of o-alkynylphenyl pyrrolidine or piperidine derivatives 1 with an appropriate electrophilic transition-metal complex, metalcontaining ammonium ylides A would be generated by the nucleophilic attack of the nitrogen atom onto the electrophilically activated alkyne moiety. Ylides A would then undergo ring expansion through a [1,2] Stevens-type rearrangement [4] to give carbene complexes B, which would undergo subsequent 1,2-alkyl migration to form N-fused tricyclic indole derivatives 2 with regeneration of the catalyst.After extensive screening of transition-metal catalysts and reaction conditions with N-(2-(prop-1-ynyl)phenyl)pyrrolidine (1 a) as the substrate, we found that the photoirradiation of a solution of 1 a and [W(CO) 6 ] (10 mol %) in toluene in the presence of 5-molecular sieves at room temperature gave the desired tricyclic indole derivative 2 a in 65 % yield (Table 1, entry 1). Photoirradiation was crucial for the efficient generation of the unsaturated tungsten species; the reaction under thermal conditions (toluene, 80 8C) resulted in lower conversion even with 300 mol % of [W(CO) 6 ] ( Table 1, entry 2).Careful analysis of the product by 2D NMR spectroscopy confirmed the formation of a tricyclic indole system with an N-fused six-membered ring and a methyl substituent at the 3 position of the indole nucleus. This result supported the validity of our original strategy. [5,6] Other metal catalysts, such as PtCl 2 , PtCl 4 , [AuPPh 3 ]SbF 6 , AuBr 3 , and [{IrCl(cod)} 2 ], were found to be inactive for this transformation under thermal or photoirradiation conditions, probably as a result of deactivation of the catalyst through strong coordination of the amine Scheme 1. Strategy for the generation of a metal-containing ammonium ylide and its tandem [1,2] Stevens-type rearrangement/1,2-alkyl migration. Table 1: Examin...

Transition Metal‐Catalyzed Synthesis of Fused Five‐Membered Aromatic Heterocycles

“…A somewhat similar double 1,2-migration cascade transformation of N,N-disubstituted o-alkynylanilines 154 was recently disclosed by Iwasawa (Scheme 9.58) [218]. 149 Furthermore, Yamamoto and coworkers illustrated that o-(alkynyl)phenylisocyanates 159 could also be efficiently employed in a similar Pt(II)-catalyzed cycloisomerization reaction, serving as surrogates of the corresponding carbamate derivatives 160, to provide N-(alkoxycarbonyl)indoles 161 in moderate to excellent yields (Scheme 9.60) [219].…”

The [4+2], not [2+2], Mechanism Occurs in the Gold‐Catalyzed Intramolecular Oxygen Transfer Reaction of 2‐Alkynyl‐1,5‐Diketones

“…These intermediates undergo both intermolecular and intramolecular cycloadditions to carbon-carbon multiple bonds, to give myriad products of synthetic importance. [1,[2][3][4][5][6][7][8][9][10] Recently, we developed a convenient approach to 2-alkynyl-1,5-dicarbonyl derivatives, 1, from the Michael addition of activated allenes to electron-deficient olefins.[11] We envisioned that if a furanium intermediate [12] (Scheme 2) could be generated from the alkynylketone 1 containing a quaternary propargylic carbon, then the usual path A [12] would be blocked, leaving path B to engender novel transformations of the oxonium intermediate.We have now found that after only 5 min at room temperature, using gold catalysis, [13,14] 2-alkynyl-1,5-diketone 1 a furnished cyclopentenylketone 2 a-an intramolecular oxygen transferred product-in excellent yield (Scheme 3, top).Of special interest is the oxygen transfer from a carbonyl group to a carbon-carbon triple bond through an oxonium intermediate, also known as alkyne-carbonyl metathesis. [15] This has also been showcased in Yamamoto and co-workers recent papers on gold or TfOH-catalyzed intramolecular oxygen transfer of w-alkynylketones to the corresponding cyclic enones (Scheme 3, bottom).…”

Target cum Flexibility: Synthesis of Indolo[1,2-b]isoquinoline Derivatives via Cobalt-Catalyzed [2+2+2] Cyclotrimerization

“…10 In 2007, Sanz and coworkers reported double lithiation of N-benzylindole derivatives and subsequent addition to an ester. 11 Very recently, Wolfe and co-workers reported an intramolecular palladium-catalyzed alkene carboamination reaction of substituted anilines.…”