Stille coupling indoles

The Suzuki coupling of arylboronic acids and aryl halides has proven to be a useful method for preparing C-aryl indoles. The indole can be used either as the halide component or as the boronic acid. 6-Bromo and 7-bromoindolc were coupled with arylboronic acids using Pd(PPh3)4[5]. No protection of the indole NH was necessary. 4-Thallated indoles couple with aryl and vinyl boronic acides in the presence of Pd(OAc)j[6]. Stille coupling between an aryl stannane and a haloindole is another option (Entry 5, Table 14.3). 

Halogenated pyrroles can serve as the aryl halide in Stille couplings with organotin reagents. Scott has used this idea to prepare a series of 3-vinylpyrroles, which are important building blocks for the synthesis of vinyl-porphyrins, bile pigments, and indoles [77]. Although 3-chloro-and 3-bromopyrroles fail completely or fared poorly in this chemistry, 3-iodopyrroles 101 work extremely well to yield 3-vinylpyrroles 102. 

In a synthesis of polyketides, Kocienski crafted indole 78 from 2-iodo-l-methylindole and the appropriate organozinc reagent 77 derived from the corresponding stannane (76), which itself was reluctant to undergo a Stille coupling [106],... 

Doi and Mori made excellent use of dihydroindole triflate 189 in Pd-catalyzed cross-coupling reactions. This compound was discussed earlier in the Suzuki section, and it also undergoes Stille couplings as illustrated below [140]. A final dehydrogenation completes the sequence to indoles. 

Stille couplings also have been exploited in the synthesis of the aromatic macrocyclic core of diazonamide A (2) [5, 20]. Pattenden s group utilized the Pd-catalyzed coupling between the 3-stannyl substituted indole 23 and the 3-bromooxazole 24 to provide a particularly expeditious route to the ring system 25 [20]. In addition, Harran s group secured the connection between bromooxazole 12 and vinylstannane 26 also using a Stille coupling [5]. 

Recently, Li successfully conducted the Suzuki and Stille reactions on the pyrazine ring of 3-bromoquinoxalin-2-ylamines [51]. Indolylquinoxaline 92 was obtained from the union of 3-bromoquinoxalin-2-ylamine 90 and l-phenylsulfonyl-2-tri-n-butylstannyl-l//-indole (91). A wide variety of heterocyclic stannanes bearing various functional groups underwent Stille coupling with 90 under the same conditions to give the corresponding adducts in 72-98% yields. 

An excellent example of the formation of a six membered ring is the hexabutyldistannane mediated ring closure of the brominated indole derivative shown in 4.1. The first step of the process is the palladium catalyzed exchange of one of the bromines to a tributylstannyl moiety, followed by the closure of the six membered ring in a Stille coupling.1... 

The formation of seven membered heterocycles and larger rings through cross-coupling reactions is quite rare (except for some macrocyclic natural products). An example of such a process is presented in 5.1. The intramolecular Stille-coupling of the tributylstannyl-indole and vinyl bromide moieties led to the formation of a seven membered ring in good yield.1... 

The bromo derivative of A -mcthylsuccinimide did also undergo Suzuki coupling when treated with naphthylboronic acid in the presence of palladium acetate, triphenylphosphine and potassium carbonate (6.3.). The coupled product was deprotected under the reaction conditions and an indole derivative was isolated in good yield, which was successfully converted into the hexacyclic naphthopyrrolo[3,4-c]carbazole structure. Using the analogous trimethylstannyl-naphthalene derivative and optimised Stille coupling conditions the desired product was isolated only in 56% yield.5... 

C-Arylation of indoles can be accomplished by means of palladium-catalyzed coupling reactions, such as the Suzuki coupling (Entry 7, Table 15.7) or Stille coupling with resin-bound 2-bromoindoles [88] or 5-bromoindoles [75]. 2-Iodoindoles have been prepared on polystyrene by iododesilylation of 2-silylindoles with NIS (Entry 8, Table 15.7), and these can be C-arylated with arylboronic acids [73]. 

The fused indoles 91 (n = 1-3) have been synthesized by Stille coupling of the stannylbenzene 92 with 2-iodo-2-enones 93, followed by intramolecular palladium-catalyzed... 

A new synthesis of 3-alkoxyindoles, for example compound 535, has been elaborated involving a Stille-coupling and a reductive annulation as outlined in Scheme 72 <2006T10829>. It has also been shown that related methodology may be useful for preparation of tetrahydrocarbazoles and related tricyclic indole systems <2007T1183>. 

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