Indolopyridines

Takayama H et al. (2003) Gluco-indole alkaloids from Nauclea cadamba in Thailand and transformation of 3alpha-dihydrocadambine into the indolopyridine alkaloid, 16-carbomethoxynaufoline. Chem Pharm Bull (Tokyo) 51(2) 232-233... 

Numerous stannanes have been coupled with halopyridines as electrophiles in the Stille coupling. One of the simplest of these is vinylstannane [82-84]. The Stille reaction of bromopyridine 95 with tributylvinyltin gave angustine (96) [84], an indolopyridine alkaloid. Bromopyridine 95 also took part in a three-component carbonylative-Stille coupling sequence to provide an entry to another indolopyridine alkaloid, naucletine (97) [84]. 

An alternative route for installing a methyl ketone is the three component carbonylative-Stille coupling with tetramethyltin. An indolopyridine alkaloid, naucletine (58), was prepared using such a sequence from pyridyl bromide 57 <95CC1675>. 

Azalene salts 90 and 92 are obtained by quaternization of the corresponding heterocyclic bases with alkyl halides or tosylates. If the heterocyclic base contains several nitrogen atoms, alkylation can produce different quaternary salts. Quaternization, however, is surprisingly selective if certain conditions are met.205 Pyrrolo- and indolopyridines containing one pyridine-and one pyrrole-type nitrogen atom in their molecular lattice are (in aprotic solvents) almost exclusively alkylated at the nitrogen atom of the pyridine... 

Acid chlorides 21 and chloroformates 23 are the most commonly used activating agents and the preferred reagents for evaluating the reactivity of other components in new Reissert-type processes. For example, in studies on the total synthesis of the indolopyridine alkaloids 42, acetyl chloride was used in the key step to prepare the common synthetic intermediate 41. In this case, an enamide moiety intramole-cularly attacks the in situ generated Ai-acylazinium salt, and the Reissert adduct is spontaneously oxidized and hydrolyzed to regain aromaticity in the last step (Scheme 7) [44, 45]. 

Scheme 7 Synthesis of indolopyridine alkaloids based on a Reissert-type process...

Iminyl radicals, generated by microwave irradiation of ( -phenyl oxime ethers such as 224, cychzed onto the indole 2-position to afford indolopyridine derivatives (225) [117]. The most likely pathway involves a 6-endo cyclization and was further exploited into a formal synthesis of neocryptolepine from gramine in five steps. 

H-benzo[d,f] [l,3]diazepines dibenzo[b,g]-l,8-naphthyridines imidazoles (glyoxalines) imidazo [1,2-a] pyridines indolopyridines 12H-indolo[2,3-a]pyridocoli-nium rings... 

The thermal cyclization of the indolyl oxime esters 320 at 650 °C to form indolopyridines 321 proceeds by a series of electrocyclic processes with loss of acetic acid (Scheme 64 2008JOC8124). Access to the isomeric indolopyridones 323 and 325 is conveniently achieved, respectively, by high-temperature FVP of the indolylacrylate 322 and low-temperature FVP of the indolinylacrylate 324 through tungsten oxide to bring about aromatization (2009S2171). 

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