C-SP Bond Formation

Scheme 36 Iron-catalyzed C sp )-C sp ) bond formation through C sp )- functionalization...

During the past years this method has been used successfully in modern biaryl synthesis, with several groups having shown its potential for C(sp )-C(sp )-bond formation [35], Heteroarenes such as substituted pyrroles, indoles, pyridones and imidazoles can act as radical acceptors in these processes [36], In addition, aryl bromides, chlorides and iodides have been used as substrates in electrochemically induced radical biaryl synthesis [37]. In a series of elegant studies, Harrowven recently applied the tin hydride-mediated radical biaryl synthesis to the preparation of helicenes [38], These reactions comprise a double C(sp )-C(sp )-bond formation an example-the impressive transformation of diiodide 10 to [7] helicene 11-is presented in Scheme 13.4. 

The tin hydride-mediated C(sp )-C(sp )-bond formation has successfully been applied as key step in the synthesis of various natural products. Amaiyttidacaea alkaloids [39], glaucine [40], cryptopleurine ]41] and an anticancer benzo]c]phenanthridine alkaloid [42] were each successfully prepared using this approach. 

This difference of affinity between RuH2(CO)(PPh3)3 and Ru3(CO)j2 toward specific functional groups has been exploited in a regioselective, catalyst-specific C(sp )-C(sp ) bond formation through the use of substrates bearing both a ketone and an imine fragment (Scheme 19.58) [79]. 

Hypervalent iodine reagents have successfully been employed in the oxidative functionalization of enolizable carbonyl compounds over the years [6]. This methodology has allowed the construction of diverse C-C bonds in the context of heterocychc synthesis and has enriched the otherwise rare repertoire of such chemistry. Zhao, Du, and coworkers [37] have recendy realized a metal-free PIFA-mediated synthesis of 3-hydroxy-2-oxindoles 34 and spirooxindoles 35 starting from anilide derivatives 33 (Scheme 8 (1)). These processes showcase an oxidative cross coupling between an aromatic carbon and a pendant aliphatic carbon, followed by further oxidative hydroxylation or spirocycUzation. Later, the authors extended the same concept to achieve C(sp )-C(sp ) bond formation, where anilide derivatives possessing terminal enol functionality underwent PIDA-... 

Zhao and Du s group [63] developed a metal-free cross-dehydrogenative coupling (CDC) of various 2-(A -arylamino)aldehydes 79 for direct aryl-aldehyde C (sp )-C(sp ) bond formation to provide a convenient approach for the synthesis of biologically important acridone derivatives 80 (Scheme 19). PIDA was used in combination with a substoichiometric amount of benzoyl peroxide as radical initiator for this oxidative intramolecular annulation reaction which presumably proceeds via the intermediacy of acyl radicals 81. 

Afterwards, Antonchick and coworkers [105] successfully extended this methodology to the oxidative cross coupling of heteroarenes and simple unfunctionalized alkanes (Scheme 40 (1)). The new C(sp )-C(sp ) bond formation occurred selectively at the electron-deficient site of the arene. The reaction was... 

The reaction of Al-methyl-Al-phenylcinnamamides with phenyliodine bis (trifluoroacetate) in the presence of Lewis acids provides 3-arylquinolin-2-ones and involves a metal-free oxidative C(sp )-C sp ) bond formation and a 1,2-aryl migration (Scheme 89). " ... 

Gartia et al. recently described a related coupling of furan with a small range of Grignard reagents using a nickel pincer catalyst 190 (Scheme 5.35). The first example is more properly a case of C(sp )—C(sp ) bond formation, and may be... 

C(sp )—C(sp ) Bond Formation with Preservation of the Chiral Center - Synthesis of (—)-Tetrodotoxln... 

The presence of one chiral center in the starting material should induce the formation of a single atropoisomer of the biarylic system. The iodoaryl 124, prepared in few classic steps, placed in the presence of palladium diacetate, the monophosphine DavePhos and potassium carbonate as base afforded the expected lactam 127 isolated as a single stereoisomer with moderate yield (47%). In a similar manner, the lactam 129, precursor of the rhazinal 123, was obtained after treatment of the iodoaryl 128 in the same reaction conditions. The C(sp )—C(sp ) bond formation was achieved following this suggested mechanism A nucleophilic attack... 

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