C—H bond alkylation

Arene-displacement reactions, characteristics, 1, 97 Arene-ene substrates, in C-H bond alkylation, 10, 218 Arene-ferracarboranes, characteristics, 3, 225-226 I // -Arene liruliiim complexes, preparation, 7, 388 (Arene)metal(diborolyl) sandwiches, synthesis, 3, 12... 

Scheme 5.5 Pd-catalyzed enantioselective C—H bond alkylation reaction reported by Yu.

Scheme 5.46 Rh-catalyzed asymmetric C—H bond alkylation reported by Murai.

In 2008, Shibata and co-workers reported a cationic iridium bidentate phosphine complex catalyzed C—H bond alkylation reaction of 2-methy-lacetophenone with alkynes and alkenes (Scheme 5.61). Compared with alkynes, the use of styrenes as acceptors requires the weakly coordinated tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF) as a counteranion of the iridium complex and a higher temperature to achieve good yields. When a norbornene was used as the acceptor, the sole example of an asymmetric ortho C—H bond alkylation product 175 was obtained in 58% yield and 70% ee. 

Scheme 5.61 Ir-catalyzed C—H bond alkylation reaction of 2-methylacetophenone with norbornene reported by Shibata.

Scheme 5.62 Ir-catalyzed C-H bond alkylation with heteroarenes reported by Hartwig.

Scheme 5.64 Ir-catal) ed asymmetric C—H bond alkylation reactions reported by Shibata.

Despite recent advances in C—H bond functionalization, the enantioselective C—H alkylation of pyridines remains almost unexplored. The only precedent example was reported by Rodewald and Jordan in 1994 using chiral-zircono-cene Cll as the catalyst. The asymmetric C—H bond alkylation of 2-pico-line to 1-hexene was obtained in 19% yield and 58% ee (Scheme 5.71). 

Scheme 19.1 (a-c) Comparing various approaches toward C-H bond alkylation. 

More recently, Ftirstner and coworkers [119] developed a tandem pyridine-directed C-H bond alkylation and cycloisomerization using a cationic rhodium catalyst generated from RhCl(PPh3)3 and AgShF (Scheme 19.83). 

More recently, Yoshikai [135] developed a cobalt-catalyzed chelation-assisted C-H bond alkylation with alkenes. The reaction was initially developed with 2-arylpyridines (Scheme 19.92) [136], The authors demonstrated the influence of the ligand on the reaction, leading selectively to the formation of the linear or the branched product. 

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