Pyridines using transition metal intermediates

Heteroatom-directed C(sp )-H bond fimctionalizalion with stoichiometric transition metals was first disclosed in 1984 [1]. In 2002, Sames and coworkers developed an efficient route to constmct the teleocidin B4 core via the activation of C(sp )-H bond to prepare two diastereomeric paUadacycle key intermediates [2]. As a follow-up work, Ru3(CO)i2-catalyzed arylation of various C(sp )-H bonds with arylboronate esters using pyridine, pyrimidine, and amidine as directing groups was reported (Scheme 1.1) [3]. The use of ketones as solvent was necessary for a successfid arylation, mainly due to the trapping effect of the ruthenium hydride species. Despite of its efficiency, this transformation needs elevated temperatures (150 °C). Further, pyridine-directed a-C(sp )-H arylation of piperidines with arylboronate esters was developed with alcohols as solvent [4]. 

Based on these precedents for C—X bond formation between C=N and alkene intermediates (derived from alkynes), the Larock group developed the first transition-metal-mediated pyridine ring formation by direct reaction between C=N and alkynes. Using terminal alkynes 11, rcrt-butylimines 10 were subjected to Sonogashira coupling followed by Cu(I)-catalyzed annulation to afford isoquinolines or pyridines 12 in moderate to good yields (46 to 95%, Scheme 19.5) [5]. A variety of terminal alkynes and aryl/alkenyl halides can be used in the reaction. The stepwise reaction also worked well to form the same products. Similarly, p- and y -carbolines were synthesized effectively, as shown in Scheme 19.6 [6]. 

Electron-deficient as well as electron-rich aryl boronic acids proved to be competent partners in the reaction, but electron-deficient boronic acids required higher temperatures. Boronic acids containing aryl halides (I, Cl) were also competent partners, providing a functional handle for further elaboration. Both primary and secondary amines have been utilised as coupling partners. A limitation of this chemistry is the inability to use nitrogen-based heterocycles due to either protodeboronation or the instability of the electron-poor sulfonyl chloride intermediate. Buchwald and coworkers later found that pyridylzinc reagents could be coupled with 2,4,6-trichlorophenyl chlorosulfate (TCPC) to access pyridine sulfonates without a transition metal catalyst." The pyridine sulfonates were subsequently treated with amines to generate sulfonamides. 

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