2-Pyridinyl directing groups

Reaction of N-(2-pyridinyl)piperazines with CO and ethylene in the presence of a catalytic amount of Rh4(CO)12 in toluene at 160°C results in a complicated carbonylation reaction, which involves dehydrogenation and carbonylation at a C-H bond (Eq. 29) [43]. In this reaction, the carbonylation proceeds at the C-H bond a to the nitrogen atom substituted by pyridine. It is found that the reaction involves two discrete reactions (a) dehydrogenation of the piperazine ring and (b) carbonylation at a C-H bond in the resulting olefin. An amide functionality can also serve as the directing group for carbonylation at the a C-H bond (Eq. 30) [44]. 

Scheme 25 Ru-catalyzed C2-arylation/alkylation of pyrrolidines and piperidines substituted at nitrogen with a 2-pyridinyl or 3,4-dihydro-2H-pyrrol-5-yl directing group and removal protocols (2006JA14220, 2013JOC9803).

Carretero used a (2-pyridinyl)sulfonyl directing group to achieve efficient palladium-catalyzed C2-alkenylation of IH-indoles and 1 H-pyrroles (117 — 118) with aUcenes as reagent (2009AGE6511) (Scheme 57). High regjoselectivity was obtained with the (2-pyridinyl)sulfonyl moiety on... 

Direct etherification via C—H activation is rarely documented, especially on heterocycles. Shi used an N-(pyridinyl-2-yl)isopropylcarboxamide as directing group for the direct methoxylation of heteroarenes including pyridines, pyridazines, and thiophenes (137 138) (Scheme 69)... 

A Rh(I) catalyst has likewise been found to promote cross-coupling between readily available benzoic acids as arylating agents and arenes bearing N-based directing groups such as pyridinyl, heteroaryl, and iminyl moieties (Scheme 22.34). The process involves the intermediacy of a mixed anhydride formed in situ by the reaction between the benzoic acid and (f-BuCO)jO [49]. 

Recently, the same type of arylation of benzylamine derivatives equipped with a 2-pyridinyl directing group was carried out with aryl halides but with the ruthenium(II) catalyst precursor ([RuCl2(p-cymene)]2) in the presence of potassium pivalate [19, 20] or directly with Ru(carboxylate)2(p-cymene) [21]. Both catalytic systems operate at 140°C for 24 h in toluene or o-xylene in the presence of 2.5-5 mol% catalyst loading and a carbonate as a base. The advantage of using the well-defined ruthenium(II)bis(carboxylate) complex is that it does not require an excess of carboxylate as it is the case with the in situ generated catalytic system. 

Phosphoramidation of the arene (5) C-H bonds with phosphotyl azides (6) has been realised in the presence of an iridium catalyst. This reaction was compatible with several directing groups such as pyridinyl, pyrazoyl, and quinolinyl, and provided AT-atyl phosphoramidates (7) in moderate to good yields (Scheme 3). ... 

Scheme 69 Cu-catalyzed methoxylation of heteroarenes directed by an A/-(pyridinyl-2-yl)isopropylcaboxamide amide group.

A Rh(m) complex was found to catalyze selective C-C bond activation in secondary aryl alcohols, which in the presence of olefins afforded C-C coupling Mizoroki-Heck products [28]. This unprecedented strategy was directed by a pyridinyl group that favored P-C elimination. Secondary alcohols (but not primary) bearing both aryl and aliphatic gronps underwent P-C... 

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