Pyridines, 2-alkyl catalytic synthesis

Transition metal complexes have been used in a number of reactions leading to the direct synthesis of pyridine derivatives from acyclic compounds and from other heterocycles. It is pertinent also to describe two methods that have been employed to prepare difficultly accessible 3-alkyl-, 3-formyl-, and 3-acylpyridines. By elaborating on reported194,195 procedures used in aromatic reactions, it is possible to convert 3-bromopyridines to products containing a 3-oxoalkyl function196 (Scheme 129). A minor problem in this simple catalytic process is caused by the formation in some cases of 2-substituted pyridines but this is minimized by using dimethyl-formamide as the solvent.196... 

Catalytic C-C bond formation via sp- C-H bond cleavage represents the ultimate reaction in organic synthesis. A relatively ideal catalytic reaction system involves the use of sp3 C-H bonds adjacent to a heteroatom such as nitrogen and oxygen atoms. Recently, Jim et al. [69] succeeded in the Ru3(CO)12-catalyzed alkylation of an sp3 C-H bond a to the nitrogen atom in benzyl-(3-methyl-2-pyridinyl)amine by means of chelation assistance (Eq. 43). In this case, the coordination of the pyridine nitrogen to the ruthenium complex followed by C-H... 

In an adaptation of the reaction to the synthesis of pyridines, a Japanese group associated with Stork5 found that alkylation of a ketone such as acetylacetone with the reagent gives (1), which on catalytic hydrogenation in the presence of palladium... 

Reviews on catalytic uses of DMAP and other 4-(dialkylamino)pyridines have appeared [9]. These bases are very efficient reagents for acylations, alkylations, silylations, phosphorylations, condensations, and transesterifications [ 10]. More recent applications of DMAP as a catalyst include a parallel synthesis of benzyl purine derivatives [11] and it has been employed as a base in the asymmetric synthesis of an amino acid via an auxiliary [12]. Uses of DMAP tethered to solid supports (of which one such example is commercially available) have been reviewed [10,13]. Such a system has recently been employed to synthesize multiple oligonucleotides linked end to end in tandem [14]. 

In 2012, Maes and co-workers reported a new transition-metal-catalyzed methodology for the direct C2-H functionalization of piperidines [67], via pyridine-directed Ru-catalyzed C(sp )-H alkylation with alkenes [68]. Based on previous work [69-73], they discovered that a combination of a bulky alcohol (2,4-dimethyl-3-pentanol) and a catalytic amount of a carboxylic acid [74] is necessary to avoid side reactions such as isomerization and/or reduction of the alkene reactant (Scheme 11). They successfully applied this method to the total synthesis of ( )-... 

As described in the preceding sections, we already had experience on the enantioselective alkylation of aldehydes with dialkylzincs and the enantioselective synthesis of 3-pyridyl alkanol. In 1990, we found the first asymmetric autocatalysis of (5)-3-pyridyl alkanol 6 in the enantioselective addition of i-Pr2Zn to pyridine-3-carbaldehyde 7 to produce more of itself of 35% ee with the same S configuration (Scheme 6) [24]. Although the ee of product 6 decreased compared to that of the initial catalyst, the newly formed predominant enantiomer of the product is the same with that of asymmetric autocatalyst 6. We claim that this is the first asymmetric autocatalysis, that is, catalytic replication of chiral compound with the generation of new stereogenic centers. 

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