Alkenyl pyridines, reduction

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

Alternatively, boronic acids react under the influence of Cu-catalysis with electrophilic iV-thioimides under mild conditions and in the absence of base (Eqn. 1-7). Various copper carboxylates can be used (e.g., CuMeSal, CuTC, and CuOAc) but not salts such as CuCl, CuCN, or CU2O. A presumed Cu(I)/Cu(III) cycle is put forth, where the thioimide is oxidatively added to the Cu(I) catalyst, and the RB(0H)2 supplies the R group on the metal (with loss of imide-B(OH)2) prior to reductive elimination. Several biaryl thioethers were made in this way (e.g., 85,86) in THF (or dioxane), along with aryl alkenyl derivative 87. All bases examined (K2CO3, NaOH, TBAF, pyridine, EtsN) inhibited the reaction. 

A rhodium-catalyzed one-pot synthesis of substituted pyridine derivatives from a,(3-unsaturated ketoximes and alkynes was developed in 2008 by Cheng and coworkers [99], Good yields of the desired pyri-dines can be obtained (Scheme 3.48). The reaction was proposed to proceed via rhodium-catalyzed chelation-assisted activation of the (3—C—H bond of a,(3-unsaturated ketoximes and subsequent reaction with alkynes followed by reductive elimination, intramolecular electro-cyclization, and aromatization to give highly substituted pyridine derivatives finally [100]. Later on, in their further studies, substituted isoquinolines and tetrahydroquinoline derivatives can be prepared by this catalyst system as well [101]. Their reaction mechanism was supported by isolation of the ort/jo-alkenylation products. Here, only asymmetric internal alkynes can be applied. 

With Zn Lewis acids, only single a-insertion of alkynes (—> 42) is observed, while with AlMes double alkenylation (— 43) dominates. It is proposed that oxidative Ni(0) insertion to the 2-CH bond, hydronickelation of the triple bond, alkenyl transfer to C-2 of the pyridine, and reductive Ni-elimination are the decisive steps in the catalytic cycle, (d) The pyridyl residue may serve as a directing group in C-H insertion reactions of phenyl substituents at pyridine mediated by transition metals like Cu and Pd. For instance, 2-phenylpyridine can be regioselectively halogenated, acetoxylated, and cyanided (- products 44, 45, and 47) in the presence of Cu(OAc)2 [92] or amidated — 46) in the presence of Pd(OAc)2 [93] ... 

An excess amount of pyridine (3 equiv) reacts with 4,4-dimethyl-2-pent)uie to provide the olefinated product in 87% yield with high regio- and stereoselectivities (E/Z >99 1). Here, diphenylzinc is a Lewis acid catalyst (20 mol %), and its role is thus different compared with the aforementioned arylation procedure where it acts as an aryl donor. The in situ activation of pyridine by a Lewis acid, such as diphenylzinc, is an operationally practical strategy toward C2 olefinated pyridines. This avoids the less practical classical alternative that involves a three-step procedure (i) activation of pyridine using stoichiometric oxidant to form pyridine IV-oxide, (ii) nickel-promoted alkenylation, and (iii) stoichiometric reduction of the V-oxide. ... 

In 2008, our group disclosed a novel method that involved the one-pot synthesis of multisubstituted pyridines 92 by Rh-catalyzed oxime-assisted alkenyl C-H bond functionalization of a, -unsaturated oximes with alkynes [48]. The scope includes a variety of a, -unsaturated oximes and symmetrical alkynes. This report is one of a few examples of Rh(I)-catalyzed alkenyl C-H bond functionalization. The mechanism is thought to occur by oxime-directed oxidative insertion of the Rh catalyst into the alkenyl C-H bond to form the hydrometalacycle LI. Hydrorhodation onto the alkyne then occurs to give L2, followed by reductive elimination to provide L3. Intermediate L3 can undergo a 6. r-electrocyclization and then a dehydration reaction to form pyridine (Eq. (5.89)). Overall, this Rh(I)-catalyzed reaction is a redox neutral. 

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