Hydrogenation with 1,4-dihydropyridines

Interestingly, 5-azaindole resists atmospheric-pressure hydrogenation with Adams catalyst in acidic medium. Also, 7-azaindole and its 1-ethoxycarbonyl derivatives are recovered from treatment with lithium aluminum hydride. This reagent readily reduced the dihydropyridine ring of 6,7-dihydro-4-methyl-7-azaindole to the corresponding 4,5,6,7-tetrahydro compound in 83% yield. ... 

According to one mechanistic interpretation, a hydrogen with a pair of electrons is transferred from ethanol to NAD, forming acetaldehyde and converting the positively charged pyridinium ring to a dihydropyridine ... 

Diacetylpyridine hydrogenated with Pd-on-charcoal in ethanol until 1 mole Hg has been absorbed 3,5-diacetyl-l,2-dihydropyridine. Y 70%. U. Eisner, Chem. Commun. 1969, 1348. 

Side-chain bromination of diethyl 2,7-dimethyl-41/-azepine-3,6-dicarboxylate (3) with bromine in carbon tetrachloride is accompanied by ring contraction to the 1,4-dihydropyridine 42, brought about by the liberated hydrogen bromide.29... 

Officially, the history of MCRs dates back to the year 1850, with the introduction of the Strecker reaction (S-3CR) describing the formation of a-aminocyanides from ammonia, carbonyl compounds, and hydrogen cyanide [4]. In 1882, the reaction progressed to the Hantzsch synthesis (H-4CR) of 1,4-dihydropyridines by the reaction of amines, aldehydes, and 1,3-dicarbonyl compounds [5], Some 25 years later, in 1917, Robinson achieved the total synthesis of the alkaloid tropinone by using a three-component strategy based on Mannich-type reactions (M-3CR) [6]. In fact, this was the earliest application of MCRs in natural product synthesis [7]. 

Recently, we established that several proton acids catalyze the metal-free reduction of ketimines under hydrogen-transfer conditions with Hantzsch dihydropyridine as the hydrogen source.Additionally, we were able to demonstrate a catalytic enantioselective procedure of this new transformation by employing a chiral Br0nsted acid as catalyst.(see Chapter 4.1). 

The Brpnsted acid catalyzed hydrogenation of quinolines with Hantzsch dihydropyridine as reducing agent provides a direct access to a variety of substituted tetrahydroquinolines (Table 4.2). The mild reaction conditions of this metal-free reduction of heteroaromatic compounds, high yields, operational simplicity and practicability, broad scope, functional group tolerance and remarkably low catalyst loading render this environment-friendly process an attractive approach to optically active tetrahydroquinolines and their derivatives (Table 4.3) (see page 176). ... 

The acidic hydrogen atoms in the side chain of alkylpyridines may interfere with the formation of o-adducts. Thus 4-isopropylpyridine reacts with phenyllithium in THF to yield a mixture of the 2-adduct 90 and l-lithio-4-(2-propyliden)-l,4-dihydropyridine (91). However, alkyllithiums, such as BuLi, (-BuLi, and MeLi, mainly yield the related 2-adducts 92.136... 

A one-step synthesis of furo[3,2-c]- and furo[3,2-6]-pyridines has been realized using a cycloaddition reaction of an alkynic compound with 3,5-dichloropyridine 1-oxide (Scheme 15) (75JA3227). Formation of (75) probably proceeds through a 1,2-dihydropyridine (73) with a subsequent 1,5-sigmatropic shift to (74) elimination of hydrogen chloride yields... 

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