Synthesis of Pyridines from Ketoximes and Terminal Alkynes via C–H Bond Functionalization

Abstract

An expedient one-pot rhodium catalyzed C–H bond functionalization/electrocyclization/dehydration procedure has been developed for the synthesis of highly substituted pyridine derivatives from terminal alkynes and α,β-unsaturated ketoximes. The use of electron deficient phosphite ligands is important to suppress dimerization of the terminal alkynes to enynes.

An Alkyne Diboration/6π‐Electrocyclization Strategy for the Synthesis of Pyridine Boronic Acid Derivatives

“…Thes ynthesis of pyridines through 6p-electrocyclization reactions represents an interesting and alternative means for the bespoke synthesis of this class of heterocyclic intermediates,a nd the reaction is compatible with ar ange of common functional groups such as esters,a ldehydes,a nd ethers. [5,6] Importantly,i nt he context of boronic acid derivatives,w e envisaged that we could take advantage of catalytic diborylation methodology [7] to transform readily available yne-eneoximes into pyridine boronic esters.A ss hown in Scheme 1, central to our objective was the activation of the alkyne substrate towards electrocyclization whilst simultaneously incorporating useful functionality.M oreover,w ee xpected that this process would selectively eliminate only one of the two boronic ester moieties;t hereby obviating the common problem of differentiating between the two boronate units generated by diboration chemistry. [8] Thesubstrates for this study were readily prepared in two steps from 2-bromo aryl aldehydes by Sonogashira coupling and condensation with O-methylhydroxylamine.…”

Synthesis of Highly Substituted Pyridines through Copper‐Catalyzed Condensation of Oximes and α,β‐Unsaturated Imines

“…In the above context, oxime derivatives have emerged as readily accessible and versatile starting materials for the transition‐metal‐catalyzed synthesis of pyridines as well as many other nitrogen‐containing heterocycles owing to the ability of the oxime functionality to undergo reductive N−O bond cleavage and/or to serve as a directing group for C−H activation . While α,β‐unsaturated oxime derivatives have been employed as C3N1 units for pyridine synthesis using alkenylboronic acids, alkynes,– or alkenes, as C2 reaction partners, oxime acetates bearing α‐protons have also found a use as C2N1 units for pyridine synthesis (Scheme a) . Guan and co‐workers developed a series of metal‐catalyzed pyridine‐forming reactions wherein two molecules of oxime acetates are condensed with a C1 source such as aldehyde, dimethylformamide, or dimethylaniline (Scheme a, i–iii) –.…”

Rhodium‐Catalyzed [2+2+2] Cycloaddition of Oximes and Diynes To Give Pyridines

“…The reactivity of the CN bond makes oximes an alternative coupling partner for cycloaddition reactions; however, only the reaction of α,β‐unsaturated oximes and alkynes has been reported to generate substituted pyridines (Scheme ) 5. In these cases, either intramolecular [4+2] cycloaddition5a or CH bond functionalization5b–d was involved, both of which occurred using a rhodium catalyst. Although there are a few reports that show that imines bearing directing groups can undergo [2+2+2] cycloaddition to afford 1,2‐dihydropyridines under conditions of high temperature (100 °C),6 the low reactivity of the CN bond remains a challenging problem for simple oximes to participate in metal‐catalyzed [2+2+2] cycloaddition (Scheme ).…”