Facile and Racemization-Free Conversion of Chiral Nitriles into Pyridine Derivatives

Abstract

The results described herein demonstrate how the very mild reaction conditions of the Co(I)-catalyzed photochemical [2 + 2 + 2] cyclocotrimerization are suited to prepare chiral compounds containing unsubstituted and polysubstituted 2-pyridyl moieties starting from chiral nitriles without any detectable loss of enantiomerical purity. This further increases the already very broad synthetic scope of this particular reaction.

Acetylene and Ethylene: Universal C2 Molecular Units in Cycloaddition Reactions

“…185a b The use of chiral nitriles did not result in racemization and led to the synthesis of a range of optically pure pyridines in 64–89% yields (Scheme 116 , bottom). 185c…”

Recent Strategies for the Synthesis of Pyridine Derivatives

“…[49] Heller et al developed a new cobalt-catalyzed [2 + 2 + 2] synthesis of chiral 2-mono-, 2,4,5-tri-, and 2,3,4,5,6-pentasubstituted pyridines from chiral nitriles and symmetrical alkynes in moderate to good yields (Scheme 36). [50] The substrate scope included nitrile-containing starting materials with stereogenic centers, both adjacent to and removed from the cyano functionality. The reaction of a nitrile with 1,6-heptadiyne provided a tethered substrate that provided an interesting 5,6-fused bicycle.…”

Six‐Membered Heterocycles: Pyridines

“…Under thermal conditions, the enantiomeric excess of the product decreases in many cases by 2-10%, which is attributed to the high reaction temperatures (>100 C) necessary to initiate the catalysis [31][32][33][34][35][36][37][38][39]. However, using the photochemical version of the reaction, this problem is circumvented, affording optically pure pyridine derivatives without detectable loss of enantiomeric purity (Scheme 16.7) [40].…”