4-HO-TEMPO-Catalyzed Redox Annulation of Cyclopropanols with Oxime Acetates toward Pyridine Derivatives

Abstract

A 4-HO-TEMPO-catalyzed redox strategy for the synthesis of pyridines through the annulation of cyclopropanols and oxime acetates has been developed. This protocol features good functional group tolerance and high chemoselectivity and also promises to be efficient for the late-stage functionalization of skeletons of drugs and natural products. Mechanism studies indicate that the reaction involves the in situ generated α,β-unsaturated ketones and imines as the key intermediates, which are derived from cyclopropanols and oxime acetates via a TEMPO/TEMPOH redox cycle, respectively. The pyridine products are formed as a result of annulation of enones with imines followed by TEMPO-catalyzed oxidative aromatization by excess oxime acetates. This method not only realizes the TEMPO-catalyzed redox reaction but also broadens the frontiers for TEMPO in catalysis.

Deconstructive Oxygenation of Unstrained Cycloalkanamines

“…To prevent the formation of c1, a well-known C-centered radical scavenger, TEMPO, [14] was employed in the reaction (Table 1). To our delight, when TEMPO (3.5 equiv) was added at the auto-oxidative stage, the self-coupling was totally inhibited and the TEMPO-trapped ring-opening product d1 was afforded in 74 % yield.…”

Visible‐Light‐Induced C4‐Selective Functionalization of Pyridinium Salts with Cyclopropanols

“…Given the utility and high prevalence of ester and aldehyde groups in synthesis,w ew ere intrigued by the possibility of avisible-light-mediated general method for the b-pyridylation of esters and aldehydes as well as ketones with wide synthetic utility.W eq uestioned whether the hydrogen atom transfer (HAT) process of amidyl radicals enables alkoxy radical generation from more challenging cyclopropanol substrates such as cyclopropanone hemiketals,w hich would be difficult to handle using photoredox approaches. Indeed, the relatively low bond dissociation energies (BDEs) of OÀHb onds in cyclopropanols (BDE % 90 kcal mol À1 ) [12] are within reach of the amidyl radical (BDE = 102 kcal mol À1 ) [13] -mediated HATr eaction. The b-carbonyl radicals generated via ar ing-opening process are poised for subsequent interception by N-amidopyridinium salts to afford bpyridyl-functionalized carbonyl products (Scheme 1c).…”

Organocatalytic Decarboxylation and Dual C(sp3)−H Bond Functionalization Toward Facile Access to Divergent 2,6‐Diarylpyridines

“…In recent times, the metal‐free approaches toward the synthesis of pyridine cores have also come to a great attention owing its high recognition in the field of organic synthesis. These metal‐free processes are established by employing diverse starting materials and synthetic intermediates [11m,o,p,12k,13–15] . In particular, α,β‐unsaturated nitriles or alkylidene malononitriles have been well explored along with DMF as a C1‐synthon to construct pyridine motifs under a transition‐metal‐free phenomenon (Scheme 1d) [15]…”