Transition-Metal-Free Access to Heteroaromatic-Fused 4-Tetralones by the Oxidative Ring Expansion of the Cyclobutanol Moiety

Abstract

Advances in the transition-metal-free cyclobutanol ring expansion to 4-tetralones under N-bromosuccinimide mediation are described. We have expanded the scope of this ring expansion methodology and investigated the effect substituents on the aromatic ring, and the cyclobutanol moiety, have on the outcome of the reaction. Limitations with certain substituents on the cyclobutanol moiety are also described. Further experimental evidence to support our mechanistic understanding is disclosed, and we now preclude the suggested involvement of a primary radical for this transformation.

Regioselective Electrochemical Cyclobutanol Ring Expansion to 1‐Tetralones

“…The groups of Zhang and Kim, on the other hand, were particularly productive in the area of tandem functionalization/semi‐pinacol rearrangements and pioneered the electrochemical synthesis of a variety of β‐functionalized cyclopentanones from vinyl‐substituted cyclobutanols [17–20,22] . Although protocols for the ring expansion of cyclobutanols to tetralones under traditional synthetic methods (e. g. [Ag], [29] [Rh], [30] [Pd], [31,32] [Ce], [33] N ‐bromosuccinimide [34–36] ) were previously disclosed, a two‐carbon ring homologation to tetralones under mild and ecological electrochemical techniques has not yet been accomplished (Scheme 1).…”

“…Similarly, conducting the reaction in other solvent mixtures, such as ethyl acetate/acetic acid or acetonitrile/water, failed to yield the desired product (Table 1, entries 8–10), whereas a decrease in yield was observed when acetonitrile/HFIP or acetonitrile/acetic acid systems were used (Table 1, entries 11–12). Consequently, acetonitrile was established as the optimal solvent for this transformation, since it favors the stabilization of transient cationic intermediates [35] and offers a large electrochemical window [41] . After studying the impact of a different supporting electrolyte on the outcome of the reaction (Table 1, entries 13–14), [Li][ClO 4 ] was found to be the most suitable electrolyte for our transformation.…”

Construction of Diverse Dihydrodibenzofuranones by Migration/Intramolecular Arylation of Iodonium Ylides

“…11 The other typical methods are also reported, which could be accessed by copper/gold-catalyzed tandem Ullmann-Goldberg cross-coupling/cyclopalladation-reductive elimination of cyclohexenones with O-iodophenol (Scheme 1(c)) 12 and transition-metal-free oxidative ring expansion of the cyclobutyl moieties (Scheme 1(d)). 13 Although several synthetic methodologies for 3,4-dihydrodibenzofuranones have been demonstrated, more general and efficient synthetic protocols are still highly needed.…”

An entry to 2-(cyclobut-1-en-1-yl)-1H-indoles through a cyclobutenylation/deprotection cascade

“…60 The use of four-membered ring building blocks in medicinal chemistry remains relatively underdeveloped as chemists depend on a small number of viable protocols towards these moieties. 61,62 Given our laboratory's interest in the use of fourmembered rings to access biologically relevant scaffolds, [63][64][65][66][67][68] we questioned if we could expand the scope of C2-alkenylation protocols to hitherto virtually inaccessible 2-(cyclobut-1-en-1yl)-1H-indole analogues through a transition-metal-free cyclobutenylation/deprotection cascade (Scheme 1c). Our implementation of these design criteria and computational studies on the mechanistic details are described herein.…”