Divergent Michael/Aldol Cascades Under Semi-Aqueous Conditions: Synthesis of Cyclopenta- and Cycloheptannulated (Hetero)arenes

Abstract

The synthesis of 3-acetoxyindanones and (hetero)arene-fused dihydrotropones was achieved via divergent annulation cascades. Under mild aqueous and basic conditions, α-substituted enone-aldehydes and 1,3-carbonyls undergo a Michael/aldol/ hemiketalization/retro-aldol cascade for the formation of 3-acetoxyindanones possessing two contiguous stereogenic centers, one of which is an all-carbon quaternary center. On the other hand, the same enone-aldehydes generate new classes of fuseddihydrotropones upon reaction with 2,4-dioxobutanoates under merely the same reaction conditions via a Michael/aldol/ lactonization/decarboxylation cascade.

Transition‐Metal‐Free Synthesis of 1‐Indanone Skeleton: A Brief Update

“…Very recently, Maurya and Ramasastry delineated the one‐pot synthesis of 2,2‐disubstituted‐3‐acetoxyindanones 68 through a divergent annulation cascade reactions [50] . In the presence of cheap and easily available NaHCO 3 in aqueous medium, α‐substituted enone‐aldehydes 66 and 1,3‐dicarbonyls 67 undergo a Michael/aldol/hemiketalization/retro‐aldol cascade to accomplish indanones bearing a quaternary carbon (Scheme 22).…”

Cobalt-Catalyzed Chemoselective Transfer Hydrogenative Cyclization Cascade of Enone-Tethered Aldehydes

“…To this end, chemoselective variation toward multifunctional substrates is generally a prerequisite to form precursors of the sequence. For instance, the intramolecular cyclization of enone-tethered electrophiles, such as aldehyde, ketone, enone, and nitro functionalities, provides a good setup for a Michael–Aldol coupling cascade reaction with nucleophiles to construct cyclic alcohol motifs. − However, such a Michael-addition-initiated cascade may be replaced by a nucleophilic attack on the more reactive electrophiles to alter the reaction sequence. , Despite a wealth of research on both cascades toward intramolecular enone-tethered aldehydes, transition-metal-catalyzed reductive cyclization remains less developed. Experimental investigations into the approach of chemoselective reductive cyclization and exploration of the different reactivities between two modes with the same catalyst would advance the potential of such strategies in depth.…”

“…As a result of preliminary examinations, the reaction was carried out with CoI 2 (10 mol %), dcpp (15 mol %), indium powder (In) (40 mol %), and i -PrOH (10 equiv) in toluene at 80 °C for 24 h under argon (Table , entry 1). Instead of the cyclic alcohol upon a typical Michael–Aldol coupling cascade, , appreciable quantities of the indene counterpart 2a , featuring an indenyl 1 H NMR signal at δ 7.49 and δ 3.88, were formed. Notably, de Bruin reported the transformation of o -cinnamyl N -tosyl hydrazones to substituted 1 H -indenes, facilitated by the native reactivity of a Co­(III) carbene radical intermediate .…”