Organocatalyzed Kabbe condensation reaction for mild and expeditious synthesis of 2,2‐dialkyl and 2‐spiro‐4‐chromanones

Abstract

An expeditious Kabbe condensation reaction for the synthesis of 2,2‐dialkyl and 2‐spiro‐chroman‐4(1H)‐ones has been developed using pyrrolidine‐butanoic acid in DMSO as bifunctional organocatalyst. Unlike existing methods, this reaction proceeds at room temperature with high yields, rendering it an attractive method to synthesize a vast variety of privileged 4‐chromones.

Total Synthesis of (+)‐Cochlearol B by an Approach Based on a Catellani Reaction and Visible‐Light‐Enabled [2+2] Cycloaddition**

“…Our final approach to (+)‐cochlearol B ( 2 ) takes advantage of these insights and through a revised design for the Catellani reaction to ultimately enable a productive [2+2] cycloaddition by disfavoring competing Heck reaction, [4+2] cycloaddition, and cyclopropanation (Scheme 5). Additionally, a Kabbe condensation [24] was employed to access chromanone 11 , which reduced the overall number of steps.…”

“…This represents one of the more complex precursors used in this class of transformations to date. [10][11][12][13][14][15][16][17][18][19][20][21][22][23] Triflate 6 is accessible through a two-step sequence of triflation preceded by Kabbe condensation [24] of commercially available precursors phenol 7 and sulcatone (8).…”

Ketones as strategic building blocks for the synthesis of natural product-inspired compounds

“…178,180,188 Scheme 33 Synthesis of 4-chromanones from ketones via the Kabbe condensation. [191][192][193] (super)stoichiometric pyrrolidine (Scheme 33a). 191 A recent variant of this reaction reported by Kapuriya combined the use of substoichiometric pyrrolidine (0.5 eq.)…”

Total Synthesis of Cochlearol B via a Catellani- and Visible Light-Enabled [2+2]-Cycloaddition Approach

“…This represents one of the more complex precursors used in this class of transformations to date. [10][11][12][13][14][15][16][17][18][19][20][21][22][23] Triflate 6 is accessible through a Kabbe condensation 24 of commercially available precursors phenol 7 and 6-methylhept-5-en-2-one (8). 25 In initial studies towards cochlearol B (2), we were able to access 6-methoxy-2-methyl-4H-chromen-4-one ( 9) via a one-pot acylation, Baker-Venkataraman rearrangement, 26 and condensation of 7 using conditions developed by Brown and coworkers.…”

“…Specifically, we postulated that a less reactive alkene could mitigate the competing Heck reaction in the Catellani step, while a conformationally restricted diene was expected to prevent undesired [4+2]-cycloadditions. Our final synthetic approach tocochlearol B (2) takes advantage of these insights and combines a Kabbe condensation 24 to access chromanone 11 with a revised design for the Catellani reaction ultimately enable a productive [2+2]-cycloaddition by foregoing competing Heck, [4+2]cycloaddition, and cyclopropanations (Fig. 5).…”