Brønsted Acid‐Mediated Formal [3+3] Annulation Between Propargylic Alcohols and 1,3‐Diketones

Abstract

A Brønsted acid-mediated formal [3 + 3] cascade annulation of propargylic alcohols with 1,3diketones proceeds through a sequential MeyerÀSchuster rearrangement/1,2-addition. This protocol, which has a wide scope and is conducted under an ambient atmosphere, enables access to a broad array of valuable chromenone derivatives related to many natural products in satisfactory yields under mild conditions. This method could be scaled up to the gram scale, which highlights the latent applicability of this transformation.

Recent Developments in the Meyer‐Schuster Rearrangement

“…On the other hand, chromenones 167 have been synthetized by reaction of cyclohexanedione with propargylic alcohols 166 in the presence of trifluoroacetic acid in THF. [91] During MSR the intermediate carbenium ions were trapped by the enol form of cyclohexanedione and, after prototropic shifts, a second cyclization afforded the targets. Extensions have been performed with various propargylic derivatives, with substituted cyclohexanediones and with cyclopentanediones.…”

Recent Advances in the Synthesis of Heterocyclics via Cascade Cyclization of Propargylic Alcohols

“…Liang's group described an efficient strategy for the construction of chromenone derivatives 50 through TFA‐mediated formal [3+3] annulation of cyclic 1,3‐diketones 49 and propargylic alcohols 1 (Scheme 17). [27] A series of tertiary and secondary propargylic alcohols underwent cascade cyclization smoothly to give the corresponding products 50 in moderate to high yields. Moreover, this protocol could be enlarged to gram scale, which provide the potential application in medicinal chemistry and synthetic chemistry.…”

Acid-catalyzed chemoselective C- and O- prenylation of cyclic 1,3-diketones

“…Owing to its atom-and step-economy, the [3+3] annulation of 1,3-cyclohexanedione with unsaturated precursors represents a more convenient and straightforward strategy. In the presence of acids or water, α,β-unsaturated aldehydes [11][12][13][14][15] and propargylic alcohols [16][17][18][19][20][21] are suitable coupling partners in this process. Despite these advances, exploiting new [3+3] annulation reactions to access 5-chromenone frameworks from other easily accessible and low-cost chemicals is still in high demand.…”