Convenient and Highly Efficient Routes to 2 H‐Chromene and 4‐Chromanone Derivatives: Iodine‐Promoted and p‐Toluenesulfonic Acid Catalyzed Cascade Cyclizations of Propynols

Abstract

A convenient strategy is presented for the easy preparation of a series of 2 H-chromenes under mild conditions through iodocyclization of readily accessible propynols. In addition, various 4-chromanones can be synthesized through a p-toluenesulfonic acid catalyzed cascade cyclization with high efficiency (yields up to 99 %). Our developed reaction systems are proven to have good functional-group applicability and can be scaled up to gram quantities in satisfactory yields. These systems also provide a new synthetic strategy for two types of important flavonoid skeleton without using costly and toxic metal catalysts. Additionally, the resulting halides could be further exploited in subsequent palladium-catalyzed coupling reactions, so these compounds could act as potential intermediates for the construction of some valuable drug molecules.

Novel and Efficient Access to Flavones under Mild Conditions: Aqueous HI‐Mediated Cascade Cyclization/Oxidative Radical Reaction of 2‐Propynolphenols

“…Followed by these preliminary mechanistic studies and the previous reports,[15d], a plausible mechanism of this transformation is tentatively proposed as shown in Scheme . The initial step involves the formation of 4‐iodo‐2 H ‐chromene intermediate 2a from the interaction of 2‐propynolphenols 1a with HI.…”

“…Recently, propargylic alcohols with two mutual activated functional groups have served as versatile synthons for the construction of various synthetic intermediates in synthetic methodology, which has made great achievements in the synthesis of carbo‐ and hetrocyclic compounds. Over the past few years, our group had reported numerous effective synthetic strategies for the synthesis of heterocyclic compounds by tandem cyclization of propargylic alcohols, such as 2 H ‐chromenes, 4‐chromanones and benzoxazoles (Scheme ) …”

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

“…4‐Chromanone derivatives are important flavonoid skeletons widely found in a variety of natural products and pharmaceutically active molecules, [48] and can be prepared from p ‐TsOH‐catalyzed cascade cyclization of 2‐propynol phenols 86 (Scheme 33). [49] The reaction involved the classic Meyer‐Schuster rearrangement process to afford the α, β ‐unsaturated ketone intermediates, which subsequently underwent intramolecular cyclization to give the final product 87 . In this case, both secondary and tertiary propargylic alcohols could work smoothly to form the corresponding products in moderate to high yields under mild conditions.…”

Catalytic Synthesis of Trifluoromethylated Allenes, Indenes, Chromenes, and Olefins from Propargylic Alcohols in HFIP

“…General procedure D: 33 Step 1. To a 0.5 M solution of ethynyl magnesium bromide (10 mmol) in THF was slowly added aryl trifluoromethyl ketone (10 mmol) in THF (20 mL).…”