Controllable Access to Furans and Dihydrofurans through Cyclization/Coupling of Internal Acetylenic β‐Ketoesters with Aryl Bromides

Abstract

Pd-catalyzed tandem cyclization/coupling of internal β-propargylic-β-ketoesters with (hetero)aryl bromides is described. Two protocols are established which selectively lead to 2-benzylidene-dihydrofurans, when isomerization is inhibited under mild conditions (temp. � 40 °C and weak base -K 2 CO 3 ), or to 2-benzylfurans when base-induced aromatization is enabled. A catalytic cycle involving oxidative addition, substitution of bromide with alkyne, rate limiting anti-selective 5-exo-dig oxocyclization followed by fast deprotonation of the oxonium intermediate, and reductive elimination is proposed based on detailed experimental and theoretical studies.

Access to 2-Alkenyl-furans via a Cascade of Pd-Catalyzed Cyclization/Coupling Followed by Oxidative Aromatization with DDQ

“…Underdevelopment of this strategy stems mainly from poor availability of more elaborated derivatives of alkylidene dihydrofurans and their high tendency to isomerize to the corresponding furans, particularly under acidic or basic conditions (Scheme b). Recently we proposed a Pd-catalyzed tandem cyclization/coupling strategy enabling access to highly substituted 2-benzylidenedihydrofurans . We envisioned that integration of this strategy with a further oxidative-aromatization step into a one-pot cascade transformation could provide an elegant and straightforward route to 2-alkenyl-3,5-furans.…”

“…Recently we proposed a Pd-catalyzed tandem cyclization/coupling strategy enabling access to highly substituted 2-benzylidenedihydrofurans. 9 We envisioned that integration of this strategy with a further oxidative-aromatization step into a one-pot cascade transformation could provide an elegant and straightforward route to 2-alkenyl-3,5-furans. Avoiding direct synthesis of the dihydrofuran is beneficial, as it not only shortens the synthetic sequence through elimination of isolation/purification steps but also minimizes the risk of undesirable isomerization.…”

Pd-Catalyzed Regioselective (Markovnikov) Addition of Aryl Boronic Acids to Terminal Alkynes of 1,3-Dicarbonyl Compounds and Cyclization/Debenzoylation of Olefinic Dicarbonyl: Access to Arylated Pyran and (E)-4-Methylene-1,6-diphenylhex-5-en-1-one

“…Hence, new general strategies for accessing olefinic dicarbonyl compounds that utilize easily available starting materials are desirable. On the other hand, propargylic alkyne of 1,3-dicarbonyl compounds are easily manipulated to highly functionalized cyclic ethers, due to enolic OH of 1,3-dicarbonyl functionalities . Most of the literature reports on these compounds involve Pd-catalyzed tandem cyclization and coupling with various coupling partners.…”

Reductive Denitrogenation of Six‐membered Cyclic Nitronates to Densely Substituted Dihydrofurans with Raney® Nickel/AcOH System

“…While the majority of the known methods rely on the cyclization of γ-hydroxycarbonyls, [7] metal-catalyzed cyclizations of functionalized alkyne/allene precursors, [8] [3 + 2]- [9] and [4 + 1]-annulations, [10] and ring closing metathesis, [11] the synthesis of 2,3-dihydrofurans by ring contraction reactions remains underdeveloped (Scheme 1, b). [12] Based on our long-term experience in the chemistry of six-membered cyclic nitronates 1, [13] we reasoned that the hitherto unknown catalytic reductive denitrogenation (RDN) of these intermediates would lead to polysubstituted 2,3-dihydrofurans (Scheme 1, c).…”