A New Route to Fused Aromatic Compounds by Using a Palladium-Catalyzed Alkylation - Alkenylation Sequence

Abstract

Selective aromatic substitution is a long-standing goal in organic chemistry. [1] Recently, a new method involving a palladium-catalyzed process based on a sequential double aromatic substitution and an intermolecular Heck reaction leading to o,o'-disubstituted vinylarenes 2 was described (Scheme 1). [2] The potential of this strategy is truly remarkable since it allows the formation of three new carbon ± carbon bonds in a one-pot process.

CH Bond Alkylation (Including Hydroarylation of Alkenes)

“…Catellani and coworkers [17], and subsequently Lautens and coworkers [18], used a strained olefin as a directing scaffold for aromatic C-H functionalization [19,20]. Indeed, palladium-catalyzed ortho alkylation terminated by a cross-coupling such as the Mizoroki-Heck reaction was successfully achieved in a domino sequence through the use of norbornene as the directing group for the ortho-C-H activation step (Scheme 19.10) [21].…”

Palladium-catalyzed ring-forming reactions: Methods and applications

“…Our group modified the reaction conditions and extended the methodology by using a difunctional acceptor (3) so that an intramolecular Heck reaction can follow the ortho alkylation leading to fused aromatic compounds 4 (Scheme 2) [4][5][6][7]. We initially demonstrated that numerous six-and seven-membered fused aromatic carbocycles (5) can be easily prepared using our optimized reaction conditions: iodoarene (1 equiv), Pd(OAc) 2 (10 mol %), tri-2-furylphosphine (22 mol %), Cs 2 CO 3 (2 equiv), norbornene (2 equiv), and bromoenoate (2 equiv) in acetonitrile at 85 °C for 12 h [4].…”

“…We initially demonstrated that numerous six-and seven-membered fused aromatic carbocycles (5) can be easily prepared using our optimized reaction conditions: iodoarene (1 equiv), Pd(OAc) 2 (10 mol %), tri-2-furylphosphine (22 mol %), Cs 2 CO 3 (2 equiv), norbornene (2 equiv), and bromoenoate (2 equiv) in acetonitrile at 85 °C for 12 h [4]. Various functional groups at different positions on the aryl iodide as well as a variety of Heck acceptors are tolerated [5].…”

Tri-2-furylphosphine

“…69 Use of TFP in Tandem Palladium-catalyzed Synthetic Sequences. 82, 83 Oppolzer has extended his approach to double olefin insertion reactions. Liebeskind has systematically investigated the coupling of cyclobutenone electrophiles with unsaturated stannanes.…”