Asymmetric Counteranion Directed Catalytic Heck/Tsuji–Trost Annulation of Aryl Iodides and 1,3-Dienes

Abstract

A chiral anion-mediated asymmetric Heck/Tsuji–Trost reaction of aryl iodides and 1,3-dienes is presented. Chiral indoline derivatives could be afforded with remarkably higher yields and enantioselectivities than our previous chiral ligand-based method. Silver carbonate is employed as both base and halide scavenger to ensure fast and recyclable exchange of the catalytic amount of chiral anions. Fast salt metathesis, as well as the acceleration effect of the chiral anion, could both benefit the stereocontrol of the reaction.

Enantioselective Synthesis of α,β‐Unsaturated Aryl Lactams by Heck‐Matsuda and Heck‐Mizoroki Arylations of Enelactams

“…Moreover, we employed 2 equiv. of silver carbonate as a base with the intent of enforcing a cationic catalytic cycle [17,18] . Under, these novel reaction conditions, using 10 mol% of the Pd catalyst, we achieved 49 % yield and 88 : 12 e.r.…”

Pd-Catalyzed Heteroannulation Using N-Arylureas as a Sterically Undemanding Ligand Platform

“…Our urea-enabled heteroannulation methodology also shows a broad scope with respect to the diene. In contrast to prior reports, − our method effectively engages structurally and functionally diverse π-coupling partners. Conjugated linear dienes bearing electron-rich aryl groups afford excellent yields of product ( 3ab – ad ) with just 1.5 mol % Pd.…”

“…Particularly notable is our method’s tolerance for sterically demanding 2- and 3-substituted dienes ( 3ap – ar ); such branching in the π-coupling partner has not previously been demonstrated in related transformations. 11 , 13 The primary limitation of our method is with internal dienes, which are unreactive under our current conditions. 19 The reaction scales readily; in fact, when performed at a 10-fold increase in scale, the product yield improved (77% at 5 mmol vs 68% at 0.5 mmol), allowing us to isolate ∼1.5 g of indoline products ( 3 a /3a′ = 85:15).…”

“…This convergent approach to indolic azaheterocycles, which are a privileged structural motif in drug discovery owing to their ubiquity in alkaloids, has received considerable interest. Despite important advances in both reactivity and enantioselectivity, − two key limitations remain: (1) the only examples using bromoanilines (rather than iodoanilines) require strained olefins, and (2) existing methodologies demonstrate limited tolerance for steric bulk in either substrate. Additionally, when dienes are used as substrates, phosphine ligands are sometimes inhibitory in these reactions .…”

Palladium-Catalyzed Asymmetric Tandem Denitrogenative Heck/Tsuji–Trost of Benzotriazoles with 1,3-Dienes

“…(Scheme b), the development of an asymmetric version of these reactions had not been explored until 2019 . Inspired by this asymmetric cycloaddition with allenes, we became very interested in the development of the asymmetric tandem denitrogenative Heck/Tsuji–Trost of benzotriazoles with readily available 1,3-dienes (Scheme c); if successful, a variety of enantioenriched hexahydrocarbazoles and indolines, which are ubiquitous structural motifs found in an array of biologically active monoterpene indole alkaloids, could be easily prepared (Figure ).…”