Pd(II)-Catalyzed Enantioselective Oxidative Tandem Cyclization Reactions. Synthesis of Indolines through C−N and C−C Bond Formation

Abstract

We have developed an efficient Pd(II)-catalyzed enantioselective oxidative tandem cyclization strategy using molecular oxygen as a green oxidant for the double 5-exo-trig cyclizations of N-(2-allylaryl) amides to afford a variety of indolines in good yields without the formation of undesired monocyclization products. By employing Pd(TFA)2/(-)-sparteine as the chiral catalyst, we obtained tandem cyclization products with high enantioselectivity (up to 91% ee).

The attempted stereoselective synthesis of chiral 2,2′-biindoline

“…4 Here we utilise the same strategy (Fig. 1), starting with the protection of 2-allylaniline 20 to produce 6 in 88% yield (Scheme 1). 5 Olefin metathesis of 6 using Grubbs II catalyst in CH 2 Cl 2 at reflux yielded the dimer 7 (61%) as a 92:8 mixture of the E/Z isomersda single recrystallisation from hexanes increased the ratio to E/Z 99:1 in 37% yield.…”

Oxidative Functionalization of Alkenes

“…A particularly interesting example was reported by Yang et al [53], who described an intramolecular enantioselective cascade reaction of 56. Initial reactions using the alkaloid (−)-spartein (58) as ligand and base led to a reaction with complete selectivity in favor of the cyclized product 57, which was isolated with 86% ee (Scheme 16.14).…”

Synthesis of Saturated Five‐Membered Nitrogen Heterocycles via Pd‐Catalyzed CN Bond‐Forming Reactions

“…Instead, initial conjugate addition of the nitrogen nucleophile to the activated alkene affords a malonate anion, which undergoes carbopalladation followed by reductive elimination to afford the pyrrolidine product. Yang has reported a related tandem cyclization for the synthesis of pyrroloindoline derivatives that also proceeds though a mechanism involving alkene aminopalladation followed by carbopalladation of a second alkene [46]. As shown below, the 2-allylaniline derivative 48 was converted to 49 in 95% yield through treatment with a catalyst composed of Pd(OAc) 2 and pyridine (Eq.…”