Highly Diastereoselective Synthesis of Trifluoromethyl Indolines by Interceptive Benzylic Decarboxylative Cycloaddition of Nonvinyl, Trifluoromethyl Benzoxazinanones with Sulfur Ylides under Palladium Catalysis

Abstract

A highly diastereoselective synthesis of trifluoromethyl-substituted indolines under palladium catalysis is disclosed. The reaction proceeds by interceptive decarboxylative benzylic cycloaddition (IDBC) of nonvinyl, trifluoromethyl benzoxazinanones with sulfur ylides. The palladium-π-benzyl zwitterionic intermediates are suggested for this transformation, and this would be the first example of an IDBC reaction.

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

“…Very recently, the groups of Gouverneur and Shibata showed in a collaborative paper that this could be extended to CF 3 -substituted benzoxazinanones ( 597 ) (Scheme 104). 345 The CF 3 group is responsible for a strongly electron-deficient benzylic carbon, resulting in a highly electrophilic palladium-π-benzyl zwitterionic intermediate by oxidative addition to Pd(0) and enabling access to CF 3 -indolines, albeit in racemic fashion.…”

An Update of Transition Metal-Catalyzed Decarboxylative Transformations of Cyclic Carbonates and Carbamates

“…benzoxazinanones, affording various trifluoromethyl-substituted indolines [19]. Moreover, a threecomponent domino reaction via decarboxylation, allylation, and N-H carbene insertion in the sequence was reported by Yang and co-workers toward the formation of various allylic sulfonecontaining amino acid derivatives (Scheme 3c) [20].…”

“…The Shibata group reported an unprecedented intermolecular cyclization of cyclic carbamate and sulfur ylides toward the formation of 4-trifluoromethyl-dihyroquinolines (Scheme 3b, path a); without externally added acceptors, a cyclization process would also be possible through an intramolecular attack of the zwitterionic π-allyl intermediate (Scheme 3b, path b) [18]. In contrast, the same group also proved [4 + 1] diastereoselective intermolecular cyclization using sulfur ylides and non-vinyl-substituted benzoxazinanones, affording various trifluoromethyl-substituted indolines [19]. Moreover, a three-component domino reaction via decarboxylation, allylation, and N-H carbene insertion in the sequence was reported by Yang and co-workers toward the formation of various allylic sulfone-containing amino acid derivatives (Scheme 3c) [20].…”

Synthesis of Both Enantiomers of Nine‐Membered CF3‐Substituted Heterocycles Using a Single Chiral Ligand: Palladium‐Catalyzed Decarboxylative Ring Expansion with Kinetic Resolution

“…The extremely nucleophilic alkoxide oxygen of A then attacks the carbonyl carbon of ( R )‐ 1 a , followed by a ring‐opening reaction by the cleavage of the N−C bond to produce the chiral zwitterion B . This step is very different from previous reaction mechanism via a Pd‐π‐benzyl zwitterion intermediate . In contrast, ( S )‐ 1 a should be sterically mismatched with A and thus prevent the reaction (kinetic resolution).…”