Regio- and Enantioselective Iridium-Catalyzed Amination of Racemic Branched Alkyl-Substituted Allylic Acetates with Primary and Secondary Aromatic and Heteroaromatic Amines

Abstract

The air and water stable π-allyliridium C,O-benzoate modified by (S)-tol-BINAP, (S)-Ir-II, catalyzes highly regio- and enantioselective Tsuji-Trost type aminations of racemic branched alkyl-substituted allylic acetates using primary or secondary (hetero)aromatic amines. Specifically, in the presence of (S)-Ir-II (5 mol%) in DME solvent at 60-70 °C, α-methyl allyl acetate 1a (100 mol%) reacts with primary (hetero)aromatic amines 2a-2l (200 mol%) or secondary (hetero)aromatic amines 3a-3l (200 mol%) to form the branched products of allylic amination 4a-4l and 5a-5l, respectively, as single regioisomers in good to excellent yield with uniformly high levels of enantioselectivity. As illustrated by the conversion of heteroaromatic amine 3m to adducts 6a-6g, excellent levels of regio- and enantioselectivity are retained across diverse branched allylic acetates bearing normal alkyl or secondary alkyl substituents. For reactants 3n-3p, which incorporate both primary and secondary aryl amine moieties, regio- and enantioselective amination occurs with complete site-selectivity to furnish adducts 7a-7c. Mechanistic studies involving amination of the enantiomerically enriched deuterium labelled acetate 1h corroborate C-N bond formation via outer-sphere addition.

Iridium‐Catalyzed Enantioselective Intermolecular Indole C2‐Allylation

“…[27] Thus, at present we are only able to achieve high levels of C2regioselectivity using aryl substituted allylic alcohols.N onetheless,wewere pleased to observe that allylic substitution is still possible under our usual reaction conditions with aliphatic allylic alcohol 1p,g iven that p-allyl complex formation is known to be more challenging for such alcohols compared with the more activated benzylic systems that are the main focus of this study. [28] On the basis of the experimental data described above,in addition to previously described theoretical evidence, [29] the following mechanism for the enantioselective direct C2allylation of indole is proposed (Scheme 6). Thec atalyst precursor [Ir(cod)Cl] 2…”

An Overview of Iridium‐Catalyzed Allylic Amination Reactions

“…Stivala and team corroborated an Ir‐catalyzed amination of alkyl substituted allylic acetate with primary, secondary and heteroaromatic amines [56] . α‐Methyl allyl acetate was taken as the substrate specifically in the presence of 5 mol% of ( S )‐Ir‐(II) in DME solvent at 60–70 °C for 24–40 h (Scheme 27).…”

Regio‐ and Enantioselective Iridium‐Catalyzed N‐Allylation of Indoles and Related Azoles with Racemic Branched Alkyl‐Substituted Allylic Acetates

“…Using SEGPHOS‐modified π‐allyliridium‐ C,O ‐benzoate catalysts, allylic aminations mediated by aliphatic amine nucleophiles occur with high levels of regio‐ and enantioselectivity . It was later found that the tol‐BINAP‐modified π‐allyliridium‐ C,O ‐benzoate ( S )‐Ir‐ I is a superior catalyst, enabling highly regio‐ and enantioselective allylation of electronically diverse primary and secondary (hetero)aryl amines …”