Nickel‐Catalyzed Conjugate Addition of Silyl Ketene Imines to In Situ Generated Indol‐2‐ones: Highly Enantioselective Construction of Vicinal All‐Carbon Quaternary Stereocenters

Abstract

The first enantioselective conjugate addition of silyl ketene imines to in situ generated indol-2-ones was performed in the presence of a chiral N,N'-dioxide/Ni catalyst. This method provides efficient access to chiral β-alkyl nitriles bearing congested vicinal all-carbon quaternary stereocenters in up to 90 % yield with 23:1 d.r. and 98 % ee. The products enable facile transformations to chiral pyrroloindoline frameworks and spirocyclohexane oxindole derivatives. A possible transition state was also proposed to explain the origin of the asymmetric induction.

Catalytic enantioselective construction of vicinal quaternary carbon stereocenters

“…Later, Liu and Feng reported an elegant formal alkylation of 3-bromooxindoles using fully substituted silyl ketene imines 102 (SKI), catalyzed by a chiral N,N 0 -dioxide 17b/Ni(II) complex (Scheme 18). 71 The resulting cyano-substituted quaternary oxindoles 103 were readily accessed in up to 90% yield, 23 : 1 dr, and 98% ee, which could undergo various diversied reactions. It was believed that the in situ-generated indol-2-one bound to the chiral Ni(II) catalyst, with its Si face blocked by the 2,4,6triisopropylphenyl group of the ligand, to facilitate the Re-face attack of SKI on the Re face of the electrophile.…”

Construction of Vicinal Quaternary Carbon Stereocenters Through Diastereo‐ and Enantioselective Oxidative 1,6‐Conjugate Addition

“…Toward this end, Liu and Feng reported an elegant enantioselective 1,4‐conjugate addition of pre‐functionalized silyl ketene imines to in situ generated indol‐2‐ones from 3‐bromooxindoles (Scheme 1 B). [6d] To our knowledge, 1,6‐conjugate addition for asymmetric synthesis of vicinal quaternary carbon stereocenters with at least one center in an acyclic chain has never been established to date [11] . On the other hand, enantioselective cross‐dehydrogenative coupling (CDC) of two easily available C−H reagents has emerged as a powerful approach for C−C bond formation whereby the net loss is H 2 [12–14] .…”

Enantioselective Synthesis of Nitriles Containing a Quaternary Carbon Center by Michael Reactions of Silyl Ketene Imines with 1-Acrylpyrazoles

“…The asymmetric catalytic reactions of SKIs have been described in acylation by Fu, in addition to aldehydes and α,β-unsaturated carbonyl compounds by Denmark, − in addition to imines by Leighton, , and in protonation by List . Our group also realized asymmetric addition to various electrophiles by the use of chiral N,N′ -dioxide-metal complex catalysts. − We have recently turned our attention to address the challenge of the construction of α,α-dialkyl-α-arylnitriles, key intermediates of multiple bioactive molecules (examples are listed in Figure a) whose stereocenters are only generated at the remote quaternary carbon (Figure b­(iii)).…”