In(III)-Catalyzed 1,2-Hydrophosphorylation of 3‑Alkynyl-3-hydroxyisoindolinones to 3,3-Disubstituted Isoindolinones Featuring Both Phosphoryl and Alkynyl Groups at the C3-Position

We report a highly regioselective 1,2-addition of P(O)–H compounds to the in situ generated β,γ-alkynyl-α-ketimine derived from 3-alkynyl-3-hydroxyisoindolinones, which provided a general protocol for the preparation of 3,3-disubstituted isoindolinones featuring both phosphoryl and alkynyl groups at a quaternary carbon center. The use of only 2–5 mol % of an inexpensive catalyst (In(ClO₄)₃·8H₂O or Bi(OTf)₃) allowed the smooth output of the desired products under mild conditions (25 °C, 0.5–24 h) with a broad substrate scope (35 examples) in up to >99% yield. The obtained products could be further elaborated based on the alkyne moiety. The initial asymmetric trial indicated that the use of BINOL-derived CPA could enable an enantioselective induction in up to a 46% yield with 77% ee.