Ti(OiPr)4‑Mediated Multicomponent Reactions Involving Triple Additions to Isonitrile Carbon Atoms

Double addition of Grignard reagents to isonitriles was achieved in the presence of stoichiometric amounts of [Ti­(OiPr)4]. Functionalized isonitrile components were obtained in situ via lithiation of chiral and achiral 2-oxazolines, and the resulting amidomethyltitanium intermediate further reacted with a range of electrophiles. The established multicomponent procedure gave rise to highly substituted 2-aminomorpholines, acyclic diamino alcohols, and prenylated amino alcohols via straightforward synthetic protocols.