Ti‐Catalyzed Barbier‐Type Allylations and Related Reactions

Versatility of titanium: Titanocene(III) complexes catalyze Barbier‐type allylations, intramolecular crotylations (cyclizations), and prenylations of a wide range of aldehydes and ketones. These reactions take place at RT under mild conditions compatible with many functional groups; provide good yields of open‐chain and cyclic homoallylic alcohols, including heterocyclic derivatives; and can be conducted enantioselectively by using enantiomerically pure titanium catalysts. magnified image Titanocene(III) complexes, easily generated in situ from commercial TiIV precursors, catalyze Barbier‐type allylations, intramolecular crotylations (cyclizations), and prenylations of a wide range of aldehydes and ketones. The reaction displays surprising and unprecedented mechanistic subtleties. In cyclizations a fast and irreversible addition of an allyl radical to a TiIII‐coordinated carbonyl group seems to occur. Intermolecular additions to conjugated aldehydes proceed through a coupling of a TiIV‐bound ketyl radical with an allyl radical. Reactions of ketones with allylic halides take place by the classical addition of an allylic organometallic reagent. The radical coupling processes enable transformations such as the highly regioselective α‐prenylation that are otherwise difficult to achieve. The mild reaction conditions and the possibility to employ titanocene complexes in only catalytic quantities are highly attractive features of our protocol. These unusual properties have been taken advantage of for the straightforward synthesis of the natural products rosiridol, shikalkin, and 12‐hydroxysqualene.