Ti-catalyzed Barbier-type allylations and related reactions.
Titanocene(III) complexes, easily generated in situ from commercial Ti(IV) 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 Ti(III)-coordinated carbonyl group seems to occur. Intermolecular additions to conjugated aldehydes proceed through a coupling of a Ti(IV)-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 alpha-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.
Estévez
Rosa E
RE
Department of Organic Chemistry, University of Granada, Faculty of Sciences, C. U. Fuentenueva s/n 18071 Granada, Spain.
Justicia
José
J
Bazdi
Btissam
B
Fuentes
Noelia
N
Paradas
Miguel
M
Choquesillo-Lazarte
Duane
D
García-Ruiz
Juan M
JM
Robles
Rafael
R
Gansäuer
Andreas
A
Cuerva
Juan M
JM
Oltra
J Enrique
JE