Ti-Catalyzed Reformatsky-Type Coupling between α-Halo Ketones and Aldehydes

Abstract

We describe the first Ti-catalyzed Reformatsky-type coupling between alpha-halo ketones and aldehydes. The reaction affords beta-hydroxy ketones under mild, neutral conditions compatible with ketones and other electrophiles. The catalytic cycle possibly proceeds via bis(cyclopentadienyl)titanium enolates.

Tandem Application of C–C Bond-Forming Reactions with Reductive Ozonolysis

“…The syn/anti ratios (~1:3 in all cases) were assigned by comparison of the 1 H NMR spectra with literature reports. 33–37 …”

Mixed disproportionation versus radical trapping in titanocene(III)-promoted epoxide openings

“…2 It has been used in many interesting transformations, such as the homolytic ring opening of epoxides, 3 the radical cascade cyclization of epoxypolyenes, 4 Michael-type coupling between aldehydes and conjugated alkenals, 5 pinacol coupling reactions, 6 H-atom transfer from water to free radicals, 7 alkenes and alkynes, 8 divergent C-C bondforming reactions with modulation by Ni or Pd, 9 metal-catalyzed Barbier-type cyclizations and a-prenylation of carbonyl derivatives, 10 and the Reformastky-type addition of a-haloketones to carbonyl compounds. 11 Interestingly, during the last few years new developments in titanocene-regenerating agents have led to many transformations being carried out using only 5-20 mol % of titanium catalyst. 12 Within this context, by using a combination of 2,4,6-collidine and trimethylsilyl chloride, developed in our laboratory, we have been able to regenerate Cp 2 TiCl 2 from different species such as titanium alkoxides, carboxylates and hydrides.…”

The Nugent Reagent: A Formidable Tool in Contemporary Radical and Organometallic Chemistry

“…Subsequently Oltra et al48 reported the first Cp 2 TiCl‐catalysed Reformatsky‐type reactions between α‐halo ketones and aldehydes (Scheme ). The reported mechanism was similar to that described by Little et al47 for reaction between α‐halo esters and aldehydes.…”