Ti/Ni-Mediated Inter- and Intramolecular Conjugate Addition of Aryl and Alkenyl Halides and Triflates

Abstract

In this work, we show that the unique combination of a nickel catalyst and Cp2TiCl allows the direct conjugate addition of aryl and alkenyl iodides, bromides, and to a lesser extent, chlorides and triflates to α,β-unsaturated carbonyls at room temperature, without requiring the previous formation of an organometallic nucleophile. The reaction proceeds inter- and intramolecularly with good functional group compatibility, which is key for the development of free protecting group methodologies. Carbo- and heterocycles of five- and six-membered rings are obtained in good yields. Moreover, some insights about the mechanism involved have been obtained from cyclic voltammetry, UV-vis, and HRTEM measurements.

Metal‐Catalyzed β‐Functionalization of Michael Acceptors through Reductive Radical Addition Reactions

“…A combination of a Ti III reagent and a nickel catalyst enabled versatile intra‐ and intermolecular coupling reactions to Michael acceptors and allowed the use of various aryl halides or triflates (Scheme ) 26d,f. Here again, a Ni 0 /Ni II mechanism was proposed, and the titanium(III) reagent was suggested to further activate the carbonyl group and to facilitate the reduction of the Ni II catalyst after the coupling process.…”

Titanocene(III) chloride mediated radical induced addition-elimination route to the synthesis of racemic and optically active trisubstituted tetrahydrofurans: Formal synthesis of magnofargesin and 7′-epimagnofargesin

“…In path B, a diradical species 16 may be formed which undergoes radical coupling to form the intermediate 15 and finally to the product 7. But, formation of aryl/vinyl radical in path B may be discarded as observed 20 by Campaña and Cuerva in a control experiment of intramolecular conjugate addition using aryl iodide and Cp 2 TiCl.…”

Reductive Umpolung Reactions with Low-Valent Titanium Catalysts

“…The striking features of this reaction were (1) the net umpolung reaction that led to a tail‐to‐tail connection of two α,β‐unsaturated compounds, and (2) it represented the first catalytic conjugate β‐alkylation for which an inexpensive, activated alkene was sufficient as coupling partner. In comparison, common Rh‐, Cu‐, Ni‐ or Pd‐catalyzed conjugate additions led to high yields and enantiomeric excesses but usually premetalated or halogenated precursors were required …”

“…In the following, the emergence of titanium(III)‐catalyzed umpolung processes will be discussed with a focus on cross‐selective coupling reactions, which have been the research topic of several labs including ours over the past years. The related reductive Ullmann and Heck couplings, which also connect equally polarized carbon atoms, will not be included, although they share the challenge of achieving cross‐selectivity …”