Influence of External Ligands and Auxiliaries on the Reactivity of Low-Valent Titanium in McMurry Reaction: Selectivity and Mechanistic Profile

Influence of various external ligands/auxiliaries on the reductive
carbonyl coupling reactions mediated by
low-valent titanium (LVT) reagents (McMurry coupling) has been
explored. The LVT species generated from Tyrlik's
TiCl3−Mg−THF system has been selected for the
reactivity-tuning trials. Our studies show that incorporation
of
about 10 equiv of pyridine (a π-acceptor ligand) with respect to
TiCl3 to the THF solvated LVT reagent could
arrest
the reductive dimerization of acetophenone at the intermediate pinacol
stage. Modulation of the LVT-species by
covalently-binding monohydroxy, 1,2- and 1,3-dihydroxy auxiliaries also
resisted deoxygenation completely to give
the pinacols in higher yields and better diastereoselectivity, as
compared to pyridine-modified LVT system. Amongst
these modified reagents, the LVT−catechol (1:1) system was found to
be the most efficient combination for total
pinacolization of aromatic carbonyl compounds, even under refluxing
conditions. The actual titanium reagent
responsible for this transformation is proposed to be a Ti(II)
complex formed in situ. Further enhancement
of
stereoselectivity (threo-selectivity) of the pinacols has
been achieved by carrying out the reactions with
LVT-complexes
modified by a variety of covalently-linking auxiliaries at low
temperatures. The results demonstrate that by the
judicious incorporation of various ligands/auxiliaries into LVT
reagents it is possible to widen the scope and
applicability of the classical McMurry reaction.