Communication
showed characteristics of both the electrochemical and the
metallic reduction. A more detailed study will be reported in
due course to further elucidate this behavior. As an important
property of reagent 3, we found it to be stable in solution
over prolonged periods of time upon exclusion of oxygen. This
allowed the preparation of stock solutions for convenient han-
dling of the reagent, which were used in the cyclic voltamme-
try experiments.[9]
Table 3. Diastereoselective pinacol coupling of aromatic aldehydes with
3 as terminal reductant.
Entry
Major product
rac/meso
Yield [%][a]
A simplified reaction mechanism is depicted in Scheme 4,
showing the pinacol coupling of benzaldehyde 19a. Reagent 3
reduces the titanocene dihalogenide to a titanium(III) species,
1a
1b
85:15
88:12
70
40[b]
2
92:8
66
3
4
93:7
47
73
85:15
[a] Combined yield of isolated products; [b] reaction with [Cp2TiCl2] as
catalyst.
the yield was decreased (40%; Table 3, entry 1b). With 4-chlo-
robenzaldehyde, the 92:8 d.r. was in range of the previously re-
ported value (Table 3,entry 2).[11d] The reaction worked well
with further aromatic aldehydes, such as 4-methoxybenzalde-
hyde and 2-thiophenecarboxaldehyde (2-thenaldehyde;
Table 3, entries 3 and 4). Overall, the diastereoselectivities were
comparable to the values reported with zinc as reductant and
MgBr2 as additive or under buffered protic conditions with Mn
and collidine hydrochloride.[11] Still, the origin of the stereose-
lectivity could not be disclosed since the previously proposed
transition states were in disagreement with our observations.
The formation of an intermediate M2+-bridged titanium dimer
Scheme 4. Proposed catalytic cycle for the pinacol coupling of 19a with
[Cp2TiI2] and 3 as reductant.
releasing one equivalent of iodotrimethylsilane per molecule
of the reduced catalyst.[9] In analogy to recent studies with
[Cp2TiIIICl] solutions, the reduced titanium(III) species is likely in
equilibrium with the ammonium chloride coordination com-
plex 22.[15] This stabilizes the catalyst in solution and prevents
premature deactivation by decomposition pathways. Aldehyde
coordination to the monomeric [Cp2TiIIII] followed by radical
combination yields the bis-titanium(IV)-coordinated pinacol
product. Based on our observations, we conclude that one
iodide remains at the titanium center in the course of the reac-
tion. Silylation of the titanium-oxygen bonds closes the catalyt-
ic cycle and instantly consumes the trimethylsilyl iodide (TMSI)
that is formed in the catalytic process. Thus, TMSI is not
formed as a byproduct. In comparison, metallic reductants pro-
duce stoichiometric quantities of a Lewis acid, which could
cause side reactions and required removal afterwards.
was ruled out due to absence of M2+ [11,12]
as well as the re-
,
vised pentavalent transition state proposed by Nicholas and
co-workers,[13] which did not match the tetravalent nature of
the titanium center.
As noted, the reactions were faster with [Cp2TiI2] than with
[Cp2TiCl2], which was an unprecedented counter ion effect.
Daasbjerg and co-workers reported that electrochemical reduc-
tion of [Cp2TiI2] initially gave [Cp2TiIIII2]À. Formation of the cata-
lytically active [Cp2TiIIII], by dissociation of IÀ, was significantly
faster in comparison to [Cp2TiIIICl2]À.[14] This would lead to
a higher concentration of the active catalyst in our case, ex-
plaining the observed effect. We confirmed the presence of ti-
tanium(III) species by cyclic voltammetry.[9] Interestingly, a mix-
ture of [Cp2TiIIII2]À, [Cp2TiIIII], [(Cp2TiIIII)2] and [Cp2Ti]+ was detect-
ed. Previously, the formation of [Cp2TiI2]À had only been de-
tected in electrochemical reduction experiments while the for-
mation of [Cp2Ti]+ had been an exclusive feature of the
reduction with metals.[14a] The reduction with 3, however,
In conclusion, we have established a procedure for titanium-
catalyzed reductive umpolung reactions in the presence of
a metal-free reducing agent. [Cp2TiI2] was found to be a superi-
or catalyst to [Cp2TiCl2] and preliminary studies confirmed the
generation of titanium(III) in the presence of tetramethylated
dihydropyrazine derivative 3. The protocol was successfully ap-
Chem. Eur. J. 2015, 21, 1 – 5
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