unknown and likely unstable. However, the dimethyl species (TFA)Tl(CH3)2 is stable in TFAH
at room temperature. Because this class of organometallic compounds are well known to undergo
rapid alkyl transfer, we examined the reaction
of (TFA)Tl(CH3)2 with Tl(TFA)3 as a means of
generating (TFA)2TlIII-Me in situ. Upon addition
of Tl(TFA)3 at room temperature to a solution
of (TFA)Tl(CH3)2 in TFAH, within minutes two
equivalents of Me TFA were cleanly generated in
quantitative yield relative to (TFA)Tl(CH3)2 based
on the stoichiometry shown in Eq. 3. Analysis of
the crude reaction mixture by means of 1H-NMR
immediately upon mixing showed a new, broad,
transient Me-species that could be the (TFA)2Tl
(CH3) intermediate. Consistent with the lack of
H/D exchange in reactions of CH4 with Tl(TFA)3
in DTFA [which we attributed to irreversible formation of the putative (TFA)2TlIII-Me intermediate from CH activation], no CH4 is generated
from these functionalization reactions of (TFA)Tl
(CH3)2 with Tl(TFA)3 in TFAH. These results are
also consistent with reports that treatment of
(OAc)2TlMe with HOAc generates MeOAc (33)
ðTFAÞTlIIIðCH3Þ2 þ TlIIIðTFAÞ3 → TFAH
2Me TFAþ 2TlIð TFAÞ ð3Þ
We have also used M06 density functional theory
(DFT) calculations to examine possible mechanisms and the energy landscape for ethane CH
functionalization, as well as to postulate a mechanism that accounts for the parallel formation of
Et TFA and EG(TFA)2. Calculation details can be
found in the supplementary materials. To begin,
we examined whether it is plausible that Tl(TFA)3
can induce functionalization of ethane by a radical
or one-electron oxidation pathway. Radical chain
mechanisms beginning with a reactive (TFA)2Tl•/
CF3COO•radical pair were ruled out because
Tl-O bond homolysis requires 52.3 kcal mol–1 of
free energy. Additionally, one-electron oxidation
and Tl-mediated hydrogen atom abstraction were
also ruled out because these pathways require
greater than 75 kcal mol–1. Instead, our calculations suggest that the most viable pathway for
ethane CH functionalization is CH activation by
means of electrophilic substitution (Fig. 3A). Calculations also suggest an identical mechanism for
methane (supplementary materials).
In the ground state for Tl(O,O-TFA)3, both
oxygen atoms of the three TFA anions coordinate
to the Tl center in an octahedral-like geometry, and
one oxygen atom in each coordinated TFA is more
tightly bound than the other. Ethane coordination
requires dissociation of one oxygen atom in a O, O-
TFA anion ligand to generate an open coordi-
nation site, to give (O,O-TFA)2(O-TFA)Tl(C2H6).
As anticipated from the conceptual model shown
in Fig. 1 (blue energy diagram), ethane coor-
dination requires a free energy change (DG) of
22.1 kcal mol–1, in part because the d10 main group
metal lacks LFSE. This ethane coordination en-
ergy in non-superacid solvent is much lower than
the >35 kcal mol–1 value found for alkane coor-
dination in superacid solvent with the d8 (bpym)
PtII system that has LFSE. Subsequent CH bond
cleavage from (O,O-TFA)2(O-TFA)Tl(C2H6)
by means of an electrophilic substitution transition-
state free energy change DG‡ = 34.2 kcal mol–1 to
generate (O,O-TFA)2(TFAH)Tl-Et is consistent
with the rates of reactions observed and with rate-
limiting CH bond cleavage. Consistent with the
experimentally measured KIE of 3.4, in this CH
bond cleavage transition state there is consid-
erable Tl-C bond formation and C-H bond
stretching. Calculation of the KIE based on this
transition state gave a value of 4.7. One prediction
based on Fig. 1 is that PbIV should be more reactive
than TlIII is. Indeed, calculation of the electrophilic
substitution transition state for Pb(O,O-TFA)4
with ethane gave a lower DG‡ of 29.2 kcal mol–1
The thermodynamics for the CH activation
step suggests that the Tl-Et species is more stable
than are the Tl(TFA)3 and ethane species (DG =
–3.1 kcal mol–1). Thus, a Tl-Et species such as
(O,O-TFA)2(TFAH)Tl-Et might be observable.
However, calculations predict that Tl-Et functionalization has a much lower barrier than that
of CH activation, and therefore, functionalization of the Tl-Et species is much more rapid than
the CH activation reaction. This explains the lack
of H/D exchange when the reactions are run in
deuterated TFAD as well as the quantitative yield
of Me TFA without any CH4 formation from the
reaction of (TFA)TlMe2 with Tl(TFA)3 in TFAH.
Calculations suggest that there is parallel formation of Et TFA and EG(TFA)2 from the Tl-Et intermediate. The two most plausible pathways for
functionalization are shown in Fig. 3B. The SN2
pathway forms Et TFA, whereas the E2 pathway
forms ethylene. Control experiments show that
although Et TFA conversion is slow, ethylene rapidly converts to EG(TFA)2 in the presence of Tl
(TFA)3 (scheme S2). Thus, this E2 pathway leads
to EG(TFA)2. The calculations suggest that although the SN2 and E2 pathways are competitive,
there is a preference for the SN2 pathway. This is
consistent with experiments showing parallel
but higher rates of formation of Et TFA relative
Consistent with the proposed electrophilic CH
activation mechanism and the experimental ob-
servations that Me TFA is less reactive than CH4,
the calculated DG‡ for CH activation of Me TFA
is ~9 kcal mol–1 higher than the DG‡ for CH ac-
tivation of CH4 (supplementary materials). Cal-
culations also reveal that the presence of the TFA
electron-withdrawing group increases the acti-
vation barrier for CH activation of the methyl
group of EtTFA to 40.4 kcal mol−1. This sug-
gests that the TFA group imparts a strong
electron-withdrawing influence even two carbon
atoms away. This result is consistent with the ob-
served slow conversion of Et TFA to EG(TFA)2.
The electrophilic mechanism is also consistent
with higher reactivity of ethane versus methane be-
cause methyl groups are electron-donating groups
(calculations are available in the supplementary
Experiment and theory taken together strongly support the proposed mechanism for alkane
functionalization involving slow, irreversible electrophilic CH activation of alkanes with third-row,
main-group cations, MnX to generate Mn-R intermediates, followed by fast M-R functionalization to generate MeX and Mn–2. In the 1970 to
1980s, patented technologies were developed to
reoxidize TlI to TlIII by using O2 in connection
with TlIII–mediated oxidation of olefins to glycols in
HOAc (34–36). Applying this reoxidation technology to reactions of other main-group d10
cations, MnX—with alkanes, either in two separate
stoichiometric reactions or, ideally, with MnX as
a catalyst—could lead to practical processes for
the selective hydroxylation of alkanes to alcohols
by using air or other oxidants, such as H2O2. The
absence of claims for reaction of ethane or other
alkanes in these patented olefin oxidation technologies is most likely due to early beliefs that
alkanes were inert to these main-group cations.
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