Journal of the American Chemical Society
Article
hydrogenations of substrates 1e and 1f comprising olefins as
different as an enol ether and a difluoroalkene take the same
course and both result in metathesis; likewise, it predicts that
the ordinary terminal alkene 1b and the much more electron
deficient enal 1k both afford the corresponding cyclopropanes.
However, Scheme 11 shows two cases, which cast doubt on
the view that this interpretation assuming a competing outer-
sphere/inner-sphere mechanism captures the full picture.
Specifically, alkenyl chloride 1g and the trisubstituted enoate
1h both show the “distal pattern” yet undergo metathesis (at
least as the major reaction channel).63 In this context, it is also
necessary to re-evaluate the small number of related examples
documented in the literature in which stoichiometric reactions
of preformed Fischer carbene complexes with enynes resulted in
either cyclopropanation or metathesis depending on the
substitution pattern (and/or the solvent).64−66 Fully convinc-
ing explanations have not been published, but it has been
speculated that the stability of the secondary carbene generated
in the case of metathesis might play a role in determining the
reaction outcome. Although this looksa priorilike a
thermodynamic argument, it cannot be discounted in the
first place but deserves further consideration.
Computational Studies and Mechanistic Discussion.
To complement the experimental data and draw a more
accurate picture of the underlying mechanism(s), detailed
computational studies were carried out using DLPNO-
CCSD(T)/def2-TZVPP single-point energies on top of
B3LYP-D3/def2-TZVP(-f) geometry optimization.67−70 The
perturbative triples correction was calculated using the so-
called semicanonical approximation.71 Solvation effects were
included at the DFT level using the implicit solvation model C-
PCM (CH2Cl2).72,73 An initial exploration of the chemical
space74 was carried out using the semiempirical tight-binding
based quantum chemistry method GFN2-xTB.75
Substrates 1a, 1b, 1e, 1f, and 1i were chosen for this
computational survey. First, extensive conformation sampling
showed that in all cases the tethered olefin is η2-ligated to the
Ru center in the most stable carbene complex A formed during
the gem-hydrogenation step, independent of the electronic
character of the double bond. Complexes of type A, as the
starting point for the computations, nicely correspond to
compound 41 characterized by X-ray diffraction (see Figure 2).
The further evolution into the cyclopropane by an outer-
sphere mechanism, as considered in our preliminary
communication with the explicit caveat that more detailed
scrutiny is necessary,9,62 has a prohibitively high activation
barrier (>35 kcal mol−1) and can hence be safely disregarded.
Rather, A first converts into a “kite-shaped” metallacycle A′
before the pathway bifurcates, in which all three C atoms
entertain bonding interactions to the metal (Figure 3).
Depending on the specific substitution pattern, A′ is either a
regular minimum on the potential energy surface or just an
“inflection point”, as in the case of enyne 1b with the terminal
alkene shown in Figure 3.76 This distorted metallacycle A′ can
cyclorevert via TSAB to afford the (invariant) metathesis
product C and the corresponding secondary carbene;
alternatively, it can evolve via TSAD into the “regular”
metallacycle D, which undergoes reductive elimination and
releases cyclopropane F (this step is facilitated by agostic
interactions in the transition state TSDE and the resulting
adduct complex E).77 For enyne 1b with the terminal alkene,
TSAD leading to the cyclopropane is 1.9 kcal mol−1 lower in
Gibbs free energy than TSAB en route to the metathesis
Figure 3. Metathesis versus cyclopropanation pathways for a carbene
complex derived from enyne 1b with a terminal alkene; as a reference
energy we used the substrate and the [Cp*RuCl] catalyst. For the
sake of simplicity, only the key intermediates and transition states
along the minimum energy pathways are shown.
product; this computational result is in excellent agreement
with the experimentally observed outcome.78 For the highly
ordered character of the transition state leading to D and of the
subsequent reductive elimination step, it is readily understood
why cyclopropanation reactions of substituted alkenes proceed
stereospecifically (compare 1i and 1j in Scheme 11; additional
examples are contained in ref 9).
This basic scenario remains the same for all substrates
investigated (1a, 1b, 1e, 1f, and 1i), but the substituents at the
alkene terminus and the electronic character of the alkene
massively affect the barrier heights. The case of the “isosteric”
difluoroalkene derivative 1f is representative (Figure 4; for the
metallacycle A′(f) formed before the pathways bifurcate is a
true intermediate rather than an inflection point. Once it is
reached, metathesis is almost barrierless and outcompetes
cyclopropanation; this computed outcome is again in accord
with experiment.
It is significant that the barriers for cyclopropanation are
fairly “insensitive” even for enynes comprising olefins as
different as a terminal and a difluorinated alkene (15.9 and
10.6 kcal mol−1, respectively).79 In striking contrast, the
barriers for metathesis are massively affected in that ΔG⧧
decreases from 17.8 kcal mol−1 for 1b to only 2.3 kcal mol−1
for 1f. The trend that the barrier for cycloreversion of the
distorted metallacycle and hence metathesis is particularly
responsive to changes of the substitution pattern and/or
polarization of the olefin (as manifested in the NPA charges)
pertains to all substrates investigated (Table 1): in essence, it is
this effect that determines the outcome.80
This computational result warrants further consideration, as
does that fact that the path leading to the cyclopropane passes
through two distinctly different metallacycles, whereas meta-
thesis involves only one. It is well established in the literature
that metallacyclobutanes in general fall into two different
categories (Figure 5).81−83 One type features a significant
agostic interaction between the metal and the Cβ atom, which
in turn results in a short M···Cβ contact, weakened Cα−Cβ
H
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX