Tutorial
pubs.acs.org/Organometallics
Tutorial on Oxidative Addition
Jay A. Labinger*
Beckman Institute and Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California
Boulevard, Pasadena, California 91125, United States
ABSTRACT: This tutorial introduces oxidative addition as a reactivity pattern and
organizing principle for organometallic chemistry. The history, characteristics, and
scope of oxidative addition are briefly surveyed, followed by a detailed examination
of the variety of mechanisms found for the oxidative addition of alkyl halides and
their relevance to practical applications.
■
INTRODUCTION
The recognition of oxidative addition as a common pattern of
reactivity has played a central role in the development of
organometallic chemistry over the second half of the 20th
century. The starting point for modern organotransition-metal
chemistry is usually taken as the discovery and structural
characterization of ferrocene in the early 1950s (of course,
there were many important earlier contributions). That inspired
a large amount of new chemistry during the next decade or
soso much, in fact, that it was not easy to codify it in any
rational manner. There was as yet no well-delineated set of
reactivity patterns that had served so effectively as organizing
principles over the preceding century of organic chemistry.1
Notably, the two most popular organometallic chemistry
textbooks of the 1960s were arranged according to periodic
group2 or ligand type.3 Either can be useful for categorizing
information, in its own way, but neither is particularly effective
in terms of explanatory power and pointing the way forward.
The 1960s saw the beginnings of determined efforts toward
systematic, reactivity-based organization, well represented by
Collman’s 1968 Accounts of Chemical Research article4 “Patterns
of Organometallic Reactions Related to Homogeneous
Catalysis”, in which he identified electron count and
coordinative unsaturation as key concepts and described
important reactivity patterns such as migratory insertion and,
especially, oxidative addition. This approach increasingly took
hold, culminating in the seminal 1980 text by Collman and
Hegedus, 5 which clearly demonstrated its pedagogical
strengths. The great utility of reactivity- and mechanismbased thinking, which has been demonstrated in all aspects of
organotransition metal chemistryboth textbook and frontier
sciencecan fairly be said to have all started with oxidative
addition.
This tutorial begins with the basic concept of oxidative
addition and issues concerning its definition and scope. It then
focuses on one particular class of oxidative addition, reactions
of alkyl and aryl halides, emphasizing the mechanistic variety
observed even for stoichiometrically similar transformations,
and concludes with the relevance of mechanistic considerations
for some practical applications. It is not intended as a
© 2015 American Chemical Society
comprehensive review but rather as an introduction to the
topic, such as might be presented in a lecture, as part of a
course on organometallic chemistry. Accordingly, the tone is
rather informal, and citations have been limited to a moderate
number of historically significant papers. Those interested in
following up on any aspects can find more details and thorough
referencing elsewhere; Hartwig’s recent textbook5 is a good
starting point.
■
VASKA’S COMPOUND AND OXIDATIVE ADDITION
The square-planar, d8, 16-electron Ir(I) complex trans-IrCl(CO)(PPh3)2 was first synthesizedrather serendipitously,
apparently6by Vaska and DiLuzio in 1961.7 That report
included the reaction with HCl. A year later the same authors
described analogous additions of Cl2 and, especially, H2.8 It
soon became clear that Vaska’s compound, as it subsequently
came to be universally known, is a highly versatile platform for
the generalized reaction of eq 1. Examples of A−B, in addition
to those already mentioned, include organic halides such as
MeI, metal halides such as SnCl4, metal hydrides such as R3SiH,
etc.4
Ir ICl(CO)(PPh3)2 + A−B → Ir IIIClAB(CO)(PPh3)2
(1)
Since this reaction involves a net formal oxidation from Ir(I)
to Ir(III) accompanied by increases in both coordination
number (4 to 6) and electron count (16 to 18), the term
oxidative addition seems obvious and logical; the first person to
use it in this context9 though (so far as I have been able to find)
was not Vaska, but rather Collman, in a 1965 paper on the
related chemistry of Ru(CO)3(PPh3)2 (eq 2).10 Note that these
are not perfect analogues: while the formal oxidation state does
increase by 2 units, from Ru(0) to Ru(II), the starting
compound is 5-coordinate, 18-electron, with one of the original
CO ligands being lost at some point. That raises the question
even at this extremely early point in the historyof what a
“pattern” really entails. Is stoichiometric similarity what matters,
Received: June 29, 2015
Published: October 26, 2015
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O2 parametersthe O−O bond length and νOOof the O2
adduct of Vaska’s compound to those of free O2 and its anions.
As Table 2 shows, the IrIII−peroxo picture looks by far the
best.13
and if so, how much variability should we allow? Or should
mechanistic similarity be the main criterion? To what extent
can we infer one from the other? These are important issues
that will recur throughout the discussion.
Ru 0(CO)3 (PPh3)2 + A−B
Table 2. Bond Parameters for Several O2 Species
→ Ru IIAB(CO)2 (PPh3)2 + CO
(2)
In retrospect, it is clear that Vaska’s compound was the ideal
starting point for studying oxidative addition. We can change
ligands virtually at will: Cl to other X-type ligands, such as
halides and pseudohalides, and PPh3 to other L-type ligands,
usually a tertiary phosphine or arsine.11 That flexibility provides
ready access to examining electronic and steric effects on the
kinetics and (in some cases) thermodynamics of the reaction.
Monitoring kinetics is likewise convenient, using either visible
or infrared spectroscopy. For the former, the starting material is
yellow, while just about every oxidative adduct is colorless; the
latter takes advantage of the fact that CO stretching bands in
metal carbonyls are strong, sharp, and highly sensitive to the
electronic environment at the metal center, reflecting the
degree of back-bonding into the CO π* orbitals.
That last feature helps sheds light on an important question:
are these reactions truly oxidative, or is this only in a formal
sense? (We do not normally think of H2 as an oxidizing agent,
but all one-electron ligands are conventionally treated as anions
for the determination of formal oxidation state, including H−.)
Table 1 shows νCO values for several examples of eq 1
νCO, cm−1
none
H2
O2
HCl
CH3I
Cl2
1969
1983
2015
2045
2047
2075
rOO, Â
νOO, cm−1
dioxygen, O2
superoxide, O2−
peroxide, O22−
IrCl(O2(CO)(PPh3)2
1.21
1.33
1.49
1.47
1556
1145
820
850
As these are apparently “real” oxidations, at least by the
criterion of νCO, we can expect certain trends in thermodynamic favorability, with the trends in kinetics quite possibly
but not necessarilyrunning in parallel. These are mostly
borne out in experience. For example, the equilibrium constants
for formation of the H2 adduct of IrCl(CO)L2 follow the
sequence L = PPh3 < P(n-Bu)3 > P(cyclohexyl)3: the first
inequality reflects the greater basicity/electron donating power
of trialkyl- vs triarylphosphines, while the second reflects steric
crowding, which is more pronounced for the 6-coordinate
product than the 4-coordinate reactant. The effect of varying
the X ligand is generally less predictable, perhaps because the
effects of electronegativity and π-donor ability can operate in
opposing senses.
Comparing complexes of different metals, especially when
the differences extend across periodic groups and electronic
configurations, is complicated by effects of net charge,
preference for 4- vs 5-coordination, etc. However, trends
within more or less isostructural complexes from the same
periodic group are usually reliable. In particular, there is a
general tendency for higher oxidation states to become
increasingly favored on descending within a group of the
periodic table (compare, for example, the M(VIII) species
FeO4, which is unknown, RuO4, a metastable, uncontrollably
powerful oxidant, and OsO4, a stable and useful reagent for
organic oxidations), and that applies to oxidative additions:
thermodynamically for certain and often kinetically as well. For
example, the H2 adducts of Rh complexes RhCl(CO)L2 are
much less stable than those of Ir analogues; likewise, the rate of
addition of RX is considerably slower for Rh than for Ir, an
effect of which we will see in the very last section.
This trend bears a good deal of responsibility for yet another
generalization, that the best homogeneous catalysts are found
among the second-row transition metalsRu, Rh and Pd in
particular. The interpretation is that generation of intermediates
by reactions such as oxidative addition is too unfavorable for
first-row-metal complexes and too favorable for third-row
complexes, such that a large energy barrier will intrude
somewhere along the catalytic cycle, whereas second-row
complexes are more likely to satisfy the Goldilocks condition.
This generalization stood up pretty well for a long time but is
probably not that useful any longer: our growing understanding
of mechanisms and factors controlling stability and reactivity
have led to effective utilization of the other two rows. We will
see some examples (Ni for cross-coupling, Ir for carbonylation)
in the concluding sections.
Table 1. CO Stretching Frequencies for IrClAB(CO)(PPh3)2
A−B
species
(including O2, which does not exactly fit the model; we will
return to that shortly). Everything else being equal (which it
strictly is not, since the geometries of the products differ: H2
and O2 add in a cis configuration and the rest in trans), a higher
νCO value indicates a higher effective oxidation state.
Note that the strong oxidant Cl2 gives the greatest increase in
νCO, while H2 appears to result in only a small (but real, and
positive) change, as we might have expected. Actually the latter
is somewhat misleading: metal−hydrogen stretching vibrations
fall in the same frequency range, typically 2000−2200 cm−1,
and if symmetry permits, observed peaks represent mixed
vibrations, so that the band at 1983 cm−1 is not a pure CO
stretch. How do we know? By simply making the D2 adduct:
νIr−D is much lower, around 1570 cm−1, so there is little or no
mixing, and νCO now appears at 2030 cm−1. Hence by this
criterion H2 is almost comparable to HX or RX in effectively
oxidizing the metal center and is apparently better than O2!
Perhaps we should not classify the reaction with O2 as an
oxidative addition?12 There are (at least) two alternate
descriptions possible for the M−O2 interaction, similar to
that for olefins: as a π adduct of neutral dioxygen, IrI(O2), or as
a “real” oxidation, where the OO π bond has effectively been
cleaved to give an η2-peroxo complex, IrIII(O22−). Or it could be
somewhere in between. To probe that issue, we can compare
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■
OXIDATIVE ADDITION OF RX: MECHANISTIC
CONSIDERATIONS
Earlier we raised this question: to what extent does
stoichiometric similarity imply mechanistic similarity? Given
the broad range of addends A−B that exhibit the stoichiometric
pattern, we might anticipate the answer: not so much. A
comprehensive survey of oxidative addition mechanisms would
far exceed the scope of this tutorial; hence, we will focus on just
one (but still quite broad) class of reactions, those of alkyl and
aryl halides, for several reasons. First, we have available a large
array of mechanistic tools from physical organic chemistry for
studying these reactions. Second, the reactions display a
surprising number of quite distinct mechanistic patterns, even
among reactions that stoichiometrically appear almost identical.
Finally, they comprise key steps in many important practical
transformations, which will be the subject of the concluding
section.
To begin, let us broaden the definition of oxidative addition
somewhat beyond eq 1, to include any reaction of a metal
complex with RX that results in both an increase in the formal
oxidation state and formation of a new M−R bond. It is
convenient to further subclassify these according to the net
change in the overall electron count, which is typically 0, +1, or
+2. We will consider these in turn.
Case 1: 0 e−. A 0-electron oxidative addition of an alkyl
halide may be represented by eq 3, where the starting metal
complex is often (not always) a coordinatively saturated 18electron anion of oxidation state m and the product also has an
18-electron count but an oxidation state of m + 2; the
coordination number has also increased by 1. Stoichiometrically, this looks a lot like a classic SN2 reactionis it? What are
the tests for the SN2 mechanism in organic chemistry? We
expect (1) overall second-order kinetics, first order in both
metal-centered nucleophile and RX, with a significantly
negative ΔS⧧ value, (2) a strong rate dependence on the
nature of R, following the sequence Me > Io > IIo ≫ IIIo and
enhanced reactivity for allylic and benzylic halides, and (3)
considerable dependence on the nature of X, with I− > Br− >
Cl−, and other leaving groups such as tosylate and triflate also
exhibiting reactivity. Perhaps most characteristic of all is (4)
inversion of configuration (Walden inversion) at carbon, for a
suitably designed R.
[LnMm]− + R−X → LnMm + 2−R + X−
Table 3. Second-Order Rate Constants for Some Reactions
of eq 4a
a
RX
k, M−1 s−1
MeCl
MeBr
MeI
EtBr
iPrBr
tBuBr
PhCH2Cl
0.85
220
2300
1.6
0.11
no reaction
440
At 25 °C; L = P(n-Bu)3.
These results seem to satisfy all the criteria for SN2 quite well,
but even Schrauzer acknowledged that demonstration of
Walden inversion would be highly desirable for definitive
proof. The paper cites “unpublished experiments” on reactions
of “asymmetric substrates” which “indicate that this mechanistic
criterion is fulfilled”, but no such results were ever published,
and it is not at all clear what they might have been. If by
“asymmetric” they meant optically active, there is a problem:
the classic experiment in organic chemistry is to measure the
optical rotation of the starting alkyl halide and the product
derived therefrom and then use known information to relate
the relative directions of those rotations to the absolute
configurations of the two species. However, not all the
necessary information was available. They would have had
the relation between sign of rotation and absolute configuration
for their starting R*X, but not for product R*M. To deduce that
they would need either a crystallographic determination of
absolute configurationwhich was difficult and rarely
performed at that timeor, more conveniently, to convert
R*M to some other species R*Y for which the relationship was
known. Again, at the time, there were no such auxiliary
conversions known with conf idence to proceed with retention or
inversion. Hence, no experiment based on optical activity could
have led to an unambiguous conclusion.
However, a conclusive demonstration of inversion was
achieved by Whitesides around the same time, using a different
metal complex and an NMR method.15 The anionic iron(0)
complex [(η5-C5H5)Fe(CO)2]− (henceforth abbreviated Fp−)
reacts with a wide range of RX to give FpR. The R group that
Whitesides devised to provide a suitable stereochemical probe
was erythro-t-BuCHDCHDOBs (where OBs is the leaving
group p-BrC6H4SO3−). As can be seen in Scheme 1, the
relationship between the two vicinal protons in the major
(3)
One of the earliest studies was carried out on the vitamin B12
analogue [CoI(DMG)2L]−, where DMG is the dimethylglyoximato monoanion and L is a neutral ligand, usually a phosphine
or substituted pyridine; these react with alkyl halides to give
alkyl−Co(III) products (eq 4).14 The kinetics are indeed
Scheme 1. Alternate Possible Outcomes for the Reaction of
Fp− with Stereolabeled RX
second order; ΔS⧧ falls in the range of −20 to −30 eu, and the
rate varies as a function of R and X much as expected, as shown
by the examples in Table 3.
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dif ferent 6-coordinate, 18-electron Co(III) species. Like the SN2
reactions discussed above, these exhibit clean second-order
kinetics, but they vary with R and X quite differently, as shown
in Table 4.17 SN2 reactions are substantially slower at more
conformer of the product will be either gauche or trans,
depending upon whether the reaction proceeds with inversion
or retention, respectively. We can determine which it is by 1H
NMR, from the Karplus relationship, which tells us that 3JH−H is
much larger for trans than for gauche. The measured 3JH−H
values were 8.6 Hz for the starting ROBs but only 4.5 Hz for
the product FpR; there was no detectable signal for the
opposite stereoisomer (which was known to have 3JH−H = 13.1
Hz from analysis of the all-proteo isotopologue; the larger value
in comparison to that of the starting ROBs reflects the greater
steric bulk of the Fp group, which results in much greater
predominance of the major rotational conformation). Hence,
this reaction proceeds entirely with inversion at carbon,
consistent with an SN2 mechanism.
So should we conclude that all reactions which follow the
pattern of eq 3 proceed by SN2 mechanisms? Not so fast!
Consider the reaction shown in eq 5, which looks virtually
Table 4. Second-Order and Relative Rate Constants for
Some Reactions of eq 6a
a
RX
k, M−1 s−1
RX
krel
MeI
EtI
i-PrI
t-BuIb
PhCH2Cl
PhCH2Br
PhCH2I
0.01
0.056
1.2
9.2
0.00049
2.33
3800
ClCH2CO2Me
BrCH2CO2Me
ICH2CO2Me
1 (defined)
3 × 104
5 × 107
At 25 °C. bNo stable Co−R obtained.
substituted carbon centers, with methyl halides as much as 2
orders of magnitude faster than ethyl halides; here the reverse is
true, with methyl iodide being substantially slower. Benzyl
halides are considerably more reactive than simple alkyl halides
in both cases. The dependence on X follows the same
directional trend in both, but the degree of that dependence is
much greater here: several orders of magnitude faster for each
step from Cl to Br to I, whereas the corresponding increases for
SN2 are only 1−2 orders of magnitude each.
identical with the reaction we’ve just examined but (when X =
I) gives a substantial amount of an isomer in addition to the
expected product. What’s going on?
Clearly there’s been a ring-opening rearrangement at some
point, and equally clearly that has not happened at the product
stage (since the unrearranged FpR is the sole product from
RBr) or in an intermediate during an SN2 reaction (which by
definition has no intermediates!). There must be an alternate,
competing mechanism, and the most likely candidate is one
that generates an intermediate cyclopropylmethyl radical, which
is known to ring open rapidly: the single electron transfer
(SET) route shown in Scheme 2. SET is known to be faster for
All of these observations are consistent with rate-determining
halogen atom abstraction by Co(II), followed by rapid capture
of the resulting alkyl radical by a second Co(II) (Scheme 3).
Scheme 2. Alternate Radical-Based Route for Reaction of
Fp− with RI
Scheme 3. Two-Step Mechanism for the Reaction of Co(II)
with RX
iodides than for bromides; that is also true for SN2, of course,
but the differentials are generally considerably larger for radical
pathways, as we will see shortly. Hence, SET cannot compete
with SN2 for X = Br, and no rearrangement is observed. With
non-halide leaving groups such as OBs, SET is even less
favorable. The formation of alkyl radicals in reactions of Fp−
with a variety of alkyl iodides was confirmed by EPR.16
This finding should warn us to be wary of extrapolating from
stoichiometry to mechanism: we must always be alert for the
possibility of parallel, competing pathways that can get us from
the same starting point to the same end point, where apparently
minor changes in reactant or reaction conditions may be
sufficient to bring about a mechanistic switch.
Case 2: 1 e−. Since we know 18-electron configurations
tend to be stable, a reaction that increases the electron count by
just 1 might be expected to be particularly favored when the
starting complex has a 17-electron configuration. The
paradigmatic example is that of pentacyanocobaltate, which
reacts with alkyl halides according to eq 6, where a 5coordinate, 17-electron Co(II) complex is converted to two
The reaction proceeds via alkyl radicals, but here we have an
inner-sphere mechanism, unlike the SET pathway for Fp−
(Scheme 2). In addition, the reaction exhibits clean secondorder kinetics, which we do not always expect when radicals are
involved; however, keep in mind that complex kinetic behavior
is typically associated with a radical chain mechanism, which
this is not.
Systems that have been shown to proceed by this mechanism
are considerably less common than the SN2 alkylations of the
previous section. They mainly involve first-row transition
metals, where we are most likely to find two stable species
differing by a single oxidation state. Some examples that follow
Scheme 3 for at least some RX include CoII(DMG)2L, obtained
by oxidation of the Co(I) nucleophiles discussed earlier,
pentaaquochromous ion, [CrII(H2O)5]2+, and vanadocene, (η5C5H5)2V. Cobaltocene reacts according to the same 1:2
stoichiometry, but does not give the analogous products
not surprisingly, as they would be 20-electron species. Instead,
we get the ionic 18-electron cobaltocenium halide, most likely
via outer-sphere SET, with the resulting alkyl radical adding to
a second Cp2Co at the Cp ring, not the Co center, to form (η5-
2[Co(CN)5 ]3 − + RX
→ [Co(CN)5 R]3 − + [Co(CN)5 X]3 −
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cyclopentadienyl)(η4-alkylcyclopentadiene)Co, which is also an
18-electron species (eq 7).
to overall trans addition, a rather awkward-looking process
(termed by some the “bacon-slicer” mechanism). However, it
was certainly possible that the brominolysis of a coordinatively
saturated transition-metal alkyl proceeds quite differently, with
a different stereochemical outcome, than that of a mercury
alkyl.
Again, to achieve a definitive result, the NMR method was
applied.21 “Simple” stereolabeled alkyl halides such as tBuCHDCHDBr proved too inert for all but the most reactive
version of Vaska’s compound, with L = PMe3, and then the
crucial region of the NMR spectrum was obscured by ligand
signals. Hence, it was necessary to design a fluorinated
analogue, which both shifted one of the 1H signals downfield,
away from the PMe3 multiplet, and provided additional data in
the form of H−F coupling constants. The reaction sequence is
shown in Scheme 4 (the epimer of the RBr reagent was also
examined, starting from the cis deuterated styrene).
Case 3: 2 e−. This case represents the original, restricted
definition of oxidative addition, and most of the seminal
mechanistic worknot surprisinglyinvolves Vaska’s compound and analogues. The earliest study was done for RX =
MeI by Halpern,18 who found
• clean second-order kinetics
• ΔS⧧ ≈ −40 eu
• the reaction is faster in more polar solvents
• EtI is much less reactive, but benzyl and allyl halides are
quite reactive
All of these observations seem most consistent with an SN2
mechanism, with the Ir(I) center acting as nucleophile. The
first step would be completely analogous to the 0 e− case
discussed above, generating a 5-coordinate, still 16-electron,
cationic intermediate, which subsequently traps I− to complete
the overall 2 e− oxidative addition. Since that trapping is the
microscopic reverse of ligand dissociation, it would be expected
to take place preferentially opposite the strongest transdirecting ligand of the intermediate, which is the methyl
group, and indeed overall trans addition (eq 8) was
subsequently established.
Scheme 4. Synthesis of a Stereolabeled RBr and the
Alternate Outcomes of Its Reaction with Ir(I)
As with the 0 e− case, confirmation by demonstration of
inversion at carbon was eagerly sought. Methyl iodide is clearly
not suitable;19 the first experiment20 was carried out using an
optically active α-bromo ester, whose decreased reactivity
relative to MeI required the use of a more basic L, PMePh2.
The results are shown in eq 9. Despite the relatively low
For the RS,SR isomers, we expect 3JH−H and 3JH−F values to
be relatively small and large, respectively (the Karplus
relationship holds for 19F NMR as well) and the opposite for
RR,SS. 19F NMR spectra of the two starting RBr compounds
are shown in Figure 1 and are in accord with expectations. Both
the 1H and 19F NMR spectra of the oxidative addition product
are shown in Figure 2; they are only interpretable on the basis
of a 50:50 mixture of both epimers, a finding confirmed by the
fact that the same spectrum is obtained using either epimer of
the starting RBr! Clearly, then, the mechanistic consequence is
neither retention nor inversion but loss of stereochemistry at
the reacting carbon center.
This disagrees with Pearson’s finding but is not necessarily
contradictory: the presence of an α-carboxylate group could
change the mechanism. Accordingly, a stereolabeled α-bromo
ester was prepared and tested, with the same outcome: the
same mixture of epimers (not 50:50 in this case, since they
differ by more than the location of H vs D) is obtained from
either epimer of RBr (eq 10). That strongly suggested that
Pearson’s findings should be revisited, and indeed they were
shown to be incorrect: reaction of the same α-bromo ester used
specific rotation of the starting RX (which was obtained by
partial resolution of the racemic α-bromo acid, followed by
esterification), it appears that the IrIII−R product retains
substantial optical activity. As noted earlier, the direction and
magnitude of its rotation tell us nothing, beyond the fact that
some stereoselective pathway appears to be operating.
Brominative cleavage regenerates the α-bromo ester with the
same direction of rotation as the starting compound, albeit with
an apparent loss of optical purity; this means that oxidative
addition and brominolysis have the same stereochemical
consequence: both go with retention or both with inversion.
Which is it? By analogy to brominolyses of alkylmercury
compounds, which were known to proceed with retention,
Pearson proposed that oxidative addition does so as welleven
though that implies front-side attack on the C−X bond leading
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other indications of that as well. In particular, in contrast to
all the cases we’ve looked at so far, these reactions do not
exhibit clean kinetics. Rates are irreproducible and do not
follow any simple rate law; reactions are very substantially
accelerated by initiators such as benzoyl peroxide and AIBN
and retarded by inhibitors such as duroquinone and galvinoxyl.
The presence of O2 can cause either acceleration or inhibition,
depending on concentration. All of these findings are
characteristic of a radical chain pathway.22
A reasonable candidate for the latter is the one shown in
Scheme 5, where Q• represents an initiator, which may either
Figure 1. 19F NMR signal for the proton gem to F of RR,SS (top) and
RS,SR (bottom) isomers of PhCHFCHDBr. In addition to the large
2
JHF value, the top spectrum shows large 3JDF and small 3JHF values
relative to the bottom spectrum. The syntheses are not perfectly
stereospecific: each sample contains about 15% of the other epimer.
Reproduced with permission from ref 22a. Copyright 1980 American
Chemical Society.
Scheme 5. Initiation and Propagation Sequences of a Radical
Chain Mechanism for Oxidative Addition of RX to Ir(I)
be deliberately added or be an adventitious impurity. The
species QIr(II) and RIr(II) are 17-electron species, isoelectronic with [Co(CN)5]3−, and can reasonably be expected to
react similarly with RX, by halogen atom abstraction. We might
expect this step to be slow relative to addition of R• to Ir(I),
since it includes breaking a bond while the addition step does
not, and thus it should determine the dependence of rate on R.
However, because rates are irreproduciblepresumably a
consequence of variable trace impurities that can serve as
either initiators or inhibitorswe cannot determine them
directly. Instead, by comparison of the relative amounts of
products obtained from a mixture of two alkyl halides, one used
as a standard reference, the effect of impurities can be
minimized and relative rates can be estimated. The values nBuBr:s-BuBr:t-BuBr ≈ 1:5:7 are very similar to the trend
observed for known radical-chain mechanisms such as hydrogenolysis by R3SnH, although the range of variation is
considerably smaller than for the reactions of [Co(CN)5]3−
(see Table 4).
However, recall that we previously saw strong evidence for
SN2 in the reaction of MeI with Vaska’s compound! Are there
two competing mechanisms here, as with Fp−? Again, we can
use a competitive test: react an Ir(I) complex with a mixture of
two alkyl halides and compare the product split with and
without added inhibitor. That should not change much if both
Figure 2. 1H (top) and 19F (bottom) NMR spectra of the product
obtained from IrCl(CO)(PMe 3 ) 2 with either isomer of
PhCHFCHDBr. Both spectra show the presence of equal amounts
of the two epimeric products: the RS,SR isomer gives a broad doublet
in 1H and a doublet of doublets in 19F (2JH−F and 3JH−F are nearly
equal for this epimer), while RR,SS gives a doublet of doublets in 1H
and a very broad doublet (shifted upfield relative to the doublet of
doublets, an isotopic shift also detectable in Figure 1) in 19F.
Reproduced with permission from ref 22a. Copyright 1980 American
Chemical Society.
by Pearson, but with a much higher starting optical purity
(obtained from optically pure lactic acid), with IrCl(CO)L2
using several different phosphine ligands gave strictly racemic
product in all cases (eq 11).
Thus, the “simple” alkyl bromide of Scheme 4 and two
different α-bromo esters all undergo loss of stereochemistry
upon oxidative addition to these Ir(I) complexes. This
immediately suggests radical intermediates, and there are
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follow the radical chain path, but it should change a lot if one
follows that path but the other does not. The results in Table 5
Scheme 6. Non-Chain Radical-Based Alternate Pathway for
Reaction of Pd(0) with Benzyl Halides
Table 5. Fraction of MeI Adduct Obtained in Reactions of
IrCl(CO)(PMe3)2 with Mixtures of MeI and Another Alkyl
Halide, without and with Added Inhibitor
Me adduct, %
competing RX
EtI
MeCHBrCO2Et
PhCH2Br
CH2CHCH2Cl
no inhibitor
with inhibitor
±
±
±
±
100
100
51 ± 5
18 ± 3
63
50
54
17
6
8
5
3
One last 2-electron case that merits attention is that of aryl
and vinyl halides. For alkyl halides, we have established an SN2
route and several radical-based routes, but neither looks all that
good here: sp2-hybridized C−X bonds are not expected to be
very susceptible to halogen atom abstraction, because of the
greater C−X bond strength, nor to nucleophilic attack (except
for aryl halides bearing additional strongly electron withdrawing
substituents). Indeed, the reactions of IrCl(CO)(PMe3)2 with
reagents such as 1,2-dichloroethylene and iodobenzene proceed
only slowly at elevated temperatures and show inhibition by
galvinoxyl.
In contrast, oxidative additions of aryl and vinyl halides to
zerovalent phosphine complexes of the group 10 metalsLnM,
where M = Ni, Pd, Ptare often facile; indeed, oxidative
additions to Pd(0) and Ni(0) are involved in a majority of the
powerful array of cross-coupling methods, as we will discuss
below. How, then, do they proceed? Some sort of SET path
may appear reasonable for Ni, since as noted earlier oneelectron-redox processes tend to be more favorable for first-row
transition metals but are less so for Pd. While definitive
mechanistic characterization has proven hard to obtain, most of
the evidence suggests that C−X bond cleavage proceeds from
an intermediate η2-haloarene adduct, with the actual bondbreaking step being more or less concerted (computational
studies differ on the precise description), as shown in eq 13.
show clearly that ethyl iodide and the α-bromo ester do react by
a radical chain path, whereas methyl iodide, benzyl bromide,
and allyl chloride do not. Related experiments show that the
radical path is much more sensitive to the nature of X, with I ≫
Br ≫ Cl, than the nonradical path, consistent with what was
seen before. In addition, it is much more sensitive to L: as we
go from L = PMe3 via PMe2Ph and PMePh2 to PPh3, reactions
proceeding by the nonradical path slow down considerably but
those that go by radicals shut down altogether.
All indications to this point are that the nonradical path is
indeed the SN2 mechanism, but we still have not demonstrated
inversion of stereochemistry. The first clear-cut example was
achieved by Stille, using optically active benzyl halides with d10
metal complexes (eq 12).23 With substitution of D for H being
the only source of asymmetry, the specific rotation is small but
is quite enough for precise measurements. Note that, as before,
we cannot deduce the configurations of the Pd complexes from
the signs of rotation a priori, but here we can convert the
benzyl−Pd species to the phenylacetate esterfor which the
relationship between sign of rotation and absolute configuration is knownby two steps that are stereochemically
unambiguous. The first, insertion of CO into a metal−carbon
bond, has been universally found to proceed with retention; the
second, oxidative cleavage of the acyl−Pd bond, does not affect
the stereocenter at all. Hence, the stereochemistry of the overall
process is identical with that of the oxidative addition step.
When L = PPh3 and X = Cl, the reaction was found to go
with 100% inversion; in contrast, with L = PEt3 and X = Cl only
72% net inversion was observed and with L = PEt3 and X = Br
the net inversion was only 19%. This suggests a competing
radical-based pathway, with trends entirely consistent with
those found for Ir(I) above: making L more electron donating
and switching from X = Cl to X = Br should both accelerate
radical reactivity more than SN2. However, in this case the
radical pathway is not the same chain mechanism established for
Ir(I), as addition of inhibitor affects neither overall reactivity
nor stereospecificity. Instead, this appears to be yet a third
radical route, an inner-sphere analogue of the SET mechanism
of Scheme 2, where the caged radical pair can collapse to give
the oxidative addition product or, less frequently, diffuse apart
to give bibenzylwhich was foundalong with other products
(Scheme 6).
Evidence includes rather small solvent effects and dependence
on other arene substituents (Hammett ρ typically ∼2),
indicating little charge separation in the transition state. This
reaction takes place neither at a coordinatively saturated 18electron PdL4 centerno surprisenor at “monounsaturated”
16-electron PdL3 but rather at the 14-electron PdL2 stage, as
shown by the dependence on [L] in kinetics. This may explain
the difference between these reactions and those of IrCl(CO)(PMe3)2: coordination of haloarene might well be possible
there too, but that would result in a coordinatively saturated
configuration from which further reaction would be disfavored;
thus, only the radical chain path of Scheme 5 is accessible, and
only at elevated temperatures. In contrast, the L2Pd0(η2haloarene) adduct is still coordinatively unsaturated, allowing
the intramolecular C−X cleavage to proceed without a large
barrier.
It is worth briefly digressing here to sketch how such kinetics
information is processed, as a potentially useful object lesson,
since it may not be immediately obvious. Consider the reaction
of Pd(PPh3)4 (which is prepared and used as the stable 18electron complex) with iodobenzene; the kinetics are first order
in both [Pd] and [PhI] and inverse first-order in [PPh3].
However, if the reacting species is the 14-electron species PdL2,
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requiring dissociation of two L’s, should not the rate be inverse
second order in [L]? Not necessarily! If we assume fast
equilibrium dissociation of first one and then a second L,
followed by rate-determining oxidative addition, we have
methodology is reflected by the 2010 Nobel Prize, which
went to Negishi, Suzuki, and Heck.
The overall catalytic cycle is represented in Scheme 7; often,
but by no means always, the oxidative addition step limits the
K1
PdL4 ⇄ PdL3 + L
Scheme 7. General Mechanistic Scheme for Cross-Coupling
Chemistry
K2
PdL3 ⇄ PdL 2 + L
k
PdL 2 + PhI → L 2PdIPh
The rate expression should thus be k[PdL2][PhI]but we
do not know [PdL2], we only know the concentration of PdL4
we started with, [Pd0]total, and what we measure is its
disappearance, generating the empirical rate expression
kobs[Pd0]total. However, [Pd0]total = [PdL4] + [PdL3] +
[PdL2], and we can relate the first two to the last using the
equilibrium expressions for dissociation of L. That gives us
[Pd0]total in terms of [PdL2], which we substitute into the rate
expression to get (all the algebra is left to the reader!)
rate =
rate of catalysis. Nearly all the earlier successes in this field were
for aryl and vinyl RX, which may seem at first surprising, as we
have seen that those oxidative additions can be more difficult
than those of alkyl halides. However, that is not the problem;
rather, when R is an alkyl group, the first intermediate,
LnMIIRX, is often prone to β-hydride elimination, shortcircuiting the cycle at an early stage.
The choice of ligand L is usually crucial for achieving a good
(or any) yield, and optimization usually needs to be done
primarily by trial and error: two very similar-looking couplings
may well have different best choices. This should not be a
surprise: several different steps are involved, and changes that
make one better may well make another worse. One reasonably
good generalization is that sterically bulkier ligands accelerate
coupling. This seems somewhat counterintuitive, if oxidative
addition is rate limiting: we observed steric retardation for
oxidative addition to IrCl(CO)L2. However, recall that
oxidative addition to PdLn requires prior dissociation to PdL2,
which will be favored for larger ligands, an effect that can more
than compensate for any steric hindrance of the oxidative
addition step per se. With extremely large ligands, rapid
oxidative addition may even proceed via the further-dissociated
12-electron PdL. For example, Pd(P(o-tolyl)3)2 reacts with aryl
bromides to give dimeric LArPd(μ-Br)2PdArL, and the kinetics
show a 1/[L] dependence, indicating dissociation of the second
L occurs before, not after, the oxidative addition. This reaction
proceeds much faster than the corresponding oxidative addition
to Pd(PPh3)4.24
Reliable methods for coupling to alkyl halides were
developed later, over the last 10 years or so, and typically
make use of large, tightly bonded phosphine ligands that hinder
β-elimination. For example, the Suzuki coupling of eq 15 can be
accomplished in good yields for primary alkyl halides using
bulky ligands such as P(cyclohexyl)3 and PMe(t-Bu)2.
Secondary alkyl halides work less well and usually require Nibased catalysts. That makes sense in terms of our earlier
mechanistic discussion: primary RX can react via an SN2 path,
but that will be considerably less favorable for a secondary alkyl
center. Hence, we need to access a radical-based mechanism,
which is generally easier to do for a first-row transition metal.
For such a route coupling of tertiary alkyl halides ought to work
as well or better, and indeed some examples thereof have been
reported.
k[Pd0]total [PhI]
[L]2
K1K 2
+
[L]
K2
+1
from which we can see that the apparent order in [L] can be
inverse second, inverse first, or even zero, according to the
magnitudes of the dissociation constants. For the present
example it must be the case that K1 is large but K2 is notin
other words, the major species in solution is PdL3so that the
first and last terms of the denominator can be neglected relative
to the middle term, giving a 1/[L] dependence.
■
OXIDATIVE ADDITION OF RX: PRACTICAL
APPLICATIONS
While there is quite a wide range of processes that involve RX
oxidative addition in at least one step, we only have space to
look at two: cross-coupling, which has become a central
component of organic synthetic methodology, and the largescale industrial synthesis of acetic acid from methanol.
Cross-Coupling Reactions. We will not attempt a
comprehensive survey of this topic herethat would easily
comprise an entire such tutorial in its own rightbut only
examine some consequences of the mechanistic aspects of RX
oxidative addition, a key step in this chemistry. As a brief
summary, the generic cross-coupling reaction can be
represented by eq 14, where R′M is one of several maingroup organometallics; each case has been named after its
original discoverer.
catalyst
R−X + R′M ⎯⎯⎯⎯⎯⎯→ R−R′ + MX
(14)
R′M = R′MgY (Kumada), R′ZnY (Negishi),
R′SnY3 (Stille), R′BY3 (Suzuki)
The catalyst is typically a phosphine complex of Pd(0) or
Ni(0), either presynthesized or generated in situ from an
appropriate M(II) precursor; additional base is usually required
as cocatalyst. There are other variants that also involve RX
oxidative addition, such as alkylation of an olefin by R (Heck
coupling) and formation of new carbon-heteroatom bonds to R
(Buchwald−Hartwig coupling). The importance of this
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Pd0, L
R−X + R′−BBN ⎯⎯⎯⎯⎯→ R−R′
base
oxidative addition of CH3I (formed in situ, noncatalytically,
from CH3OH and HI). The overall catalytic conversion is then
completed by insertion of CO into the Rh−CH3 bond to form
an acetyl, reductive elimination of acetyl iodide, and hydrolysis
to give the acetic acid along with regenerating HI (Scheme 8).
(15)
A striking demonstration of the involvement of radical
intermediates can be found in the enantioselctive Negishi
coupling reaction shown in eq 16, which gives the coupled
[Rh], I−
CH3OH + CO ⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→ CH3COOH
180 ° C, 30 atm
(17)
Scheme 8. Sequence of Reactions Adding up to
Carbonylation of Methanol by the Monsanto Process
products in up to 99% ee, even though the starting RX is
racemic!25 As we saw in the discussion of Ir complexes above,
normally radical intermediates do not lead to stereoselectivity:
how does this work? The oxidative addition step generates an
intermediate planar indenyl radical, which is captured by Ni to
give R−Ni; but with a chiral ligand on Ni, capture at one of the
two faces of the radical will be energetically more favorable than
the other. If the difference can be made sufficiently largeas it
clearly canhigh enantioselectivity can be achieved.
The closest analogue to the chain mechanism established for
IrCl(CO)(PMe3) (Scheme 5) would consist of R• adding to
Ni(0) to give RNiI, followed by abstraction of X to give RNiIIX.
Recent mechanistic studies suggest that the oxidative addition
step in eq 16 does not follow that route. Instead, a chain
mechanism involving Ni(I), Ni(II), and Ni(III), but not Ni(0),
appears to operate.26 It is very likely that the participation of
the organozinc coupling reagent plays a role in accessing this
alternate route, which may be preferred not because the
oxidative addition step is more favorable but rather because
reductive elimination from an RR′NiII species might become a
slower bottleneck. We have here yet another reminder of the
mechanistic diversity exhibited by oxidative additions of RX;
given that diversity, and the ingenuity exhibited by synthetic
chemists in working out optimal choices of ligands and reaction
conditions, it is probably not much of an exaggeration to
predict that cross-coupling methodology based on RX oxidative
addition could be made to work on just about any combination
one can think of.
Acetic Acid Synthesis. Acetic acid is a large-scale industrial
product, around 6.5 million tons per year, and the vast majority
(75% or more) is made by carbonylation of methanol,27 a route
that became dominant around 1970 when the Rh-based
Monsanto process was developed. More recently, in the
1990s, BP introduced the competing Ir-based Cativa process.
Both cases rely on a key oxidative addition step.
The Monsanto process is represented by eq 17; when
operating properly, it gives acetic acid in >99% selectivity on
the basis of consumed methanol (∼90% based on CO). Some
interesting features include (1) the Rh can be loaded in just
about any (soluble) form, (2) the overall rate is first order in
total [Rh] but zero order in both [CH3OH] and CO pressure,
and (3) the rate is first order in [I−]. These suggest that all the
Rh is converted to a preferred species under reaction conditions
and that the rate-limiting step involves an I-containing reagent,
most likely CH3I. Extensive mechanistic study by a number of
laboratories confirmed that the dominant species in solution is
an anionic Rh(I) complex, [RhI2(CO)2]−, which undergoes
The detailed kinetics of the oxidative addition and insertion
steps have been worked out (Scheme 9)28 and confirm that
Scheme 9. Rates and Energetics for the Oxidative Addition
and Insertion Steps of the Monsanto Process Mechanisma
a
Reproduced with permission from ref 28. Copyright 1996 The Royal
Society for Chemistry.
under standard catalytic conditions the oxidative addition step
has the highest activation energy. Despite much effort, attempts
to extend this chemistry to carbonylation of higher alcohols
have not met with much success, and on the basis of everything
we have seen so far, we can understand why. If the oxidative
addition of CH3I follows an SN2 path, as we would expect, then
a parallel route involving oxidative addition of higher RX will be
much slower. Separate measurements of the kinetics of the
oxidative addition step gave the following relative rates: if that
for MeI is defined as 1000, then EtI is around 3, n-PrI ∼1.7, and
i-PrI ∼4. The increase on going from primary to secondary
alkyl suggests the possibility of contributions from a competing
radical mechanism, and indeed the higher RI’s did not exhibit
clean second-order kinetics, unlike MeI, until a radical
scavenger was added. It was estimated that the radical
component might account for ∼20% of the overall EtI reaction
and presumably still more for i-PrI. In any case, this alternate
pathway is far too slow to compensate for the greatly
diminished SN2 reactivity.
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indeed, under some conditions the rate of the insertion step can
be as much as 105 times slower for Ir than for Rha
consequence of the greater M−C bond strength for the thirdrow metalwhich might seem to rule out Ir as a viable catalyst.
Nonetheless, the catalytic process can be operated with Ir, at
overall rates comparable to or even somewhat better than for
Rh. It turns out that the neutral species IrIIII2Me(CO)3
undergoes insertion considerably faster than anionic [IrIIII2Me(CO)3]−, the analogue of the Rh complex where insertion
occurs in the Monsanto cycle (Scheme 8); however, neutral
IrII(CO)3 is not at all reactive toward MeI for the oxidative
addition step. If [I−] is carefully managed so that the key
species in both the neutral and anionic cycles can exist in
substantial concentration in solution, then both oxidative
addition and insertion can proceed at useful rates (Scheme
10). That management is accomplished by the addition of a
promoting I− scavenger, such as InI3.29 This so-called Cativa
process is much more stable to reaction conditionsprobably
in large part because the greater M−CO bond strength retards
ligand loss leading to precipitationand hence has taken over
for most recent installations.
Given the apparently excellent selectivity of the Monsanto
process, what incentive might there be for considering an Irbased alternative? There is a cost factor: in the 1970s that
would have seemed entirely discouraging, as Ir was much more
expensive than Rh, typical for second- vs third-row metals
(Table 6), the latter almost always being more scarce. However,
Table 6. Prices of Metals, in USD/troy oza
Fe: 0.015
Ru: 63
Os: 400
a
Co: 1.17
Rh: 950
Ir: 560
Ni: 0.48
Pd: 695
Pt: 1067
Cu: 0.22
Ag: 16
Au: 1179
From various Web sites on 6/23/15.
all that changed when the use of Rh in automobile catalytic
converters was introduced, with the demand factor completely
swamping the supply factor: Rh is now more expensive than Ir.
Another consideration: it was noted above that the selectivity in
CO is “only” 90%, with some being lost to CO2 as a result of
competing water-gas shift chemistry (eq 18). In principle, one
might think that could be alleviated by minimizing water
content, but that turns out not to work: if the latter drops
below 15% or so, the catalyst precipitates out as RhI3. Hence,
stable operation becomes a significant concern.
CO + H 2O ⇄ CO2 + H 2
■
CONCLUSION
Hopefully this tutorial has served to do several things: to define
and illustrate oxidative addition as a ubiquitous pattern of
reactivity in organotransition metal chemistry, to demonstrate
how mechanistic understanding has been elucidated over the
years, to explore the variety of mechanisms that have been
established even for a relatively restricted class of reactions and
to show how apparently minor alterations in reactants can
completely shift from one mechanism to another, and finally to
make use of this mechanistic information in understanding how
important practical catalytic applications have been developed.
(18)
How about reactivity? We would anticipate that the ratelimiting oxidative addition step would be considerably more
favored for the third-row metal, at least thermodynamically and
probably kinetically as well. That is the case: [IrI2(CO)2]− adds
MeI around 150 times faster than the Rh analogue. However,
that will not necessarily result in improved catalytic turnover:
another step could become rate limiting. That is also the case:
Scheme 10. Mechanism of the Cativa Process, Showing the Interplay of Anionic and Neutral Intermediatesa
a
The red arrows outline the dominant catalytic cycle. Reproduced with permission from ref 29. Copyright 2004 American Chemical Society.
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This complexity can certainly make the rational design and
optimization of catalysts a challenging task: one might almost
call the range of mechanistic behavior “bewildering.” However,
I would prefer “exhilarating”, to call attention to the wealth of
possibilities for applications of organotransition-metal chemistry and homogeneous catalysis that is made accessible by
mechanistic diversityand is by no means limited to oxidative
additions of alkyl halides.
■
A Conversation about Science (co-edited with sociologist of science
Harry Collins), published by the University of Chicago Press in 2001,
and Up f rom Generality: How Inorganic Chemistry Finally Became a
Respectable Field, published by Springer in 2013.
■
REFERENCES
(1) I have discussed elsewhere how the increased attention to
mechanism, beginning around the 1950s, was a key factor in raising the
status of inorganic chemistry as a subdiscipline, eventually reaching
parity with organic and physical chemistry: Labinger, J. A. Up from
Generality: How Inorganic Chemistry Finally Became a Respectable Field;
Springer: Heidelberg, Germany, 2013.
(2) King, R. B. Transition-Metal Organometallic Chemistry: An
Introduction; Academic Press: New York, 1969.
(3) Green, M. L. H. Organometallic Compounds; Methuen: London,
1968; Vol. 2 (The Transition Elements).
(4) Collman, J. P. Acc. Chem. Res. 1968, 1, 136−143.
(5) Collman, J. P.; Hegedus, L. S. Principles and Applications of
Organotransition Metal Chemistry; University Science Books: Mill
Valley, CA, 1980.. A second edition, with the same title but with two
additional co-authors (Jack Norton and Richard Finke), appeared in
1987. More recently, a substantially reworked and expanded version
was published: Hartwig, J. J. Organotransition Metal Chemistry: From
Bonding to Catalysis; University Science Books: Sausalito, CA, 2010.
(6) The preparation involves heating a solution of iridium chloride
and PPh3 in a high-boiling oxygenated solvent, such as ethylene glycol
or dimethyl formamide, at temperatures close to 200 °C for a number
of hours; the solvent serves as both reductant and source of carbonyl.
According to one commentator, the first synthesis succeeded only
because Vaska forgot and left it heating overnight: Kirss, R. U. Bull.
Hist. Chem. 2013, 38, 52−60.
(7) Vaska, L.; DiLuzio, J. W. J. Am. Chem. Soc. 1961, 83, 2784−2785.
(8) Vaska, L.; DiLuzio, J. W. J. Am. Chem. Soc. 1962, 84, 679−680.
(9) Earlier usages refer to formally oxidative reactions of unsaturated
organic molecules, such as the addition of Cl2 to an olefin.
(10) Collman, J. P.; Roper, W. R. J. Am. Chem. Soc. 1965, 87, 4008−
4009.
(11) Actually this is not quite so straightforward: the original
synthesis6 works only for PPh3. A “general” synthesis involves refluxing
“IrCl3·nH2O” in a high-boiling alcoholic solvent under CO until the
color fades to yellow, signifying formation of [IrCl(CO)3]n; addition of
2 equiv of any L gives the desired IrCl(CO)L2. In my hands (and
others as well, anecdotally), the first step, reduction to an Ir(I)
carbonyl, worked only about one time in four so long as the IrCl3 came
from Johnson-Matthey; it never worked if it came from Engelhard.
Reliable preparation of a wide variety of IrCl(CO)L2 complexes
required devising an independent route for almost every case.
(12) Hartwig (see ref 5, p 262) has suggested the term “oxidative
ligations” for reactions that do not involve bond cleavages, such as O2
addition and protonation. It is not clear how useful a distinction this is;
moreover, protonation does involve cleavage of an H−X bond at some
point in the reaction sequence.
(13) The initial crystallographic determination reported an O−O
bond length of 1.30 Â , more superoxide-like, whereas the value for the
analogous iodide was in the peroxide range. The difference was
attributed to the lower electronegativity of I vs Cl, releasing more
electron density to the O2 moiety (and also resulting in somewhat
greater thermodynamic stability for the O2 adduct):4 Ibers, J. A.; La
Placa, S. J. Science 1964, 145, 920−921. The apparent discord between
the O2 bond length and stretching frequency was never satisfactorily
explaineduntil a decade later, when studies on a different O2
complex suggested the strong possibility of an erroneous measurement
resulting from radiation-induced crystal damage: Nolte, M. J.;
Singleton, E.; Laing, M. J. Am. Chem. Soc. 1975, 97, 6396−6400. ).
The structure of IrCl(O2(CO) (PPh3)2 was finally redetermined in
2008, giving the currently accepted O−O bond length shown in Table
2: Lebel, H.; Ladjel, C.; Bélanger-Gariépy, F.; Schaper, F. J. Organomet.
Chem. 2008, 693, 2645−2648. A number of cautionary tales might be
AUTHOR INFORMATION
Corresponding Author
*E-mail for J.A.L.: [email protected].
Notes
The authors declare no competing financial interest.
Biography
Jay Labinger is Administrator of the Beckman Institute and Faculty
Associate in Chemistry at Caltech. His undergraduate and graduate
education took place respectively at Harvey Mudd College and
Harvard University, where he received his Ph.D. in inorganic chemistry
with the late John Osborn in 1974, on the mechanism of oxidative
addition of alkyl halides (the subject of this tutorial). From there he
went to Princeton, to do a postdoc with Jeffrey Schwartz on
organometallic chemistry of the early transition metals, after which he
took a faculty position at the University of Notre Dame, where he
began a program in mechanistic organometallic chemistry and
homogeneous catalysis, particularly homogeneous approaches to
syngas conversion.
In 1981 he decided to see what an industrial career was like, joining
Occidental Petroleum’s lab in Irvine, CA, to continue his work in
syngas conversion. When Oxy management abandoned their venture
into fundamental research after less than a year, he moved to ARCO in
Chatsworth, CA, to join another new lab and to lead a program in
heterogeneous catalysis, on the oxidative coupling of methane. This
time it took two years before ARCO management decided to close the
lab. Having (finally) learned his lesson, he returned to academia in
1986, recruited by Harry Gray to become the founding (and only, to
date) Administrator of the then-nascent Beckman Institute at Caltech.
During his nearly 30 years at Caltech, in addition to his administrative
work, he has carried out an active research program, mostly in
collaboration with his colleague John Bercaw as well as several others,
especially Harry Gray and Mark Davis. This work has spanned a
variety of projects in organometallic chemistry and catalysis, focusing
particularly on C−H bond activation and other energy-related topics,
resulting in around 150 articles and reviews. He has also developed
strong interests in the connections between science and other
scholarly areas, with a number of contributions on literary, historical,
and cultural aspects of science, including two books: The One Culture?
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told about struggles to interpret incorrect crystallographic findings,
which are often taken as unimpeachable no matter how improbable
they look; the “bond-stretch isomerism” controversy is a prime
example: Parkin, G. Chem. Rev. 1993, 93, 887−911. Labinger, J. A. C.
R. Chim. 2002, 5, 235−44.
(14) Schrauzer, G. N.; Deutsch, E. J. Am. Chem. Soc. 1969, 91, 3341−
3350.
(15) Whitesides, G. M.; Boschetto, D. J. J. Am. Chem. Soc. 1969, 91,
4313−4314. Actually, Whitesides’ expressed goal in this paper was to
establish the stereochemistry of the migratory insertion reaction, as
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bonus.
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DOI: 10.1021/acs.organomet.5b00565
Organometallics 2015, 34, 4784−4795