Benzylic C?H Functionalisation by [Et3SiH+KOtBu] leads to Radical Rearrangements in o-tolyl Aryl Ethers, Amines and Sulfides

Article abstract of DOI:10.1002/adsc.202000356

Reaction of Et₃SiH+KO^tBu with diaryl ethers, sulfides and amines that feature an ortho alkyl group leads to rearrangement products. The rearrangements arise from formation of benzyl radicals, likely formed through hydrogen atom abstraction by triethylsilyl radicals. The rearrangements involve cyclisation of the benzyl radical onto the partner arene, which, from computation, is the rate determining step. In the case of diaryl ethers, Truce-Smiles rearrangements arise from radical cyclisations to form 5-membered rings, but for diarylamines, cyclisations to form dihydroacridines are observed. (Figure presented.).

Full text of DOI:10.1002/adsc.202000356

Title: Benzylic C-H functionalisation by [Et₃SiH + KOtBu]
leads to radical rearrangements in o-tolylaryl ethers, amines and
sulfides
Authors: Jude Arokianathar, Krystian Kolodziejczak, Frances Bugden,
Kenneth Clark, Tell Tuttle, and John Murphy
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000356
Link to VoR: https://doi.org/10.1002/adsc.202000356

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Benzylic C-H functionalisation by [Et3SiH + KOtBu] leads to
radical rearrangements in o-tolyl aryl ethers, amines and
sulfides
Jude N. Arokianathar, Krystian Kolodziejczak, Frances E. Bugden, Kenneth F. Clark,
Tell Tuttle* and John A. Murphy*
Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United
Kingdom. tell.tuttle@strath.ac.uk; john.murphy@strath.ac.uk
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. Reaction of Et3SiH + KOtBu with diaryl ethers, In the case of diaryl ethers, Truce-Smiles rearrangements
sulfides and amines that feature an ortho alkyl group leads to arise from radical cyclisations to form 5-membered rings,
rearrangement products. The rearrangements arise from but for diarylamines, cyclisations to form dihydroacridines
formation of benzyl radicals, likely formed through are observed.
hydrogen atom abstraction by triethylsilyl radicals. The
rearrangements involve cyclisation of the benzyl radical onto
the partner arene, which, from computation, is the rate
determining step.
Keywords: radical; Truce-Smiles rearrangement; silane;
KOtBu.
Introduction
In 2013, Grubbs et al. reported[1] that heating Et3SiH
with KOtBu afforded a novel reagent which has since
been shown to carry out a wide range of chemical
transformations.[1-11] (Schemes
1 and 2). This
versatile reagent achieves regioselective silylation
reactions of indoles 1 and other heterocycles.[1,3,5,6] at
lower temperatures, cleavage of Ar-O bonds in aryl
[4]
ethers 3,[1] and Ar-S bond cleavage in thioethers 5
at higher temperatures. In addition, the reagent
debenzylates N-benzylindoles, 7,[7] reduces fused
aromatic hydrocarbons, (e.g. 9) to their dihydro
counterparts,[7] and converts primary and secondary
amines, e.g. 11 to their silylated derivatives,[9,10] in
this case, 12. The analogous silane, Et2SiH2, (and less
efficiently, Et3SiH) in combination with KOtBu,
converts styrenes, e.g. 13 to their hydrosilylated
derivatives, in this case, 14.[8]
Scheme 2. Recent transformations by Et3SiH + KOtBu.
It appears that many different types of reactive
species may be produced from heating Et3SiH with
KOtBu, and the nature of the reactive species present
in this mixture is really not fully understood. Houk,
Stoltz et al. detected[5] TEMPO-SiEt3, 15, following
addition of TEMPO, which provides evidence for
Scheme 1. Early transformations with Et3SiH + KOtBu.
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
triethylsilyl radicals 16, and Jeon et al. have proposed
K+ [Et2Si(H)2OtBu] and analogue 17 as hydrogen
atom transfer agents (and ultimately, hydrosilylation
agents).[8] The radical anion 18 has also been
proposed to play an active role.[1,7] As an indication
of the range of mechanisms under consideration, both
radical[5] and non-radical[6] mechanisms have been
proposed for the silylation reactions of indoles 1. Our
recent efforts have reported novel reactions that
provide new information on the diverse pathways
open to this reagent.[7,10,11]
As mentioned above, diaryl ethers were studied by
Grubbs et al. who reported Ar-O bond cleavages, e.g.
34. The more recently published proposal[4] for the
mechanism involves ipso silyl radical addition to an
aryl ring at the site of substitution, i.e. at the carbon
involved in the Ar-O bond, followed by
fragmentation of the C-O bond. In principle, electron
transfer from a species such as 18 to the * system of
a diaryl ether, might also produce cleavage of the aryl
ether,[1] and our original experiments were designed
to explore the nature of the cleavages. This paper
now reports our results.
radical-induced Truce-Smiles rearrangement.[13-18]
Hydrogen atom abstraction from the methyl group of
19 forms radical 21. This radical then undergoes
rearrangement via the spirocyclic radical 22, which
rearomatises in forming phenoxyl radical 23 that is
quenched in due course.
Efforts then focused on optimisation of the reaction
with substrate 19 through variation of temperature,
reaction time, nature of the silane and nature of the
base and solvent, prior to using those optimised
conditions to study the scope of the reaction with a
variety of substrates. Initially, a temperature study
was conducted at 70 C, 100 C and 150 C, but all
proved inferior to our standard 130 C (see Table 1).
Table 1. Effect of varying temperature on aryl migration
reaction of 19.
Entry Temperature, T ( C) 20 (%)[a] 19 (%)[a]
1[b]
2
3
130
70
100
150
78
0
57
75
0
86
28
0
4
[a]% yield determined by internal NMR standard (1,3,5-trimethoxybenzene); [b]isolated by
column chromatography
Results and Discussion
A survey of reaction times showed that yields
suffered when the reaction was conducted for a
shorter period than 18 h (Table 2).
When substrate 19, (substrates were routinely
synthesised via standard reactions, such as Ullmann
or Chan-Lam coupling reactions. For details of their
preparation and characterisation, see S.I.), was
subjected to our standard Et3SiH/KOtBu reaction
Table 2. Effect of varying reaction time on rearrangement
of 19.
o
conditions (3 eq. of both reagents at 130 C for 18 h)
Entry Reaction Time
20 (%)[a]
19 (%)[a]
in the absence of solvent, rearranged product 20
(78%) was isolated (Scheme 3). Control thermal
reactions (i) with KOtBu but with no Et3SiH, (ii) with
Et3SiH but with no KOtBu and (iii) with neither
reagent (a purely thermal rearrangement is known at
1[b]
2
3
18 h
10 min
30 min
6 h
78
3
54
63
0
74
25
17
4
o
320 C[12]) returned only starting material, which
[a]% yield determined by internal NMR standard (1,3,5-trimethoxybenzene); [b] isolated
by column chromatography
confirmed that the combination of Et3SiH and KOtBu
was essential for the transformation.
Varying the nature of the silane showed that tri-n-
alkylsilanes as well as methyldiphenylsilane and
phenyldimethylsilane worked comparably well
(Table 3).
Table 3. Effect of varying silane on aryl migration reaction
of 19.
Entry
Silane
20 (%)[a]
19 (%)[a]
1[b]
2
3
4
5
Et3SiH
Ph3SiH
Ph2MeSiH
PhMe2SiH
(iPr)3SiH
nPr3SiH
78
35
73
77
0
0
38
0
0
100
0
6
7
74
43
Et2SiH2
27
[a]% yield determined by internal NMR standard (1,3,5-trimethoxybenzene); [b] isolated
by column chromatography
Scheme 3. Truce-Smiles rearrangement of radical 21.
Given the evidence for triethylsilyl radicals in these
reaction mixtures, this rearrangement looks to be a
On the other hand, triphenylsilane was much less
effective and triisopropylsilane gave no conversion at
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
all, suggesting that substantial stabilisation of the
silyl radical in triphenylsilyl radical, or substantial
steric hindrance around silicon, in the triisopropyl
radical, adversely affected the rearrangement.
Interestingly, the reagent that Jeon et al. found to
work most effectively in their hydrosilylation
reactions,[8] diethylsilane, Et2SiH2, was much less
effective in this transformation (Entry 7).
selectively activated for conversion to 29. The
sensitivity of substrates to the alternative and simpler
fragmentative mode of reaction witnessed by Grubbs
et al. was seen with propylphenyl phenyl ether 26,
where the simple fragmentation product 32 was seen
in low yield (2%), alongside the rearrangement
product 31 (34%) and starting material 26 (42%).
Table 4. Effect of varying the base on rearrangement
reaction of 19.
Entry
Base
20 (%)[a] 19 (%)[a]
1[b]
2
3
KOtBu
NaOtBu
NaH
78
0
0
90
0
18
0
100
30
80
4
KH
KH
5[c]
6
KOH
KOEt
KOEt
KHMDS
LDA
0
89
7
13
0
0
31
100
83
8[c]
9
10
0
100
[a]% yield determined by internal NMR standard (1,3,5-trimethoxybenzene); [b] isolated
by column chromatography; [c]reaction conducted in the absence of triethylsilane.
In a study of the influence of different bases on the
reaction, KOtBu was effective for the aryl migration
of substrate 19 to phenol 20 (Entry 1, Table 4).
Switching to NaOtBu only yielded starting material
19 (Entry 2). Similarly, no conversion was seen when
using NaH as the base (Entry 3). However, with KH,
rearranged product 20 was observed, albeit to a lesser
extent than with KOtBu (Entry 4). A control
experiment (absence of Et3SiH) showed that KH
alone cannot cause aryl migration to occur (Entry 5).
These results show the great importance of the
potassium ion present in the base for the
rearrangement of 19 to 20 and, more generally, for
the silane-base system. This was consistent with
results from the Grubbs, Stoltz and Jeon groups in
their study of different reactions as well as with our
earlier studies.[1,2-4,6,8] KOH, which was employed for
C(sp)-H bond silylation by Grubbs et al., [19] gave no
conversion of substrate 19 (Entry 6). KOEt (Entry 7)
gave only a 13 % yield of phenol 20 from compound
19 and KHMDS and LDA both proved ineffective
(Entries 9 and 10).
With these results, the diaryl ethers, 24-27 were
prepared and tested under the optimum solvent-free
conditions (Scheme 4). Xylylphenyl ether 24 afforded
rearranged product 28 (46%) together with some
starting material (21%). Symmetrical resorcinol
diphenyl ether 25 gave benzhydryl-substituted
resorcinol 29 (15%), together with starting material
(51%). The double-migration observed in forming 29,
and the absence of a product showing a single-
migration, such as 30, is in line with the fact that
while 30 would be an intermediate in the process, C-
H abstraction from a CH2 benzylic position in 30 is
easier than from the CH3 group in 25, and so 30 is
Scheme 4. Probing the scope of the rearrangement.
Substrate 27 provided useful information on the
routes to activation for rearrangement. It does not
feature an easily abstractable benzylic H-atom, as C-
H bonds to sp2-carbons are so strong, but the terminal
sp3-methyl group C-H bonds in cinnamyl compound
27 should have similar bond strength to the benzylic
C-H in 19. Abstraction of the cinnamyl C-H would
form radical 33. Scheme 5 shows the evolution of
radical 33 to the unexpected product 20. Radical 33
undergoes a Truce-Smiles rearrangement to give
radical 35. Cyclisation to give 36 followed by a
fragmentation and hydrogen atom abstraction via
benzyl radical 37 leads to vinyl ether 38, and then
facile hydrolysis of the vinyl ether would afford the
observed product 20.
Alternatively, a benzyl radical 39 could be reached by
a different route, namely through hydrogen atom
transfer (HAT), as proposed in Jeon’s work. In Jeon’s
examples, the benzyl radical that is formed by HAT
to the styrene undergoes silylation (as seen in 1314,
Scheme 1). In this case, that benzyl radical 39 has an
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
alternative exit via a Smiles rearrangement, resulting
in phenol 31.
Scheme 6. Fragmentation of substrate 41.
At that stage, we decided to explore one remaining
parameter relating to our parent case 1920, i.e. the
effect of solvent. Table 5 shows that THF was the
solvent of choice. Accordingly, we returned to
substrates 45 and 46, and compared their reactivity in
THF with that under solvent-free conditions. Scheme
7 shows that the addition of THF has a profound
effect on the outcome of the reactions of these
substrates, leading to rearranged products 52 (53%)
and 54 (34%) respectively.
Table 5. Effect of solvent on aryl migration reaction of 19.
Scheme 5. Proposal for the formation of phenols 20 and 31
from substrate 27.
Entry
1[c]
Solvent[a]
20 (%)[b] 19 (%)[b]
A point of concern for us was the mass balance in our
reactions. With so many likely types of reactive
species present, it was not surprising that a range of
alternative products might be formed, but we
wondered whether some products might be volatile.
Accordingly, substrate 41 was selected (Scheme 6).
This substrate has the advantage of being derived
from a phenyl-substituted phenol, and therefore the
products arising should not be volatile. Also, this
substrate is symmetrical and this should limit the
number of by-products. In this case, reaction under
our standard conditions afforded the phenylcresol 42
(74%), and an inseparable mixture of m-
methylbiphenyl 43 and silylated counterparts 44.
Interestingly, no product of Smiles rearrangement
was observed.
Continuing our exploration of the scope of the
reaction, substrates 45 and 46 were now assessed
(Scheme 7). Although they differed from substrate 19
only by a single alkyl group, their reactions took
completely different courses than 19, under
analogous conditions. Thus, 45 gave the two phenols
that would result from simple fragmentation, 50 (5%)
and 51 (64%). Likewise, the p-cresol derivative 46
gave 50 (11%) and 53 (38%).
78
0
-
2
3
4
Hexane
Toluene
THF
16
8
88
58
0
24
30
0
3
91
5[d]
6
THF
1,4-Dioxane
[a] 5 mL of solvent used; [b] % yield determined by internal standard
(1,3,5-trimethoxybenzene); [c] isolated by column chromatography; [d] 2
mL of THF used
The pyridine substrates 47 and 48 were next
examined. In these cases, the rearrangement products
55 and 56 respectively, as well as o-cresol, 50, were
obtained under solvent-free and THF conditions. At
this stage, it is not possible to define the role of THF.
It is clear that potassium ions are of critical
importance for this reagent, so it is not too surprising
that the nature of its solvation should also be
important.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
of the rearrangement product increased and of the
fragmentation product decreased.
To compare the effect of other linking atoms to the
oxygen of diaryl ethers, sulfur-linked substrate 49
was explored, and gave the rearrangement product 57
(43%) under solvent-free conditions and the same
product (55%) when conducted in THF as solvent.
Scheme 8. Rearrangement of diarylamines.
As these reactions generally afforded greater yields of
rearrangement product when conducted in THF as
solvent, the next substrates, i.e. N-linked substrates,
58 and 59, were tested only under the THF conditions
(Scheme 8). These nitrogen-linked substrates gave
very different results than the diphenyl ether
substrates. Firstly, urea 59 afforded methylacridine
60 (13%) as the sole isolated product under our
standard conditions. In this case, the benzyl radical
62 (Scheme 8) underwent formation of the 6-
membered ring in 63 as opposed to the 5-exo-trig
reaction to the spiro-intermediate of a Smiles
rearrangement. Radical 63 could then be converted to
dihydroacridine 61 by deprotonation followed by
electron transfer.[20] As dihydroacridines are easily
converted to acridines in air, this explains the
additional isolation of 60 (13%) following
purification. In the reaction of 59, it was not clear at
what stage the N(C=O) bond in the urea had cleaved.
Early cleavage by nucleophilic reaction by KOtBu
would leave a nitrogen anion that might then undergo
hydrogen atom abstraction from the benzylic position,
leading to rearrangement. To explore whether this
Scheme 7. Rearrangements in THF as solvent, compared
to solvent-free conditions
The formation of o-cresol 50 as the sole ‘simple
fragmentation’ product of these substrates (no
pyridones were observed) would be consistent either
with selective addition of a radical (H atom or
triethylsilyl radical) to the pyridine ring, or with
selective electron transfer to the electron-deficient
pyridine ring in 47 and 48, followed by fragmentation.
In these reactions, the rearrangement product 55
(17%) or 56 (21%) was also seen from substrates 47
and 48, respectively. When these substrates were
treated with the reagent in THF as solvent, the yields
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
was a possibility, substrate 58 was subjected to the
rearrangement reaction, but using an extra equivalent
of KOtBu to deprotonate the amine N-H. This
substrate was efficiently converted to the
dihydroacridine 61 (57%) together with the acridine
60 (12%). With the formation of a new 6-membered
ring, the regiochemistry of the rearrangement for
nitrogen-linked substrates was clearly different than
for their oxygen-linked counterparts, and the reasons
for this will be discussed later in the paper, in
conjunction with computational results.
these reactions, therefore, the concentration of
abstractable Si-H hydrogens available to a transient
radical at any instant, may be much lower.
Halogen atom abstraction by silyl radicals is a more
normal method of creating radicals on substrates. [19]
Therefore, 1-(bromomethyl)-2-phenoxybenzene 64
was reacted with TTMSS (tristrimethylsilylsilane) in
the presence of AIBN. No rearranged product 20 was
observed, but debrominated compound 19 (61 %)
was formed. This means that the benzylic radical
undergoes hydrogen atom abstraction from TTMSS
faster than aryl migration under these conditions
Table 6. Probing substrate 19 with silyl radicals generated
from radical initiators with silane.
[a]% yield determined by internal standard (1,3,5-trimethoxybenzene).
Scheme 9. Reaction of bromide 64 with TTMSS.
Entry
Silane
Radical T (C) 20
19
Initiator
(%)[a]
(%)[a]
Computational results.
1
2
3
4
5
6
Et3SiH
Et3SiH
Et3SiH
TTMSS
TTMSS
TTMSS
BPO
DTBP
AIBN
BPO
DTBP
AIBN
130
130
95
130
130
95
0
0
0
0
0
0
81
77
85
92
99
86
The above results contrast the regiochemistry of
rearrangements seen with diaryl ethers and
diarylamines. In the case of diaryl ethers, and also for
the sulfide case 49, the benzyl radical cyclises to
form a 5-membered ring in a spirobicyclic system,
which then expels an aryloxyl or arylthiyl radical to
give a Smiles rearrangement. Cyclisation to form 5-
membered rings is the expected outcome from such
radical cyclisations. However, formation of a benzyl
radical in the corresponding diarylamine cases results
in cyclisation to form a 6-membered ring, which is
unusual.
We rationalise this by looking at Scheme 10, which
also incorporates the headline results of our DFT
calculations. In the calculations, trimethylsilane was
used in place of tiethylsilane for reasons of
computational economy. Trimethylsilyl radical
abstracts a hydrogen atom from substrate 19 to form
21. Radical 21 undergoes cyclisation to spiro-
intermediate 22 with a very accessible barrier of 25.2
kcal mole-1. Fuller computational details are available
in the SI file, which show that that step is the rate
determining step in the conversion of 1920. By
comparison, the corresponding diarylamine, o-
tolylphenylamine is likely to be in its deprotonated
form, i.e. it is likely to exist as its potassium salt, 65.
Hydrogen atom abstraction provides radical 66. The
kinetic barrier to cyclisation to from the spiro
intermediate is now a much higher 31.5 kcal mole-1,
while the cyclisation to the 6-membered ring
intermediate has a barrier of 22.8 kcal mole-1.
Conversion of 66 to 68 represents the rate
determining step in to conversion to 69.
[a]% yield determined by internal standard (1,3,5-trimethoxybenzene);
BPO = benzoyl peroxide; DTBP = di-t-butyl peroxide; AIBN = 2,2’-
azobisisobutyronitrile; TTMSS = tris(trimethylsilyl)silane.
At this stage, our view was that the mechanism of the
rearrangement of all of the relevant substrates
involved an initial H-atom abstraction from the
substrate by triethylsilyl radicals to give the benzyl
radicals as intermediates. We were keen to compare
these results with approaches where the same benzyl
radical intermediates could be generated in a more
conventional manner, using a silane with a thermal
radical initiator. Accordingly, we took both
triethylsilane and tris(trimethylsilyl)silane and our
simplest substrate 19 and treated them, in parallel
experiments, with azoisobutyronitrile (AIBN),
dibenzoyl peroxide (BPO) and di-tert-butylperoxide
(DTBP) to see if the same rearrangement could be
triggered (entries 1-6, Table 6). However, no rearr-
angement product 20 was seen in any of the six
experiments. The Si-H bond of triethylsilane is quite
strong, while TTMSS was developed as a silane that
is more susceptible to Si-H bond cleavage.[21] If
benzyl radicals are formed under these conditions
from 19, then the kinetics of the Smiles
rearrangement must be a lot slower than the kinetics
of quenching of the radical by silane. Whereas the
experiments in Table 6 feature high concentrations of
silanes as quenching agents, this is likely to be very
different from the cases studied in this paper with
KOtBu + Et3SiH. When these two reagents are heated
together, it is known that hydrogen gas is liberated
into the headspace of the reaction vessel, and this can
arise, for example, from conversion of 17 to 18. In
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
In summary, reaction of Et3SiH + KOtBu on diaryl
ethers, sulfides and amines with an ortho alkyl group
leads to rearrangement products. The rearrangements
arise from formation of benzyl radicals through
hydrogen atom abstraction, likely by triethylsilyl
radicals. The rearrangements involve cyclisation of
the benzyl radical onto the partner arene, which is the
rate determining step. In the case of diaryl ethers,
Truce-Smiles rearrangements are observed, arising
from radical cyclisations to form 5-membered rings,
but for diarylamines, cyclisations to form
dihydroacridines are observed. This preference for N-
linked substrates is borne out by very recent reductive
rearrangements of N-aryl indoles in the presence of
t
11]
the same reagents, i.e. Et3SiH and KO Bu.[
Dedication
This paper is dedicated to Professor Bernd Giese on the occasion
of his 80th birthday.
Acknowledgements
We thank the University of Strathclyde for funding and the
EPSRC-funded ARCHIE-WeSt High Performance Computer
(www.archie-west.ac.uk) for computational resource via EPSRC
grant no. EP/K000586/1.
Scheme 10. Energy barriers for rearrangement of benzyl
radicals
Intuitively, the difference can be rationalised, by
considering the extent of resonance delocalisation of
a heteroatom lone pair over an aryl ring. In 21, an
oxygen lone pair can delocalise over both aryl rings.
If this radical cyclises to spiro-intermediate 22, the
delocalisation of the oxygen lone pair is now
confined to just one aromatic ring (delocalisation area
shown in blue), so there is an energy sacrifice in
getting to the spiro-intermediate. This sacrifice will
be greater for a nitrogen lone pair than for an oxygen
(or sulfur) lone pair because a nitrogen lone pair is
more available to undergo resonance delocalisation.
For a nitrogen anion, e.g. 66, the penalty for loss of
delocalisation by the N-‘lone pair’ over one of the
aryl rings will be more extreme than for neutral
nitrogen, but for neutral or anionic nitrogen, the loss
of resonance energy will be greater than for oxygen.
The loss of resonance energy in these intermediates
will be partially reflected in the transition state
leading to the spiro-intermediates. By contrast,
cyclisation 6668 provides much greater
delocalisation of the charge and spin (delocalisation
area shown in blue), and again this is likely reflected
in the transition state 6668. This is in line with the
efficient formation of products 60 and 61 from anion
66.
References
[1] A. Fedorov, A. A. Toutov, N. A. Swisher, R. H.
Grubbs, Chem. Sci. 2013, 4, 1640–1645.
[2] A. A. Toutov, W.-B. Liu, K. N. Betz, A. Fedorov,
B. M. Stoltz, R. H. Grubbs, Nature 2015, 518, 80–
84.
[3] A. A. Toutov, W.-B. Liu, K. N. Betz, B. M. Stoltz,
R. H. Grubbs Nat. Protoc. 2016, 10, 1897–1903.
[4] A. A. Toutov, M. Salata, A. Fedorov, Y.-F. Yang,
Y. Liang, R. Cariou, K. N. Betz, E. P. A. Couzijn,
J. W. Shabaker, K. N. Houk, R. H. Grubbs, Nat.
Energy 2017, doi.org/10.1038/nenergy.2017.8
[5] W.-B. Liu, D. P. Schuman, Y.-F. Yang, A. A.
Toutov, Y. Liang, H. F. T. Klare, N. Nesnas, M.
Oestreich, D. G. Blackmond, S. C. Virgil, S.
Banerjee, R. N. Zare, R. H. Grubbs, K. N. Houk,
B. M. Stoltz, J. Am. Chem. Soc. 2017, 139, 6867–
6879.
[6] S. Banerjee, Y.-F. Yang, I. D. Jenkins, Y. Liang,
A. A. Toutov, W.-B.; Liu, D. P. Schuman, R. H.
Grubbs, B. M. Stoltz, E. H. Krenske, K. N. Houk,
R. N. Zare, J. Am. Chem. Soc. 2017, 139, 6880–
6887.
[7] A. J. Smith, A. Young, S. Rohrbach, E. F.
O’Connor, M. Allison, H.-S. Wang, D. L. Poole, T.
Tuttle, J. A. Murphy, Angew. Chem. Int. Ed. 2017
56, 13747–13751.
,
[8] P. Asgari, Y. Hua, C. Thiamsiri, W.
Prasitwatcharakorn, A. Karedath, X. Chen, S.
Conclusion
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
Sardar, K. Yum, G. Leem, B. S. Pierce, K. Nam, J.
Gao, J. Jeon, Nature Catalysis 2019, 2, 164–173.
[15] Z.-M. Chen, X.-M. Zhang, Y.-Q. Tu, Chem. Soc.
Rev. 2015, 44, 5220–5245.
[9] A. A. Toutov, K. N. Betz, A. M. Romine, R. H.
[16] T. J. Snape, Chem. Soc. Rev. 2008, 37, 2452–2458.
[17] K. Plesniak, A. Zarecki, J. Wicha, Top. Curr.
Chem. 2007, 275, 163–250.
Grubbs,
US
Patent
Application
US
2019/0218232A1.
[10] F. Palumbo, S. Rohrbach, T. Tuttle, J. A. Murphy,
Helv. Chim. Acta. 2019, 102, e1900235.
[11] A. J. Smith, D. Dimitrova, J. N. Arokianathar, K.
Kolodziejczak, A. Young, M. Allison, D. L. Poole,
S. G. Leach, J. A. Parkinson, T. Tuttle, J. A.
[18] For a review of aryl migrations in radical systems,
see A. Studer, M. Bossart Tetrahedron 2001, 57,
9649−9667.
[19] A. A. Toutov, K. N. Betz, D. P. Schuman, W.-B.
Liu, A. Fedorov, B. M. Stoltz, R. H. Grubbs, J.
Am. Chem. Soc. 2017, 139, 1668–1674.
[20] A. Studer, D. P. Curran, Angew. Chem. Int. Ed.
2011, 50, 5018−5022.
Murphy, Chem. Sci. 2020, 11, 3719–3726.
o
[12] For thermal rearrangement of 19

20 at 320 C
under vacuum, see: A. Factor, H. Finkbeiner, R. A.
Jerussi, D. M. White, J. Org. Chem. 1970, 35, 57–
62.
[21] C. Chatgilialoglu, Chem. Rev. 1995, 95, 1229–
1251.
[13] C. M. Holden, M. F. Greaney, Chem. Eur. J. 2017
23, 8992–9008.
,
[14] I. Allart-Simon, S. Gerard, J. Sapi, Molecules 2016
21, 878.
,
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000356
Advanced Synthesis & Catalysis
FULL PAPER
Benzylic C-H functionalisation by [Et3SiH +
KOtBu] leads to radical rearrangements in o-
tolylaryl ethers, amines and sulfides
Adv. Synth. Catal. Year, Volume, Page – Page
J. N. Arokianathar , K. Kolodziejczak , F. E.
Bugden, K. F. Clark, T. Tuttle*, J A. Murphy*
9
This article is protected by copyright. All rights reserved.