KOtBu as a single electron donor? Revisiting the halogenation of alkanes with CBr4 and CCl4

Article abstract of DOI:10.3390/molecules23051055

The search for reactions where KO^tBu and other tert-alkoxides might behave as single electron donors led us to explore their reactions with tetrahalomethanes, CX₄, in the presence of adamantane. We recently reported the halogenation of adamantane under these conditions. These reactions appeared to mirror the analogous known reaction of NaOH with CBr₄ under phase-transfer conditions, where initiation features single electron transfer from a hydroxide ion to CBr₄. We now report evidence from experimental and computational studies that KO^tBu and other alkoxide reagents do not go through an analogous electron transfer. Rather, the alkoxides form hypohalites upon reacting with CBr₄ or CCl₄, and homolytic decomposition of appropriate hypohalites initiates the halogenation of adamantane.

Full text of DOI:10.3390/molecules23051055

molecules
Article
KOtBu as a Single Electron Donor? Revisiting the
Halogenation of Alkanes with CBr4 and CCl4
ID
ID
Katie J. Emery ID , Allan Young, J. Norman Arokianathar, Tell Tuttle * and John A. Murphy *
Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL,
UK; katie.polly.emery@gmail.com (K.J.E.); a.young@strath.ac.uk (A.Y.); jude.arokianathar@strath.ac.uk (J.N.A.)
* Correspondence: tell.tuttle@strath.ac.uk (T.T.); John.murphy@strath.ac.uk (J.A.M.);
Tel.: +44-(0)141-548-2389 (J.A.M.)
Academic Editor: John C. Walton
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 8 April 2018; Accepted: 26 April 2018; Published: 1 May 2018
Abstract: The search for reactions where KOtBu and other tert-alkoxides might behave as single
electron donors led us to explore their reactions with tetrahalomethanes, CX4, in the presence
of adamantane. We recently reported the halogenation of adamantane under these conditions.
These reactions appeared to mirror the analogous known reaction of NaOH with CBr4 under
phase-transfer conditions, where initiation features single electron transfer from a hydroxide ion
to CBr4. We now report evidence from experimental and computational studies that KOtBu and
other alkoxide reagents do not go through an analogous electron transfer. Rather, the alkoxides
form hypohalites upon reacting with CBr4 or CCl4, and homolytic decomposition of appropriate
hypohalites initiates the halogenation of adamantane.
Keywords: halogenation; potassium tert-butoxide; alkanes; dihalocarbenes; hypohalite
1. Introduction
Recent reports have described transition-metal-free reactions, such as the coupling of haloarenes
with arenes [1–4
], that are promoted by a combination of KOtBu and an organic additive. The reactions
proceed by a radical mechanism, with a single electron transfer (SET) step initiating the formation of
the radicals. It has previously been reported that KOtBu is capable of reductively activating a range of
substrates via single electron transfer [5,6], and this led some authors to propose that tert-butoxide
anion is responsible for the initiation of these coupling reactions, either alone or in complexation with
an additive, such as 1,10-phenanthroline, in the ground state [2,3,7–11]. However, recent publications
have shown that the KOtBu base reacts with the organic additive to form an electron donor in situ.
SET from this electron donor then initiates the radical chain mechanism, not SET from tert-butoxide
anion [12–
14]. The investigations begged the question: “under what circumstances would KOtBu
behave as a single electron donor?” To answer that question, we were drawn to the research of
Schreiner and Fokin et al., who reduced CBr4 using aqueous NaOH and a phase-transfer catalyst
in a two-phase system that led to the bromination of adamantane [15
reaction of hydroxide anion with CBr4 led to the tribromomethyl radical
reflected direct electron transfer from hydroxide to CBr4 (Scheme 1). This tribromomethyl radical
undergoes a chain reaction, where it abstracts a hydrogen atom from adamantane to form the
alkyl radical and bromoform . The adamantyl radical abstracts a bromine atom from CBr4,
forming adamantyl bromide and regenerating the tribromomethyl radical 15]. The reactions of the
,16]. They demonstrated that
4, and concluded that this
4
5
7
6
7
8
4 [
tribromomethyl radical show diagnostic high selectivities for abstracting tertiary CH hydrogen atoms
(to ultimately form 1-bromoadamantane) over secondary (CH2) counterparts (which would ultimately
form 2-bromoadamantane).
Molecules 2018, 23, 1055; doi:10.3390/molecules23051055
www.mdpi.com/journal/molecules

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◦
Recently, we showed that KOtBu reacts with CBr4 and adamantane (40 C, 96 h) to afford
bromoadamantane—in a reaction that appears to mirror the work of Schreiner and Fokin et al.—with
NaOH, although phase-transfer conditions were not used [17]. The oxidation potential of KOtBu in
DMF (0.10 V vs. SCE) [
8
] is not too different from the reduction potential of CBr4 in DMF ( 0.31 V
−
vs. SCE) [18]. It was therefore proposed that KOtBu might reduce CBr4 through an electron transfer
mechanism, but the door was left open to further investigation. The aim of this paper is to explore the
chemistry of KOtBu and related tertiary alkoxides in this context.
Scheme 1. The Schreiner–Fokin mechanism for the bromination of alkanes from reaction of hydroxide
with carbon tetrabromide [15].
2. Results
The analogy of the proposed reaction of KOtBu with CBr4 or CCl4 (Scheme 2) to the
Schreiner–Fokin reaction of NaOH with this halide is striking (Scheme 1). Upon donation of an
electron, the alkoxide anion
either hydrogen atom transfer (HAT) to form 11, or
9
would form the corresponding alkoxyl radical 10, which can undergo
-scission to form the derived ketone 12 (for
β
appropriate R). Either the alkoxyl radical 10 or the methyl radical can abstract a hydrogen atom from
adamantane; the adamantyl radical would then propagate the reaction as in Scheme 1. In order to
detect the product from the
β-scission of the alkoxyl radical 10, and bearing in mind the volatility of
acetone from -scission of tert-butoxyl radicals, we synthesized potassium 2-phenylpropan-2-olate 14
β
and used it as a base to explore a range of reaction conditions (Table 1).
Scheme 2. The proposed mechanism for single electron transfer (SET) from tert-alkoxides to CBr4.
Surprisingly, and in contrast to the case for KOtBu, exposure of 14 to CBr4 in dichloromethane
solvent at 40 ◦C led to no bromination of adamantane (Table 1, entry 1). The products (2,2-dibromo-

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1-methylcyclopropyl)benzene 16, methylstyrene 17 and (2,2-dichloro-1-methylcyclo-propyl)benzene
19 were observed, in addition to 2-phenylpropanol 15 and unreacted adamantane 18 (Table 1, entry 1).
To avoid the complexity of having compounds bearing different halogens in the reaction mixture,
the reaction was repeated in dichloromethane using CCl4 as the reagent, instead of CBr4 (Table 1,
entry 2). Although we had no evidence of light-sensitivity, we conducted this and all future experiments
in foil-covered flasks [19]. The reaction yielded (2,2-dichloro-1-methylcyclopropyl)-benzene 19 as
the major product. Note that a blank reaction in dichloromethane (absence of CX4) resulted in the
formation of product, bis((2-phenylpropan-2-yl)oxy)methane (20, 52%) (Table 1, entry 3) [20].
◦
Table 1. The reaction of the potassium 2-phenylpropan-2-olate 14 in dichloromethane at 40 C a.
16 (%)
17 (%)
18 (%)
19 (%)
15 (%)
20 (%)
Entry
Substrate 18 (mmol)/Additive (mmol)
Yields Based on 0.5 mmol
Yields Based on [14] 2 mmol
1
2
3
18 (0.5)/CBr4 (0.5)
18 (0.5)/CCl4 (0.5)
18 (0.5)/-
31
-
-
10
3
2
82
76
90
14
50
-
82
67
55
-
3
24
a
All yields are calculated using 1,3,5-trimethoxybenzene as the internal standard (10 mol %) in 1H-NMR unless
stated in the experimental information. As a precaution, reactions were conducted in foil-covered flasks. The yields
of 16 19 were calculated using adamantane 18 as the limiting reagent (0.5 mmol). However, the yields of 15 and 20
–
were calculated based on the alkoxide 14 used (2 mmol).
We propose that both (2,2-dibromo-1-methylcyclopropyl)-benzene 16 and (2,2-dichloro-1-
methylcyclopropyl)benzene 19 are formed from methylstyrene 17. The formation of methylstyrene is
therefore greatly encouraged in the presence of CBr4, consistent with the conversion of the alkoxide
to a leaving group (i.e., a hypobromite) (Scheme 3A). It is known that hypobromites are formed
from reaction of KOtBu with halogens, X2 [21] (and that hypohalites are precursors to alkene
halogenation by radical mechanisms [21,22]), so this reaction shows that they also form from reaction
with tetrahalomethanes. The potassium 2-phenylpropan-2-olate 14 nucleophilically attacks a molecule
of CBr4 to form the hypobromite 21 and eliminate a CBr3 anion 22. The hypobromite 21 then undergoes
an elimination to form methylstyrene 17. The formation of (2,2-dibromo-1-methylcyclopropyl)benzene
16 occurs by decomposition of the tribromomethyl anion to CBr2 23, which attacks methylstyrene 17
(Scheme 3A).
Analogous to the formation of (2,2-dibromo-1-methylcyclo-propyl)benzene 16, the isolation
of (2,2-dichloro-1-methylcyclo-propyl)benzene 19 means that carbenes (in this case, CCl2 27) are
formed under the reaction conditions (Scheme 3B). The carbene 27 forms when the potassium
2-phenylpropan-2-olate 14 deprotonates the solvent, CH2Cl2, and the resulting CHCl2 anion 24
undergoes halogen exchange with CBr4 to form bromodichloromethane 25. A second deprotonation
would lead to the bromodichloromethyl anion 26, and decomposition of this anion would lead to the
dichlorocarbene 27.
In the blank reaction (without CBr4) (Table 1, entry 3), bis((2-phenylpropan-2-yl)oxy)methane
20 is formed by the nucleophilic displacement of chloride from dichloromethane by two molecules
of potassium 2-phenylpropan-2-olate 14 (Scheme 4) [23,24]. The fact that bis((2-phenylpropan-2-
yl)oxy)methane 20 is only observed in the absence of CBr4 suggests that the reaction of potassium
2-phenylpropan-2-olate 14 with dichloromethane is slower than the reaction with CBr4.

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Scheme 3.
methylcyclopropyl)-benzene 16 and (
methylcyclopropyl)benzene 19 (not shown).
(A
) The proposed mechanism for the formation of methylstyrene 17 and (2,2-dibromo-1-
B
) the CCl2 carbene 27, that is used to form (2,2-dichloro-1-
Scheme 4. Formation of bis((2-phenylpropan-2-yl)oxy)methane 20.
Reflecting on the fact that potassium 2-phenylpropan-2-olate 14 did not give rise to halogenation
of adamantane (Table 1), while halogenation was observed when KOtBu was used as the alkoxide
(the ratio of adamantane 18:1-bromoadamantane 31:2-bromoadamantane 51 was determined to
be 39:3.3:1 [17]), this suggests that either the two alkoxide bases do not react with CBr4 through
analogous mechanisms, or that the halogenation reaction was intercepted and inhibited when 14
was used. Interception could occur if methylstyrene 17—formed in the reaction from potassium
2-phenylpropan-2-olate 14—shuts down the radical chain pathway. To probe this possibility, the
reaction of KOtBu with CBr4 and adamantane 18 was repeated in the presence of methylstyrene 17
(1 equiv., Scheme 5).
The addition of methylstyrene 17 completely inhibited the bromination of adamantane, which
suggests that it can shut down the radical mechanism, perhaps by acting as a preferential source
of hydrogen atoms, relative to adamantane 18, for the radical intermediates in the reaction.
Computationally, the competition between methylstyrene and adamantane as a source of H atoms

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was modeled using CBr3 radicals, which showed that hydrogen atom abstraction by the CBr3 radical
}
from methylstyrene 17 (∆G = 10.7 kcal/mol and ∆Grxn = −7.7 kcal/mol) is thermodynamically and
}
kinetically more favorable than from adamantane 18
(
∆
G = 13.9 kcal/mol and
∆
Grxn = 1.1 kcal/mol)
(see Supplementary Materials).
Scheme 5. Using methylstyrene 17 to block the bromination of adamantane.
All yields were calculated using 1,3,5-trimethoxybenzene as the internal standard (10 mol %) in
the 1H-NMR. The yield of 18 was calculated based on recovery of adamantane 18, the yield of 16 and
19 was calculated based on CBr4. (Note that alkoxide (4 eq.) is capable of forming methylstyrene 17.)
With the knowledge that methylstyrene 17 is capable of preventing bromination of adamantane,
why does bromination succeed when KOtBu 29 + CBr4 alone are used? The two hypobromites, tert-butyl
hypobromite and 21, may undergo elimination at different rates; additionally, 2-methylpropene (b.p.
−
6.9 ◦C) exists as a gas at the reaction temperature. Such a volatile product would likely be found
principally in the headspace above the reaction, rather than in solution, and therefore halogenation of
adamantane 18 could occur.
As mentioned earlier, Wirth et al. [19] used tert-butyl hypobromite to achieve the bromination of
alkanes (while Walling [20] used tert-butyl hypochlorite to achieve chlorination) and proposed that
the mechanism was initiated via homolysis of the O–Br bond of tert-butyl hypobromite. Either the
bromine radical or the tert-butoxyl radical could abstract the H atom from adamantane. Propagation
could then occur when the adamantyl radical abstracts a Br atom from CBr4 [13] or from tert-butyl
hypobromite [23].
To gain further information on mechanism, an alternative alkoxide, potassium triphenylmethanolate
30, was prepared and subjected to the reaction conditions with CBr4 and adamantane 18 (Table 2).
◦
Table 2. The reaction of potassium triphenylmethanolate 30 in dichloromethane at 40 C a.
Entry
Additive (mmol)
18 (%)
31 (%)
33 (%)
34 (%)
32 (%)
1
2
18 (0.5) CBr4 (0.5)
18 (0.5)
49
87
7
0
5
1
12
0
88
81
a
All yields were calculated using 1,3,5-trimethoxybenzene as the internal standard (10 mol %) in the 1H-NMR
unless stated in the experimental information. The yields of 18 31 33 34 were calculated using adamantane 18 as
,
,
,
the limiting reagent. However, the yield of 32 was calculated based on the alkoxide 30.
Reaction of potassium triphenylmethanolate 30 with adamantane in the presence of CBr4 afforded
products 1-bromoadamantane 31 (7%) and triphenylmethanol 32 (88%), as well as two additional
products, benzophenone 33 (5%) and 4-benzhydrylphenol 34 (12%) (Table 2, entry 1). When CBr4
was not present in the reaction mixture, triphenylmethanol 32 (81%) was isolated following workup,
together with a trace (1%) of benzophenone 33 (Table 2, entry 2). Further analysis of the starting

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material showed trace amounts of 33 present in the commercially supplied triphenylmethanol 32
.
Background formation of benzophenone 33, in trace amounts from heterolytic fragmentation of similar
tertiary alkoxides with expulsion of a phenyl anion, is also precedented [25,26].
The important difference between the reaction in the presence of CBr4 and in its absence (Table 2,
entry 1 and entry 2, respectively) is the formation of 4-benzhydrylphenol 34, which can arise through
the hypobromite 35 (Scheme 6). Potassium triphenylmethanolate 30 reacts with CBr4 to generate the
hypobromite 35. This hypobromite can react by three pathways (1) the OBr anion leaves to form
the stabilized cation 36; (2) the O–Br bond fragments ionically with simultaneous migration of a
phenyl moiety to form cation 38; or (3) the O–Br bond undergoes homolysis to form alkoxyl radical
40 and a bromine radical, for which there is literature precedent [23]. If pathway (1) is followed, the
carbocation 36 is attacked by another molecule of potassium triphenylmethanolate 30 and, due to
steric effects, the alkoxide attacks at the para position of one of the benzene rings. In doing so, the
species 37 is formed, which, following tautomerism and hydrolytic workup, leads to 34. Alternatively,
36 affords triphenylmethanol 32 on workup. Pathways (2) and (3) ultimately lead to the formation
of benzophenone 33; pathway (2) involves the formation of intermediate 38, which reacts with water
on workup to form 39 and, ultimately, benzophenone 33. Pathway (3) involves formation of the
alkoxyl radical 40, which could form via O–Br homolysis of 35 or, alternatively, by SET from potassium
triphenylmethanolate 30 to a molecule of CBr4. This alkoxyl radical might undergo β-scission to form
benzophenone 33. However, alternatively, the radical 40 could undergo a neophyl-like rearrangement
to form radical 41 (Scheme 6) [27]. The product 43 forms when the radical 42 abstracts a bromine
atom from either CBr4 or the hypobromite 35, and 43, in turn, upon workup, undergoes a hydrolytic
conversion to benzophenone 33. Previous fragmentations of related alkoxyl radicals have been
studied [28–32]. The enhanced formation of benzophenone 33 in the presence of CBr4 could occur
through either β-scission of the alkoxyl radical 40 (Scheme 6B), or the ionic mechanism (Scheme 6A).
Scheme 6. Proposed pathway for the formation of 32, 33 and 34 from 30: (A) through ionic
intermediates and (B) through radical intermediates.
The study above provides evidence for significant formation of hypohalites from alkoxides 14
and 30. However, it might be possible for the OtBu anion in KOtBu to behave differently. The absence

Molecules 2018, 23, 1055
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of electron-withdrawing aryl groups would render it more electron-rich, and, therefore, it might be a
better candidate than the other alkoxides to undergo electron transfer.
To probe the ability of alkoxides to donate a single electron, computational modeling
was implemented to calculate the energy profile for the SET from both KOtBu and potassium
2-phenylpropan-2-olate 14 to CBr4 in dichloromethane (Figure 1) [33]. Our previous calculations
had been based on the classical Nelsen four-point method [34], but, since that time, we published a
more accurate complexation method [33] for predicting the activation free energy and the relative
free energy of reactions. (The calculations were conducted using the M06-2X functional [35
the 6-311++G(d,p) basis set [37 41] on all atoms, except for the bromine. Bromine was modeled with
the MWB28 relativistic pseudo-potential and associated basis set [42]. All calculations were carried
out using the C-PCM implicit solvent model [43 44] with the dielectric constant for dichloromethane
= 8.93) or carbon tetrachloride ( = 2.228) as appropriate. All calculations were performed in
Gaussian09 [45]).
,36] with
–
,
(ε
ε
Figure 1. Computational modelling of SET from alkoxides, KOtBu and potassium 2-phenylpropan-2-
olate 14 to CBr4 in dichloromethane.
The energy barriers for SET from either KOtBu or potassium 2-phenylpropan-2-olate 14, to a
}
molecule of CBr4 were calculated to be
the corresponding
∆
G = +35.4 kcal/mol and +36.1 kcal/mol, respectively (while
∆
Grxn values were +13.9 and +18.9 kcal/mol) (Figure 1). When the energy barrier
was calculated for the reactions with CCl4, a similar energy profile was obtained for the SET from
either of the two alkoxides to a molecule of CCl4 (see Supplementary Materials). The energy barriers
calculated were ∆
G} = 42.5 kcal/mol and 44.5 kcal/mol for SET to CCl4 from KOtBu and potassium
2-phenylpropan-2-olate 14, respectively.◦ These barriers for reactions of both CBr4 and CCl4 are not
accessible for a reaction performed at 40 C, even as an initiation step. These computationally derived

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energy profiles for the SET step indicate that the initiation for this halogenation of adamantane 18 is
not via SET from the alkoxide; the likely alternative radical pathway arises through homolysis of the
hypohalite intermediate [19]. (Importantly, our computation predicts a barrierless, but endergonic,
profile for homolysis of the O–Br bond in tBuO–Br with ∆Grxn = +27.6 kcal/mol [34]. This is a highly
t
endergonic reaction, but as it is simply an initiation step, few BuO–Br molecules are required to
undergo homolysis).
3. Experimental Section
3.1. Computational Methods
The calculations were run using the M06-2X functional [35,36] with the 6-311++G(d,p) basis
set [37–41] on all atoms except bromine. Bromine was modeled with the MWB28 relativistic
pseudo-potential and associated basis set [42]. All calculations were carried out using the C-PCM
implicit solvent model [43,44] as implemented in Gaussian09 [45].
3.2. General Experimental Information
All reagents were bought from commercial suppliers and used without further purification
unless stated otherwise. All the reactions were carried out under argon atmosphere. Diethyl ether,
tetrahydrofuran, dichloromethane and hexane were dried with a Pure-Solv 400 solvent purification
system, marketed by Innovative Technology Inc. (Herndon, VA, USA). Organic extracts were, in general,
dried over anhydrous sodium sulfate (Na2SO4). A Büchi rotary evaporator was used to concentrate the
reaction mixtures. Thin layer chromatography (TLC) was performed using aluminium-backed sheets of
silica gel and visualized under a UV lamp (254 nm). The plates were developed using phosphomolybdic
acid or KMnO4 solution. Column chromatography was performed to purify compounds by using silica
gel 60 (200–400 mesh).
The electron transfer reactions were carried out within a glove box (Innovative Technology
Inc.) under nitrogen atmosphere, and performed in an oven-dried or flame-dried apparatus using
anhydrous solvents, which were degassed under reduced pressure, then purged with argon and dried
over activated molecular sieves (3 Å), prior to being sealed and transferred to the glovebox. All solvent
or samples placed into the glovebox were transferred through the port, which was evacuated and
purged with nitrogen 10 times before entry. When the reaction mixtures were prepared, the reaction
vessel was removed from the glove box and the rest of the reaction was performed in a fumehood.
Proton (1H) NMR spectra were recorded at 400.13, 400.03 and 500.16 MHz on Bruker AV3, AV400
and AV500 spectrometers, respectively. Carbon (13C) NMR spectra were recorded using broadband
decoupled mode at 100.61, 100.59 and 125.75 MHz on Bruker AV3, AV400 and AV500 spectrometers,
respectively. Spectra were recorded in either deuterated chloroform (CDCl3) or deuterated dimethyl
sulfoxide (d6-DMSO), depending on the solubility of the compounds. The chemical shifts are reported
in parts per million (ppm), calibrated on the residual non-deuterated solvent signal, and the coupling
constants, J, are reported in Hertz (Hz). The peak multiplicities are denoted using the following
abbreviations: s, singlet; d, doublet; t, triplet; q, quartet; sx, sextet; m, multiplet; br s, broad singlet; dd,
doublet of doublets; dt, doublet of triplets; td, triplet of doublets.
Infrared spectra were recorded on an ATR-IR spectrometer. Melting points were determined
on a Gallenkamp melting point apparatus. The mass spectra were recorded by either gas-phase
chromatography (GCMS) or liquid-phase chromatography (LCMS), using various ionization
techniques, as stated for each compound: atmospheric pressure chemical ionization (APCI), electron
ionization (EI), electrospray ionization (ESI). GCMS data were recorded using an Agilent Technologies
7890A GC system coupled to a 5975C inert XL EI/CI MSD detector. Separation was performed using
the DB5MS-UI column (30 m
carrier gas. LCMS data were recorded using an Agilent 6130 Dual source mass spectrometer with
×
0.25 mm
×
0.25 µ
m) at a temperature of 320 ◦C, using helium as the
Agilent 1200, Agilent Poroshell 120ECC 4.6 mm × 75 mm × 2.7 um column.

Molecules 2018, 23, 1055
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High-resolution mass spectrometry (HRMS) was performed at the University of Wales, Swansea,
in the EPSRC National Mass Spectrometry Centre. Accurate mass was obtained using atmospheric
pressure chemical ionization (APCI), chemical ionization (CI), electron ionization (EI), electrospray
ionization (ESI) or nanospray ionization (NSI) with a LTQ Orbitrap XL mass spectrometer.
3.3. Synthesis of Alkoxide, Potassium 2-Phenylpropan-2-Olate 14
Potassium hydride (586 mg, 15 mmol, 1.0 eq.) was added to a flame-dried three-necked flask,
◦
equipped with a vacuum tap. Under an argon atmosphere, at
−
78 C, a solution of 2-phenylpropanol
15 (2.04 g, 15 mmol) in anhydrous diethyl ether (20 mL), as added and the reaction mixture, was
◦
stirred at
−
78 C for 1 h, then at RT overnight. The solvent was removed under vacuum and the crude
material was dried for 1 h to ob◦tain potassium 2-phenylpropan-2-olate 14 (2.46 g, 14.1 mmol, −931%) as
(film)/cm 3503,
max
an off-white solid m.p. 128–132 C; (Found: (GCMS-EI) C9H11O (M-K) 135.08);
ν
2972, 1663, 1444, 1433, 1236, 1161, 1067, 1029, 955, 881, 861, 764; 1H-NMR (400 MHz, d6-DMSO)
(6 H, s, 2
CH3), 7.15–7.19 (1 H, m, ArH), 7.26–7.30 (2 H, m, ArH), 7.45–7.47 (2 H, m, ArH); 13C-NMR
(100 MHz, d6-DMSO) 31.9 (2 CH3), 70.5 (C), 124.4 (2 CH), 125.8 (CH), 127.7 (2 CH), 150.5 (C).
δ 1.41
×
δ
×
×
×
The product was put under an argon atmosphere and transported into the glovebox immediately.
3.4. Blank Reaction (No KOtBu) of CBr4 with Adamantane 18
Adamantane 18 (68 mg, 0.5 mmol), CBr4 (166 mg, 0.5 mmol, 1.0 eq.) and dichloromethane
◦
(3.13 mL) were added to an oven-dried pressure tube and the reaction mixture was stirred at 40 C for
90 h in the dark. The reaction mixture was cooled to RT and quenched with aqueous hydrochloric acid
(1 M, 5 mL) and extracted with diethyl ether (4
over Na2SO4, filtered and concentrated in vacuo. H-NMR (400 MHz, CDCl3)
CH2), 1.88 (4 H, br s, CH); 13C-NMR (100 MHz, CDCl3)
×
10 mL). The organic phases were combined, dried
1
δ
1.76–1.75 (12 H, m,
CH). (The yield of
δ
28.5 (6
×
CH2), 37.9 (4
×
adamantane 18
[
46] (93%) was determined by adding 1,3,5-trimethoxybenzene to the crude mixture
1
as an internal standard for H-NMR). These signals are consistent with the literature values and
reference samples.
3.5. Reactions of Potassium 2-Phenylpropan-2-Olate 14 with Adamantane 18 and CBr4/CCl4
3.5.1. Table 1, Entry 1
Potassium 2-phenylpropan-2-olate 14 (349 mg, 2 mmol, 4.0 eq.), adamantane 18 (68 mg, 0.5 mmol),
CBr4 (166 mg, 0.5 mmol, 1.0 eq.) and dichloromethane (3.13 mL) were added to an oven-dried
◦
pressure tube, and the reaction mixture was stirred at 40 C for 90 h. The reaction mixture was
cooled to RT and quenched with aqueous hydrochloric acid (1 M, 5 mL) and extracted with diethyl
ether (4
×
10 mL). The organic phases were combined, dried over Na2SO4, filtered and concentrated
in vacuo. The yield of 2-phenylpropanol 15 (66%), (2,2-dibromo-1-methylcyclopropyl)-benzene 16
(33%), methylstyrene 17 (18%), adamantane 18 (91%) and (2,2-dichloro-1-methylcyclopropyl)benzene
19 (17%) were determined by adding 1,3,5-trimethoxybenzene to the crude mixture as an internal
standard for 1H-NMR. The products were identified by the following characteristic signals; 1H-NMR
(400 MHz, CDCl3)
2.17 (1 H, d, J = 7.6 Hz) for (2,2-dibromo-1-methylcyclopropyl)benzene 16
s), 5.37 (1 H, s) for methylstyrene 17 1.75–1.77 (12 H, m), 1.88 (4 H, br s) for adamantane 18
1.68 (3 H, s), 1.96 (1 H, d, J = 7.2 Hz) for (2,2-dichloro-1-methylcyclopropyl)benzene 19
13C-NMR
(100 MHz, CDCl3) 31.9, 72.7, 124.5, 126.8, 128.4 for 2-phenylpropanol 15 27.9, 33.9, 128.5, 128.6
for (2,2-dibromo-1-methylcyclopropyl)-benzene 16 22.0, 112.5 for methylstyrene 17 28.5, 37.9
for adamantane 18 25.7, 36.6 for (2,2-dichloro-1-methylcyclo-propyl)benzene 19. These signals
δ
1.60 (6 H, s) for 2-phenylpropanol 15
;
δ
1.72 (3 H, s), 1.78 (1 H, d, J = 7.6 Hz),
;
δ
2.16 (3 H, s), 5.09 (1 H,
;
δ
; δ
;
δ
; δ
;
δ
; δ
;
δ
are consistent with the literature values and reference samples. The compounds 16 and 19 were
inseparable, so pure samples of 16 and 19 were prepared for comparison- see below.

Molecules 2018, 23, 1055
10 of 16
3.5.2. Preparation of 16
KOtBu 29 (224 mg, 2 mmol, 4.0 eq.), HCBr3 (0.04 mL, 0.5 mmol, 1.0 eq.) and methylstyrene
17 (0.07 mL, 0.5 mmol) were added to an oven-dried pressure tube. Dichloromethane (3.13 mL)
was added and the reaction mixture was stirred at 40 ◦C for 90 h. The reaction mixture was cooled
to RT and quenched with aqueous hydrochloric acid (1 M, 5 mL) and extracted with diethyl ether
(4
×
10 mL). The organic phases were combined, dried over Na2SO4, filtered and concentrated
in vacuo. The crude material was purified by column chromatography (100% hexane) to give
(2,2-dibromo-1-methylcyclopropyl)benzene 16
[
18] (82.4 mg, 57%) as a colorless oil [Found: (GCMS-CI)
+
C10H11Br2 (M + H)+ 288.7];
ν
(film)/cm−1 1496, 1445, 1426, 1060, 1019, 763, 691; 1H-NMR (400
max
MHz, CDCl3)
δ
1.72 (3 H, s, CH3), 1.78 (1 H, d, J = 7.6 Hz, CH2), 2.17 (1 H, d, J = 7.6 Hz, CH2), 7.29–7.38
27.9 (CH3), 33.8 (CH2), 35.9 (C), 36.9 (C), 127.4 (CH),
(5 H, m, ArH); 13C{1H}-NMR (100 MHz, CDCl3)
δ
128.5 (2
×
CH), 128.6 (2
×
CH), 142.5 (C); m/z (CI) 292.6 [(M + H)+, 81Br81Br, 61%), 290.6 [(M + H)+,
79Br81Br, 100), 288.7 [(M + H)+, 79Br79Br, 70)].
3.5.3. Preparation of 19
KOtBu 29 (224 mg, 2 mmol, 4.0 eq.), HCCl3 (0.04 mL, 0.5 mmol, 1.0 eq.) and methylstyrene
17 (0.07 mL, 0.5 mmol) were added to an oven-dried pressure tube. Dichloromethane (3.13 mL)
was added and the reaction mixture was stirred at 40 ◦C for 90 h. The reaction mixture was cooled
to RT and quenched with aqueous hydrochloric acid (1 M, 5 mL) and extracted with diethyl ether
(4
×
10 mL). The organic phases were combined, dried over Na2SO4, filtered and concentrated
in vacuo. The crude material was purified by column chromatography (100% hexane) to give
(2,2-dichloro-1-methylcyclopropyl)benzene 19
[
ν
18] (63.7 mg, 63%) as a colorless oil [Found: (HRMS-EI)
•+
−1
200.0157. C10H10Cl2 (M) requires 200.0160];
(film)/cm 1497, 1446, 1425, 1075, 1033, 1026, 936,
max
868, 772, 754, 697, 595; 1H-NMR (400 MHz, CDCl3)
δ
1.60 (1 H, d, J = 7.2 Hz, CH2), 1.68 (3 H, s, CH3),
1.96 (1 H, d, J = 7.2 Hz, CH2), 7.27–7.38 (5 H, m, ArH); 13C-NMR (100 MHz, CDCl3)
25.7 (CH3), 32.0
CH), 141.4 (C); m/z (CI) 203.9 ((M)•+
35Cl35Cl, 100).
δ
(CH2), 36.6 (C), 66.0 (C), 127.4 (CH), 128.6 (2
×
CH), 128.7 (2
×
,
37Cl37Cl, 12%), 201.9 ((M)•+
,
35Cl37Cl, 70), 199.9 ((M)•+
,
3.5.4. Table 1, Entry 2
Potassium 2-phenylpropan-2-olate 14 (349 mg, 2 mmol, 4.0 eq.), adamantane 18 (68 mg, 0.5 mmol),
CCl4 (0.05 mL, 0.5 mmol, 1.0 eq.) and dichloromethane (3.13 mL) were added to an oven-dried pressure
◦
tube and the reaction mixture was stirred at 40 C for 90 h in the dark. The reaction mixture was
cooled to RT and quenched with aqueous hydrochloric acid (1 M, 5 mL) and extracted with diethyl
ether (4
×
10 mL). The organic phases were combined, dried over Na2SO4, filtered and concentrated
in vacuo. The yield of 2-phenylpropanol 15 (67%), methylstyrene 17 (3%), adamantane 18 (76%),
(2,2-dichloro-1-methylcyclopropyl)benzene 19 (50%) and bis((2-phenylpropan-2-yl)oxy)-methane 20
(3%) were determined by adding 1,3,5-trimethoxybenzene to the crude mixture as an internal standard
1
1
for H-NMR. The products were identified by the following characteristic signals; H-NMR (400
MHz, CDCl3) 1.60 (6 H, s) for 2-phenylpropanol 15 2.17 (3 H, s), 5.10 (1 H, s), 5.38 (1 H, s) for
methylstyrene 17 1.76–1.78 (12 H, m), 1.89 (4 H, br s) for adamantane 18 1.68 (3 H, s), 1.97 (1 H,
d, J = 7.2 Hz) for (2,2-dichloro-1-methylcyclopropyl)benzene 19 4.51 (2 H, s), 7.20–7.24 (2 H, m) for
bis((2-phenylpropan-2-yl)oxy)methane 20 31.9, 72.7, 124.5, 126.8, 128.4
13C-NMR (100 MHz, CDCl3)
for 2-phenylpropanol 15 22.0, 112.6 for methylstyrene 17 28.5, 37.9 for adamantane 18 25.6,
δ
; δ
;
δ
; δ
;
δ
;
δ
;
δ
;
δ
; δ
36.6 for (2,2-dichloro-1-methylcyclopropyl)benzene 19. These signals are consistent with the literature
values and reference samples.
3.5.5. Table 1, Entry 3
Potassium 2-phenylpropan-2-olate 14 (349 mg, 2 mmol, 4.0 eq.), adamantane 18 (68 mg, 0.5 mmol)
and dichloromethane (3.13 mL) were added to an oven-dried pressure tube and the reaction mixture

Molecules 2018, 23, 1055
11 of 16
was stirred at 40 ◦C for 90 h in the dark. The reaction mixture was cooled to RT and quenched with
aqueous hydrochloric acid (1 M, 5 mL) and extracted with diethyl ether (4 10 mL). The organic phases
×
were combined, dried over Na2SO4, filtered and concentrated in vacuo. The yield of 2-phenylpropanol
15 (39%), methylstyrene 17 (1%), adamantane 18 (84%) and bis((2-phenylpropan-2-yl)oxy)methane
20 (52%) were determined by adding 1,3,5-trimethoxybenzene to the crude mixture as an internal
standard for 1H-NMR. The products were identified by the following characteristic signals; 1H-NMR
(400 MHz, CDCl3)
s) for methylstyrene 17
7.20–7.24 (2 H, m) for bis((2-phenylpropan-2-yl)oxy)methane 20
72.7, 124.5, 149.2 for 2-phenyl-2-propanol 15 28.5, 37.9 for adamantane 18; δ
δ
1.60 (6 H, s) for 2-phenylpropanol 15
1.75–1.77 (12 H, m), 1.88 (4 H, br s) for adamantane 18
13C-NMR (100 MHz, CDCl3)
29.5, 77.7, 86.8, 146.9
;
δ
2.16 (3 H, s), 5.09 (1 H, s), 5.37 (1 H,
4.51 (2 H, s),
31.9,
;
δ
; δ
;
δ
;
δ
for bis((2-phenylpropan-2-yl)oxy)methane 20. These signals are consistent with the literature values
and reference samples. This crude material was purified by column chromatography (0–5% ethyl
acetate in hexane) to give bis((2-phenylpropan-2-yl)oxy)methane 20 (44.7 mg, 26%) as a colorless oil
(Found: (HRMS-ESI) 302.2118. C19H28O2N (M + NH4)+ requires 302.2115); νmax (film)/cm−1 2978,
2934, 1493, 1447, 1381, 1364, 1258, 1153, 1072, 1018, 991, 818, 762; 1H-NMR (400 MHz, CDCl3)
(12 H, s, 4 × CH3), 4.50 (2 H, s, CH2), 7.20–7.23 (2 H, m, ArH), 7.27–7.31 (4 H, m, ArH), 7.38–7.40 (4 H,
m, ArH); 13C-NMR (100 MHz, CDCl3)
C), 86.8 (CH2), 125.9 (4 CH), 126.9
δ 1.59
δ
29.5 (4 × CH3), 77.7 (2
×
×
(2 × CH), 128.2 (4 × CH), 146.9 (2 × C).
3.6. Reaction of KOtBu in Dichloromethane
KOtBu 29 (224 mg, 2 mmol, 4.0 eq.), CBr4 (166 mg, 0.5 mmol, 1.0 eq.), adamantane 18 (68 mg,
0.5 mmol) and dichloromethane (3.13 mL) were added to an oven-dried pressure tube and the reaction
◦
mixture was stirred at 40 C for 90 h in the dark. The reaction mixture was cooled to RT and quenched
with aqueous hydrochloric acid (1 M, 5 mL) and extracted with diethyl ether (4
×
10 mL). The organic
phases were combined, dried over Na2SO4, filtered and concentrated in vacuo. The ratio of adamantane
18:1-bromoadamantane 31:2-bromoadamant-ane 51 was determined to be 39:3.3:1 from the 1H-NMR
spectrum of the crude mixture. The products were identified by the following characteristic signals;
1H-NMR (400 MHz, CDCl3)
18 1.73 (6 H, m, CH2 3), 2.10 (3 H, br s, CH
31 47]; 1.96–2.00 (2 H, m, CH2), 2.15 (2 H, br s, CH
δ
1.74–1.76 (12 H, m, CH2
3), 2.36 (6 H, m, CH2
2), 2.33 (2 H, br s, CH
×
6), 1.88 (4 H, br s, CH
3) for 1-bromoadamantane
2), 4.68 (1 H, br s, CH)
×
4) for adamantane
;
δ
×
×
×
[
δ
×
×
for 2-bromoadamantane 51 [48]; 13C-NMR (100 MHz, CDCl3) δ 28.5, 37.9 adamantane 18; δ 32.8, 35.7,
49.5 for 1-bromoadamantane 31; 36.6, 39.1 for 2-bromoadamantane 51. These signals are consistent
with the literature values and reference samples.
3.7. Reactions of Adamantane 18 with CBr4, Methylstyrene 17 and KOtBu 29 (Scheme 5)
KOtBu 29 (224 mg, 2 mmol, 4.0 eq.), CBr4 (166 mg, 0.5 mmol, 1.0 eq.), methylstyrene 17 (0.07 mL,
0.5 mmol, 1.0 eq.), adamantane 18 (68 mg, 0.5 mmol) and dichloromethane (3.13 mL) were added
◦
to an oven-dried pressure tube and the reaction mixture was stirred at 40 C for 90 h in the dark.
The reaction mixture was cooled to RT and quenched with aqueous hydrochloric acid (1 M, 5 mL)
and extracted with diethyl ether (4
×
10 mL). The organic phases were combined, dried over Na2SO4,
filtered and concentrated in vacuo. The yield of (2,2-dibromo-1-methylcyclopropyl)benzene 16 (59%),
methylstyrene 17 (3%), adamantane 18 (75%) and (2,2-dichloro-1-methylcyclopropyl)benzene 19 (40%)
were determined by adding 1,3,5-trimethoxybenzene to the crude mixture as an internal standard for
1H-NMR. The products were identified by the following characteristic signals; 1H-NMR (400 MHz,
CDCl3)
δ
1.72 (3 H, s), 1.78 (1 H, d, J = 7.6 Hz) for (2,2-dibromo-1-methylcyclopropyl)benzene 16
;
δ
5.09
1.60
(1 H, s), 5.37 (1 H, s) for methylstyrene 17
;
δ
1.75–1.78 (12 H, m), 1.88 (4 H, br s) for adamantane 18;
δ
(1 H, d, J = 7.2 Hz), 1.69 (3 H, s), 1.97 (1 H, d, J = 7.2 Hz) for (2,2-dichloro-1-methylcyclopropyl)benzene
19
16
;
;
13C-NMR (100 MHz, CDCl3)
27.9, 33.9, 36.9, 142.5 for (2,2-dibromo-1-methylcyclopropyl)benzene
28.5, 37.9 for adamantane 18; δ 25.7, 32.0, 36.6, 141.4 for (2,2-dichloro-1-methylcyclopropyl)benzene
δ
δ
19. These signals are consistent with the literature values and reference samples [49,50].

Molecules 2018, 23, 1055
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3.8. Synthesis of Alkoxide, Potassium Triphenylmethanolate 30
Potassium hydride (802 mg, 20 mmol, 1.0 eq.) was added to a flame-dried three-necked flask,
equipped with a vacuum tap. Under an argon atmosphere, at –78 ◦C, a solution of triphenylmethanol
32 (5.21 g, 20 mmol) in anhydrous tetrahydrofuran (25 mL) was added and the reaction mixture was
stirred at
−
78 ◦C for 1 h, then at RT overnight. The solvent was removed on the house vacuum line
and the crude material was dried for 1 h to give potassium triphenylmethanolate 30 (5.07 g, 17 mmol,
85%) as an off-white solid, m.p. 238 ◦C (dec.); (Found: (GCMS-EI) C19H16O (M)•+ 260.1 (under the
MS analysis 30 is protonated to the alcohol)); νmax (film)/cm−1 3057, 3022, 1595, 1487, 1443, 1414,
1329, 1155, 1053, 1009, 891, 756; 1H-NMR (400 MHz, d6-DMSO)
(6 H, m, ArH), 7.34–7.37 (6 H, m, ArH); 13C-NMR (100 MHz, d6-DMSO)
126.0 (6 × CH), 128.2 (6 CH), 157.6 (3 C). The product was put under an argon atmosphere and
transported into the glove box immediately.
δ
6.93–6.98 (3 H, m, ArH), 7.04–7.08
84.7 (C), 123.6 (3 CH),
δ
×
×
×
3.9. Reactions of Potassium Triphenylmethanolate 30 at 40 ◦C
3.9.1. Table 2, Entry 1
Potassium triphenylmethanolate 30 (597 mg, 2 mmol, 4.0 eq.), CBr4 (166 mg, 0.5 mmol, 1.0 eq.),
adamantane 18 (68 mg, 0.5 mmol) and dichloromethane (3.13 mL) were added to an oven-dried
pressure tube and the reaction mixture was stirred at 40 ◦C for 90 h in the dark. The reaction mixture
was cooled to RT and quenched with aqueous hydrochloric acid (1 M, 5 mL) and extracted with diethyl
ether (4
×
10 mL). The organic phases were combined, dried over Na2SO4, filtered and concentrated
in vacuo. The yield of adamantane 18 (49%), 1-bromoadamantane 31 (7%), triphenylmethanol
32 (88%), benzophenone 33 (5%) and 4-benzhydrylphenol 34 (12%) were determined by adding
1,3,5-trimethoxybenzene to the crude mixture as an internal standard for 1H-NMR. The products were
identified by the following characteristic signals; 1H-NMR (400 MHz, CDCl3)
1.88 (4 H, br s) for adamantane 18
31 47]; 7.27–7.34 (15 H, m) for triphenylmethanol 32
7.82 (4 H, d, J = 8.0 Hz) for benzophenone 33 51];
m) for 4-benzhydrylphenol 34
52]; 13C-NMR (100 MHz, CDCl3)
49.3, 35.5, 32.6 for 1-bromoadamantane 31 82.2, 127.4, 128.0, 147.0 for triphenylmethanol 32; δ
δ
1.75–1.78 (12 H, m),
1.74 (6 H, m), 2.12 (3 H, br s), 2.38 (6 H, m) for 1-bromoadamantane
7.49 (4 H, d, J = 8.0 Hz), 7.60 (2 H, d, J = 8.0 Hz),
5.49 (1 H, s), 6.73–6.77 (2 H, m), 6.97–7.00 (2 H,
28.3, 37.7 for adamantane 18
56.1,
;
δ
[
δ
; δ
δ
[
[
δ
; δ
;
δ
115.3, 144.3 for 4-benzhydroxylphenol 34. These signals are consistent with the literature values and
reference samples. This crude material was purified by column chromatography (0%–10% ethyl acetate
in hexane) to give both benzophen-one 33
[
51] (7 mg, 4%) as a yellow oil (Found: (GCMS-EI) C13H10O
1
(M)•+ 182.0); νmax (film)/cm−1 3057, 1655, 1597, 1445, 1275, 1175, 939, 918, 808, 762; H-NMR (400
MHz, CDCl3)
ArH); 13C-NMR (100 MHz, CDCl3)
196.7 (C) and 4-benzhydrylphenol 34
(M)•+ 260.1); νmax(film)/cm−1 3366, 2361, 2336, 1595, 1508, 1491, 1449, 1238, 1173, 1103, 1030, 816, 800,
750, 735; 1H-NMR (400 MHz, CDCl3)
4.82 (1 H, br s, OH), 5.49 (1 H, s, CH), 6.73–6.77 (2 H, m, ArH),
6.97–7.00 (2 H, m, ArH), 7.11–7.13 (4 H, m, ArH), 7.19–7.32 (6 H, m, ArH); 13C-NMR (100 MHz, CDCl3)
56.1 (CH), 115.3 (2 CH), 126.4 (2 CH), 128.4 (4 CH), 129.5 (4 CH), 130.7 (2 CH), 136.4 (C),
144.3 (2 × C), 154.1 (C).
Triphenylmethanol 32 1H-NMR (400 MHz, CDCl3)
7.57 (2 H, d, J = 8.4 Hz, ArH); 13C-NMR (100 MHz, CDCl3)
δ
7.49 (4 H, t, J = 8.0 Hz, ArH), 7.60 (2 H, t, J = 8.0 Hz, ArH), 7.82 (4 H, d, J = 8.0 Hz,
128.2 (4 CH), 130.2 (4 CH), 132.6 (2 CH), 137.5 (2 C),
52] (18.9 mg, 7%) as a yellow oil (Found: (GCMS-EI) C19H16O
δ
×
×
×
×
[
δ
δ
×
×
×
×
×
δ
2.79 (1 H, s, OH), 7.26–7.34 (15 H, m, ArH),
82.2 (C), 127.4 (CH), 128.1 (6 CH), 147.0
δ
×
(9 × C). These signals are consistent with a commercial sample used as a reference.
3.9.2. Table 2, Entry 2
Potassium triphenylmethanolate 30 (597 mg, 2 mmol, 4.0 eq.), adamantane 18 (68 mg, 0.5 mmol)
and dichloromethane (3.13 mL) were added to an oven-dried pressure tube and the reaction mixture
was stirred at 40 ◦C for 90 h in the dark. The reaction mixture was cooled to RT and quenched with

Molecules 2018, 23, 1055
13 of 16
aqueous hydrochloric acid (1 M, 5 mL) and extracted with diethyl ether (4
were combined, dried over Na2SO4, filtered and concentrated in vacuo. The yield of adamantane
×
10 mL). The organic phases
18 (87%), triphenylmethanol 32 (81%) and benzophenone 33 (1%) were determined by adding
1
1,3,5-trimethoxybenzene to the crude mixture as an internal standard for H-NMR. The products
were identified by the following characteristic signals; 1H-NMR (400 MHz, CDCl3)
δ
1.75–1.78 (12 H,
7.27–7.34 (15 H, m) for triphenylmethanol 32 7.49 (4 H, d,
J = 8.0 Hz, ArH), 7.60 (2 H, d, J = 8.0 Hz, ArH), 7.82 (4 H, d, J = 8.0 Hz, ArH) for benzophenone 33
13C-NMR (100 MHz, CDCl3)
28.3, 37.7 for adamantane 18 82.2, 127.4, 128.0, 147.0 triphenylmethanol
m), 1.88 (4 H, br s) for adamantane 18
;
δ
, δ
;
δ
; δ
32 [49]. These signals are consistent with the literature values and reference samples.
4. Conclusions
This study has led to a revision of earlier thoughts on the mechanism for the halogenation of
adamantane 18 by using a combination of KOtBu and CBr4. It is proposed that the mechanism does
not occur through SET, as was previously believed, but proceeds through hypobromite intermediates
(Scheme 7). The alkoxide in the reaction mixture, 53, forms a hypobromite in the presence of CBr4.
The hypobromite 54 can undergo reaction along two pathways. The first option is an elimination
reaction to form the alkene 57, which reacts with carbenes formed in the reaction to afford final product
58. The second pathway is the O–Br bond homolysis of the hypobromite 54. This forms the alkoxyl
radical 55 and a bromine radical. These radical intermediates perform a hydrogen atom abstraction
from adamantane 18 to form adamantyl radical 56 (alternatively, the hydrogen atom abstraction may
occur at the C-2 position to ultimately give the 2-Br isomer). The radical 56 will abstract a bromine
from a hypobromite molecule 54, or from CBr4, to form 31 and an alkoxyl radical 55, or CBr3 radical.
The radical formed will propagate the chain pathway by hydrogen atom abstraction from adamantane
18, thus creating a radical chain mechanism. Thus, it appears that the search for reactions where
ground-state KOtBu behaves as an electron donor must continue. The outcomes of this project have
led us to reexamine the remaining claims [3,4] of this phenomenon.
Scheme 7. The modified mechanism for halogenation of adamantane.
Supplementary Materials: The following are available online, (i)Additional computational analysis and xyz
coordinates relating to all computed structures (ii) Table S1 “The reaction of tert-butyl hypochlorite 46 in
dichloromethane or carbon tetrachloride as solvent” (iii) Table S2. tert-Butyl hypobromite 50 in bromination of
adamantane 18; (iv) Experimental procesdures and spectroscopid data in support of the experiments discussed in
those Tables (v) NMR spectra of key products.
Author Contributions: K.J.E., A.Y., J.N.A., T.T., J.A.M. conceived and designed the experiments; K.J.E., A.Y., J.N.A.
performed the experiments, K.J.E., A.Y., J.N.A., T.T., J.A.M. analyzed the data, K.J.E., T.T., J.A.M. wrote the paper.
Acknowledgments: We thank the EPSRC and University of Strathclyde for the funding. Grant Number:
EP/L505080/1. Further thanks to EPSRC National Mass Spectrometry Service Centre, Swansea, for the
high-resolution mass spectra results.
Conflicts of Interest: There are no conflicts to declare.

Molecules 2018, 23, 1055
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Sample Availability: Samples of the compounds are not available.
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