Catechols as Sources of Hydrogen Atoms in Radical Deiodination and Related Reactions

Article abstract of DOI:10.1002/anie.201604950

When used with trialkylboranes, catechol derivatives, which are low-cost and low toxicity, are valuable hydrogen atom donors for radical chain reactions involving alkyl iodides and related radical precursors. The system 4-tert-butylcatechol/triethylborane has been used to reduce a series of secondary and tertiary iodides, a xanthate, and a thiohydroxamate ester. Catechol derivatives are right in the optimal kinetic window for synthetic applications, as demonstrated by highly efficient radical cyclizations. Cyclizations leading to the formation of quaternary centers can be performed in an all-at-once process (no slow addition of the hydrogen atom donor) at standard concentrations. The H-donor properties of catechol derivatives can be fine-tuned by changing their substitution pattern. In slow radical cyclization processes, an enhanced ratio of cyclized/uncyclized products was obtained by using 3-methoxycatechol instead of 4-tert-butylcatechol.

Full text of DOI:10.1002/anie.201604950

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201604950
German Edition: DOI: 10.1002/ange.201604950
Hydrogen Atom Donors
Catechols as Sources of Hydrogen Atoms in Radical Deiodination and
Related Reactions
Guillaume Povie, Leigh Ford, Davide Pozzi, Valentin Soulard, Giorgio Villa, and
Philippe Renaud*
Abstract: When used with trialkylboranes, catechol deriva-
tives, which are low-cost and low toxicity, are valuable
hydrogen atom donors for radical chain reactions involving
alkyl iodides and related radical precursors. The system 4-tert-
butylcatechol/triethylborane has been used to reduce a series of
secondary and tertiary iodides, a xanthate, and a thiohydrox-
amate ester. Catechol derivatives are right in the optimal kinetic
window for synthetic applications, as demonstrated by highly
Figure 1. Rate constants for the hydrogen transfer between various
hydrogen atom donors and a primary alkyl radical.
efficient radical cyclizations. Cyclizations leading to the
formation of quaternary centers can be performed in an all-
at-once process (no slow addition of the hydrogen atom donor)
at standard concentrations. The H-donor properties of catechol
derivatives can be fine-tuned by changing their substitution
pattern. In slow radical cyclization processes, an enhanced
ratio of cyclized/uncyclized products was obtained by using 3-
methoxycatechol instead of 4-tert-butylcatechol.
5 ꢀ 106 mÀ1 sÀ1, to ensure an efficient chain process and to
provide a sufficient lifetime for the radical to be involved in
radical rearrangements before the hydrogen atom is deliv-
ered. Among all the possible sources of hydrogen atoms, only
a few of them are close to these optimal values (Figure 1, gray
region).
À
R
adical reactions are becoming an increasingly attractive
Reagents based on O H hydrogen donors such as
tool in synthetic organic chemistry, and more particularly in
the synthesis of densely functionalized compounds like
natural products and biologically relevant molecules.[1]
Among all radical reactions, processes involving a final
hydrogen atom transfer from a triorganotin hydride have
played a unique role in their development towards synthetic
applications.[2] Owing to the toxicity of these tin reagents,
several alternatives based on molecules possessing a weakly
alcohols and water are particularly attractive owing to their
availability, low toxicity, and low price, but they need to be
activated to become hydrogen atom donors. Upon complex-
ation with a boron Lewis acid such as trimethyl- and
triethylborane[12] the O H bonds of water and alcohols is
À
considerably weakened,[13] and such complexes have been
used in radical-mediated deoxygenation and deiodination
reactions.[12a,b,14] However, this approach gives rise to H-
donors that are about two orders of magnitude less potent
than tin hydride derivatives.[15] We have reported that
catechols can be used as a source of hydrogen atoms in
radical reactions involving organoborane radical precur-
sors.[16] For instance, a mild procedure for the protonolysis
of organoboranes has been developed based on a highly
efficient radical chain process.[16a] Interestingly, catechols are
excellent H-donors for alkyl radicals with rate constants in the
desired range (gray region in Figure 1). Herein, we report that
catechols, in the presence of organoboranes, are becoming
a highly attractive source of hydrogen atoms for a variety of
transformations such as deiodination, decarboxylation, and
deoxygenation reactions.
[3]
[4]
[5]
À
À
À
bound hydrogen atom, for example, Si H, Ge H, C H,
[6]
[7]
[8]
[9]
À
À
À
À
S H, B H, P H, or O H, have been developed with
variable success depending on the applications.[10] These
reagents do not, however, outperform tin hydride in terms
of simplicity of use, synthetic efficacy, or price.
A crucial point in the development of good alternatives to
tin hydride for a wide range of applications such as simple
dehalogenation and cyclization reactions, is to design a hydro-
gen donor (H-donor) with the right ability to transfer
a hydrogen atom. An overview of the rate constants for the
hydrogen atom transfer to primary alkyl radicals from various
reagents at 258C is given in Figure 1. An ideal value for most
synthetic applications would be slightly below that of Bu3SnH
(kH = 2.7 ꢀ 106 mÀ1 sÀ1 at 308C),[11] that is, between 1 ꢀ 105 and
N-tosyl-4-iodopiperidine 1a was used as a model substrate
to find optimal reaction conditions and 4-tert-butylcatechol
(TBC) was chosen for its commercial availability, low price,
solubility in organic solvents, and excellent H-donor proper-
ties. The use of 1.0 equiv of TBC and 1.3 equiv of triethylbor-
ane (BEt3) gave the best results. The reaction proceeded
equally well in various apolar solvents (hexane, benzene,
toluene, 1,2-dichloroethane, or dichloromethane), whereas
the use of the hydrogen bond acceptor solvents Et2O, EtOAc,
or t-BuOMe led to lower conversions of the iodide, which is
[*] Dr. G. Povie, Dr. L. Ford, Dr. D. Pozzi, V. Soulard, Dr. G. Villa,
Prof. Dr. P. Renaud
Department of Chemistry and Biochemistry, University of Bern
Freiestrasse 3, 3012 Bern (Switzerland)
E-mail: philippe.renaud@dcb.unibe.ch
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
http://dx.doi.org/10.1002/anie.201604950.
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presumably due to a less efficient chain process resulting from
the lower rate of hydrogen atom transfer in such solvents.[17]
In dichloromethane at room temperature, the reaction
afforded the deiodinated product 2a in 88% yield (Table 1,
entry 1). Under these conditions, the reduction of adamantyl
iodide 1b proceeded efficiently, yielding adamantane 2b in
95% yield (GC) after 6 hours (Table 1, entry 2). A similar
result was obtained after only three hours when the reaction
was performed at 808C in 1,2-dichloroethane using di-tert-
butyl hyponitrite as an initiator (Table 1, entry 3). Cholesteryl
iodide 1c proved to be more defiant, as complete conversion
could never be achieved (Table 1, entries 4 and 5). Never-
theless, on a 40 mmol scale, cholest-5-ene 2c could be
obtained in 71% yield after recrystallization (Table 1,
entry 6). Secondary iodides 1d and 1e were also efficiently
deiodinated (Table 1, entries 7 and 8). Remarkably, the
iodobromoderivative 1e was selectively deiodinated in 87%
yield. Under the same reaction conditions (room temper-
ature), the deoxygenation of cyclododecyl xanthate 1 f
yielded the expected cyclododecane 2 f in 64% yield
(Table 1, entry 9). Using di-tert-butyl hyponitrite as an
initiator in refluxing 1,2-dichloroethane, xanthate 1 f was
entirely consumed after 5 hours, providing 2 f in high yield
(Table 1, entry 11). The reductive decarboxylation of the
adamantyl thiohydroxamate ester 1g,[18] furnished the corre-
sponding rearranged thioester and adamantane 2b in circa 1:1
ratio at room temperature. As for xanthate 1 f, increasing the
temperature to 808C dramatically enhanced the formation of
adamantane 2b to 93% (Table 1, entry 11). It is worth
mentioning that initiation with air proved to be less efficient
than with di-tert-butyl hyponitrite in all of the reactions
conducted in refluxing 1,2-dichloroethane.
The 11B NMR spectrum of BEt3 (0.3m) in a degassed 1.0m
solution of TBC in C6D6 displays an identical chemical shift
(d = 86.9 ppm) as in a solution of only C6D6 (Dd < 0.05 ppm).
Reciprocally, the 1H NMR spectrum of TBC is not affected by
the presence of BEt3, ruling out any significant complex
formation that would enhance the H-donor ability of
TBC.[12b,15c] Therefore, we believe that a mechanism closely
related to that reported for the protonolysis of organoboranes
is operating for this reaction[16a] as depicted in Scheme 1. The
Table 1: Deiodination, deoxygenation, and decarboxylation reactions.
Scheme 1. Proposed mechanism for the deiodination process.
ethyl radical formed in the initiation step enters the chain
process by abstracting an iodine atom to generate the desired
alkyl radical [Eq. (1)]. Then, the alkyl radical abstracts
a hydrogen atom from catechol to deliver the product 2 and
the phenoxyl radical A [Eq. (2a)]. Reaction of the phenoxyl
radical A with Et3B affords the monoborinate ester 3 as well
as an ethyl radical that can sustain the chain process
[Eq. (2b)]. Interestingly, compound 3 may also act as H-
donor in a second chain process (pathway b). Hydrogen
transfer from 3 to the alkyl radical gives the product 2 and
a new phenoxyl radical B [Eq. (2b)] that can undergo an
intramolecular homolytic substitution to furnish B-ethylcate-
cholborane 4 and an ethyl radical that propagates further the
chain process [Eq. (3b)]. Hydrogen atom exchange between
phenoxy radicals is known to take place with high rates,[19]
thus pathways a and b may be closely interlinked through
Entry
Substrate
Product Temp.[a]
Time [h]
Yield of 2 [%][b]
1
2
3
4
5
6
7
8
1a
1b
1b
1c
1c
1c
1d
1e
1 f
1 f
1g
2a
2b
2b
2c
2c
2c
2d
2e
2 f
2 f
2b
rt
rt
838C
rt
838C
rt[d]
rt
rt
rt
838C
838C
10
6
3
10
4
30
10
5
88
95[c]
96[c]
76
58
71
74
87
9
10
11
12
5
4
64
87[c,e]
93[c]
[a] Conditions: Et3B (1.3 equiv), TBC (1.0 equiv), 0.3m, in CH2Cl2 open to
air at rt or in refluxing 1,2-dichloroethane (838C) using (t-BuON)2
(6 mol%) as an initiator. [b] Yields of isolated product unless otherwise
mentioned. [c] Yields determined from GC. [d] 40 mmol scale. [e] Aver-
age yield over three runs.
2
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Table 2: Chemoselective deiodination reactions.
a rapid equilibrium between radicals A and B [Eq. (4)].
Preliminary investigations have shown that the monoborinate
ester 3 is a better hydrogen atom donor than catechol towards
alkyl radicals and it has been assumed that 3 was involved as
a repair agent in a recently reported thiol–ene coupling
process.[20,21]
À
À
Entry
R X
Reacted 1a/R X
Yield of 2a [%][a,b]
The delicate part of the reaction arises from the use of an
ethyl radical to sustain the chain since the direct reduction of
the ethyl radical by TBC competes with the iodine atom
transfer reaction. The rate constant for the iodine atom
transfer process between a primary alkyl radical (1-octyl) and
a secondary alkyl iodide has been reported by Newcomb to be
5.1 ꢀ 105 mÀ1 sÀ1 at 508C.[22] This rate constant is about half as
large than the one we have reported for the reduction of
secondary alkyl radical by 4-tert-butylcatechol at 808C (kH =
1.3 ꢀ 106 mÀ1 sÀ1)[16a] and very close to that reported by Villa for
the reduction of a primary alkyl radical (kH = 6.2 ꢀ 105 mÀ1 sÀ1
at 508C).[23] As a consequence, at low concentrations of the
starting alkyl iodide (near the end of the reaction), most of the
ethyl radicals are converted into ethane (Scheme 2) and the
À
1
2
C6H5CH2 N3
C6H5
n-C12H25
n-C12H25
n-C12H25
ꢀ15
ꢀ100
4.0
7.4
1.3
92 (97)
82 (85)
72 (83)
55 (93)
54 (95)
À
I
2[c]
3[d]
4[e]
I
I
À
À
À
I
[a] Yields of isolated product. [b] Yields in parenthesis are based on
consumed 1a. [c] Using 0.9 equiv BEt3. [d] Using 0.5 equiv BEt3. [e] Using
Bu3SnH (1.0 equiv) and azobisisobutyronitrile (AIBN; 0.2 equiv) in
refluxing benzene.
To investigate the application of catechols in radical
cyclization processes, the behavior of iodoacetals[25] was next
examined. The results are summarized in Table 3. 2-(Alk-2-
enyloxy)-3-iodopyran derivatives 8a–f were prepared by
iodoetherification reactions involving 2-H-dihydropyranes
5–7, allylic alcohols and N-iodosuccinimide (NIS; see the
Supporting Information). The 5-exo-trig cyclization of 3-
oxahex-5-enyl radicals is known to be faster than the 5-
hexenyl carbon analogues.[26] As expected, treatment the
iodoacetal 8a (0.3m solution in dichloromethane) with
1.3 equiv of BEt3 and 1 equiv of TBC at room temperature
afforded exclusively the cyclized product 9a in 82% yield.[27]
The 2:1 endo/exo ratio is in accordance with previous reports
involving this system.[28] Similarly, the silyl ether 8b and the
bromide 8c yielded the cis-bicyclic products 9b and 9d in
82% and 71% yield under the same reaction conditions.
Cyclizations involving the formation of quaternary carbon
centers were investigated next with substrates 8d–f. Under
our standard reaction conditions (0.3m in TBC), 8d gave an
85:15 mixture of cyclized/non-cyclized products 9d/10d. To
optimize the formation of the cyclized product, other catechol
derivatives were tested. Interestingly, 3-methoxycatechol
enhanced the ratio of cyclized/uncyclized products 9d/10d
to 95:5 and pure 9d was isolated in 88% yield. As
a comparison, the reaction was also run with tributyltin
hydride as a source of hydrogen atoms. Even when the
reaction was run under dilute conditions (0.07m), the reaction
afforded a 45:55 mixture of 9d/10d, and pure 9d could only
be isolated in 41% yield. Similar results were obtained with
8e where radical cyclization was even slower than in the case
of 8d. By using 4-methoxycatechol, the cyclized product was
the major product (9e/10e 75:25) and 9e was isolated in 67%
yield, whereas the tin hydride method (0.008m) afforded
mainly the non-cyclized product 10e (9e/10e 23:77). Finally,
9 f, the minor diastereomer obtained during the iodoether-
ification leading to 9e, was also examined. Only the bicyclic
compound 9 f was obtained in 74% yield of isolated product
when using 3-methoxycatechol as a source of hydrogen atom.
The formation of a non-cyclized product of type 10 could not
be observed in this reaction.
Scheme 2. Competition between iodine atom transfer and reduction
for a primary alkyl radical chain carrier.
deiodination cannot reach completion.[24] The presence of the
monoborinate ester 3, possibly present in larger amount at the
end of the reaction, may also favor the unproductive
reduction of the ethyl radical. Likewise, competition between
addition to the thiocarbonyl group and direct reduction of the
ethyl radical may account for the limited conversion observed
when reactions with xanthate 1 f or thiohydroxamate ester 1g
were conducted at room temperature.
To illustrate further the synthetic potential of the TBC/
Et3B system for deiodination reactions, the chemoselectivity
of the reaction was investigated by running the deiodination
of the secondary iodide 1a in the presence of functionalized
co-substrates known to be reactive under radical processes.
The results are summarized in Table 2. The deiodination
process of the secondary iodide 1a is highly selective in the
presence of benzyl azide (Table 2, entry 1) and phenyl iodide
(Table 2, entry 2). In these two cases, the use of 1.3 equiv of
BEt3 did not lead to any significant consumption of the co-
À
substrates R X. The selective deiodination of the secondary
iodide 1a in the presence of a primary iodide (n-dodecyl
iodide) was examined next and proved to be more challeng-
ing. When 0.9 equiv of Et3B was used, consumption of the
secondary iodide was four times larger than that of the n-
dodecyl iodide and 2a could be isolated in 72% yield. The
ratio of consumed 1a vs. n-dodecyl iodide could be increase to
7.4 when 0.5 equiv of BEt3 was used. For comparison, in
entry 4, a reaction with 1.0 equiv of Bu3SnH lead to a 1.3:1
ratio of consumed secondary vs. primary iodide.
The improvement of the yield of the cyclized product 9d
and 9e when using 3-methoxycatechol instead of 4-tert-
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Table 3: Radical cyclization of iodoacetals 8a–f.
properties of catechol derivatives can be fine-tuned by
playing with the substitution pattern. This particular aspect
of their chemistry has been demonstrated by using 3-
methoxycatechol, a slower H-donor reagent than 4-tert-
butylcatechol, to optimize slow radical cyclization processes.
Acknowledgements
The Swiss National Science Foundation (Project
200020_152782) and the State Secretariat for Education,
Research and Innovation (SBFI Nr. C14.0096, COST Action
CM1201) are gratefully acknowledged for financial support.
We are also grateful to BASF Corporation for generous gift of
triethylborane.
Keywords: catechols · cyclizations · hydrogen atom donors ·
phenols · radicals
À
Entry Iodide X H
Product 9/10[a] Yield of 9 [%][b]
1
8a
8b
8c
8d
8d
8d
8e
8e
8e
TBC (0.3m)[c]
9a
9b
9c
9d
9d
9d
9e
9e
9e
9 f
ꢀ95:5[d]
ꢀ95:5[d]
ꢀ95:5[d]
85:15
95:5
45:55
82
82
71
72
88
41
n.d.
67
n.d.
74
[1] a) Encyclopedia of Radicals In Chemistry Biology and Materi-
als, Vol. 1 – 4 (Eds.: C. Chatgilialoglu, A. Studer), Wiley, New
York, 2012; b) Radicals in Organic Synthesis, Vol. 1, 2 (Eds.: P.
Renaud, M. P. Sibi), Wiley-VCH, Weinheim, 2001.
[2] a) H. Jasch, M. R. Heinrich in Encyclopedia of Radicals in
Chemistry, Biology and Materials, Vol. 2 (Eds.: C. Chatgilialoglu,
A. Studer), Wiley, New York, 2012, pp. 529 – 560; b) W. P.
Neumann, Synthesis 1987, 665 – 683.
2
3
4
5
TBC (0.3m)[c]
TBC (0.3m)[c]
TBC (0.3m)[c]
MOC (0.2m)[e]
Bu3SnH (0.07m)[f]
TBC (0.3m)[c]
6
7 g
g[g]
9 g
60:40
75:25
MOC (0.1m)[e]
Bu3SnH (0.008m)[f]
MOC (0.2m)[e]
23:77
[3] a) B. Giese, J. Dickhaut, C. Chatgilialoglu in Handbook of
Reagents for Organic Synthesis: Reagents for Silicon-Mediated
Organic Synthesis, Vol. 2 (Eds.: C. Chatgilialoglu, A. Studer),
Wiley, New York, 2011, pp. 747 – 754; b) C. Chatgilialoglu,
Chem. Eur. J. 2008, 14, 2310 – 2320.
[4] H. Yorimitsu, K. Oshima, Inorg. Chem. Commun. 2005, 8, 131 –
142.
[5] J. C. Walton, A. Studer, Acc. Chem. Res. 2005, 38, 794 – 802.
[6] F. Dꢁnꢂs, M. Pichowicz, G. Povie, P. Renaud, Chem. Rev. 2014,
114, 2587 – 2693.
1g[g] 8 f
ꢀ95:5[d]
[a] Ratio determined by GC, assuming an equal response factor for the
isomeric compounds 9 and 10. [b] Yields of isolated product. [c] TBC
(1 equiv, 0.3 m), NaHCO3 (1 equiv), Et3B (1.3 equiv), CH2Cl2, rt, air.
[d] The monocyclic product 10 was not detected. [e] 3-Methoxycatechol
(MOC; 1 equiv, 0.2 m), NaHCO3 (1 equiv), Et3B (1.3 equiv), CH2Cl2, rt,
air. [f] Bu3SnH (1.3 equiv), Et3B (0.1 equiv), benzene, rt, air. [g] p-
ClBz=p-chlorobenzoyl.
[7] a) T. Kawamoto, I. Ryu, Org. Biomol. Chem. 2014, 12, 9733 –
9742; b) S.-H. Ueng, M. Makhlouf Brahmi, E. Derat, L. Fen-
sterbank, E. Lacꢃte, M. Malacria, D. P. Curran, J. Am. Chem.
Soc. 2008, 130, 10082 – 10083; c) A. Solovyev, S.-H. Ueng, J.
Monot, L. Fensterbank, M. Malacria, E. Lacꢃte, D. P. Curran,
Org. Lett. 2010, 12, 2998 – 3001.
[8] a) D. Leca, L. Fensterbank, E. Lacꢃte, M. Malacria, Chem. Soc.
Rev. 2005, 34, 858 – 865; b) V. V. Popik, A. G. Wright, T. A.
Khan, J. A. Murphy in e-EROS Encyclopedia of Reagents for
butylcatechol is in full agreement with the work of Villa, who
reported that 3-methoxycatechol reduces primary alkyl
radicals five times slower than 4-tert-butylcatechol.[23] This
difference of reactivity can be rationalized by the fact that
both hydrogen atoms of 3-methoxycatechol are involved in
intramolecular hydrogen bonds,[29] whereas only one hydro-
gen is involved in hydrogen bonding for 4-tert-butylcate-
chol.[30]
In summary, we have demonstrated that simple catechol
derivatives can be used with trialkylboranes as hydrogen
atom donors for radical chain reactions. For instance,
excellent results have been obtained with 4-tert-butylcatechol,
a well-established antioxidant, stabilizer, and polymerization
inhibitor for various alkenes.[31,32] These reagents are not only
commercially available and cheap, but they possess also
a very moderate toxicity.[33] Interestingly, the hydrogen atom
donor properties of catechol derivatives are right in the
optimal kinetic window for synthetic applications as demon-
strated here by highly efficient radical cyclizations leading to
the formation of quaternary centers. Finally, the H-donor
Organic
047084289X.rh047084075.
[9] G. Povie, P. Renaud, Chimia 2013, 67, 250 – 252.
Synthesis,
Wiley,
2001,
DOI:
10.1002/
[10] a) A. Parsons, Chem. Br. 2002, 38, 42 – 44; b) A. Studer, S.
Amrein, Synthesis 2002, 835 – 849; c) A. Gansꢄuer, L. Shi, M.
Otte, I. Huth, A. Rosales, I. Sancho-Sanz, N. M. Padial, J. E.
Oltra in Radicals in Synthesis III (Eds.: M. Heinrich, A.
Gansꢄuer), Springer, Berlin, Heidelberg, 2012, pp. 93 – 120.
[11] C. Chatgilialoglu, K. U. Ingold, J. C. Scaiano, J. Am. Chem. Soc.
1981, 103, 7739 – 7742.
[12] a) M. R. Medeiros, L. N. Schacherer, D. A. Spiegel, J. L. Wood,
Org. Lett. 2007, 9, 4427 – 4429; b) D. A. Spiegel, K. Wiberg, L. N.
Schacherer, M. R. Medeiros, J. L. Wood, J. Am. Chem. Soc. 2005,
127, 12513 – 12515; c) F. Allais, J. Boivin, V. T. Nguyen, Beilstein
J. Org. Chem. 2007, 3, 46; see also No. 45 and 47.
4
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
These are not the final page numbers!

Angewandte
Communications
Chemie
[13] Similar water activation have been observed in water–
[24] D. P. Curran, T. R. McFadden, J. Am. Chem. Soc. 2016, 138,
7741 – 7752.
[25] X. J. Salom-Roig, F. Dꢁnꢂs, P. Renaud, Synthesis 2004, 1903 –
1928.
[26] A. L. J. Beckwith, S. A. Glover, Aust. J. Chem. 1987, 40, 157 –
173.
[27] Under standard reaction conditions, minor quantities of allylic
alcohol were isolated arising from the cleavage of the acetal. The
use of NaHCO3 as a heterogeneous base completely suppressed
this side reaction.
[28] a) K. Fujita, T. Nakamura, H. Yorimitsu, K. Oshima, J. Am.
Chem. Soc. 2001, 123, 3137 – 3138; b) K. Takami, S. Mikami, H.
Yorimitsu, H. Shinokubo, K. Oshima, Tetrahedron 2003, 59,
6627 – 6635.
[29] R. Amorati, S. Menichetti, E. Mileo, G. F. Pedulli, C. Viglianisi,
Chem. Eur. J. 2009, 15, 4402 – 4410.
[30] M. C. Foti, L. R. C. Barclay, K. U. Ingold, J. Am. Chem. Soc.
2002, 124, 12881 – 12888.
[31] a) J. M. Watson, US patent 4061545, 1977; b) J. M. Watson, J. R.
Butler, K. A. Mikkelson, US patent 4466904, 1984; c) J. T.
Merril, US patent 6960279, 2005.
titanium(III) complexes: J. M. Cuerva, A. G. Campana, J.
Justicia, A. Rosales, J. L. Oller-Lopez, R. Robles, D. J. Cardenas,
E. Bunuel, J. E. Oltra, Angew. Chem. Int. Ed. 2006, 45, 5522 –
5526; Angew. Chem. 2006, 118, 5648 – 5652.
[14] D. Pozzi, E. M. Scanlan, P. Renaud, J. Am. Chem. Soc. 2005, 127,
14204 – 14205.
[15] a) J. Jin, M. Newcomb, J. Org. Chem. 2007, 72, 5098 – 5103; b) J.
Jin, M. Newcomb, J. Org. Chem. 2008, 73, 4740 – 4742; c) G.
Povie, M. Marzorati, P. Bigler, P. Renaud, J. Org. Chem. 2013, 78,
1553 – 1558; d) W. Tantawy, H. Zipse, Eur. J. Org. Chem. 2007,
5817 – 5820.
[16] a) G. Villa, G. Povie, P. Renaud, J. Am. Chem. Soc. 2011, 133,
5913 – 5920; b) G. Povie, G. Villa, L. Ford, D. Pozzi, C. H.
Schiesser, P. Renaud, Chem. Commun. 2010, 46, 803 – 805.
[17] a) P. A. MacFaul, K. U. Ingold, J. Lusztyk, J. Org. Chem. 1996,
61, 1316 – 1321; b) D. W. Snelgrove, J. Lusztyk, J. Banks, P.
Mulder, K. U. Ingold, J. Am. Chem. Soc. 2001, 123, 469 – 477;
c) L. Barclay, C. Edwards, M. Vinqvist, J. Am. Chem. Soc. 1999,
121, 6226 – 6231.
[18] a) S. Kim, C. J. Lim, S.-E. Song, H.-Y. Kang, Chem. Commun.
2001, 1410; b) S. Kim, C. J. Lim, S.-E. Song, H.-Y. Kang, Synlett
2001, 688.
[19] M. C. Foti, K. U. Ingold, J. Lusztyk, J. Am. Chem. Soc. 1994, 116,
9440 – 9447.
[20] a) G. Povie, A.-T. Tran, D. Bonnaffꢁ, J. Habegger, Z. Hu, C.
Le Narvor, P. Renaud, Angew. Chem. Int. Ed. 2014, 53, 3894 –
3898; Angew. Chem. 2014, 126, 3975 – 3979.
[32] Additional information on the uses of TBC can be found in the
summary of data for chemical selection from the National
Toxicology Program, https://ntp.niehs.nih.gov/testing/status/
background/execsumm/b/butylcatechol/index.html, [accessed:
9-June-2016].
[33] National Toxicology Program, Toxicity Report Series, Number
70,
https://ntp.niehs.nih.gov/ntp/htdocs/st_rpts/tox070.pdf
[21] The characterization of compounds 3 and 4 has been reported
elsewhere: see Ref. [20].
[accessed: 09 June 2016].
[22] M. Newcomb, R. M. Sanchez, J. Kaplan, J. Am. Chem. Soc. 1987,
109, 1195 – 1199.
Received: May 20, 2016
[23] G. Villa, Ph.D. Dissertation Thesis, University of Bern, 2010.
Published online: && &&, &&&&
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Hydrogen Atom Donors
Simple catechols, when used with trie-
thylborane, are excellent hydrogen atom
donors for radical chain reactions involv-
ing alkyl iodides and related radical
precursors. As a concequence, highly
efficient radical cyclizations leading to the
formation of quaternary centers can be
performed in a concerted process (no
slow addition of the hydrogen atom
donor) at standard concentrations.
G. Povie, L. Ford, D. Pozzi, V. Soulard,
G. Villa, P. Renaud*
&&&& — &&&&
Catechols as Sources of Hydrogen Atoms
in Radical Deiodination and Related
Reactions
6
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
These are not the final page numbers!