Sulfonylative and Azidosulfonylative Cyclizations by Visible-Light-Photosensitization of Sulfonyl Azides in THF

Article abstract of DOI:10.1002/chem.201704380

The generation of sulfonyl radicals from sulfonyl azides using visible light and a photoactive iridium complex in THF is described. This process was used to promote sulfonylative and azidosulfonylative cyclizations of enynes to give several classes of highly functionalized heterocycles. The use of THF as the solvent is critical for successful reactions. The proposed mechanism of radical initiation involves the photosensitized formation of a triplet sulfonyl nitrene, which abstracts a hydrogen atom from THF to give a tetrahydrofuran-2-yl radical, which then reacts with the sulfonyl azide to generate the sulfonyl radical.

Full text of DOI:10.1002/chem.201704380

A Journal of
Accepted Article
Title: Sulfonylative and Azidosulfonylative Cyclizations by Visible-Light-
Photosensitization of Sulfonyl Azides in THF
Authors: Shaoqun Zhu, Atchutarao Pathigoolla, Grace Lowe, Darren
Walsh, Mick Cooper, William Lewis, and Hon Wai Lam
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: Chem. Eur. J. 10.1002/chem.201704380
Link to VoR: http://dx.doi.org/10.1002/chem.201704380
Supported by

10.1002/chem.201704380
Chemistry - A European Journal
FULL PAPER
Sulfonylative and Azidosulfonylative Cyclizations by Visible-
Light-Photosensitization of Sulfonyl Azides in THF
Shaoqun Zhu, Atchutarao Pathigoolla, Grace Lowe, Darren A. Walsh, Mick Cooper, William Lewis, and
Hon Wai Lam*
Abstract: The generation of sulfonyl radicals from sulfonyl azides
using visible light and a photoactive iridium complex in THF is
described. This process was used to promote sulfonylative and
azidosulfonylative cyclizations of enynes to give several classes of
highly functionalized heterocycles. The use of THF as the solvent is
critical for successful reactions. The proposed mechanism of radical
initiation involves the photosensitized formation of a triplet sulfonyl
nitrene, which abstracts a hydrogen atom from THF to give a
tetrahydrofuran-2-yl radical, which then reacts with the sulfonyl azide
to generate the sulfonyl radical.
Introduction
Azides are highly versatile functional groups because they
undergo many different reactions.[ 1 , 2 ] The recent, dramatic
increase in the use of visible light photocatalysis in synthesis[3]
has led to its application in reactions of organic azides, resulting
in several interesting new processes.[ 4 ] Aryl,[4a–c,i] alkyl,[4a]
Scheme 1. Sulfonyl azides in visible light photocatalysis.
alkenyl,[4c] and acyl[4d,j] azides, as well as azidoformates[4f] have
been employed in reductions,[4a] radical additions to nitriles,[4a]
which is incorporated into the products. Depending upon the
nitrene insertions,[4b,d] rearrangements,[4c] aziridinations,[4c,f]
enyne, the products can also contain the azide group, a useful
aminations,[4i]
and
cascade
handle for further derivatizations.[1,2]
Results and Discussion
Sulfonylative cyclizations
enantioselective
enolate
cyclizations.[4j] Azidoiodanes have also been used in radical
azidations.[4e,g,h]
However, sulfonyl azides have hardly been explored in
visible light photocatalysis. To our knowledge, the only example
reported used a sulfonyl azide as a precursor to a sulfonyl
nitrene, which, in the presence of acid, reacted with N-
methylpyrrole in a C–H amidation (Scheme 1A).[4d] Given the
versatility of sulfonyl azides,[1,2] their application in other classes
of photocatalytic reactions could lead to valuable new synthetic
opportunities. Herein, we describe radical cyclizations of enynes
which use sulfonyl azides, visible light, and a photoactive iridium
complex to give several classes of highly functionalized
oxacycles and azacycles (Scheme 1B). In contrast to the
aforementioned example,[4d] the overall net outcome is not
cleavage of a nitrogen–nitrogen bond of the sulfonyl azide, but
cleavage of the sulfur–nitrogen bond to give a sulfonyl radical,
Prior reports of photocatalytic reactions of organic azides invoke
the formation of reactive intermediates such as nitrogen-
centered radicals,[4a,i,j] azide radicals,[4e,g,h] and nitrenes.[4b–d,f] We
therefore hoped that cyclohexa-2,5-dienone-tethered alkyne 1a,
which contains several unsaturated functional groups, would
react productively with para-toluenesulfonyl azide (2a) under
photocatalytic conditions (Table 1). Surprisingly, irradiation of a
mixture of 1a and 2a (1.2 equiv) with white LEDs in the presence
of 1.0 mol% of [Ir(dtbbpy)(ppy)2]PF6 (Ir 1) at room temperature
(22 °C) gave essentially no reaction (<5% conversion) in toluene,
EtOAc, dioxane, MeCN, DCE, DMF, MeOH, or Et2O. In contrast,
the reaction in THF for 36 h did result in consumption of 1a to
give 6,6-bicycle 3a in 85% yield (entry 1).[ 5 ] Unexpectedly,
however, and despite the existing precedent,[4] there was no
incorporation of nitrogen into 3a. Instead, 3a results from
addition of a sulfonyl radical[6] to the alkyne of 1a, followed by 6-
exo-trig cyclization. Products 4 and 5, which would be derived
from the addition of sulfonamidyl or azide radicals, respectively,
were not observed. To our knowledge, the use of sulfonyl azides
as sulfonylating agents without simultaneous incorporation of
nitrogen is extremely rare.[7] Raising the temperature to 32 °C
increased the yield of 3a to 90% (entry 2). Addition of TsOH·H2O
(0.1 equiv) decreased the reaction time from 36 h to 24 h and 3a
was isolated in 91% yield (entry 3). Other photocatalysts
[Ir(bpy)(ppy)2]PF6 (Ir 2) and [Ir(dtbbpy){dF(CF3)ppy}2]PF6 (Ir 3)
were also tested, and although these gave good yields of 3a, the
[]
Dr. S. Zhu, Dr. A. Pathigoolla, G. Lowe, Dr. D. A. Walsh, Prof. H. W.
Lam
The GSK Carbon Neutral Laboratories for Sustainable Chemistry,
University of Nottingham, Jubilee Campus, Triumph Road,
NG7 2TU (UK)
Dr. S. Zhu, Dr. A. Pathigoolla, G. Lowe, Dr. D. A. Walsh, Dr. M.
Cooper, Dr. W. Lewis, Prof. H. W. Lam
School of Chemistry, University of Nottingham, University Park,
Nottingham, NG7 2RD (UK)
E-mail: hon.lam@nottingham.ac.uk
Homepage: http://www.nottingham.ac.uk/~pczhl/
Supporting information for this article is available on the WWW
under http://dx.doi.org/
This article is protected by copyright. All rights reserved.

10.1002/chem.201704380
Chemistry - A European Journal
FULL PAPER
Table 1. Evaluation of conditions for sulfonylative cyclization.[a]
the process is compatible with phenyl groups (3a and 3g–3l)
and aryl groups containing alkyl or halide substituents (3d and
3f). 3-Pyridyl or 2-thienyl groups on the alkyne are also well-
tolerated (3b and 3e).
A substrate containing a methyl-
substituted alkyne underwent successful sulfonylative cyclization
but the product 3c was isolated together with an isomer resulting
from initial addition of the sulfonyl radical to the methyl-
substituted alkyne carbon, as a 5:1 mixture. Changing the
substituent at the quaternary center of the substrates from
methyl (3a–3c and 3g–3l) to ethyl (3d and 3e) or phenyl (3f) is
possible, and various other sulfonyl azides are compatible (3g–
3l). Finally, by using terminal alkyne 1g, the 6,5-bicycle 6 was
formed in 90% yield.[5]
Azidosulfonylative cyclizations
Although the sulfonylative cyclizations shown in Table
2
Yield (%)[b]
represent a new mode of reactivity of sulfonyl azides in the
presence of visible light and a photoactive complex, we were
interested in whether the same reaction system could install
nitrogen functionality into the products. Pleasingly, by replacing
the electron-deficient alkene in the enyne with a more electron-
rich alkene, the reaction pathway is switched over to
Entry
Catalyst
Ir 1
Temp (°C)
Additive
–
Time (h)
36
1
2
3
4
5
22
32
32
32
32
85
90
91
92
87
Ir 1
–
36
Ir 1
TsOH·H2O
TsOH·H2O
TsOH·H2O
24
Ir 2
72
8
]
azidosulfonylative cyclization (Table 3).[
For example,
Ir 3
32
irradiation of 1,6-enyne 7a and para-toluenesulfonyl azide (2a,
1.5 equiv) with white LEDs in THF at 32 °C, in the presence of
1.0 mol% of Ir 1 gave, after 36 h, azidosulfonylation product 8a
in 45% NMR yield along with the non-azidated product 9a in 12%
NMR yield (entry 1).[5] Increasing the quantity of 2a to 2.0
equivalents gave a slightly higher yield of 3a (entry 2). As with
the sulfonylative cyclizations (Table 1), Ir 2 and Ir 3 were inferior
to Ir 1 (Table 3, entries 3 and 4). However, with Ir 1, increasing
the quantity of 2a further to 3.0 equivalents led to a notable
increase in conversion and a faster reaction, and 8a was
isolated in 65% yield after 18 h with none of 9a detected (entry
6).
[a] Reactions were conducted with 0.10 mmol of 1a in THF (2.5 mL) under a
nitrogen atmosphere. [b] Yield of isolated product.
reaction times were longer (entries 4 and 5). No conversion was
observed in the absence of the iridium complex or in the dark,
indicating that both the photocatalyst and light are essential.
Table 2 presents the reactions of various sulfonyl azides and
cyclohexa-2,5-dienone-tethered alkynes 1, which gave products
3a–3l in 55–91% yield.[5] Regarding the alkyne substituent R3,
Table 2. Scope of sulfonylative cyclizations.[a]
Table 3. Evaluation of conditions for azidosulfonylative cyclization.[a]
Entry Catalyst
2a
(x equiv)
Time Conversion
Yield 8a
Yield 9a
(h)
36
36
36
36
18
(%)[b]
66
(%)[b]
(%)[b]
1
2
3
4
5
Ir 1
Ir 1
Ir 2
Ir 3
Ir 1
1.5
2.0
2.0
2.0
3.0
45
48
12
8
87
28
15
0
44
20
0
>95
70 (65)[c]
<5
[a] Reactions were conducted with 0.40 mmol of 1a in THF (2.0 mL) under a
nitrogen atmosphere. [b] Determined by 1H NMR analysis with 1,3,5-
trimethoxybenzene as an internal standard. [c] Yield of isolated product.
With effective conditions available, the scope of this process
was explored (Table 4).[5] Sulfonyl azides containing various aryl
or alkyl substituents reacted successfully with 7a to give
dihydropyrans 8a–8f (entries 1–6). Variation of the aryl
substituent of the alkyne to 4-chlorophenyl, 3-methoxyphenyl, or
2-thienyl groups was tolerated (entries 7–9), as was cyclization
onto a cyclohexylidene group (entries 10 and 12). By using
[a] Reactions were conducted with 0.20 mmol of 1 in THF (2.5 mL) under a
nitrogen atmosphere. Yields are of isolated products. [b] Product 3c was
isolated together with a 6,5-bicyclic isomer resulting from initial addition of the
sulfonyl radical to the methyl-substituted alkyne carbon, in a 5:1 ratio (see the
Supporting Information). [c] Using 3.0 equivalents of the sulfonyl azide.
This article is protected by copyright. All rights reserved.

10.1002/chem.201704380
Chemistry - A European Journal
FULL PAPER
Table 4. Scope of azidosulfonylative cyclizations.[a]
Entry
Substrate
Product
R
Time
(h)
Yield
(%)b
1
2
3
4
5
6
8a 4-MeC6H4
8b 4-IC6H4
8c 4-F3CC6H4
8d 2-naphthyl
8e 2,4,5-Cl3C6H2
8f Et
18
36
36
36
36
52
65
83
89
73
91
80
7
8
9
8g 4-ClC6H4
8h 3-MeOC6H4
8i 2-thienyl
48
15
52
46
75
40
(1)], while cyclization of 7e on a 3.0 mmol scale at 0.6 M
concentration gave 10b in 74% yield [Eq. (2)]. A small quantity
of diene 11 was also isolated from the latter reaction.
Initial mechanistic considerations
10
11
12
8j
36
24
24
61
76
88
Given that the only reported example of
a visible light
photocatalytic reaction of a sulfonyl azide proceeds through a
sulfonyl nitrene (see Scheme 1A),[4d] the generation of sulfonyl
radicals in the reactions described herein was intriguing from a
mechanistic standpoint. The observation that THF is a uniquely
effective solvent suggests the reaction medium plays a key role
in radical initiation. The reactions shown in Table 2 result from
overall addition of a sulfonyl group and a hydrogen atom to the
substrate. We therefore assumed that, in addition to its
suspected role in radical initiation, the effectiveness of THF in
the sulfonylative cyclizations arises from its ability to act as a
hydrogen atom donor.[9]
10a
10b
13
14
10c
8k
36
36
66
45
To shed light on this latter issue, 1a with reacted with para-
toluenesulfonyl azide (2a) in THF-D8 with Ir
2 as the
photocatalyst [Eq. (3)]. With the standard quantity of 2a (1.2
equiv), this reaction was much slower than the corresponding
reaction using non-deuterated THF (Table 1, entry 4). However,
increasing the quantity of 2a to 10.0 equivalents and raising the
temperature to 50 °C gave, after 96 h, a 45% yield of a mixture
of isotopologues 3a, [D]-3a, and [D]2-3a, which contain varying
numbers of deuterium atoms at the methylene carbon adjacent
to the carbonyl group.[ 10 ] The major component was the
15
16
10d
10e
24
36
93
54
monodeuterated compound [D]-3a (likely
a
mixture of
diastereomers), while the non-deuterated compound 3a was a
minor component. Mass spectrometry suggested a trace (ca.
<5%) of the dideuterated compound [D]2-3a was present. This
result is consistent with the final product-forming step being
hydrogen/deuterium abstraction from THF, which may be rate-
limiting. The presence of all three isotopologues may be
[a] Reactions were conducted with 0.40 mmol of 7 in THF (2.0 mL) under a
nitrogen atmosphere. [b] Yield of isolated product.
substrates containing terminal alkynes, tetrahydrofurans 10a–
10c containing exocyclic alkenylsulfones were produced in 66–
88% yield (entries 11–13). Replacement of the ether tether with
a sulfonamide led to various azacycles 8k, 10d, and 10e (entries
14–16).
Conducting the reactions on a larger scale at higher
concentrations allowed the catalyst loading to be reduced to
0.5 mol% and importantly, the quantity of the sulfonyl azide to be
lowered to 1.5 equivalents. For example, cyclization of 7g on a
2.0 mmol scale at 0.4 M concentration gave 8k in 46% yield [Eq.
This article is protected by copyright. All rights reserved.

10.1002/chem.201704380
Chemistry - A European Journal
FULL PAPER
explained by reversible, acid-catalyzed hydrogen−deuterium
exchange through enol intermediates.
the sulfonyl azide 2 in a chain propagation step gives the
product 8 and regenerates the sulfonyl radical 12.[2d] The
formation of the non-azidated byproduct 9 (Table 3) can be
explained by radical 18 undergoing competitive hydrogen atom
abstraction with the solvent, THF.
Proposed radical chain mechanisms
We consider it likely that the sulfonylative cyclizations operate
11
]
through radical chain mechanisms (Scheme 2).[
First,
The role of THF in radical initiation
irradiation of the sulfonyl azide 2a in the presence of the iridium
complex and THF produces the sulfonyl radical 12. Possible
pathways for this initiation are discussed below. Addition of 12 to
the alkyne of the substrate 1a gives an alkenyl radical 13, which
cyclizes onto one of the alkenes to give a new radical 14. It is
well-known that electrophilic enolate radicals such as 14 do not
react with sulfonyl azides to give azidation products.[2d] However,
a hydrogen abstraction from THF, as suggested by the results of
Eq. (3), would give product 3a along with the nucleophilic
tetrahydrofuran-2-yl radical 15.[9] In a chain propagation step, 15
could react with the sulfonyl azide to give azide 16 and
regenerate the sulfonyl radical 12. The beneficial effect of
TsOH·H2O is not currently known.
Although both the sulfonylative and azidosulfonylative
cyclizations are readily explained by radical chain mechanisms
(Schemes
2 and 3), the question remains of how the
combination of visible light, photoactive iridium complex, THF,
and the sulfonyl azide leads to the generation of sulfonyl radicals.
In principle, single-electron-transfer from the photoexcited
iridium complex to the electrophilic sulfonyl azide, followed by
fragmentation of the resulting radical anion would give an azide
anion and the requisite sulfonyl radical 12. Single-electron-
transfer to organic azides has been postulated in photocatalytic
red
reactions.[4a,i] However, the reduction potential E1/2 of para-
toluenesulfonyl azide (2a) was measured by cyclic voltammetry
to be –1.22 V vs. SCE in MeCN,[12] and it would appear that the
photoexcited states of the iridium complexes Ir 1–3 are
insufficiently reducing to promote this electron transfer efficiently
(Ir 1, E*III/IV = –0.96 V vs. SCE;[3e] Ir 2, E*III/IV = –0.85 V vs.
SCE,[13] and Ir 3, E*III/IV = –0.89 V vs. SCE[3e]). The superiority of
THF over other solvents is also not readily explained by an
electron transfer mechanism.
Scheme 2. Proposed mechanism for sulfonylative cyclization.
We believe the azidosulfonylative cyclizations also proceed
through a radical chain cycle (Scheme 3).[8,11] After radical
initiation, the sulfonyl radical 12 adds to the alkyne of 7a to give
alkenyl radical 17, which undergoes 6-exo-trig cyclization onto
the alkene to give tertiary radical 18. Azidation of 18 with
Scheme 4. Radical initiation by triplet sensitization.
A second mechanism that we consider more likely begins
with irradiation of Ir 1 (depicted as IrIII) to give the photoexcited
*IrIII species 19 (Scheme 4). Triplet sensitization of the sulfonyl
azide by an energy transfer mechanism gives 20, which then
loses dinitrogen to give a triplet nitrene 21. This pathway is
consistent with the only reported example of a visible light
photocatalytic reaction of a sulfonyl azide (Scheme 1A), which
also proceeds through a sulfonyl nitrene.[4d] The formation of a
sulfonyl nitrene from UV irradiation of a sulfonyl azide with
14
]
benzophenone as
a
triplet sensitizer is also known.[
Furthermore, other electron-deficient azides such as acyl azides
and azidoformates are known to produce nitrenes by triplet
sensitization with photoactive metal complexes.[4b–d,f] The triplet
Scheme 3. Proposed mechanism for azidosulfonylative cyclization.
This article is protected by copyright. All rights reserved.

10.1002/chem.201704380
Chemistry - A European Journal
FULL PAPER
nitrene 21 could then abstract a hydrogen atom from THF to
give tetrahydrofuran-2-yl radical 15 and sulfonamidyl radical 22.
In relevant precedent, it is known that triplet sulfonyl nitrenes
can abstract a hydrogen atom from the methine carbon of i-
PrOH.[14] Azidation of 15 with the sulfonyl azide would then
provide the sulfonyl radical 12 to enter the chain mechanisms
shown in Schemes 2 and 3. The sulfonamidyl radical 22 could
then undergo a second hydrogen abstraction with THF to give
para-toluenesulfonamide (23). It should be noted that we did
observe the formation of small quantities of 23 in all of the
reactions reported in Tables 2 and 4, which lends some support
for the participation of triplet nitrene intermediates.
Furthermore, reaction of 1,6-enyne 7a with 2a in DCE rather
than THF gave aziridine 24 in 42% yield [Eq. (4)]. Evidently, in
the absence of THF, the putative triplet nitrene 21 reacts with
the alkene of 7a to give 24, presumably by a stepwise radical
addition and ring closure as described by Yoon and co-
workers.[4f]
Conclusions
We have described sulfonylative and azidosulfonylative
cyclizations of enynes that give several classes of highly
functionalized heterocycles. These reactions operate through
radical chain mechanisms, with the combination of sulfonyl azide,
THF, visible light, and a photoactive iridium complex serving as
a “smart initiation”
radicals. Radical initiation begins with the photosensitized
formation of a triplet nitrene from the sulfonyl azide, followed by
hydrogen atom transfer from THF to the nitrene to give a
tetrahydrofuran-2-yl radical, which then reacts with the sulfonyl
azide to produce the sulfonyl radical. By using an azidoformate
instead of the sulfonyl azide, the tetrahydrofuran-2-yl radical can
be intercepted by electron-deficient alkenes. This work further
demonstrates that spin-selective formation of triplet nitrenes
from organic azides using visible light photocatalysis can serve
as a powerful platform for new reaction development.[15]
[11a]
system for the generation of sulfonyl
Received:
((will
be
filled
in
by
the
editorial
staff))
Published online on ((will be filled in by the editorial staff))
Acknowledgements
This work was supported by the University of Nottingham, the
European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie grant agreement
No. 657194 (Individual Fellowship to A.P.), the Engineering and
Physical Sciences Research Council (EPSRC Leadership
Fellowship to H.W.L., grants EP/I004769/1 and EP/I004769/2),
the EPSRC Centre for Doctoral Training in Sustainable
Chemistry (studentship to G.L., grant EP/L015633/1), and
GlaxoSmithKline. We thank Dr. Catherine A. Ortori (University of
Nottingham) for assistance with mass spectrometry, and Dr.
Hamish B. Hepburn (ICIQ – Institute of Chemical Research of
Catalonia) for helpful discussions. Finally, we thank the
reviewers for valuable input in suggesting possible reaction
mechanisms.
Implications for other reactions
As discussed above, our collective results point to the formation
of tetrahydrofuran-2-yl radical 15 from the reaction of THF with a
triplet sulfonyl nitrene 21 derived from a sulfonyl azide 2
(Scheme 4). Although this process leads to the generation of
sulfonyl radicals by subsequent reaction of 15 with the sulfonyl
azide 2, we questioned whether 15 could be formed by the
reaction of THF with triplet nitrenes derived from azides which
are unreactive toward 15. If so, it might be possible to utilize 15
in a carbon–carbon bond-forming reaction.
In the event, irradiation of phenyl acrylate (25) in THF in the
presence of Ir 1 (1.0 mol%) and benzyl azidoformate (26, 0.2
equiv) gave addition product 27 in an unoptimized 42% yield [Eq.
(5)]. The reaction of phenyl vinyl ketone (28) gave similar results,
producing 29 in 34% yield [Eq. (6)]. No reaction was observed
when these reactions were repeated in the absence of the azide
or the photocatalyst under otherwise identical conditions.
Conflicts of interest
The authors declare no conflict of interest.
Keywords: azide • cyclization • iridium • photocatalysis • radical
reaction
[1]
[2]
a) in Organic Azides: Syntheses and Applications (Eds.: S. Bräse, K.
Banert), John Wiley & Sons, Ltd, 2010. b) S. Bräse, C. Gil, K. Knepper,
V. Zimmermann, Angew. Chem., Int. Ed. 2005, 44, 5188.
For reviews of the radical chemistry of azides, see: a) X. Huang, J. T.
Groves, ACS Catal. 2016, 6, 751. b) C. Jimeno, P. Renaud, in Organic
Azides: Syntheses and Applications, John Wiley & Sons, Ltd, 2010, pp.
239. c) M. Minozzi, D. Nanni, P. Spagnolo, Chem. Eur. J. 2009, 15,
7830. d) P. Panchaud, L. Chabaud, Y. Landais, C. Ollivier, P. Renaud,
S. Zigmantas, Chem. Eur. J. 2004, 10, 3606.
[3]
For selected reviews of visible light photoredox catalysis in organic
synthesis, see: a) M. Fagnoni, D. Dondi, D. Ravelli, A. Albini, Chem
Rev 2007, 107, 2725. b) T. P. Yoon, M. A. Ischay, J. Du, Nature Chem.
2010, 2, 527. c) J. M. Narayanam, C. R. Stephenson, Chem. Soc. Rev.
2011, 40, 102. d) J. W. Tucker, C. R. Stephenson, J. Org. Chem. 2012,
77, 1617. e) C. K. Prier, D. A. Rankic, D. W. MacMillan, Chem Rev
2013, 113, 5322. f) D. M. Schultz, T. P. Yoon, Science 2014, 343,
This article is protected by copyright. All rights reserved.

10.1002/chem.201704380
Chemistry - A European Journal
FULL PAPER
1239176. g) R. A. Angnes, Z. Li, C. R. D. Correia, G. B. Hammond, Org.
Biomol. Chem. 2015, 13, 9152. h) X. Lang, J. Zhao, X. Chen, Chem.
Soc. Rev. 2016, 45, 3026. i) M. H. Shaw, J. Twilton, D. W. C. MacMillan,
J. Org. Chem. 2016, 81, 6898. j) N. A. Romero, D. A. Nicewicz, Chem.
Rev. 2016, 116, 10075.
G. Li, Chem. Sci. 2015, 6, 6654. h) R. Zhu, S. L. Buchwald, J. Am.
Chem. Soc. 2015, 137, 8069. i) Z. Zhang, X.-J. Tang, W. R. Dolbier,
Org. Lett. 2016, 18, 1048. j) Y.-L. Zhu, B. Jiang, W.-J. Hao, A.-F. Wang,
J.-K. Qiu, P. Wei, D.-C. Wang, G. Li, S.-J. Tu, Chem. Commun. 2016,
52, 1907. k) S. K. Pagire, S. Paria, O. Reiser, Org. Lett. 2016, 18, 2106.
l) Z. Huang, Q. Lu, Y. Liu, D. Liu, J. Zhang, A. Lei, Org. Lett. 2016, 18,
3940. m) D. Zheng, J. Yu, J. Wu, Angew. Chem., Int. Ed. 2016, 55,
11925.
[4]
a) Y. Chen, A. S. Kamlet, J. B. Steinman, D. R. Liu, Nature Chem. 2011,
3, 146. b) X. D. Xia, J. Xuan, Q. Wang, L. Q. Lu, J. R. Chen, W. J. Xiao,
Adv. Synth. Catal. 2014, 356, 2807. c) E. P. Farney, T. P. Yoon, Angew.
Chem., Int. Ed. 2014, 53, 793. d) E. Brachet, T. Ghosh, I. Ghosh, B.
König, Chem. Sci. 2015, 6, 987. e) G. Fumagalli, P. T. G. Rabet, S.
Boyd, M. F. Greaney, Angew. Chem., Int. Ed. 2015, 54, 11481. f) S. O.
Scholz, E. P. Farney, S. Kim, D. M. Bates, T. P. Yoon, Angew. Chem.,
Int. Ed. 2016, 55, 2239. g) Y. Wang, G.-X. Li, G. Yang, G. He, G. Chen,
Chem. Sci. 2016, 7, 2679. h) P. T. G. Rabet, G. Fumagalli, S. Boyd, M.
F. Greaney, Org. Lett. 2016, 18, 1646. i) X. Huang, R. D. Webster, K.
Harms, E. Meggers, J. Am. Chem. Soc. 2016, 138, 12636. j) D. B.
Bagal, S.-W. Park, H.-J. Song, S. Chang, Chem. Commun. 2017, 53,
8798.
[7]
[8]
H.-S. Dang, B. P. Roberts, J. Chem. Soc., Perkin Trans 1 1996, 1493.
Photochemical azidosulfonylative reactions of β-pinene, 1,6-dienes,
and two 1,6-enynes, using 0.5 equivalents of the radical initiator di-tert-
butyldiazene have been reported previously. See: N. Mantrand, P.
Renaud, Tetrahedron 2008, 64, 11860.
[9]
For examples of THF serving as a hydrogen atom donor in photoredox-
catalyzed reactions, see: a) Q. Y. Lin, X. H. Xu, F. L. Qing, Org. Biomol.
Chem. 2015, 13, 8740. b) Q.-Y. Lin, X.-H. Xu, K. Zhang, F.-L. Qing,
Angew. Chem., Int. Ed. 2016, 55, 1479.
[10] The relative quantities of 3a, [D]-3a, and [D]2-3a could not be
determined accurately, but a very approximate estimation of the ratio of
[D]-3a and 3a is ca. 4:1 by 1H NMR analysis.
[5]
[6]
The structures of 3a, 3g, 3i, 3l, 6, 8a, 8e, and 10b were confirmed by
X-ray crystallography. The structure of 3c was confirmed by X-ray
crystallography of the diol 30 formed by dihydroxylation of the alkene of
the α,β-unsaturated ketone (see the Supporting Information).
[11] For a discussion of radical chain reactions in photocatalytic reactions,
see: a) A. Studer, D. P. Curran, Angew. Chem., Int. Ed. 2016, 55, 58. b)
M. A. Cismesia, T. P. Yoon, Chem. Sci. 2015, 6, 5426.
For selected, recent examples of sulfonyl radical generation from
precursors other than sulfonyl azides, see: a) Q. Lu, J. Zhang, G. Zhao,
Y. Qi, H. Wang, A. Lei, J. Am. Chem. Soc. 2013, 135, 11481. b) Q. Lu,
J. Zhang, F. Wei, Y. Qi, H. Wang, Z. Liu, A. Lei, Angew. Chem., Int. Ed.
2013, 52, 7156. c) X. Li, X. Xu, P. Hu, X. Xiao, C. Zhou, J. Org. Chem.
2013, 78, 7343. d) A. Kariya, T. Yamaguchi, T. Nobuta, N. Tada, T.
Miura, A. Itoh, RSC Adv. 2014, 4, 13191. e) D. Xia, T. Miao, P. Li, L.
Wang, Chem. Asian. J 2015, 10, 1919. f) A. U. Meyer, S. Jager, D. P.
Hari, B. König, Adv. Synth. Catal. 2015, 357, 2050. g) Z. Z. Chen, S.
Liu, W. J. Hao, G. Xu, S. Wu, J. N. Miao, B. Jiang, S. L. Wang, S. J. Tu,
[12] Cyclic voltammetry of TsN3 (2a) was performed in MeCN using n-
Bu4NPF6 as the electrolyte and ferrocene as an internal standard. See
the Supporting Information.
[13] J. I. Goldsmith, W. R. Hudson, M. S. Lowry, T. H. Anderson, S.
Bernhard, J. Am. Chem. Soc. 2005, 127, 7502.
[14] M. T. Reagan, A. Nickon, J. Am. Chem. Soc. 1968, 90, 4096.
[15] The research data associated with this publication can be found at DOI:
http://dx.doi.org/10.17639/nott.328
This article is protected by copyright. All rights reserved.

10.1002/chem.201704380
Chemistry - A European Journal
FULL PAPER
FULL PAPER
S. Zhu, A. Pathigoolla, G. Lowe, D. A.
Walsh, M. Cooper, W. Lewis, H. W.
Lam*
Page No. – Page No.
Sulfonylative and Azidosulfonylative
Cyclizations by Visible-Light-
Photosensitization of Sulfonyl Azides in
THF
The generation of sulfonyl radicals from sulfonyl azides using visible light
photocatalysis is described. This process was used to promote azidosulfonylative
and sulfonylative cyclizations of various enynes to give several classes of highly
functionalized heterocycles. The use of THF as the solvent is critical for successful
reactions.
This article is protected by copyright. All rights reserved.