Iron-Catalyzed Radical Acyl-Azidation of Alkenes with Aldehydes: Synthesis of Unsymmetrical β-Azido Ketones

Article abstract of DOI:10.1021/acs.orglett.8b03688

An iron-catalyzed acyl-azidation of alkenes under mild reaction conditions has been developed. Aromatic aldehydes or aliphatic aldehydes can be used as the acyl radical precursors; TMSN₃ is used as the azido source; TBHP is the initiator. The s

Full text of DOI:10.1021/acs.orglett.8b03688

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Iron-Catalyzed Radical Acyl-Azidation of Alkenes with Aldehydes:
Synthesis of Unsymmetrical β‑Azido Ketones
Liang Ge,†,‡ Yajun Li,† and Hongli Bao*,†,‡
†Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Center for Excellence in Molecular Synthesis, Fujian
Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002,
People’s Republic of China
‡University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China
S
* Supporting Information
ABSTRACT: An iron-catalyzed acyl-azidation of alkenes under
mild reaction conditions has been developed. Aromatic
aldehydes or aliphatic aldehydes can be used as the acyl radical
precursors; TMSN3 is used as the azido source; TBHP is the
initiator. The synthesized unsymmetrical β-azido ketones can be
easily transformed into valuable functionalized compounds, such
as γ-aminol, γ-azido alcohol, β-azido oxime, β-azido ester, and
triazoles.
Scheme 1. Radical Acyl-Functionalization of Alkenes with
Aldehydes
irect vicinal difunctionalization of alkenes which installs
Dtwo functional groups on a CC bond in a single
process has emerged as a powerful tool for the generation of
highly useful and complex skeletons.1 Hydroacylation of
alkenes, introducing a valuable carbonyl group into the
structure, has great advantages in the transformation of alkenes
and has been demonstrated to be a very reliable method.2
Approaches that can introduce a carbonyl group and another
functional group into a molecule, further broadening the
synthetic applications of alkene difunctionalization, are highly
desirable but remain challenging.
Radical difunctionalization of alkenes is a rapid and
convenient method in which to convert alkenes into more
complex molecules.3 Initiated by a radical precursor or
irradiation, radical hydroacylation of alkenes often employs
aldehydes as the source of acyl radicals (Scheme 1a).4
Recently, several radical difunctionalizations of alkenes have
been developed. Wallentin et al. developed iridium-catalyzed
intramolecular radical difunctionalization of alkenes with
aromatic carboxylic acids5 or aromatic carboxylic anhydrides6
as the source of acyl radicals, affording a range of oxindole
derivatives under light irradiation. Xu et al. reported that aroyl
chlorides could also be used as the precursor to the acyl
radicals in such reactions7 and developed a method for the
intramolecular synthesis of diverse fused pyran derivatives.8
Intramolecular radical acylation−phosphorylation in the syn-
thesis of phosphonate chroman-4-ones, employing a silver salt
as the catalyst and K2S2O8 as an oxidant, has also been
reported (Scheme 1b).9 For intermolecular radical difunction-
alization of alkenes, Taniguchi et al.10 and Li et al.11
independently disclosed efficient synthetic protocols to obtain
β-hydroxy and β-peroxy carbonyl compounds from vinyl
arenes using the reaction of carbazates and aldehydes in the
presence of O2 or tert-butyl hydroperoxide (TBHP) as the co-
oxidant (Scheme 1c). Chen’s group reported that vanadyl
species can also trigger the reaction which leads to β-
hydroxycarbonyl compounds.12 Subsequently, intermolecular
radical fluoroacylation of alkenes catalyzed by a silver catalyst
has been reported by Duan and co-workers, with α-
oxocarboxylic acids as the acyl radical precursors and
Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-
[2.2.2]octane) bis(tetrafluoroborate) as the fluorine source.13
Although this radical difunctionalization of alkenes has been
developed, the scope of the useful functional groups is still
narrow and some other disadvantages should be considered.
Received: November 19, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03688
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
First, although different acyl radical precursors, such as
aldehydes, aromatic carboxylic acids, aromatic carboxylic
anhydrides, aroyl chlorides, or even carbazates have been
employed, aldehydes provide atom economy and availability
and are the best sources. Second, in most cases, the use of
aliphatic aldehydes is very rare. Finally, nonfriendly reaction
conditions, such as elevated temperatures, precious metal
catalysts, or toxic solvents are often involved.
Herein we report our development of a ligand-free, iron-
catalyzed radical acyl-azidation of alkenes for the synthesis of
unsymmetrical β-azido ketones (Scheme 1d). Aliphatic or
aromatic aldehydes serve as the acyl radicals, simple alkenes, or
activated alkenes as the substrates, and azidotrimethylsilane
(TMSN3) serves as the azido source. The β-azido ketones
produced in this reaction can be easily transformed into
valuable functionalized compounds, such as γ-aminols, γ-azido
alcohols, β-azido oximes, β-azido esters, or triazoles. Very
recently, Wang et al. reported the only example of acyl-
azidation of alkenes, using (salen)Mn(III) species as the
catalyst, iodosobenzene as the oxidant (iodobenzene as the
side product), and sodium azide as the azido source.14 The
development of more environment-friendly catalytic systems is
still highly desired.
We initiated our study by evaluating the parameters of the
reaction, including the metal catalysts, additives, solvents, and
temperatures in the reaction of styrene (1a) with benzaldehyde
(2a) and TMSN3 (3) (Table 1). First, metal catalysts were
screened with hexane as the solvent at 50 °C. Fe(OTf)3 was
found to be the most effective catalyst, with the reaction
providing the desired product (4aa) in 40% yield (entries 1−
9). Several other solvents were then tested (entries 10−17),
and it was found that MTBE was optimum. The yield of 4aa
increased when the reaction time was extended at a reduced
temperature (entries 18 and 19). Decreasing or increasing the
loading of the catalyst did not improve the yield of 4aa (entries
20 and 21). When TMSN3 was added portionwise during an
interval time of 3 h, better performance was observed (entry
22). The best yield of the desired product was obtained when
the quantity of TMSN3 was decreased to 2.5 equiv (entry 23).
A scale-up reaction (5 mmol) could afford the product 4aa in
63% yield (entry 24).
With the optimized reaction conditions in hand, the scope of
the alkenes in the reaction was investigated (Scheme 2).
Reactions of o-, m-, or p-alkyl-substituted vinylarenes with
benzaldehyde (2a) afforded the corresponding products
(4ba−4ea) in 58−83% yield. Vinylarenes containing halogens
reacted to give 4fa−4ia in moderate yields (47−65%).
Vinylarenes bearing an ester or a free carboxyl group also
participated in this reaction, affording products 4ja and 4ka
respectively, in moderate yields. 1,1-Disubstituted vinylarenes,
such as 4la, are a suitable substrate for this reaction, and a
good yield (64%) can be obtained. Heterocyclic compounds
can be used to carry out the reaction, affording the desired
product (4ma) with a 42% yield. α,β-Unsaturated carbonyl
compounds were also found to be compatible with the reaction
conditions, giving the acylazidation products (4oa−4sa) in
moderate yields (36−74%). Conjugated dienes proved to be
suitable substrates for the reaction, delivering the product
(4ta) with a terminal CC bond in 56% yield, but unactivated
alkenes showed a lower efficiency affording the corresponding
product (4ua) in only 25% yield.
Table 1. Optimization of the Reaction Conditions
b
entry
catalyst
solvent
hexane
temp
yield
1
2
3
4
5
6
7
8
Ni(OTf)2
CuOTf
AgOTf
Zn(OTf)2
Sc(OTf)2
Fe(OTf)3
FeCl2
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
50 °C
40 °C
25 °C
25 °C
25 °C
25 °C
25 °C
25 °C
−
hexane
hexane
hexane
hexane
hexane
hexane
hexane
hexane
benzene
THF
cyclohexane
DCE
1,4-dioxane
Ether
MTBE
DME
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
12%
−
−
−
40%
7%
7%
3%
FeCl3
FeBr3
9
10
11
12
13
14
15
16
17
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
Fe(OTf)3
41%
16%
37%
11%
39%
36%
49%
34%
60%
64%
46%
58%
71%
c
18
d
19
e
20
f
21
22
g
h
i
23
76%(67%)
63%
j
24
a
1a (0.5 mmol), 2a (2.5 mmol), 3 (1.5 mmol), TBHP (70% in water,
1.25 mmol), cat. (2 mol %), solvent (1 mL) at given temperature for
b
c
d
e
12 h. 1H NMR yield. 40 °C, 24 h. 25 °C, 24 h. Fe(OTf)3 (1 mol
f
g
%), 25 °C, 24 h. Fe(OTf)3 (5 mol %), 25 °C, 24 h. 3 (1.5 mmol)
h
was added portion-wise, Fe(OTf)3 (2 mol %), 25 °C, 24 h. 3 (1.25
mmol) was added portionwise, Fe(OTf)3 (2 mol %), 25 °C, 24 h.
i
j
Isolated product in parentheses. 1a (5 mmol), 2a (25 mmol), 3 (15
mmol), TBHP (70% in water, 12.5 mmol), Fe(OTf)3 (2 mol %),
MTBE (12 mL) 25 °C, 24 h.
aryl aldehydes bearing either electron-donating or electron-
withdrawing groups proceeded with moderate to good yields
(4jb−4jf). It was noted that electron-donating groups are
more efficient than electron-withdrawing groups. Multiple
substituted aryl aldehydes were found to afford the
corresponding products (4jg and 4jh) in moderate yields.
Aryl aldehyde containing hydroxyl groups also underwent this
reaction, giving the product (4ji) in 36% yield. The reaction of
naphthaldehydes occurred to produce 4jj and 4jk with
moderate yields. Functional groups, such as (trimethylsilyl)-
ethynyl and morpholino, were compatible with the reaction
conditions and gave 4jm and 4jn, respectively. Heteroarenes,
prevalent in many biologically relevant molecules, are
compatible with the reaction conditions, and aldehydes
containing thiophene, furan, and benzo[b]thiophene motifs
when subjected to the reaction provided the desired products
(4jo−4jq) with moderate yields.
Encouraged by the success with aromatic aldehydes,
aliphatic aldehydes and α,β-unsaturated aldehydes were then
investigated giving the results summarized in Scheme 4. The
reactions of a variety of aliphatic aldehydes with 1j proceeded
smoothly under the standard conditions to give the
corresponding products (4jr−4jy) in good yields. Not only
saturated aliphatic aldehydes (4jr−4jt) but also unsaturated
Subsequently, we studied the substrate scope of aromatic
aldehydes (Scheme 3). In general, the reactions of a variety of
B
DOI: 10.1021/acs.orglett.8b03688
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a b
,
aliphatic aldehydes (4jv−4jy) are suitable substrates. The
reaction was further supported by the compatibility of α,β-
unsaturated aldehydes. Myrtenal and β-methyl acrolein could
be successfully converted into the corresponding acyl-azidation
products (4jx and 4jy) in good yields.
Scheme 2. Substrate Scope for Acyl-Azidation of Alkenes
Further transformations of the acyl-azidation products were
explored (Scheme 5). It is noteworthy that carbonyl azides
a
Scheme 5. Transformations of Acyl-Azidation Products
a
(i) Cu(OAc)2, 2-aminophenol, DCM/H2O, rt. (ii) LAH (2.0 equiv),
ether, rt, 12 h. (iii) NaBH4, MeOH, rt. (iv) NH2OH−HCl, NaOH,
H2O, EtOH, 60 °C, 10 h. (v) Sc(OTf)3 (5 mol %), m-CPBA (5.0
equiv), 40 °C, 48 h.
a
could be used successfully in the efficient synthesis of a range
of molecules which could be useful building blocks. The click
reaction of 4aa with butyn-2-one gave β-carbonyl triazole (5).
γ-Aminol (6) was prepared from 4aa after a simple reduction
reaction. With the reduction conditions carefully controlled,
the γ-azido alcohol (7) could be obtained with the azido group
untouched. The condensation reaction of an acyl-azidation
product with hydroxylamine hydrochloride gave the oxime (8)
which may be applied to the synthesis of biological or
polymeric materials. A β-amino acid derivative (9) could be
produced through the Baeyer−Villiger oxidation reaction.
Furthermore, the acyl-azidation products could also be
converted into triazoles (10−13) with internal alkynes
(Scheme 6).
1 (0.5 mmol), 2a (2.5 mmol), 3 (1.25 mmol), TBHP (1.25 mmol),
b
MTBE (1 mL), 24 h, 3 was added portionwise. Isolated product.
c
d
Fe(OTf)3 (10 mol %), MTBE (0.5 mL), PhH (0.5 mL). Fe(OTf)3
e
(10 mol %). Determined by GC-MS.
Scheme 3. Substrate Scope for Acyl-Azidation of Aromatic
Aldehydes
a b
,
Scheme 6. Further Transformations of Acyl-Azidation
Products
a
1j (0.5 mmol), 2 (2.5 mmol), 3 (1.25 mmol), TBHP (1.25 mmol),
b
MTBE (1 mL), 24 h, 3 was added portionwise. Isolated product.
Scheme 4. Substrate Scope for Acyl-Azidation of Aliphatic
a b
,
Aldehydes and α,β-Unsaturated Aldehydes
We performed preliminary experiments to probe the
mechanism of the reaction (Scheme 7). Radical trapping
experiments were conducted with 1.5 equiv of TEMPO
(2,2,6,6-tetramethyl-1-piperidinyloxy) and BHT (dibutyl-
hydroxytoluene). These reactions did not afford any desired
product, and instead, compounds 14, 15, and 16 were detected
by GC-MS analysis (Scheme 7a). This is consistent with the
radical nature of the reaction, in which the otherwise
propagating radical cycle was effectively interrupted by
TEMPO and BHT. The formation of compound 14 indicates
that an acyl radical was produced in the reaction, while the
formation of compound 16 suggests that an azido radical was
produced in the reaction. To further support this hypothesis,
compound 17 bearing a cyclopropylmethyl moiety (a radical
clock) was synthesized (Scheme 7b). As expected, the reaction
a
1j (0.5 mmol), 2 (2.5 mmol), 3 (1.25 mmol), TBHP (1.25 mmol),
b
MTBE (1 mL), 24 h, 3 was added portionwise. Isolated product.
C
DOI: 10.1021/acs.orglett.8b03688
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
In conclusion, a ligand-free iron-catalyzed acyl-azidation of
alkenes under mild reaction conditions has been developed
with aromatic aldehydes or aliphatic aldehydes as the acyl
radical precursors, TMSN3 as the azido source, and TBHP as
the initiator. A range of alkenes has been employed for the
synthesis of unsymmetrical β-azido ketones, which can be
easily transformed into valuable functionalized compounds,
such as γ-aminol, γ-azido alcohol, β-azido oxime, β-azido ester,
and triazoles. Mechanistic studies suggest the involvement of
an acyl radical, and a radical pathway has been proposed for
the mechanism.
Scheme 7. Mechanistic Studies
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03688.
of 17 with 2a and TMSN3 afforded the ring-opened product
18 in 58% yield, further supporting the involvement of radical
species in the reaction.
Experimental procedures, characterization of new
compounds, synthetic application, mechanistic studies,
NMR spectra (PDF)
Based on these mechanistic studies, a catalytic mechanism
for the acyl-azidation reaction is proposed (Scheme 8).
Scheme 8. Proposed Catalytic Cycle for Acyl-Azidation
Reaction
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: hlbao@fjirsm.ac.cn.
ORCID
Yajun Li: 0000-0001-6690-2662
Hongli Bao: 0000-0003-1030-5089
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Key R&D Program of China
(2017YFA0700103), the NSFC (Grant Nos. 21502191,
21672213, and 21871258), the Strategic Priority Research
Program of the Chinese Academy of Sciences (Grant No.
XDB20000000), and the Haixi Institute of CAS (Grant No.
CXZX-2017-P01) for financial support.
REFERENCES
■
(1) (a) Yin, G.; Mu, X.; Liu, G. Palladium(II)-Catalyzed Oxidative
Difunctionalization of Alkenes: Bond Forming at a High-Valent
Palladium Center. Acc. Chem. Res. 2016, 49, 2413−2423. (b) Romero,
R. M.; Woste, T. H.; Muniz, K. Vicinal difunctionalization of alkenes
with iodine(III) reagents and catalysts. Chem. - Asian J. 2014, 9, 972−
983. (c) McDonald, R. I.; Liu, G.; Stahl, S. S. Palladium(II)-catalyzed
alkene functionalization via nucleopalladation: stereochemical path-
ways and enantioselective catalytic applications. Chem. Rev. 2011, 111,
2981−3019. (d) Jensen, K. H.; Sigman, M. S. Mechanistic approaches
to palladium-catalyzed alkene difunctionalization reactions. Org.
Biomol. Chem. 2008, 6, 4083−4088. (e) Besset, T.; Poisson, T.;
Pannecoucke, X. Direct Vicinal Difunctionalization of Alkynes: An
Efficient Approach Towards the Synthesis of Highly Functionalized
Fluorinated Alkenes. Eur. J. Org. Chem. 2015, 2015, 2765−2789.
(f) Besset, T.; Poisson, T.; Pannecoucke, X. Recent progress in direct
introduction of fluorinated groups on alkenes and alkynes by means of
C-H bond functionalization. Chem. - Eur. J. 2014, 20, 16830−16845.
(g) Bataille, C. J.; Donohoe, T. J. Osmium-free direct syn-
dihydroxylation of alkenes. Chem. Soc. Rev. 2011, 40, 114−128.
(h) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. C-C,
C-O, C-N bond formation on sp2 carbon by Pd(II)-catalyzed
reactions involving oxidant agents. Chem. Rev. 2007, 107, 5318−5365.
Initially, an iron(II) species (A) undergoes a single-electron
transfer with TBHP to afford the iron(III) species (B) and a
tert-butyloxyl radical, which can decompose to a methyl radical
or release an azido radical from TMSN3. Then, the tert-
butyloxyl radical (or the methyl radical or the azido radical)
abstracts an H-atom from the aldehyde to afford an acyl
radical.11b,15 The acyl radical then is trapped by an alkene to
produce a more stable carbon-centered radical. Upon ligand
exchange with TMSN3, the iron(III) species (B) is converted
into an iron(III) species (C), which then undergoes azido
group transfer with the stabilized carbon-centered radical to
afford the acyl-azidation product, regenerating the iron catalyst.
D
DOI: 10.1021/acs.orglett.8b03688
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(2) (a) Leung, J. C.; Krische, M. J. Catalytic intermolecular
hydroacylation of C−C π-bonds in the absence of chelation
assistance. Chem. Sci. 2012, 3, 2202−2209. (b) Jun, C.-H.; Jo, E.-
A.; Park, J.-W. Intermolecular Hydroacylation by Transition-Metal
Complexes. Eur. J. Org. Chem. 2007, 2007, 1869−1881. (c) Willis, M.
C. Transition metal catalyzed alkene and alkyne hydroacylation.
Chem. Rev. 2010, 110, 725−748. (d) Murphy, S. K.; Park, J. W.; Cruz,
F. A.; Dong, V. M. Organic chemistry. Rh-catalyzed C-C bond
cleavage by transfer hydroformylation. Science 2015, 347, 56−60.
(e) Biju, A. T.; Kuhl, N.; Glorius, F. Extending NHC-catalysis:
coupling aldehydes with unconventional reaction partners. Acc. Chem.
Res. 2011, 44, 1182−1195.
free oxidative tandem coupling of activated alkenes with carbonyl
C(sp2)−H bonds and aryl C(sp2)−H bonds using TBHP. Chem. Sci.
2013, 4, 2690−2694. (d) Wei, W.-T.; Yang, X.-H.; Li, H.-B.; Li, J.-H.
Oxidative Coupling of Alkenes with Aldehydes and Hydroperoxides:
One-Pot Synthesis of 2,3-Epoxy Ketones. Adv. Synth. Catal. 2015,
357, 59−63.
(12) Yang, W. C.; Weng, S. S.; Ramasamy, A.; Rajeshwaren, G.;
Liao, Y. Y.; Chen, C. T. Vanadyl species-catalyzed complementary
beta-oxidative carbonylation of styrene derivatives with aldehydes.
Org. Biomol. Chem. 2015, 13, 2385−2392.
(13) Wang, H.; Guo, L. N.; Duan, X. H. Silver-catalyzed
decarboxylative acylfluorination of styrenes in aqueous media.
Chem. Commun. 2014, 50, 7382−7384.
(14) Zhang, L.; Liu, S.; Zhao, Z.; Su, H.; Hao, J.; Wang, Y.
(Salen)Mn(III)-catalyzed chemoselective acylazidation of olefins.
Chem. Sci. 2018, 9, 6085−6090.
(3) Lan, X.-W.; Wang, N.-X.; Xing, Y. Recent Advances in Radical
Difunctionalization of Simple Alkenes. Eur. J. Org. Chem. 2017, 2017,
5821−5851.
(4) (a) Chatgilialoglu, C.; Crich, D.; Komatsu, M.; Ryu, I. Chemistry
of Acyl Radicals. Chem. Rev. 1999, 99, 1991−2070. (b) Yoshikai, K.;
Hayama, T.; Nishimura, K.; Yamada, K.; Tomioka, K. Thiol-catalyzed
acyl radical cyclization of alkenals. J. Org. Chem. 2005, 70, 681−683.
(c) Vu, M. D.; Das, M.; Liu, X. W. Direct Aldehyde Csp(2) -H
Functionalization through Visible-Light-Mediated Photoredox Catal-
ysis. Chem. - Eur. J. 2017, 23, 15899−15902. (d) Macías, F. A.;
Molinillo, J. M. G.; Massanet, G. M.; Rodríguez-Luis, F. Study of
photochemical addition of acyl radical to electron-deficient olefins.
Tetrahedron 1992, 48, 3345−3352. (e) Macias, F. A.; Molinillo, J. M.
G.; Collado, I. G.; Massanet, G. M.; Rodriguez-Luis, F. An efficient
and mild entry to 1,4-dicarbonyl compounds via photochemical
addition of acyl radical to electron-deficient olefins. Tetrahedron Lett.
1990, 31, 3063−3066. (f) Hsu, D.-S.; Chen, C.-H.; Hsu, C.-W.
Synthesis of Spiranes by Thiol-Mediated Acyl Radical Cyclization.
Eur. J. Org. Chem. 2016, 2016, 589−598. (g) Esposti, S.; Dondi, D.;
Fagnoni, M.; Albini, A. Acylation of electrophilic olefins through
decatungstate-photocatalyzed activation of aldehydes. Angew. Chem.,
Int. Ed. 2007, 46, 2531−2534. (h) Dong, S.; Wu, G.; Yuan, X.; Zou,
C.; Ye, J. Visible-light photoredox catalyzed hydroacylation of
electron-deficient alkenes: carboxylic anhydride as an acyl radical
source. Org. Chem. Front. 2017, 4, 2230−2234. (i) Chudasama, V.;
Fitzmaurice, R. J.; Caddick, S. Hydroacylation of alpha,beta-
unsaturated esters via aerobic C-H activation. Nat. Chem. 2010, 2,
592−596. (j) Boger, D. L.; Mathvink, R. J. Intramolecular acyl radical-
alkene addition reactions: macrocyclization reactions. J. Am. Chem.
Soc. 1990, 112, 4008−4011.
(15) (a) Matcha, K.; Antonchick, A. P. Metal-free cross-dehydrogen-
ative coupling of heterocycles with aldehydes. Angew. Chem., Int. Ed.
2013, 52, 2082−2086. (b) Wang, J.; Liu, C.; Yuan, J.; Lei, A. Copper-
catalyzed oxidative coupling of alkenes with aldehydes: direct access
to alpha,beta-unsaturated ketones. Angew. Chem., Int. Ed. 2013, 52,
2256−2259. (c) Leifert, D.; Daniliuc, C. G.; Studer, A. 6-Aroylated
phenanthridines via base promoted homolytic aromatic substitution
(BHAS). Org. Lett. 2013, 15, 6286−6289. (d) Zhao, J.; Li, P.; Xia, C.;
Li, F. Direct N-acylation of azoles via a metal-free catalyzed oxidative
cross-coupling strategy. Chem. Commun. 2014, 50, 4751−4754. (e) Li,
J.; Wang, D. Z. Visible-Light-Promoted Photoredox Syntheses of
alpha,beta-Epoxy Ketones from Styrenes and Benzaldehydes under
Alkaline Conditions. Org. Lett. 2015, 17, 5260−5263.
(5) Bergonzini, G.; Cassani, C.; Wallentin, C. J. Acyl Radicals from
Aromatic Carboxylic Acids by Means of Visible-Light Photoredox
Catalysis. Angew. Chem., Int. Ed. 2015, 54, 14066−14069.
(6) Bergonzini, G.; Cassani, C.; Lorimer-Olsson, H.; Horberg, J.;
Wallentin, C. J. Visible-Light-Mediated Photocatalytic Difunctional-
ization of Olefins by Radical Acylarylation and Tandem Acylation/
Semipinacol Rearrangement. Chem. - Eur. J. 2016, 22, 3292−3295.
(7) Xu, S.-M.; Chen, J.-Q.; Liu, D.; Bao, Y.; Liang, Y.-M.; Xu, P.-F.
Aroyl chlorides as novel acyl radical precursors via visible-light
photoredox catalysis. Org. Chem. Front. 2017, 4, 1331−1335.
(8) Li, C. G.; Xu, G. Q.; Xu, P. F. Synthesis of Fused Pyran
Derivatives via Visible-Light-Induced Cascade Cyclization of 1,7-
Enynes with Acyl Chlorides. Org. Lett. 2017, 19, 512−515.
(9) Zhao, J.; Li, P.; Li, X.; Xia, C.; Li, F. Straightforward synthesis of
functionalized chroman-4-ones through cascade radical cyclization-
coupling of 2-(allyloxy)arylaldehydes. Chem. Commun. 2016, 52,
3661−3664.
(10) Taniguchi, T.; Sugiura, Y.; Zaimoku, H.; Ishibashi, H. Iron-
catalyzed oxidative addition of alkoxycarbonyl radicals to alkenes with
carbazates and air. Angew. Chem., Int. Ed. 2010, 49, 10154−10157.
(11) (a) Liu, W.; Li, Y.; Liu, K.; Li, Z. Iron-catalyzed carbonylation-
peroxidation of alkenes with aldehydes and hydroperoxides. J. Am.
Chem. Soc. 2011, 133, 10756−10759. (b) Lv, L.; Lu, S.; Guo, Q.;
Shen, B.; Li, Z. Iron-catalyzed acylation-oxygenation of terminal
alkenes for the synthesis of dihydrofurans bearing a quaternary
carbon. J. Org. Chem. 2015, 80, 698−704. (c) Zhou, M.-B.; Song, R.-
J.; Ouyang, X.-H.; Liu, Y.; Wei, W.-T.; Deng, G.-B.; Li, J.-H. Metal-
E
DOI: 10.1021/acs.orglett.8b03688
Org. Lett. XXXX, XXX, XXX−XXX