A metal-free approach to access ketones, amides, and nitriles employing TBAI/TBHP oxidative system in water

Article abstract of DOI:10.1080/00397911.2019.1669183

Hydrocarbons, benzylamines, and heteroaromatic-bearing amines have been efficiently employed as substrates in allylic and benzylic oxidations via C(sp3)–H bond activation by TBAI/TBHP in water. This operationally simple method allows access to ketones, nitriles, and amides in moderate to high yields and a regio- and chemoselective late-stage functionalization.

Full text of DOI:10.1080/00397911.2019.1669183

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
A metal-free approach to access ketones, amides,
and nitriles employing TBAI/TBHP oxidative
system in water
Suzane Quintana Gomes & Airton G. Salles Jr
To cite this article: Suzane Quintana Gomes & Airton G. Salles Jr (2019): A metal-free approach
to access ketones, amides, and nitriles employing TBAI/TBHP oxidative system in water, Synthetic
Communications, DOI: 10.1080/00397911.2019.1669183
To link to this article: https://doi.org/10.1080/00397911.2019.1669183
View supplementary material
Published online: 01 Oct 2019.
Submit your article to this journal
Article views: 15
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=lsyc20

R
SYNTHETIC COMMUNICATIONSV
https://doi.org/10.1080/00397911.2019.1669183
A metal-free approach to access ketones, amides, and
nitriles employing TBAI/TBHP oxidative system in water
Suzane Quintana Gomes and Airton G. Salles Jr
~
Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, Sao
Paulo, Brazil
ABSTRACT
ARTICLE HISTORY
Received 13 July 2019
Hydrocarbons, benzylamines, and heteroaromatic-bearing amines
have been efficiently employed as substrates in allylic and benzylic
oxidations via C(sp3)–H bond activation by TBAI/TBHP in water. This
operationally simple method allows access to ketones, nitriles, and
amides in moderate to high yields and a regio- and chemoselective
late-stage functionalization.
KEYWORDS
Allylic oxidation; benzylic
oxidation; in water; metal-
free oxidation
GRAPHICAL ABSTRACT
Introduction
Catalytic procedures for the C–H bond functionalization have emerged as powerful
tools to introduce and expand molecular diversity.[1] From the point of view of sustain-
able synthesis, mild C–H bond activation strategies could avoid the need for prior func-
tionalization and this synthetic advantage is amplified by the application of this
methodology to late-stage modification of biologically active compounds.[2]
In this context, selective oxidation of C–H bonds is a useful synthetic transformation
and can convert simple hydrocarbons into oxygen-containing pharmaceuticals and bio-
active products.[3] Among these transformations, benzylic and allylic oxidations are of
CONTACT Airton G. Salles, Jr
University of Campinas, Monteiro Lobato Street, P.O. Box 6154, Campinas 13084-862, Sao Paulo, Brazil.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
hoffman@unicamp.br
Department of Organic Chemistry, Institute of Chemistry,
~
Supplemental data for this article is available online at on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
S. GOMES AND A. SALLES
paramount importance in synthetic chemistry.[4] Although outstanding progress in this
field has been made in the past few years,[5] substantial challenges still remain, such as
achieving efficient metal-free benzylic and allylic oxidation. Thus, the development of
catalytic systems more attractive than the traditional transition-metal oxidative transfor-
mations is of ongoing importance. Recently, the use of catalytic amount of tetrabuty-
lammonium iodide (TBAI) in combination with oxidants has gained increasing
attention.[6] However; most of transformations were performed in organic solvents and,
in spite of some reports,[7] the use of water as a reaction medium in this system is not
extensively explored. Water is an environmentally benign solvent and a reasonably
redox inert compound. As such, it could be a convenient solvent for oxidative and
reductive organic transformations.
Considering the interest in developing sustainable synthetic strategies relying upon
environmentally innocuous processes, we focused our attention on the use of an oxida-
tion system featuring TBAI as a catalyst and water as a solvent. Herein, we report a
metal-free benzylic and allylic oxidation in water catalyzed by TBAI and employing
TBHP as oxidant (Scheme 1). Under the optimized reaction conditions, hydrocarbons,
benzyl amines, heteroaromatic-bearing amines, and a steroid are oxidized selectively in
moderate to high yields.
Scheme 1. Previous work and our approach for allylic/benzylic C(sp3)–H oxidation.

R
SYNTHETIC COMMUNICATIONSV
3
Table 1. Optimization of reaction conditionsa.
Entry
Catalyst (equiv.)
Oxidant (equiv.)
Solvent
Yield (%)b
1
2
3
4
5
6
TBAI (0.2)
TBAI (0.2)
TBAI (0.2)
TBAI (0.2)
TBAI (0.2)
TBAI (0.25)
TBAI (0.25)
TBAI (0.25)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (5)
TBHP (5)
TBHP (3)
TBHP (5)
TBHP (5)
MeCN
DMF
61
65
69
78
82
89
75
55
traces
0
70
59
67
traces
traces
DMSO
Water
Water
Water
Water
Water
Water
Water
Water
Water
Water
Water
Water
7
8c
9
10
11
12
13
14d
15
TBAI (0.25)
KI (0.25)
TBAI (0.25)
TBAI (0.25)
TBAI (0.25)
I2 (0.25)
TBHP (5)
H2O2 (5)
K2S2O8 (5)
O2
aReaction conditions: 1 (1 mmol), solvent (1 mL), catalyst, oxidant, 85 ꢀC, 8 h. bYield of isolated product. 50 ꢀC. dUnder
c
O2 atmosphere.
Entry in bold refers to the higher yield obtained in the optimization.
Results and discussion
As an initial study, the commercially available 1,2,3,4–tetrahydronaphthalene 1 was
selected as a model substrate. By using 3 equiv. of TBHP (70% in water) as oxidant,
TBAI (0.20 equiv.) at 85 ꢀC in acetonitrile, 61% of the desired product 2 was formed
after 8 h (Table 1, entry 1). Among the solvents investigated, DMF and DMSO also
afforded product 2 in moderate yield (Table 1, entries 2 and 3). When water was
employed as solvent the transformation delivered 2 in 78% yield (Table 1, entry 4).
Maintaining the amount of TBAI and increasing the amount of TBHP to 5 equiv. gave
the product in 82% yield (Table 1, entry 5). Increasing the amount of TBAI (0.25
equiv.) improved the isolated yield to 89% (Table 1, entry 6). Maintaining the amount
of TBAI (0.25 equiv.) and decreasing the amount of TBHP to 3 equiv. proved detrimen-
tal to the yield (Table 1, entry 7). At lower temperature, the yield decreased consider-
ably (Table 1, entry 8). Control experiments demonstrated that all the reagents were
essential to obtain considerable conversion to 2 (Table 1, entries 9–11). Alternative oxi-
dants such as H2O2, K2S2O8, and O2 led to inferior results (Table 1, entries 12–14).
Finally, using I2 as the sole oxidant gave product 2 in traces (Table 1, entry 13).
We subsequently investigated the scope with regard to a range of chemical motifs. As
shown in Table 2, benzylic and allylic hydrocarbons performed well in this reaction giv-
ing access to the corresponding ketones in moderate to high yields (Table 2, entries
1–4). Interestingly, alkene 5 gave the diketone 6 in 60% yield whereas alkene 7 gave the
monoketone 8 in 68% yield. We hypothesize that the cyclopropyl moiety in 5 might
provide extra stabilization (due to highly strained structure and, consequently, low-lying
LUMO) of the corresponding radical in both positions; thus, the oxidation occurs twice.
We observed complete aromatization of 1,2-dihydronaphthalene under the reaction
conditions (Table 2, entry 5). A secondary benzylic amine (tetrahydroisoquinoline) was

4
S. GOMES AND A. SALLES
Table 2. Substrate scope of TBAI/TBHP oxidation under standard
conditionsa.
aReaction conditions: substrate (1 mmol), H2O (1 mL), TBAI (0.25 equiv.), TBHP (5
equiv.), 85 ꢀC, 8 h. Yields of isolated products are given. bPerforming the same
reaction employing only TBHP (no catalyst used) gave product 10 in traces.

R
SYNTHETIC COMMUNICATIONSV
5
converted into the amide in good yield (Table 2, entry 6). We were surprised to find
that the reaction of a series of substituted benzylamines delivered the corresponding
nitriles in high yields (Table 2, entries 7 – 11). There are only a few reports in the litera-
ture describing metal-free strategies to accomplish such transformation.[8] Benzylamines
bearing electron-donating and electron-withdrawing substituents were all compatible
with the reaction conditions. Furthermore, when using heteroaromatic-bearing amines,
we also isolated the corresponding amides in high yields (Table 2, entries 12 and 13).
To the best of our knowledge, for both amines (2-picolylamine and furfurylamine),
there are no reports of this transformation using a complete metal-free approach.[9]
To demonstrate the synthetic utility of this process, we applied our protocol to the
late-stage functionalization of b-sitosterol 28. This compound contains two allylic posi-
tions and a hydroxyl group all prone to oxidation; nevertheless, we obtained the corre-
sponding 7-ketositosterol 29 as a single product in 55% yield, recovering the starting
material unreacted (Table 2, entry 14). The regio- and chemoselectivity of this trans-
formation demonstrate the practicality and mildness of the protocol, thus offering an
alternative strategy for the modification of biologically relevant structures containing
these chemical motifs. Recently, Lam and coworkers[10] described the use of TBAI/
TBHP in dichloromethane for the allylic oxidation of steroids. The yields were compar-
able to the one obtained using our protocol but the authors reported 48 h of reaction
time. Employing our approach, the poor solubility of the sitosterol in water may impair
the yield; nevertheless, water as a solvent is in line with the green chemistry initiative
and allows, in our case, a faster reaction.
Next, the reusability of the aqueous medium was inspected for the benzylic oxidation
of 1,2,3,4–tetrahydronaphtalene 1 under the optimized conditions (Scheme 2, I, see the
Supporting Information for details and further discussion). After a first run, the aque-
ous solution containing the catalyst was extracted with ethyl acetate giving product 2 in
full conversion and recharged with 1 and TBHP. The subsequent run under identical
reaction conditions gave product 2 in partial conversion (84%). A third run allowed the
recovery of starting material unreacted. Alternatively, we tested the recyclability of the
aqueous medium regarding two different starting materials (Scheme 2, II). In this
experiment, the possibility to isolate different products using the same aqueous solution
in subsequent runs was evaluated. Oxidation of 1,2,3,4–tetrahydronaphthalene 1 under
the optimized conditions provided product 2 in full conversion after extraction. The
aqueous solution was then recharged with 4-methoxybenzylamine 18 and TBHP leading
to product 19 in 52% conversion. Despite moderate conversion, this result demon-
strated the capability of the protocol to operate over two distinct starting materials with
no product cross-contamination during the recycle.
Based on the literature precedence[8(a),11], we propose two different reaction pathways
to access ketones and nitriles (Scheme 3, using 1,2,3,4–tetrahydronaphthalene and ben-
zylamine as representative substrates). Heating the aqueous solution of TBHP produces
hydroxyl radical and t-butoxy radical (Scheme 3). In the presence of 1,2,3,4–tetrahydro-
naphthalene (Path I), hydrogen atom transfer leads to the corresponding benzylic rad-
ical,[12] which terminates with hydroxyl radical giving the intermediate alcohol. Anion
-
I3 formed from TBHP and iodide[13] (the presence of triiodide in the reaction medium
was evidenced performing the Iodine Test with starch, see the Supporting Information

6
S. GOMES AND A. SALLES
Scheme 2. Recyclability of TBAI catalyst in benzylic oxidations.

R
SYNTHETIC COMMUNICATIONSV
7
Scheme 3. Proposed reaction mechanism.
for details) enters into the reaction pathway performing the oxidation of the alcohol to
the observed ketone and releasing I- to return to the cycle. For benzylamine (Path II),
the hydrogen atom transfer furnishes an a–amino radical. In the presence of iodine
formed from TBHP and iodide, oxidation takes place and delivers the intermediate
imine. Iodide is released in this path as well, thus going back to the cycle. Another
round of hydrogen atom transfer and oxidation leads to the observed nitrile.
For 2-picolylamine and furfurylamine, we hypothesize the presence of electron-with-
drawing heteroatoms in the intermediate nitriles[8(a)] would lead to faster hydration of
this groups furnishing the corresponding amides[14] (Scheme 3, bottom). Whereas for
tetrahydroisoquinoline the intermediate imine would be promptly hydrated and oxi-
dized (by I3ꢁ, for instance) giving the detected amide (Scheme 3, bottom).

8
S. GOMES AND A. SALLES
Conclusions
In conclusion, we have developed an alternative metal-free approach to perform allylic
and benzylic oxidations in water of different classes of compounds in moderate to high
yields. The protocol uses simple reagents and is applicable to a broad functional group
scope giving access to ketones, nitriles, and amides. The mildness and functional group
tolerance of this transformation were demonstrated in the regio- and chemoselective
late-stage functionalization of b-sitosterol. Moreover, we anticipate that this general
method might be a scalable strategy to conveniently access chemical functions
herein addressed.
Experimental procedure
Materials and methods
All reagents were purchased from commercial suppliers (Sigma-Aldrich) and used with-
out further purification, all solvents were analytical grade. Temperatures above room
temperature were maintained by using a mineral oil bath heated on a hotplate, and
reaction temperatures are reported as the temperature of the bath surrounding the ves-
sel. Column chromatography was performed using silica gel (230–400 mesh) following
standard techniques. Thin-layer chromatography (TLC) was performed using silica gel
GF254, 0.25 mm thickness, visualization was accomplished with short wave UV light or
KMnO4 staining solution followed by heating.
Hydrogen nuclear magnetic resonance spectra (1H NMR) were obtained at 250, 400,
and 500 MHz in CDCl3 solutions, at ambient temperature. Carbon-13 nuclear magnetic
resonance spectra (13C NMR) were obtained at 100 MHz and 125 MHz in CDCl3 solu-
tions, at ambient temperature. Chemical shifts (d) are given in ppm and the residual
1
solvent signals were used as references for H and 13C NMR spectra (CDCl3: dH ¼
7.27 ppm, dC ¼ 77.00 ppm). High-resolution mass spectra were recorded on
ThermoScientific LTQ FT Ultra and Q Exactive Orbitrap spectrometers working with
an electron spray ionization (ESI).
General procedure for the allylic/benzylic oxidation and oxidation of
benzylamines
Water (1.0 ml), substrate (1 mmol), TBAI (0.25 equiv.) and TBHP (70% in water)
(5 equiv.) were added to a 20-ml test tube and the mixture was stirred at 85 ꢀC for 8 h.
After completion of the reaction, ethyl acetate (5 mL) was added for quenching. The
aqueous layer was extracted with ethyl acetate (3 ꢂ 10 mL), the combined organic layers
were dried over anhydrous Na2SO4 and concentrated. The crude product mixture was
purified by flash column chromatography (EtOAc/Hexanes gradient).
Funding
~
ꢀ
~
~
We thank Fundac¸ao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo, Brazil)
for financial support [FAPESP 2017/18400-6]. This study was financed in part by the

R
SYNTHETIC COMMUNICATIONSV
9
~
ꢁ
Coordenac¸ao de Aperfeic¸oamento de Pessoal de Nıvel Superior - Brasil (CAPES) - Finance
Code 001.
ORCID
Airton G. Salles
http://orcid.org/0000-0002-9423-2552
References
[1] (a) Gensch, T.; Hopkinson, M. N.; Glorius, F.; Wencel-Delord, J. Mild Metal-Catalyzed
C–H Activation: Examples and Concepts. Chem. Soc. Rev. 2016, 110, 1147. DOI: 10.1039/
C6CS00075D. (b) Roudesly, F.; Oble, J.; Poli, G. Metal-Catalyzed C–H Activation/
Functionalization: The Fundamentals. J. Mol. Catal. A Chem. 2017, 426, 275. DOI: 10.
1016/j.molcata.2016.06.020.
[2] (a) Li, J. J. C-H Bond Activation in Organic Synthesis; CRC Press Taylor & Francis Group:
Boca Raton, FL, 2015. (b) Wencel-Delord, J.; Glorius, F. C-H Bond Activation Enables the
Rapid Construction and Late-Stage Diversification of Functional Molecules. Nat. Chem.
2013, 5, 369. DOI: 10.1038/nchem.1607. (c) Caro-Diaz, E. J. E.; Urbano, M.; Buzard, D. J.;
Jones, R. M. C–H Activation Reactions as Useful Tools for Medicinal Chemists. Bioorg.
Med. Chem. Lett. 2016, 26, 5378. DOI: 10.1016/j.bmcl.2016.06.036.
[3] (a) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidation of Organic Compounds;
Academic Press: New York, NY, 1981. (b) Newhouse, T.; Baran P. S. Wenn C-H-
€
Bindungen Sprechen Konnten - Selektive Oxidationen Von C-H-Bindungen. Angew.
Chem. 2011, 123, 3422–3435. DOI: 10.1002/ange.201006368. (c) Wang, Y.; Kuang, Y.;
Wang, Y. Rh 2 (Esp) 2 -Catalyzed Allylic and Benzylic Oxidations. Chem. Commun. 2015,
51, 5852. DOI: 10.1039/C4CC10336J.
[4] Weidmann, V.; Maison, W. Allylic Oxidations of Olefins to Enones. Synthesis 2013, 43,
2201. DOI: 10.1055/s-0033-1338491.
[5] (a) Sterckx, H.; Morel, B.; Maes, B. U. W. Catalytic Aerobic Oxidation of C(sp3 )–H
Bonds. Angew. Chem. Int. Ed. Engl. 2019, 58, 7946. DOI: 10.1002/anie.201804946. (b)
Chen, K.; Zhang, P.; Wang, Y.; Li, H. Metal-Free Allylic/Benzylic Oxidation Strategies
with Molecular Oxygen: Recent Advances and Future Prospects. Green Chem. 2014, 16,
2344. DOI: 10.1039/c3gc42135j. (c) Dohi, T.; Takenaga, N.; Goto, A.; Fujioka, H.; Kita, Y.
Clean and Efficient Benzylic C–H Oxidation in Water Using a Hypervalent Iodine
Reagent: Activation of Polymeric Iodosobenzene with KBr in the Presence of montmoril-
lonite-K10. J. Org. Chem. 2008, 73, 7365. DOI: 10.1021/jo8012435. (d) Zhao, Y.; Yeung,
Y.-Y. An Unprecedented Method for the Generation of Tert-Butylperoxy Radical using
DIB/TBHP Protocol: Solvent Effect and Application on Allylic Oxidation. Org. Lett. 2010,
12, 2128. DOI: 10.1021/ol100603q. (e) Wusiman, A.; Tusun, X.; Lu, C. D. Dirhodium(II)
Complexes of 2-(Sulfonylimino)Pyrrolidine: Synthesis and Application in Catalytic
Benzylic Oxidation. Eur. J. Org. Chem. 2012, 2012, 3088. DOI: 10.1002/ejoc.201200292. (f)
Li, Y. C.; Lee, T. B.; Wang, T. Y.; Gamble, A. V.; Gorden, A. E. V. Allylic C–H
Activations Using Cu(II) 2-Quinoxalinol Salen and Tert-Butyl Hydroperoxide. J. Org.
Chem. 2012, 77, 4628. DOI: 10.1021/jo300372q.
[6] (a) Wu, X. F.; Gong, J. L.; Qi, X. A Powerful Combination: Recent Achievements on Using
TBAI and TBHP as Oxidation System. Org. Biomol. Chem. 2014, 12, 5807. DOI: 10.1039/
C4OB00276H. (b) Tong, C.; Gan, B.; Yan, Y.; Xie, Y.-Y. TBAI/K2S2O8-Facilitated Reaction
of Sulfonylhydrazides with Alkynes: Facile Synthesis of (E)-b-Iodovinyl Sulfones. Synth.
Commun. 2017, 47, 1927. DOI: 10.1080/00397911.2017.1337152. (c) Ji, P. Y.; Zhang, M. Z.;
Xu, J. W.; Liu, Y. F.; Guo, C. C. Transition-Metal-Free TBAI-Facilitated
Addition-Cyclization
of
N-Methyl-N-arylacrylamides
with
Arylaldehydes
or
Benzenesulfonohydrazides: Access to Carbonyl- and Sulfone-Containing N-Methyloxindoles.
J. Org. Chem. 2016, 81, 5181. DOI: 10.1021/acs.joc.6b00773. (d) Chen, J.; Jiang, Y.; Yu, J.-T.;

10
S. GOMES AND A. SALLES
Cheng, J. TBAI-Catalyzed Reaction between N-Tosylhydrazones and Sulfur: A Procedure
toward 1,2,3-Thiadiazole. J. Org. Chem. 2016, 81, 271. DOI: 10.1021/acs.joc.5b02280. (e)
Wen, J.; Wei, W.; Xue, S.; Yang, D.; Lou, Y.; Gao, C.; Wang, H. Metal-Free Oxidative
Spirocyclization of Alkynes with Sulfonylhydrazides Leading to 3-Sulfonated Azaspiro[4,
5]trienones. J. Org. Chem. 2015, 80, 4966. DOI: 10.1021/acs.joc.5b00361. (f) He, Y.; Hang,
D.; Lu, M. A Simple and Practical Method for the Oxidation of Thiols to Disulfides at Mild
Conditions without Solvents. Phosphorus, Sulfur Silicon Relat. Elem. 2012, 187, 1118. DOI:
10.1080/10426507.2012.674585. (g) Wu, J.; Liu, Y.; Ma, X.; Liu, P.; Gu, C.; Dai, B. Metal-
Free Oxidation of Secondary Benzylic Alcohols Using Aqueous TBHP. Synth. Commun.
2016, 46, 1747. DOI: 10.1080/00397911.2016.1223307. (h) Wu, J.; Liu, Y.; Ma, X.; Liu, P.;
Gu, C.; Dai, B. Highly Selective Copper-Catalyzed Oxidation of Benzyl Alcohols to
Aromatic Aldehydes in Water at Room Temperature. Appl. Organometal. Chem. 2016, 30,
577. DOI: 10.1002/aoc.3473. (i) Wu, J.; Liu, Y.; Liu, P.; Gu, C. A Simple, Mild and Efficient
Oxidation of Benzylic Alcohols in the Presence of NBS/KOAc in Aqueous Solution. Lett.
Org. Chem. 2017, 14, 254. DOI: 10.2174/1570178614666170221142818. (j) Wu, J.; Liu, Y.;
Ma, X.; Liu, P.; Gu, C.; Dai, B. Cu(II)-Catalyzed Ligand-Free Oxidation of Diarylmethanes
and Second Alcohols in Water. Chin. J. Chem. 2017, 35, 1391. DOI: 10.1002/cjoc.
201700115.
[7] (a) Gao, Y.; Hu, G.; Zhong, J.; Shi, Z.; Zhu, Y.; Su, D. S.; Wang, J.; Bao, X.; Ma, D.
Nitrogen-Doped sp2-Hybridized Carbon as a Superior Catalyst for Selective Oxidation.
Angew. Chem. Int. Ed. Engl. 2013, 52, 2109. DOI: 10.1002/anie.201207918. (b) Wang, H.;
Wang, Z.; Huang, H.; Tan, J.; Xu, K. KO t Bu-Promoted Oxidation of (Hetero)Benzylic
C(sp3)–H to Ketones with Molecular Oxygen. Org. Lett. 2016, 18, 5680. DOI: 10.1021/acs.
orglett.6b02914. (c) Satheesh, V.; Sengoden, M.; Punniyamurthy, T. “on Water” C(sp3)–H
Functionalization/C–O/C–N Bonds Formations: Synthesis of Functionalized Oxazolidines
and Imidazolidines. J. Org. Chem. 2016, 81, 9792. DOI: 10.1021/acs.joc.6b01850. (d) Ma, J.
; Hu, Z.; Li, M.; Zhao, W.; Hu, X.; Mo, W.; Hu, B.; Sun, N.; Shen, Z. DDQ/tert-Butyl
Nitrite-Catalyzed Aerobic Oxidation of Diarylmethane sp3 C–H Bonds. Tetrahedron 2015,
71, 6733. DOI: 10.1016/j.tet.2015.07.042. (e) He, C.; Zhang, X.; Huang, R.; Pan, J.; Li, J.;
Ling, X.; Xiong, Y.; Zhu, X. Synthesis of Structurally Diverse Diarylketones through the
Diarylmethyl sp3 CH Oxidation. Tetrahedron Lett. 2014, 55, 4458. DOI: 10.1016/j.tetlet.
2014.06.047.
[8] (a) Zhang, J.; Wang, Z.; Wang, Y.; Wan, C.; Zheng, X.; Wang, Z. A Metal-Free Catalytic
System for the Oxidation of Benzylic Methylenes and Primary Amines under Solvent-Free
Conditions. Green Chem. 2009, 11, 1973. DOI: 10.1039/b919346b. (b) Lambert, K. M.;
Bobbitt, J. M.; Eldirany, S. A.; Kissane, L. E.; Sheridan, R. K.; Stempel, Z. D.; Sternberg,
F. H.; Bailey, W. F. Metal-Free Oxidation of Primary Amines to Nitriles through Coupled
Catalytic Cycles. Chemistry 2016, 22, 5156. DOI: 10.1002/chem.201600549. (c) Veisi, H.
Direct Oxidative Conversion of Alcohols, Amines, Aldehydes, and Benzyl Halides into the
Corresponding Nitriles with Trichloroisocyanuric Acid in Aqueous Ammonia. Synthesis
2010, 2010, 2631. DOI: 10.1055/s-0029-1218827. (d) Primo, A.; Puche, M.; Pavel, O. D.;
ꢁ
Cojocaru, B.; Tirsoaga, A.; Parvulescu, V.; Garcıa, H. Graphene Oxide as a Metal-Free
Catalyst for Oxidation of Primary Amines to Nitriles by Hypochlorite. Chem. Commun.
(Camb.) 2016, 52, 1839. DOI: 10.1039/c5cc09463a.
[9] Xu, W.; Jiang, Y.; Fu, H. Copper-Catalyzed Aerobic Oxidative Synthesis of Primary
Amides from (Aryl)methanamines. Synlett 2012, 23, 801. DOI: 10.1055/s-0031-1290302.
[10] Lam, Y. P.; Yeung, Y. Y. Metal-Free Allylic Oxidation of Steroids Using TBAI/TBHP
Organocatalytic Protocol. Chem Asian J. 2018, 13, 2369. DOI: 10.1002/asia.201800256.
[11] (a) Li, L. T.; Li, H. Y.; Xing, L. J.; Wen, L. J.; Wang, P.; Wang, B. Potassium Iodide
Catalyzed Simultaneous C3-formylation and N-Aminomethylation of Indoles with 4-
Substituted-N,N-Dimethylanilines. Org. Biomol. Chem. 2012, 10, 9519. DOI: 10.1039/
c2ob26636a. (b) Gogoi, P.; Konwar, D. Transition-Metal- and Organic-Solvent-Free: A
Highly Efficient Anaerobic Process for Selective Oxidation of Alcohols to Aldehydes and
Ketones in Water. Org. Biomol. Chem. 2005, 3, 3473. DOI: 10.1039/b509527a.

R
SYNTHETIC COMMUNICATIONSV
11
[12] Chatgilialoglu, C.; Crich, D.; Komatsu, M.; Ryu, I. Chemistry of acyl radicals. Chem. Rev.
1999, 99, 1991. DOI: 10.1021/cr9601425.
[13] Svensson, P. H.; Kloo, L. Synthesis, Structure, and Bonding in Polyiodide and Metal
Iodide-Iodine Systems. Chem. Rev. 2003, 103, 1649. DOI: 10.1021/cr0204101.
[14] For the hydration of nitriles under oxidative conditions see: Zhan, W.; Ji, L.; Ge, Z. m.;
Wang, X.; Li, R. t. A Continuous-Flow Synthesis of Primary Amides from Hydrolysis of
Nitriles Using Hydrogen Peroxide as Oxidant. Tetrahedron. 2018, 74, 1527. DOI: 10.1016/
j.tet.2018.02.017.