Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

Article abstract of DOI:10.3762/bjoc.14.39

[Bis(trifluoroacetoxy)iodo]benzene (BTI) and (diacetoxyiodo)benzene (DIB) efficiently promote the formation of acylnitroso species from hydroxamic acids in the presence of various dienes to give the corresponding hetero-Diels-Alder (HDA) adducts in moderate to high yields. The present method could be applied to the HDA reactions of acylnitroso species with o-benzoquinones generated by the oxidative dearomatization of guaiacols.

Full text of DOI:10.3762/bjoc.14.39

Oxidative cycloaddition of hydroxamic acids with dienes or
guaiacols mediated by iodine(III) reagents
Hisato Shimizu1, Akira Yoshimura2,3, Keiichi Noguchi4, Victor N. Nemykin5,
Viktor V. Zhdankin2 and Akio Saito*1
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2018, 14, 531–536.
1Division of Applied Chemistry, Institute of Engineering, Tokyo
University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei,
Tokyo 184-8588, Japan, 2Department of Chemistry and Biochemistry,
University of Minnesota, Duluth, MN 55812, USA, 3The Tomsk
Polytechnic University, Tomsk 634050, Russia, 4Instrumentation
Analysis Center, Institute of Engineering, Tokyo University of
Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo
184-8588, Japan, and 5Department of Chemistry, University of
Manitoba, Winnipeg, MB R3T 2N2, Canada
doi:10.3762/bjoc.14.39
Received: 25 December 2017
Accepted: 16 February 2018
Published: 28 February 2018
This article is part of the Thematic Series "Hypervalent iodine chemistry in
organic synthesis".
Guest Editor: T. Wirth
Email:
Akio Saito* - akio-sai@cc.tuat.ac.jp
© 2018 Shimizu et al.; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
acylnitroso; benzoquinone; cycloaddition; dearomatization; iodine(III)
Abstract
[Bis(trifluoroacetoxy)iodo]benzene (BTI) and (diacetoxyiodo)benzene (DIB) efficiently promote the formation of acylnitroso
species from hydroxamic acids in the presence of various dienes to give the corresponding hetero-Diels–Alder (HDA) adducts in
moderate to high yields. The present method could be applied to the HDA reactions of acylnitroso species with o-benzoquinones
generated by the oxidative dearomatization of guaiacols.
Introduction
The hetero-Diels–Alder (HDA) reaction of N-acylnitroso ated in these reactions, is often complicated [2-5]. Although the
species with dienes provides the facile and highly stereoselec- Swern–Moffat oxidation [6], Dess–Martin oxidation [7], and
tive synthesis of 1,2-oxazines, which have been widely recog- metal-mediated/catalyzed oxidation reactions [8-12] are known
nized as useful synthons in the synthesis of biologically active as alternative methods [13,14], these methods suffer from a
natural products [1]. Generally, in the presence of dienes, acyl- narrow scope and/or low product yields. Furthermore, in the
nitroso species are in situ generated from hydroxamic acids cases where these oxidation methods are inapplicable, a two-
with oxidants due to their instabilities (Scheme 1, route a). step procedure based on the liberation of the acylnitroso species
Among the oxidants, tetra-n-alkylammonium periodates are by thermolysis of anthracenyl cycloadducts (route b) is widely
commonly employed for these HDA reactions, however, the used [15,16]. Therefore, there is a need to develop novel oxida-
removal of the tetra-n-alkylammonium salts, massively gener- tion methods of hydroxamic acids for HDA reactions.
531

Beilstein J. Org. Chem. 2018, 14, 531–536.
Scheme 1: Hetero-Diels–Alder (HDA) reactions of N-acylnitroso species.
As part of our research on the syntheses of heterocycles by method could be applied to HDA reactions with not only simple
iodine(III)-mediated/catalyzed oxidative cycloaddition reac- dienes but also with masked o-benzoquinones (MOBs) gener-
tions [17-19], we have found that iodine(III) reagents are effec- ated by the oxidative dearomatization of guaiacols.
tive in the oxidation of N–O bonds of oximes in the cycloaddi-
tion reaction of in situ formed nitrile oxides [20,21]. Although Results and Discussion
Adam and Bottke’s group have demonstrated that (diace- Our initial studies commenced with the screening of solvents
toxyiodo)benzene (DIB) and iodosylbenzene are applicable and I(III) reagents for the oxidative cycloaddition reaction of
to the ene reactions of acylnitroso species derived from hydroxamic acid 1a with 1,3-cyclohexadiene (2a, Table 1). In
hydroxamic acids [22], the iodine(III)-mediated oxidative the presence of BTI (1.5 equiv), in polar solvents such as meth-
cycloaddition reaction of hydroxamic acids with dienes anol, tetrahydrofuran (THF), acetonitrile, and ethyl acetate
is still unknown. Herein, we report the HDA reaction of (Table 1, entries 1–4), or in organochlorine solvents such as
acylnitroso species generated from hydroxamic acids by chloroform, dichloroethane (DCE), and dichloromethane
[bis(trifluoroacetoxy)iodo]benzene (BTI) or DIB. The present (DCM, Table 1, entries 6–8), the HDA reactions smoothly
Table 1: Screening of I(III) reagents and solvents for HDA reaction of 1a with 2a.
entry
I(III) reagent
solvent
temp. (°C)
time (h)
3aa (%)a
1
BTI
MeOH
THF
rt
24
24
24
24
24
24
24
1
78
2
BTI
rt
85
3
BTI
MeCN
EtOAc
heptane
CHCl3
DCE
rt
81
4
BTI
rt
89
5
BTI
rt
41
6
BTI
rt
89
7
BTI
rt
89
8
BTI
DCM
rt
98
9
BTIb
DIB
DCM
rt
1
98
10
11
12
13
DCM
rt
1
96
PhIO
IBA-OTf
IBA-OTf
DCM
rt
1
90
DCM
40
−40
24
24
0 (4: 85c)
80
DCM
aIsolated yields. b1.1 equiv. cYield was determined by 1H NMR analysis.
532

Beilstein J. Org. Chem. 2018, 14, 531–536.
proceeded at room temperature within 24 h to give the desired Furthermore, the TfOH-mediated formation of nitrone from
endo-cycloadduct 3aa in 78–98% yield. In particular, the reac- such HDA adducts has been reported [23]. It should be
tion in DCM led to a full conversion to 3aa within 1 h (Table 1, mentioned that the structures of 3aa and 4 were determined by
entry 8) and a reduced amount of BTI (even 1.1 equiv) brought single crystal X-ray analysis [24].
about the similar result (3aa: 98%, Table 1, entry 9). Although
replacing BTI with DIB or iodosylbenzene (1.5 equiv) afforded Next, we investigated the oxidative cycloaddition reactions of
the HDA adducts 3aa in 96 and 90% yields, respectively hydroxamic acids 1a–c with various dienes 2 under the optimal
(Table 1, entries 10 and 11), BTI showed better results (Table 1, conditions (Table 2). Similarly to the benzoyl derivative 1a, the
entries 8 and 9). On the other hand, the use of IBA-OTf, which carbamate analogues 1b (R1 = OBn) and 1c (R1 = Ot-Bu)
was effective in the oxidative cycloaddition reaction of oximes reacted with 1,3-cyclohexadiene (2a, 2 equiv) in the presence of
[20,21], gave nitrone-trifluoromethanesulfonic acid (TfOH) BTI (1.5 equiv) [25] at room temperature for 1 h to give the cor-
complex 4 at 40 °C for 24 h in 85% yield (Table 1, entry 12). responding HDA adducts 3ba and 3ca in 99 and 85% yields, re-
Furthermore, when IBA-OTf was employed at lower tempera- spectively (Table 2, entries 1–3). However, in the reactions of
ture (−40 °C), the HDA adduct 3aa was obtained in 80% yield 1a–c with more reactive dienes such as cyclopentadiene (2b)
(Table 1, entry 13). These results suggest that the initially and 9,10-dimethylanthracene (2c), DIB (1.1 equiv) showed
formed 3aa is converted into 4 by TfOH derived from IBA- better results, thereby affording the HDA adducts 3ab and
OTf. To test this hypothesis, the oxazine 3aa was treated with 3ac–3cc in 69–82% yields (Table 2, entries 4–7). In case of less
TfOH in DCM at 40 °C for 18 h and afforded 4 quantitatively. reactive dienes such as 2,3-dimethyl-1,3-butadiene (2d) and
Table 2: BTI or DIB-mediated oxidative HAD reactions of 1a–c with various dienes.
entry
3
X
Y
yield (%)a
1
2
3
3aa (R1 = Ph)
2
2
2
1.1 (BTI)
1.5 (BTI)
1.5 (BTI)
98
99
85
3ba (R1 = OBn)
3ca (R1 = Ot-Bu)
4
3ab
2
1.1 (DIB)
82
5
6
7
3ac (R1 = Ph)
2
2
2
1.1 (DIB)
1.1 (DIB)
1.1 (DIB)
69
78
76
3bc (R1 = OBn)
3cc (R1 = Ot-Bu)
8
3ad (R1 = Ph)
5
5
5
1.1 (BTI)
1.5 (BTI)
1.5 (BTI)
61
73
55
9
3bd (R1 = OBn)
3cd (R1 = Ot-Bu)
10
11
12
13
3ae (R1 = Ph)
5
5
5
1.1 (BTI)
1.5 (BTI)
1.5 (BTI)
49b
65b
49c
3be (R1 = OBn)
3ce (R1 = Ot-Bu)
aIsolated yields. bDistal:proximal = 2:1. cDistal:proximal = 1:1.
533

Beilstein J. Org. Chem. 2018, 14, 531–536.
isoprene (2e), by the use of BTI (1.1 or 1.5 equiv) [25] along substituted 6ad (53%) and methoxycarbonyl-substituted 6ae
with the increase in the amount of diene to 5 equiv, the HDA (28%).
adducts 3ad–3cd and 3ae–3ce were obtained in moderate to
good yields (3ad–3cd: 55–73%, 3ae–3ce: 49–65%; Table 2, In most cases of the attempted reactions of 1a with simple
entries 8–13). The HDA adducts 3ae–3ce derived from 2e were dienes or guaiacols, benzoyl anhydride was detected as a by-
isolated as mixtures of regioisomers (distal:proximal = 2:1 or product. Since benzoyl anhydride is known to be formed via the
1:1 as determined by 1H NMR analysis).
dimerization of benzoylnitroso compounds [35], these results
suggest that acylnitroso species would be generated from 1a by
As a further application of the iodine(III)-mediated oxidative iodine(III) reagents. Therefore, the high endo selectivities of
cycloaddition reactions, the present method was extended to 1,2-oxadines 3aa–3ca, 3ab, and 6 would depend on the avoid-
HDA reactions with masked o-benzoquinones (MOBs) gener- ance of electrostatic repulsion between the nitrogen lone pairs
ated by the oxidative dearomatization [26-29] of guaiacols with of acylnitroso species with π-electrons of the electron-rich
methanol (Scheme 2). Liao’s and other groups have developed dienes in the exo transition states (exo-lone-pair effect) [36].
the DA reactions with MOBs as dienes [30-33], which recently Furthermore, the regioselectivities observed for 3ae, 3be
were employed in the HDA reactions of acylnitroso species [12,36], and 6 [34] are in consistency with experimental data as
[34]. However, in the HDA reactions with MOBs, the oxida- well as the results of FMO and DFT calculations. The decline in
tion of the hydroxamic acids to the acylnitroso species requires regioselectivity of 3ce may be due to steric repulsion between
other oxidants such as tetra-n-alkylammonium periodates. To the sterically hindered tert-butyloxycarbonyl group in 1c with
our delight, the sole use of DIB in a mixed solvent of DCM and the 2-methyl substituent of isoprene.
methanol gave the endo-cycloadduct 6aa as a single regio-
isomer in 84% yield starting from hydroxamic acid 1a and Conclusion
guaiacol (5a, Scheme 2). The structure of 6aa was determined In summary, we demonstrated that BTI and DIB promote the
by single crystal X-ray analysis [24]. It should be mentioned formation of acylnitroso species from hydroxamic acids in the
that a slow addition of 1a to the solution of 5a and DIB over a presence of various simple dienes to give the corresponding
period of 3 h was essential for an effective formation of 6aa. HDA adducts in moderate to high yields. The present method
Furthermore, this procedure could be applied successfully could be applied to a one-pot reaction involving the generation
to the oxidative cycloaddition reaction of 1a with various guaia- of MOBs by the dearomatization of guaiacols followed by the
cols 5b–g and to the reaction of hydroxamic acids 1b and 1c HDA reactions of acylnitroso species with MOBs as dienes.
with 5a. The corresponding products 6ab–6ag, 6ba, and 6ca Our findings provide an extended scope of dienes for the HDA
were obtained with complete regioselectivities in 70–89% reactions and HDA reactions of acylnitroso species with MOBs
yields, albeit low to moderate yields in cases of the bromo- using single oxidants.
Scheme 2: DIB-mediated oxidative HDA reactions of 1a–c with various guaiacols.
534

Beilstein J. Org. Chem. 2018, 14, 531–536.
9. Flower, K. R.; Lightfoot, A. P.; Wan, H.; Whiting, A.
Supporting Information
J. Chem. Soc., Perkin Trans. 1 2002, 2058–2064.
doi:10.1039/B206430H
Supporting Information File 1
Experimental section.
10.Iwasa, S.; Fakhruddin, A.; Tsukamoto, Y.; Kameyama, M.;
Nishiyama, H. Tetrahedron Lett. 2002, 43, 6159–6161.
doi:10.1016/S0040-4039(02)01277-7
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-39-S1.pdf]
11.Porter, D.; Poon, B. M.-L.; Rutledge, P. J. Beilstein J. Org. Chem.
2015, 11, 2549–2556. doi:10.3762/bjoc.11.275
12.Lewis, R. B.; Read de Alaniz, J. Tetrahedron 2017, 73, 4045–4051.
doi:10.1016/j.tet.2016.11.046
Supporting Information File 2
X-ray structure of 3aa.
13.Quadrelli, P.; Invernizzi, A. G.; Caramella, P. Tetrahedron Lett. 1996,
37, 1909–1912. doi:10.1016/0040-4039(96)00151-7
14.Davey, M. H.; Lee, V. Y.; Miller, R. D.; Marks, T. J. J. Org. Chem. 1999,
64, 4976–4979. doi:10.1021/jo990235x
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-39-S2.cif]
15.Keck, G. E.; Webb, R. R.; Yates, J. B. Tetrahedron 1981, 37,
4007–4016. doi:10.1016/S0040-4020(01)93275-2
16.Monbaliu, J.-C.; Marchand-Brynaert, J.; Peeters, D. Tetrahedron Lett.
2009, 50, 2555–2558. doi:10.1016/j.tetlet.2009.03.062
17.Saito, A. ARKIVOC 2017, No. (i), 84–98.
Supporting Information File 3
X-ray structure of 4.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-39-S3.cif]
doi:10.24820/ark.5550190.p009.965
Supporting Information File 4
X-ray structure of 6aa.
18.Yagyu, T.; Takemoto, Y.; Yoshimura, A.; Zhdankin, V. V.; Saito, A.
Org. Lett. 2017, 19, 2506–2509. doi:10.1021/acs.orglett.7b00742
19.Baba, T.; Takahashi, S.; Kambara, Y.; Yoshimura, A.; Nemykin, V. N.;
Zhdankin, V. V.; Saito, A. Adv. Synth. Catal. 2017, 359, 3860–3864.
doi:10.1002/adsc.201700934
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-39-S4.cif]
20.Yoshimura, A.; Nguyen, K. C.; Klasen, S. C.; Saito, A.; Nemykin, V. N.;
Zhdankin, V. V. Chem. Commun. 2015, 51, 7835–7838.
doi:10.1039/C5CC02009C
Acknowledgements
21.Yoshimura, A.; Nguyen, K. C.; Rohde, G. T.; Saito, A.; Yusubov, M. S.;
Zhdankin, V. V. Adv. Synth. Catal. 2016, 358, 2340–2344.
doi:10.1002/adsc.201600331
This work was partially supported by JSPS Grants-in-Aid for
Scientific Research (C) (Grant No 15K07852) and by JSPS
Fund for the Promotion of Joint International Research (Grant
No 16KK0199). V.V.Z. and A.Y. are also thankful to Tomsk
Polytechnic University (VIU-316/2017).
22.Adam, W.; Bottke, N.; Krebs, O.; Saha-Möller, C. R. Eur. J. Org. Chem.
1999, 1963–1965.
doi:10.1002/(SICI)1099-0690(199908)1999:8<1963::AID-EJOC1963>3
.0.CO;2-3
23.Bodnar, B. S.; Miller, M. J. Tetrahedron Lett. 2009, 50, 796–798.
doi:10.1016/j.tetlet.2008.11.120
ORCID® iDs
Viktor V. Zhdankin - https://orcid.org/0000-0002-0315-8861
24.CCDC-1813170 (3aa), CCDC-1812653 (4), and CCDC-1812654 (6aa)
contain the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via
Akio Saito - https://orcid.org/0000-0002-8291-2059
References
1. Bodnar, B. S.; Miller, M. J. Angew. Chem., Int. Ed. 2011, 50,
http://www.ccdc.cam.ac.uk/data_request/cif.
25.In the reactions of the carbamate analogues 1b and 1c using 1.1 equiv
of BTI, the starting materials were recovered in 10–15%.
26.Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856–866.
doi:10.1021/ar000194n
5630–5647. doi:10.1002/anie.201005764
2. Keck, G. E.; Fleming, S. A. Tetrahedron Lett. 1978, 19, 4763–4766.
doi:10.1016/S0040-4039(01)85725-7
3. Kirby, G. W.; Sweeny, J. G. J. Chem. Soc., Perkin Trans. 1 1981,
3250–3254. doi:10.1039/p19810003250
27.Kita, Y.; Fujioka, H. Pure Appl. Chem. 2007, 79, 701–713.
doi:10.1351/pac200779040701
4. Krchňák, V.; Moellmann, U.; Dahse, H.-M.; Miller, M. J.
J. Comb. Chem. 2008, 10, 94–103. doi:10.1021/cc700140h
5. Monbaliu, J.-C. M. R.; Cukalovic, A.; Marchand-Brynaert, J.;
Stevens, C. V. Tetrahedron Lett. 2010, 51, 5830–5833.
doi:10.1016/j.tetlet.2010.08.117
28.Pouységu, L.; Deffieux, D.; Quideau, S. Tetrahedron 2010, 66,
2235–2261. doi:10.1016/j.tet.2009.12.046
29.Turner, C. D.; Ciufolini, M. A. ARKIVOC 2011, No. (i), 410–428.
30.Lai, C.-H.; Shen, Y.-L.; Liao, C.-C. Synlett 1997, 1351–1352.
doi:10.1055/s-1997-1053
6. Martin, S. F.; Hartmann, M.; Josey, J. A. Tetrahedron Lett. 1992, 33,
3583–3586. doi:10.1016/S0040-4039(00)92508-5
31.Lai, C.-H.; Shen, Y.-L.; Wang, M.-N.; Rao, N. S. K.; Liao, C.-C.
J. Org. Chem. 2002, 67, 6493–6502. doi:10.1021/jo020171h
32.Arjona, O.; Medel, R.; Plumet, J.; Herrera, R.; Jiménez-Vázquez, H. A.;
Tamariz, J. J. Org. Chem. 2004, 69, 2348–2354.
doi:10.1021/jo030307r
7. Jenkins, N. E.; Ware, R. W., Jr.; Atkinson, R. N.; King, S. B.
Synth. Commun. 2000, 30, 947–953. doi:10.1080/00397910008087108
8. Dao, L. H.; Dust, J. M.; Mackay, D.; Watson, K. N. Can. J. Chem. 1979,
57, 1712–1719. doi:10.1139/v79-274
33.Deffieux, D.; Fabre, I.; Titz, A.; Léger, J.-M.; Quideau, S. J. Org. Chem.
2004, 69, 8731–8738. doi:10.1021/jo048677i
535

Beilstein J. Org. Chem. 2018, 14, 531–536.
34.Lu, P.-H.; Yang, C.-S.; Devendar, B.; Liao, C.-C. Org. Lett. 2010, 12,
2642–2645. doi:10.1021/ol100840n
35.Corrie, J. E. T.; Kirby, G. W.; Mackinnon, J. W. M.
J. Chem. Soc., Perkin Trans. 1 1985, 883–886.
doi:10.1039/p19850000883
36.Leach, A. G.; Houk, K. N. J. Org. Chem. 2001, 66, 5192–5200.
doi:10.1021/jo0104126
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