Iodine catalysed intramolecular C(sp3)-H functionalization: synthesis of 2,5-disubstituted oxazoles from N-arylethylamides

Article abstract of DOI:10.1039/c5ra13441b

Iodine catalyzed synthesis of 2,5-disubstituted oxazoles from N-arylethylamides through intramolecular C(sp³)-H functionalization under metal-free conditions is described. The method is tolerable to a wide range of substrates having a variety of functional groups with moderate to good yields of the products.

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Iodine
catalysed
intramolecular
C(sp3)−H
functionalization: Synthesis of 2, 5−disubstitutedoxazoles
from N−arylethylamides
Received 00th January 20xx,
Accepted 00th January 20xx
Supravat Samanta, Ramachandra Reddy Donthiri, Milan Dinda and Subbarayappa
Adimurthy*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Iodine catalyzed synthesis of 2, 5-disubstitutedoxazoles from N- synthesis of pharmaceutical fine chemicals because of
arylethylamides through intramolecular C(sp3)-H functionalization
under metal-free conditions is described. The method is tolerable
for wide range of substrates having variety of functional groups
with moderate to good yields of products.
A) Rabinson – Gabriel condensation:
In addition to biologically active molecules for the drug discovery,
oxazoles are also the key intermediates for the synthesis of natural
products, pharmaceutical and agricultural products.1ꢀ6 Additionally,
oxazole moieties are used as fluorescent dyes,7 in polymer
industries,8 and also serve as ligands in various metalꢀcatalysed
organic transformations.9 As a result the development of more facile
synthetic methods to access the oxazole derivatives has become a
great interest to the chemists.
B) Cyclisation of preꢀactivated enamides:
C) Direct cyclization of enamides:
Considering the importance of oxazole moieties, many groups
have developed the vital methods for the synthesis of substituted
oxazoles.10ꢀ15 Among the reported methods the conversion of acyclic
precursors to oxazole is the common strategy.11ꢀ13 For example
Robinson−Gabriel condensation is a versatile cyclisation strategy to
synthesise a range of substituted oxazoles (Scheme 1A).11 On the
other hand enamides bearing βꢀvinylic carbon heteroatom (Br, and
S) were subjected for the synthesis of oxazoles12 (Scheme 1B). A
step forward to the aforementioned strategies, several examples of
transition metal catalyzed direct vinylic C−H functionalization of
enamides have also been described (Scheme 1C).13 Recently, Stahl
and Buchwald groups were independently reported copper
Scheme 1: Reported strategies for oxazole synthesis
their residual toxicity is a central issue to consider. Moreover,
transition metalꢀcatalyzed reactions also generate hazardous
waste which is environmentally problematic and hence, should
be avoided wherever possible. Very recent reports from Ghosh
et al, and Bathula et al described the synthesis of substituted
oxazoles from
stoichiometric use of N
N
−
arylethylamides with more than
−
bromosuccinimide (NBS),14 these
methods also suffers drawbacks such as generation of organic
waste (succinimide) in the effluent and is not applicable to
obtain 2, 5ꢀdisubstituted oxazoles. At the outset of our interest
towards the development of new strategies for the synthesis of
mediated/catalysed vinylic C
to obtain 2, 5
disubstituted oxazoles.13(h,
approaches are effective, the cyclisation of N
to oxazoles through C(sp3)
H functionalization under transition
−H functionalization of enamides
i)
−
Although these
arylethylamides
−
−
metalꢀfree conditions would be a convenient method to access
the substituted oxazoles (Scheme 2). The separation of metal
catalyst from the products is of particular importance for the
Scheme 2: Oxazole synthesis from
N− arylethylamides
Academy of Scientific & Innovative Research, Process Development & Engineering
Cell, CSIR–Central Salt & Marine Chemicals Research Institute, G.B. Marg,
Bhavnagar-364 002. Gujarat (INDIA). E-mail: adimurthy@csmcri.org
Electronic Supplementary Information (ESI) available: [Detailed experimental
procedures and spectroscopic data]. See DOI: 10.1039/x0xx00000x
various heterocyclic compounds,16aꢀe we wish to report herewith
a metalꢀfree synthesis of oxazoles through intramolecular
C(sp3)
−H) functionalization (Scheme 2). To the best of our
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knowledge, no such reports exist for the synthesis of 2, K2S2O8, KHSO5, H2O2 and DTBP (Table 1, entries 14−17). Then we
disubstituted oxazoles from N arylethylamides. focused on the effect of other solvents for the present transformation
We initiated our studies with N−phenethylbenzamide 1a as by fixing the temperature at 100 °C, reaction time 36 h, I2 (20 mol
5−
−
starting substrate, which has been subjected to oxidative %) and the oxidant TBHP (5.0 equivalents). With the several
intramolecular C−O bond formation to obtain 2, 5−diphenyloxazole solvents tested for the reaction, the yield of 2a was not improved
2a with catalytic amount of iodine source and TBHP as the oxidant (Table 1, entries 18−23). However, the best result was obtained in
based on our recent reports on such reactions16f,g and the results are acetonitrile as the solvent (entry 6) for the present transformation.
illustrated in Table 1. Initially we tested the reaction with 20 mol%
In order to generalize the present transformation, we have applied
of KI as an iodine source, TBHP (5.0 eqv.) as an oxidant and this strategy to various N−arylethylamide derivatives (Table 2). The
acetonitrile as the solvent at 100 °C for 36 h, 15% of desired product halogens (Br, Cl & F) present on the paraꢀposition of aryl ring
2a was observed (Table 1, entry 1). Then we have screened out other
Table 2. Substrate scope for 2, 5ꢀdisubstituted oxazolesa
iodine sources under these reaction conditions up to 35% yield of
desired product 2a could be obtained (Table 1, entries 2−5). When
the reaction was performed under the same conditions with 20 mol%
Table 1 Optimisation of reaction conditionsa
aReaction conditions otherwise stated: 0.2 mmol of 1a, 1.0 mmol of TBHP
b
(decane), 20 mol % catalyst in 1.0 mL of CH3CN at 100 °C for 36 h; 10
mol% I2. DTBP= Diꢀtertꢀbutyl peroxide.
aReaction conditions otherwise stated: 0.2 mmol of 1a, 1.0 mmol of TBHP
of elemental iodine, 68% of 2a was isolated (Table 1, entry 6). By
decreasing the reaction time to 24 h or reaction temperature to 80 °C (5ꢀ6 M in decane solution), 20 mol % I2 in 1.0 mL of CH3CN at 100 °C for
36 h.
the yield of 2a was dropped to 55% and 28% respectively (Table 1,
entries 7 and 8). Further, its yield was decreased by decreasing the
amount of oxidant (TBHP) or I2 (Table 1, entries 9−11) and no
reaction or traces amount of 2a was observed in the absence of I2 or
TBHP (Table 1, entries 12 and 13) or with other oxidants such as
attached to the ethylene chain of N−phenethylbenzamide 1a do not
affect the yield of the corresponding products (2b–2d). In the case of
orthoꢀmethoxy phenyl and pyridyl substituted amides, moderate
2 | J. Name., 2012, 00, 1-3
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iodine radical, eliminates the hydroiodic acid and converts to
intermediate D. Further, D undergoes addition, substitution and
elimination processes (through E and F) in the presence of iodine
and provides the final product 2a.
yields of corresponding products observed (2e and 2f). To extend the
scope of the present transformation, we focused on the various
groups attached to the carbonyl carbon of N−arylethylamides. The
halogen (Br, Cl & F) substituents on the aryl ring irrespective of
their position (either o/m/p) provided the corresponding products in
good yields (2g−2m). Notably, the strong electron withdrawing
groups such as nitro and fluoromethyl substituents at paraꢀposition
of aryl ring afforded corresponding products in 74% and 76% of
yield respectively (2n and 2o). However, the electron donating
substituents (Me and OMe) gave comparatively low yields (2p and
2q). Hetero aromatic amides, such as N−phenethylthiopheneꢀ2ꢀ
carboxamide, N−phenethylpicolinamide, N−phenethylnicotinamide
and N−phenethylisonicotinamide were also reactive under the
optimised conditions and provided moderate yields of corresponding
oxazoles
(2r−2u).
Amides
like
Nꢀ
phenethylcyclohexanecarboxamide and N−phenethylpivolamide
underwent to this procedure smoothly and afford the corresponding
oxazoles in good yield (2v and 2w). Finally the present procedure
has been successfully applied for a variety of substituted aryl rings
containing N−phenethylbenzamides and obtained respective
oxazoles in good yields (2x−2z and 2aa−2ae).Aliphatic amides such
as Nꢀ Octylbenzamide and Nꢀdecylbenzamide afforded low yield of
the desired products 2af, 2ag. As can be seen from the yields and
broad range of substituted products of Table 2, including
heteroaromatic amides and aliphatic amides, the present protocol
indicates its versatile nature.
Scheme 4. Proposed Mechanism
Conclusions
In conclusion, we have developed a new approach for the
synthesis
of
2,
5−disubstitutedoxazoles
employing
N−arylethylamides with the catalytic amount of iodine and TBHP as
an oxidant. Present method is appreciable as it is applicable for wide
range of substrates with variety of functional group tolerance under
metalꢀfree conditions.
Acknowledgements
CSIR−CSMCRI Communication No.063/2015. S.S., D. R. R. and
M. D. are thankful to AcSIR for their Ph. D. enrolment and the
“Analytical Discipline and Centralized Instrumental Facilities” for
providing instrumentation facilities. S. S. and M. D. and D. R. R. are
also thankful to CSIR and UGC New Delhi, India for their
fellowships. We thank DST, Government of India (SR/S1/OCꢀ
13/2011), for financial support and CSIR−CSMCRI (OLP−0076) for
partial assistance.
Scheme 3 Mechanistic Experiments
Notes and references
To understand the mechanistic path of present transformation we
performed some control experiments, in presences of TEMPO as a
radical scavenger under the optimised conditions, no desired product
was observed and starting material 80 % recovered. But the expected
intermediate 3 was detected in the reaction mixture by HRMS
(supporting information S52). It indicates that, the reaction may
proceed through a radical pathway. In the case of N−methylꢀNꢀ
phenethylbenzamide, 75 % of starting substrate was recovered
(Scheme 3 (eqn. 2)). Further it represents that, free N−H is essential
1
(a) Oxazoles: Synthesis, Reactions and Spectroscopy, Part B, Vol. 60,
(Ed.:D. C. Palmer), John Wiley and Sons, Hoboken, NJ, 2004; (b) E.
Riego, D. Hernandez, F. Albericio and M. Alvarez, Synthesis, 2005,
1907; (c) D. W. Knight, Oxazole and its Derivatives, in:Heterocycles in
Natural Product Synthesis, (Eds.: K.C.Majumdar, S. K. Chattopadhyay),
WileyꢀVCH, Weinheim, 2011.
2
3
For reviews, see: (a) Z. Jin, Nat. Prod. Rep., 2011, 28, 1143; (b) Z. Jin,
Nat. Prod. Rep., 2013,30, 869; (c) M. V. Metelev, D. A. Ghilarov,
Mol.Biol., 2014, 48, 29; (d) P. Comba, N. Dovalil, L. R. Ghan, G. R.
Hanson and M. Westphal, Dalton Trans., 2014, 43,1935; (e) B. Axelrod
and J. R. Belzile, J. Org. Chem., 1958, 23, 919.
(a) J. Linder, T. P. Garner, H. E. L. Williams, M. S. Searle and C. J.
Moody, J. Am. Chem. Soc. 2011., 133, 1044; (b) T. Doi, M. Yoshida, K.
Shinꢀya, T. Takahashi, Org. Lett., 2006, 8, 4165.
for this transformation.
On the basis of the above observations and the literature reports,14b,17
a plausible mechanism has been proposed (Scheme 4). Initially the
reaction of 1a with iodine generates corresponding N−iodo
intermediate A, it undergoes homolytic cleavage in the presence of
peroxide and subsequently it generates another intermediate B.
Through its 1, 5 proton shift forms C, which in the presence of
4
5
M. Lachia, C. J. Moody, Nat. Prod. Rep., 2008, 25, 227.
(a) Y. Momose, T. Maekawa, T. Yamano, M. Kawada, H. Odaka, H.
Ikeda and T. Sohda, J. Med. Chem., 2002, 45, 1518; (b) I. E. Andersson,
T. Batsalova, B. Dzhambazov, L. Edvinsson, R. Holmdahl, J. Kihlberg
and A. Linusson, Org. Biomol. Chem., 2010, 8, 2931; (c) P. Raval, M.
This journal is © The Royal Society of Chemistry 20xx
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Jain, A. Goswami, S. Basu, A. Gite, A. Godha, H. Pingali, S. Raval, S.
Giri, D. Suthar, M. Shah and P. Patel, Bioorg. Med. Chem. Lett., 2011,
21, 3103; (d) W. S. Yang, K. Shimada, D. Delva, M. Patel, E. Ode, R.
Skouta and B. R. Stockwell, ACS Med. Chem. Lett., 2012, 3, 35. (e) M.
Rusch, S. Zahov, I. R.Vetter, M. Lehr and C. Hedberg, Bioorg. Med.
Chem., 2012, 20, 1100; (f) X. Lu, X. Liu, B. Wan, S. G. Franzblau, L.
Chen, C. Zhou and Q. You, Eur. J. Med. Chem., 2012, 49, 164; (g) J.
D. R. Kronenthal, J. Singh, P. D. Pansegrau and R. H. Mueller,
Tetrahedron Lett., 1992, 33, 7835. (c) S. K. Chattopadhyay, J. Kempson,
A. McNeil, G. Pattenden, M. Reader, D. E. Rippon and D. Waite, J.
Chem. Soc. Perkin Trans. 1., 2000, 2415; (d) K. Schuh, and F.Glorius,
Synthesis, 2007, 15, 2297. (ii) C−S bond: (a) N. C. Misra, H. Ila, J. Org.
Chem., 2010, 75, 5195; (b) S. Vijay Kumar, B. Saraiah, N. C. Misra, and
H. Ila. J. Org. Chem., 2012, 77, 10752.
Zhou, J. Jin, Y. Zhang, Y. Yin, X. Chen, B. Xu, Eur. J. Med. Chem., 13 (a) R. Martin, A. Cuenca, and S. L. Buchwald, Org. Lett. 2007, 9, 5521;
2013, 68, 222; (h) M. J. Choi, E. S. No, D. A. Thorat, J. W. Jang, H.
Yang, J. Lee, H. Choo, S. J. Kim, J. Lee, H. Choo, S. J. Kim, C. S. Lee,
S.Y. Ko, J. Lee, G. Nam and A.N. Pae, J. Med. Chem., 2013, 56, 9008;
(i) R. E. Thompson, F. Collin, A. Maxwell, K. A. Jolliffe and R. J.
Payne, Org. Biomol. Chem., 2014, 12, 1570.
(a) Q. Zhao, S. Liu, Y. Li and Q. Wang, J. Agric. Food Chem., 2009, 57,
2849; (b) P. Guo, J.ꢀH. Huang, Q.ꢀC. Huang, X.ꢀH. Qian, Chin.Chem.
Lett., 2013, 24, 957.
(b) H. Zhou, W. ꢀJ. Chung, Y. ꢀH. Xu and T. ꢀP. Loh, Chem. Commun.,
2009, 3472; (c) L. Yang, C. ꢀH. Lei, D. ꢀX. Wang, Z. ꢀT. Huang, M. ꢀX.
Wang, Org. Lett., 2010, 12, 3918. (d) Y. ꢀH. Xu, Y. K. Chok and T. ꢀP.
Loh, Chem. Sci., 2011, 2, 1822; (e) T. Besset, N. Kuhl, F. W. Patureau
and F. Glorius, Chem. Eur. J., 2011, 17, 7167; (f) H. ꢀJ. Zhang, and C.
Bolm, Org. Lett., 2011, 13, 3900; (g) K. D. Hesp, R. G. Bergman, J. A.
Ellman, J. Am. Chem. Soc., 2011, 133, 11430; (h) A. E. Wendlandt, S. S.
Stahl, Org. Biomol. Chem., 2012, 10, 3866; ( i) C. W. Cheung and S. L.
Buchwald, J. Org. Chem., 2012, 77, 7526.
6
7
(a) R. Y. Iliashenko, N. Y. Gorobets and A. O. Doroshenko, Tetrahedron
Lett., 2011, 52, 5086; (b) F. MahuteauꢀBetzer and S. Piguel, Tetrahedron 14 (a) M. Dinda, S. Samanta, S. Eringathodi and P. K. Ghosh, RSC Adv.,
Lett., 2013, 54, 3188; (c) J. Min, J. W. Lee, Y.ꢀH. Ahn and Y.ꢀT. Chang,
J. Comb. Chem., 2007, 9, 1079.
(a) R. L. Beyer, Y. Singh and D. P. Fairlie, Org. Lett., 2008, 10, 3481; (b)
2014, 4, 12252; (b) S. R. Bathula, M. P. Reddy, K. K. Durga Rao
Viswanadham, P. Sathyanarayana, and M. S. Reddy, Eur. J. Org. Chem.,
2013, 4552.
8
9
J. J. Intemann, E. S. Hellerich, B. C. Tlach, M. D. Ewan, C. A. Barnes, 15 (a). C. Hempel, B. J. Nachtsheim, Synlett., 2013, 24, 2119; (b) H. A.
A. Bhuwalka, M. Cai, J. Shinar, R. Shinar and M. JeffriesꢀEl,
Macromolecules., 2012, 45, 6888; (c) O. Grotkopp, A. Ahmad, W. Frank
and T. J. Muller, Org. Biomol. Chem., 2011, 9, 8130.
Samimi and S. Mohammadi, Synlett., 2013, 24, 223; (c). Y. Zheng, X.
Li, C. Ren, D. ZhangꢀNegrerie, Y. Du, K. Zhao, J. Org. Chem., 2012, 77,
10353; (d) H. Jiang, H. Huang, H. Cao, C. Qi, Org. Lett., 2010, 12, 5561;
(e) N. Yasmin and J. K. Ray, Synlett., 2009, 2825; (f). Y. ꢀM. Pan, F. ꢀJ.
Zheng, H. ꢀX. Lin, Z. ꢀP. Zhan, J. Org. Chem., 2009, 74, 3148; (g) K.
Murai, Y. Takahara, T. Matsushita, H. Komatsu and H. Fujioka, Org.
Lett., 2010, 12, 3456; (h) J. F. SanzꢀCervera, R. Blasco, J. Piera, M.
Cynamon, I. Ibáñez, M. Murguía and S. Fustero, J. Org. Chem., 2009,
74, 8988; (i) Q. ꢀH. Gao, Z. Fei, Y. ꢀP. Zhu, M. Lian, F. –C. Jia, M. ꢀC.
Liu, N. –F. She and A. –X. Wu, Tetrahydron., 2013, 69, 22.
(a) J. Mazuela, A.Paptchikhine, O. Pamies, P. G. Andersson and M.
Diéguez, Chem. Eur. J., 2010, 16, 4567; (b) J. Mazuela, P. Tolstoy, O.
Pàmies, P. G. Andersson and M. Diéguez, Org. Biomol. Chem., 2011, 9,
941.
10 See for two component reactions for the synthesis of oxazoles (a) W. He,
C. Li and L. Zhang, J. Am. Chem. Soc., 2011, 133, 8482; (b) I. Cano, E.
Álvarez, M. C. Nicasio and P. J. Perez, J. Am. Chem. Soc., 2011, 133,
191; (c) J. Xie, H. Jiang, Y.Cheng and C. Zhu, Chem. Commun.. 2012, 16 (a) D. C. Mohan, R. R. Donthiri, S. N. Rao and S. Adimurthy, Adv.
48, 979; (d) W. ꢀJ. Xue, Q. Li, Y.ꢀP. Zhu, J. ꢀG. Wang and A. ꢀX. Wu,
Chem.Commun., 012, 48, 3485; (e) M. Zheng, L. Huang, H. Huang, X.
Li, W. Wu, and H. Jian Org. Lett., 2014, 16, 5906; (f) Y. Bai, W. Chen,
Y. Chen, H. Huang, F. Xiao and G. ꢀJ. Deng, RSC Adv., 2015, 5, 8002;
(g) J. L. Bailey and R. R. Sudini, Tetrahedron Lett., 2014, 55, 367.;(h)
P. Hu, Q.Wang, Y. Yan, S. Zhang, B. Zhang and Z.Wang, Org. Biomol.
Chem., 2013, 11, 4304; (i) C. Wan, J. Zhang, S. Wang, J. Fan and Z.
Wang., Org. Lett., 2010, 12, 2338; (j) C. Wan, L. Gao, Q. Wang, J.
Zhang and Z. Wang, Org. Lett., 2010, 12, 3902.
Synth. Catal., 2013, 355, 2217; (b). R. R. Donthiri, V Pappula, N. N. K.
Reddy, D.Bairagi, and S. Adimurthy, J. Org. Chem., 2014, 79 ,11277;
(c) D. C. Mohan, S. N. Rao and S. Adimurthy J. Org. Chem., 2013, 78,
1266; (d) D. C. Mohan, Ch. Ravi, S. N. Rao and S. Adimurthy, Org.
Biomol. Chem., 2015, 13, 3556; (e) D. C. Mohan, S. N. Rao, C. Ravi and
S. Adimurthy, Org. Biomol. Chem., DOI: 10.1039/C5OB00381D; (f) R.
D. Patil, G. Joshi and S. Adimurthy, Ind. Eng. Chem. Res., 2010, 49,
8100; (g) S. Samanta, P. Venkatanarayana, D. Milan and S. Adimurthy,
Org. Biomol. Chem., 2014, 12, 9453.
11 (a) I. J. Turchi and M. J. S. Dewar, Chem. Rev., 1975, 75, 389; (b) I. J. 17 See the references in support of mechanism: (a) T. Dohi, N. Takenaga,
Turchi, Ind. Eng.Chem. Prod. Res. Dev., 1981, 20, 32; (c) J. Revuelta, F.
Machetti, S. Cicchi, In Modern Heterocyclic Chemistry; AlvarezꢀBuilla,
J.; Vaquero,J. J.; Barluenga, J., Eds.; WileyꢀVCH Verlag & Co.:
Weinheim,Germany, 2011; Vol. 2. For the recent examples of synthetic
methods to oxazoles, see: (d) B. Shi, A. J. Blake, W. Lewis, I. B.
Campbell, B. D. Judkins and C. J. Moody, J. Org. Chem., 2010, 75, 152;
(e) J. P. Weyrauch, A. S. K. Hashmi, A. Schuster, T. Hengst, S. Schetter,
A. Littmann, M.Rudolph, M. Hamzic, J. Visus, F. Rominger, W. Frey
and J. W. Bats, Chem. Eur. J., 2010, 16, 956.
A. Goto, A. Maruyama and Y. Kita, Org. Lett., 2007, 9, 3129; (b) S.
Guyenne, E. I. León, A. Martín, I. PérezꢀMartín and E. Suárez, J. Org.
Chem., 2012, 77, 7371; (c) L. R. Reddy, B. V. S. Reddy and E. J. Corey,
Org. Lett., 2006, 8, 2819; (d) E. J. Corey and W. R. Hertler, J. Am.
Chem. Soc., 1960, 82, 1657; (e) S. L. Titouania, J. ꢀP. Lavergne, P.
Viallefonta and E. Jacquierb, Tetrahedron, 1980, 36, 2961; (f) S. Tang ,
Y. Wu , W. Liao , R. Bai , C. Liu and A. Lei, Chem. Commun., 2014,
50, 4496.
12 (i) C−Br bond: (a) C. Shin, Y. Sato, H. Sugiyama, K. Nanjo, J.
Yoshimura, Bull. Chem. Soc. Jpn., 1977, 50, 1788; (b) J. Das, J. A. Reid,
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Graphical Abstract
Iodine Catalyzed Intramolecular C(sp3)−H Functionalization: Synthesis
of 2, 5−disubstitutedoxazoles from N−Arylethylamides
Supravath Samantha, Ramachandra Reddy Donthiri, Milan Dinda and Subbarayappa Adimurthy*
Abstract: Iodine catalyzed synthesis of 2, 5
through intramolecular C(sp3)
H functionalization under metal
and is tolerable for wide range of substrates with variety of functional groups.
−
substitutedoxazoles from N
−arylethylamides
−
−free conditions is described