View Article Online ChemComm - weizmann.ac.il
Transcript of View Article Online ChemComm - weizmann.ac.il
This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication.
Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the author guidelines.
Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the ethical guidelines, outlined in our author and reviewer resource centre, still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.
Accepted Manuscript
rsc.li/chemcomm
ChemCommChemical Communicationswww.rsc.org/chemcomm
ISSN 1359-7345
COMMUNICATIONMarilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyen et al. Reactivity diff erences of Sc
3N@C
2n (2n = 68 and 80). Synthesis of the
fi rst methanofullerene derivatives of Sc3N@D
5h-C
80
Volume 52 Number 1 4 January 2016 Pages 1–216
ChemCommChemical Communications
View Article OnlineView Journal
This article can be cited before page numbers have been issued, to do this please use: U. K. Das, L.
Shimon and D. Milstein, Chem. Commun., 2017, DOI: 10.1039/C7CC08322J.
Journal Name
COMMUNICATION
This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-‐3 | 1
Please do not adjust margins
Please do not adjust margins
Received 00th January 20xx, Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Imidazoles Synthesis by Transition Metal Free, Base-‐Mediated Deaminative Coupling of Benzylamines and Nitriles Uttam Kumar Das,a Linda J. W. Shimonb and David Milstein*a
A transition metal free, straightforward synthetic method for the preparation of substituted imidazoles is reported herein. Base promoted, deaminative coupling of benzylamines with nitriles results in the one-‐step synthesis of 2,4,5-‐trisubstituted imidazole with liberation of ammonia. This protocol provides a practical strategy for synthesis of valuable imidazole derivatives from readily available starting materials.
N-‐heterocycles are key structural units frequently found in several drugs, dyes, and biologically active molecules used in pharmaceutical and agrochemical industries.1 Among the nitrogen-‐containing heterocyclic compounds, the imidazole motif is of key importance. It is an essential motif in many natural products and in living organisms, and is present in compounds such as histidine, histamine, vitamin B12, pilocarpine alkaloids, nucleic acid bases and biotin.2 Imidazoles have a wide range of applications in the pharmaceutical industry.1a, 3 Noteworthy, some of the compounds have antifungal,4 anticancer,5 antitumor,6 antibacterial,7 antiplasmodium,8 and anti-‐inflammatory.9 properties. In academia and industry the popular classical approach for the synthesis of imidazoles involves traditional cyclocondensation methods (Figure 1, a).10 Most literature reports involve modified condensation methods of carbonyl compounds and ammonium salts.11 In a large number of reports, substituted imidazoles have been prepared via transition metal-‐free methods,12 catalytic C–H activation,13 transition metal catalysis14, and cycloaddition reactions of methylene isocyanides to unsaturated bonds15. In 2011, García et. al. reported nickel catalyzed hydrogenative coupling of aromatic nitriles to form 2,4,5-‐trisubstituted imidazoles (Figure 1, b).16
Figure 1. Strategies for synthesis of substituted imidazoles (a, b); coupling of nitriles and amines (c); this work (d). While synthetically useful, several of these methods suffer from drawbacks such as low yields, low selectivity, harsh conditions, multi-‐step synthetic operations, and tedious isolation procedures.11b, 12c, d, 16b Some of the cases employ noble metal-‐based catalysts which are expensive and rare.14c In this respect, the design of economical, highly efficient, mild and straightforward approaches for imidazole preparation is of prime importance. In general, the development of inexpensive, transition-‐metal-‐free, environmentally benign protocols for organic synthesis and material science is currently an area of much interest.17 Our group has developed recently the hydrogenative coupling of nitriles and amines to give secondary, self-‐coupled imines, as well as cross-‐imines, as major products using Ru-‐PNN18a and Fe-‐PNP18b pincer systems. Coupling of benzylic amines with nitriles generally produces imines, secondary amines, or other adducts (Figure 1, c).18, 19
Page 1 of 4 ChemComm
Che
mC
omm
Acc
epte
dM
anus
crip
t
Publ
ishe
d on
14
Nov
embe
r 20
17. D
ownl
oade
d by
Wei
zman
n In
stitu
te o
f Sc
ienc
e L
ibra
ry o
n 14
/11/
2017
12:
23:5
6.
View Article OnlineDOI: 10.1039/C7CC08322J
COMMUNICATION Journal Name
2 | J. Name., 2012, 00, 1-‐3 This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Please do not adjust margins
Table 1. Optimization study.a
[a] 1 mmol benzylamine (1a), 2 mmols benzonitrile (2a), 1 mmol base and 3 mL solvent were used. [b] G.C yield [c] Yield of isolated product. KHMDS = potassium hexamethyldisilazane. Herein, we report a new, transition metal free, KOtBu promoted intermolecular C-‐C and C-‐N coupling of benzylamines with nitriles to form 2,4,5-‐trisubstituted imidazoles. To our knowledge there is no report on imidazole synthesis by coupling of nitriles and benzylamines. In optimization studies the coupling of benzylamine (1a) with benzonitrile (2a) was chosen as a model reaction. As shown in Table 1, coupling of one equivalent 1a with two equivalents 2a in presence of one equivalent potassium tert-‐butoxide (KOtBu) in 3 mL THF at 110°C, followed by workup with water/EtOAc, resulted in formation of 2,4,5-‐triphenyl-‐1H-‐imidazole (3a) in 85% yield after 8h (Table 1, entry 1). A brief solvent scope examination showed that THF, dioxane and toluene are effective solvents (Table 1). The reaction of 1a with 2a in toluene in the presence of one equivalent of KOtBu at 110°C produced 90% of 2,4,5-‐triphenyl-‐1H-‐imidazole (3a) after 12 h. (Table 1, entry 4). Raising the temperature to 130°C, 3a was obtained in 96% yield after 5 h (Table 1, entry 5). The efficacy of other bases was also studied (entries 6-‐11). Using equivalent amount of KH or KHMDS at 130 °C in toluene, 80% and 86% of 3a was obtained after 5 h, respectively (Table 1, entries 6–7). However, using weaker bases or performing the reaction at room temperature, did not result in any imidazole product (Table 1, entries 9–12). The coupling reaction of benzylamines with nitriles bearing both aliphatic and aromatic substituents, in presence of KOtBu, afforded exclusively 2,4,5-‐trisubstituted imidazoles in high yields (Scheme 1). As shown in scheme 1, coupling of the para-‐substituted benzylamines and benzonitriles proceeds smoothly to selectively afford the corresponding substituted imidazoles in good to excellent 77%−98% isolated yields (Scheme 1, 3a-‐3e).
Scheme 1. Synthesis of 2,4,5-‐trisubstituted imidazoles mediated by KOtBu.a [a] Reaction conditions: benzylic amine (1 mmol), nitrile (2 mmol), KOtBu (1 mmol), toluene (3 mL), 130°C, 5-‐12 hrs. All yields are for isolated products. [#] Yield of gram scale reaction. [*] Yields of tautomeric mixture. [b] Amine and nitrile molar ratio was 1:3. Coupling of benzylamine with benzonitrile gave 2,4,5-‐triphenyl-‐1H-‐imidazole (lophine) in 96% yield (Scheme 1, 3a). 4-‐methyl-‐ benzylamine and 4-‐methoxy-‐benzylamine yielded the imidazole derivatives 3b and 3c in 92% and 98% yield, respectively. However, 4-‐chloro benzylamine and 4-‐fluoro benzylamine produced the imidazoles 3d and 3e in somewhat lower yields, 77% and 82%, respectively, perhaps due to the lower nucleophilicity of the amine. Benzylamine p-‐substituted with the strong electron withdrawing -‐CF3 group was completely inactive under the optimized condition. To further explore the scope of the reaction, various substituted aromatic nitriles were reacted with benzyl amines, giving moderate to excellent isolated yields (71–93%) of the corresponding imidazole products (Scheme 1, 3f-‐3j). 4-‐Methyl-‐
Entry Base Solvent T(°C) T(h) Yield(%)b 1. KOtBu THF 110 8 85 2. KOtBu THF 110 12 90 (86)c 3. KOtBu Dioxane 110 12 80 4. KOtBu Toluene 110 12 91 5. KOtBu Toluene 130 5 98 (96)c 6. KH Toluene 130 5 80 7. KHMDS Toluene 130 5 86 8. KHMDS Toluene 130 12 90 9. NaOEt Toluene 130 12 -‐ 10. KOH THF 130 12 -‐ 11. NaOH Toluene 130 12 -‐ 12. KOtBu Toluene 25 36 -‐ 13. KOtBu MeOH 65 24 -‐ 14. KOtBu DCM 65 12 -‐ 15. KOtBu Benzene 100 12 65
Page 2 of 4ChemComm
Che
mC
omm
Acc
epte
dM
anus
crip
t
Publ
ishe
d on
14
Nov
embe
r 20
17. D
ownl
oade
d by
Wei
zman
n In
stitu
te o
f Sc
ienc
e L
ibra
ry o
n 14
/11/
2017
12:
23:5
6.
View Article OnlineDOI: 10.1039/C7CC08322J
Journal Name COMMUNICATION
This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-‐3 | 3
Please do not adjust margins
Please do not adjust margins
benzonitrile and 4-‐methoxy-‐benzonitrile gave nearly identical yields in the reactions with benzylamine (3f and 3g). Coupling of 4-‐tert-‐butoxy benzonitrile with benzylamine gave 79% of the corresponding imidazole (3h). The coupling reaction scope with respect to aliphatic nitriles was also examined. Isobutyronitrile (2e) was coupled with benzylamine in presence of KOtBu at 130°C overnight in good yield. The imidazole product, 2,4(5)-‐diisopropyl-‐5(4)-‐phenyl-‐1H-‐imidazole (3i) was isolated in 95% yield and was structurally characterized by single-‐crystal X ray crystallography (Figure 2). As expected, cyclohexanecarbonitrile (2f) followed the same trend and produced 2,4(5)-‐dicyclohexyl-‐5(4)-‐phenyl-‐1H-‐imidazole (3j) in 85% yield. The bulkier nitriles like 3,4-‐dimethoxynitrile and naphthalene-‐2-‐carbonitrile were also coupled with benzylamine to produce tri-‐substituted imidazoles in good yields (3n and 3o). The yields of all products shown in Scheme 1 are for the pure products as judged by NMR spectroscopy. Except for 3a, 3k and 3l all products are present as a mixture of tautomer. However, reactions of secondary amines or aliphatic amines with benzonitrile were not successful under the standard conditions at present. We have observed that 4-‐fluorobenzonitrile undergoes fluoride substitution reaction with KOtBu in toluene at 130 °C to form 4-‐(tert-‐butoxy) benzonitrile in 95% yield.20 However, we got compound 3h in 71% isolated yield from the reaction of benzylamine with 4-‐fluoro-‐benzonitrile in the presence of 3.5 equivalent of KOtBu. Following the same procedure, we isolated 2.63 g (89%) of 2,4,5-‐triphenyle imidazole (Scheme 1, 3a#) from a gram scale reaction between 1.07 g of benzylamine and 2.06 g of benzonitrile in presence of 1.11 g of KOtBu in a 100mL pressure tube using 20 mL of toluene. Figure 2. Molecular structure of 2,5-‐diisopropyl-‐4-‐phenyl-‐1H-‐imidazole (3i). Thermal ellipsoids are drawn at 50% probability. Selected hydrogen atoms are omitted for clarity (see Supporting Information). We were interested in the mechanism of formation of the tri-‐substituted imidazole products (3) by coupling of amines and nitriles (Scheme 2). Direct addition of benzylamine to benzonitrile, forming N-‐benzylbenzimidamide (A) as intermediate is expected. Such a transformation was reported.19c, d, 21 Our observation that secondary benzyl amines do not react suggests that the addition to the nitrile is inhibited by N-‐substitution of the amine. In support of the
intermediacy of (A), reaction of N-‐benzylbenzimidamide (A) and benzonitrile under the same reaction conditions resulted in 93% yield of the desired 2,4,5-‐triphenyl-‐1H-‐imidazole (3a) (Scheme 3, eq. 1). We also observed that, aliphatic amines are unreactive towards this coupling reaction, hence the benzylic-‐CH2 is essential in this imidazole synthesis.17h Compound A reacts in presence of a strong base with the nitrile leading to C-‐C bond formation at the benzylic carbon, liberating ammonia to effectively afford the potassium salt of trisubstituted imidazole product (B). This potassium salt (B) precipitated from the solution and was characterized by 1H MNR spectroscopy in DMSO-‐d6. Formation of KOtBu in solution was confirmed by GC-‐MS. The salt B is converted to pure 3 after workup with water (see Supporting Information). Noteworthy, addition of the radical scavengers galvinoxyl or TEMPO resulted in no noticeable effect on the yield of 3a (Scheme 3, eq. 2). This indicates that radical intermediates are not involved in this base-‐mediated imidazole formation reaction. Scheme 2. Plausible mechanism of the substituted imidazole synthesis by coupling of benzyl amines and nitriles. Scheme 3. Mechanistic experiments. In conclusion, we have developed a base-‐mediated, transition metal free, novel synthetic methodology of substituted imidazoles by coupling of readily available benzyl amines and nitriles. The reaction is promoted by KOtBu and liberates NH3. We believe that this step-‐economical, straightforward and easy to handle methodology for the synthesis of 2,4,5-‐trisubstituted imidazoles has significant synthetic potential. We acknowledge the European Research Council (ERC AdG 692775) support of this research. U. K. D is thankful to The Science & Engineering Research Board (SERB), DST, and Govt. of India for the SERB Overseas Postdoctoral Fellowship.
Page 3 of 4 ChemComm
Che
mC
omm
Acc
epte
dM
anus
crip
t
Publ
ishe
d on
14
Nov
embe
r 20
17. D
ownl
oade
d by
Wei
zman
n In
stitu
te o
f Sc
ienc
e L
ibra
ry o
n 14
/11/
2017
12:
23:5
6.
View Article OnlineDOI: 10.1039/C7CC08322J
COMMUNICATION Journal Name
4 | J. Name., 2012, 00, 1-‐3 This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins
Please do not adjust margins
Conflicts of interest There are no conflicts to declare.
References 1 (a) B. Cui, B. L. Zheng, K. He and Q. Y. Zheng, J. Nat. Prod., 2003, 66,
1101; (b) S. Tsukamoto, T. Kawabata, H. Kato, T. Ohta, H. Rotinsulu, R. E. P. Mangindaan, R. W. M. Van Soest, K. Ukai, H. Kobayashi and M. Namikoshi, J. Nat. Prod., 2007, 70, 1658; (c) J. Zhong, Nat. Prod. Rep., 2009, 26, 382; (d) M. Roue, I. Domart-‐ Coulon, A. Ereskovsky, C. Djediat, T. Perez and M. L. Bourguet-‐Kondracki, J. Nat. Prod., 2010, 73, 1277; (e) L. Zhang, X. M. Peng, G. L. Damu, R. X. Geng and C. H. Zhou, Med. Res. Rev., 2014, 34, 340.
2 (a) V. Kumar, M. P. Mahajan, Heterocycles in Natural Product Synthesis, ed. K. C. Majumdar, and S. K. Chattopadhyay, Wiley-‐VCH, Weinheim, 2011, pp. 507–533; (b) S. Arshadi, A. R. Bekhradnia and A. Ebrahimnejad, Can. J. Chem., 2011, 89, 1403; (c) S. N. Azizi, P. Shakeri, M. J. Chaichi, A. Bekhradnia, M. Taghavi and M. Ghaemy, Spectrochim. Acta, Part A, 2014, 122, 482; (d) G. K Gupta, V. Kumar and K. Kaur, Nat. Prod. J., 2014, 4, 73.
3 (a) B. Forte, B. Malgesini, C. Piutti, F. Quartieri, A. Scolaro and G. Papeo, Mar. Drugs, 2009, 7, 705;(b) K. Bonezzi, G. Taraboletti, P. Borsotti, F. Bellina, R. Rossi and R. Giavazzi, J. Med. Chem., 2009, 52, 9606; (c) J. Dietrich, V. Gokhale, X. Wang, L. H. Hurley and G. A. Flynn, Bioorg. Med. Chem. 2010, 18, 292; (d) A. Bhatnagar, P. K. Sharma and N. Kumar, Int. J. Pharm Tech Res., 2011, 3, 268; (e) B. Sadek, Pharma Chem., 2011, 3, 410;(f) S. N. Riduan and Y. Zhang, Chem. Soc. Rev., 2013, 42, 9055; (g) C. H. Jin, M. Krishnaiah, D. Sreenu, V. B. Subrahmanyam, K. S. Rao, H. J. Lee, S. J. Park, K. Lee, Y. Y. Sheen and D. K. Kim, J. Med. Chem., 2014, 57, 4213; (h) E. Vessally, S. Soleimani-‐Amiri, A. Hosseinian, L. Edjlalid and A. Bekhradnia, RSC Adv., 2017, 7, 7079.
4 (a) D. J. Wolff, G. A. Datto and R. A. Samatovicz, J. Biol. Chem. 1993, 268, 9430; (b) N. Sennequier, D. Wolan and D. J. Stuehr, J. Biol. Chem., 1999, 274, 930; (c) H. Koga, Y. Nanjoh, K. Makimura and R. Tsuboi, Med. Mycol., 2009, 47, 640; (d) V. Zoete, O. Michielin, U. F. Rohrig, S. R. Majjigapu, M. Chambon, S. Bron and L. Pilotte, Eur. J. Med. Chem., 2014, 84, 284.
5 (a) S. Baroniya, Z. Anwer, P. K. Sharma, R. Dudhe and N. Kumar, Der Pharmacia Sinica, 2010, 1, 172; (b) E. M. Perchellet, J. –P. Perchellet and P. W. Baures, J. Med. Chem., 2005, 48, 5955.
6 (a) M. Fukui, M. Inaba, S. Tsukagoshi and Y. Sakurai, Cancer Res., 1982, 42, 1098; (b) G. J. Atwell, J. Fan, K. Tan and W. A. Denny, J. Med. Chem., 1998, 41, 4744; (c) S. Y. Al-‐Raqa, A. M. S. ElSharief, S. E. Khalil and A. M. Al-‐Amri, Heteroat. Chem., 2006, 7, 643.
7 (a) A. Vijesh, A. M. Isloor, S. Telkar, S. Peethambar, S. Rai and N. Isloor, Eur. J. Med. Chem., 2011, 46, 3531. (b) W. R. Roush, J. Y. Choi, M. S. Plummer, J. Starr, C. R. Desbonnet, H. Soutter and J. Chang, J. Med. Chem., 2012, 55, 852; (c) L. Yurttaş, M. Duran, Ş. Demirayak, H. K. Gençer and Y. Tunalı, Bioorg. Med. Chem. Lett., 2013, 23, 6764.
8 J. Z. Vlahakis, C. Lazar, I. E. Crandall and W. A. Szarek, Bioorg. Med. Chem., 2010, 18, 6184.
9 (a) J. C. Lee, J. T. Laydon and P. C. Mcdonnell, Nature, 1994, 372, 739; (b) J. L. Adams, J. C. Boehm, T. F. Gallagher, S. Kassis, E. F. Webb, R. Hall, M. Sorenson, R. Garigipati, D. E. Griswoldc and J. C. Lee, Bioorg. Med. Chem. Lett., 2001, 11, 2867.
10 (a) H. Debus, Justus Liebigs Ann. Chem., 1858, 107, 199. (b) B. Radzisewski, Chem. Ber., 1882, 15, 2706. (c) T. Benincori, E. Brenna and F. J. Sannicolo, Chem. Soc., Perkin Trans., 1, 1993, 675. (d) W. Marckwald, Chem. Ber., 1892, 25, 2359. (e) A. M. Vanleusen, J. Wildeman and O. Oldenziel, J. Org. Chem., 1977, 42, 1153.
11 (a) D. F. Frantz, L. Morency, A. Soheili, J. A. Murry, E. J. J. Grabowski and R. D. Tillyer, Org. Lett., 2004, 6, 843; (b) S. Zaman, K. Mitsuru and A. D. Abell, Org. Lett., 2005, 7, 609. (c) K. Illgen, S. Nerdinger, D. Behnke and C. Friedrich, Org. Lett., 2005, 7, 39; (d) S. A. Siddiqui, U. C. Narkhede, S. S. Palimkar, T. Daniel, R. J. Lahoti and K. V.
Srinivasan, Tetrahedron, 2005, 61, 3539; (e) V. Zuliani, G. Cocconcelli, M. Fantini, C. Ghiron and M. Rivara, J. Org. Chem., 2007, 72, 4551; (f) G. Bratulescu, Synthesis, 2009, 2319. (g) M. Adib, S. Ansari, S. Feizi, J. A. Damavandi and P. Mirzaei, Synlett, 2009, 3263; (h) T. S. Chundawat, N. Sharma, P. Kumari and S. Bhagat, Synlett, 2016, 27, 404.
12 (a) C. Kison and T. Opatz, Chem. -‐Eur. J. 2009, 15, 843; (b) C. Chen, W. Hu, P. Yan and G. C. Senadi, J. Wang, Org. Lett., 2013, 15, 6116; (c) S. Pusch and T. Opatz, Org. Lett., 2014, 16, 5430; (d) L. Xiang, Y. Niu, X. Pang, X. Yang and R. Yan, Chem. Commun., 2015, 51, 6598; (e) S. Aly, M. Romashko and B. A. Arndtsen, J. Org. Chem., 2015, 80, 2709; (f) X. Zhang, P. Wu, Y. Fu, F. Zhang and B. Chen, Tetrahedron Letters, 2017, 58, 870; (g) X. Zhou, H. Ma, C. Shi, Y. Zhang, X. -‐X. Liu and G. Huang, Eur. J. Org. Chem., 2017, 237.
13 (a) K. L. Tan, R. G. Bergman and J. A. Ellman, J. Am. Chem. Soc., 2001, 123, 2685; (b) Y. Fukumoto, K. Sawada, M. Hagaihara, N. Chatani and S. Murai, Angew. Chem. Int. Ed., 2002, 41, 2779; (c) B. Sezen and D. Sames, J. Am. Chem. Soc., 2003, 125, 10580.
14 (a) D. Tang, P. Wu, X. Liu, Y. X. Chen, S. B. Buo, W. L. Chen, J. G. Li and B.-‐H. Chen, J. Org. Chem., 2013, 78, 2746; (b) S. Mitra, A. K. Bagdi, A. Majee and A. Hajra, Tetrahedron Lett., 2013, 54, 4982; (c) H. Hong, Y. Shao, L. Zhang and X. Zhou, Chem. -‐Eur. J., 2014, 20, 8551; (d) T. Kumar, D. Verma, R. F. S. Menna-‐ Barreto, R. F. S.; W. O. Valenca, E. N. da Silva Junior and I. N. N. Namboothiri, Org. Biomol. Chem., 2015, 13, 1996; (e) Y. Zhu, C. Li, J. Zhang, M. She, W. Sun, K. Wan, Y. Wang, B. Yin, P. Liu and J. Li, Org. Lett., 2015, 17, 3872.
15 (a) C. Kanazawa, S. Kamijo and Y. Yamamoto, J. Am. Chem. Soc., 2006, 128, 10662; (b) B. Pooi, L. Lee, K. Choi, H. Hirao and S. H. Hong, J. Org. Chem., 2014, 79, 9231; (c) X.Huang, X. Cong, P. Mi and X. Bi, Chem. Commun., 2017, 53, 3858.
16 (a) J. J. García, P. Zerecero-‐Silva, G. Reyes-‐Rios, M. G. Crestani, A. Arévalo and R. Barrios-‐Francisco, Chem. Commun. 2011, 47, 10121; (b) A. Tlahuext-‐Aca, O. Hernández-‐Fajardo, A. Arévalo and J. J. García, Dalton Trans. 2014, 43, 15997.
17 (a) W. Liu, H. Cao, H. Zhang, H. Zhang, K. H. Chung, C. He, H. Wang, F. Y. Kwong and A. Lei, J. Am. Chem. Soc., 2010, 132, 16737; (b) T. Truong, and O. Daugulis, J. Am. Chem. Soc., 2011, 133, 4243; (c) J. H. Kim, J. Kim, S. H. Cho and S. Chang, J. Am. Chem. Soc., 2011, 133, 16382; (d) C.–L. Sun and Z.–J. Shi, Chem. Rev., 2014, 114, 9219; (e) A. Yadav, A. Verma, S. Patel, A. Kumar, V. Rathore, Meenakshi, S. Kumar and S Kumar, Chem. Commun., 2015, 51, 11658; (f) A. A. Toutov, W.-‐B. Liu, K. N. Betz, A. Fedorov, B. M. Stoltz and R. H. Grubbs, Nature, 2015, 518, 80; (g) J. Chen and J. Wu, Angew. Chem. Int. Ed., 2017, 56, 3951; (h) M. Li, O. Gutierrez, S. Berritt, A. Pascual-‐Escudero, A. Yeşilçimen, X. Yang, J. Adrio, G. Huang, E. Nakamaru-‐Ogiso, M. C. Kozlowski and P. J. Walsh, Nat. Chem., 2017, doi:10.1038/nchem.2760.
18 (a) D. Srimani, M. Feller, Y. Ben-‐David and D. Milstein, Chem. Commun., 2012, 48, 11853; (b) S. Chakraborty, G. Leitus and D. Milstein, Angew. Chem. Int. Ed., 2017, 56, 2074.
19 (a) N. Habersaat, R. Fröhlich and E. -‐U. Würthwein, Eur. J. Org. Chem., 2004, 2567; (b) J. Kuang, B. Chena and S. Ma, Org. Chem. Front., 2014, 1, 186; (c) P. Debnath, M. Baeten, N. Lefevre, S. Van Daele and B. U. W. Maes, Adv. Synth. Catal., 2015, 357, 197; (d) S. D. Veer, K. V. Katkar and K. G. Akamanchi, Tetrahedron Let., 2016, 57, 4039.
20 (a) E. S. Childress, Y. Kharel, A. M. Brown, D. R. Bevan, K.R. Lynch and W. L. Santos, J. Med. Chem., 2017, 60, 3933.
21 (a) P. Debnath and K. C. Majumdar, Tetrahedron Let., 2014, 55, 6976; (b) B. Morel, P. Franck, J. Bidange, S. Sergeyev, D.A. Smith, J. D. Moseley and B. U. W. Maes, ChemSusChem, 2017, 10, 624.
Page 4 of 4ChemComm
Che
mC
omm
Acc
epte
dM
anus
crip
t
Publ
ishe
d on
14
Nov
embe
r 20
17. D
ownl
oade
d by
Wei
zman
n In
stitu
te o
f Sc
ienc
e L
ibra
ry o
n 14
/11/
2017
12:
23:5
6.
View Article OnlineDOI: 10.1039/C7CC08322J