Letter Cite This: Org. Lett. 2018, 20, 7104−7106
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Transition-Metal-Free Arylations of In-Situ Generated Sulfenates with Diaryliodonium Salts Hao Yu, Zhen Li, and Carsten Bolm* Institute of Organic Chemistry, RWTH Aachen University Landoltweg 1, 52074 Aachen, Germany
Org. Lett. 2018.20:7104-7106. Downloaded from pubs.acs.org by UNIV OF SOUTH DAKOTA on 11/16/18. For personal use only.
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ABSTRACT: A transition-metal-free arylation of sulfenate anions generated from β-sulfinyl esters with diaryliodonium salts was developed. In this process, a new C−S bond is formed under mild reaction conditions providing a wide range of S,S-diaryl and S-alkyl S-aryl sulfoxides.
S
ulfoxides are prevalent in natural products1 and have also been applied as active ingredients in pharmaceuticals and crop-protecting agents.2 Furthermore, sulfoxides serve as chiral auxiliaries, ligands for metal complexes, and organocatalysts.3 Due to their importance, extensive research has been devoted to the synthesis of sulfoxides, in particular those with S-aryl groups.4 Along these lines, highly viable synthetic methods based on palladium-catalyzed arylations of sulfenates (RSO−) with aryl halides have emerged (Scheme 1).5 The pioneering
route e)11 and aryl 2-(trimethylsilyl)ethyl sulfoxides12 with CsF (Scheme 1, route f)13 proved applicable, as demonstrated by Perrio and Walsh, respectively. In both reactions the in-situ formed sulfenates underwent palladium-catalyzed cross couplings with aryl halides or triflates to give diaryl sulfoxides and heteroaryl aryl sulfoxides. In light of this background and noting the many advances in the development of transitionmetal-free C−C, C−N, C−O, and C−S bond-forming processes,14 we wondered about a protocol for achieving both sulfenate generation and consecutive aryl sulfoxide formation without the presence of a transition metal catalyst. The realization of this concept is reported here. The key for establishing the new protocol was the use of hypervalent iodine reagents,15,16 which have recently caught significant attention as mild and environmentally benign agents with high reactivity and wide tolerance of diverse functional groups combined with good stability and low toxicity. Among them, diaryliodonium salts are of particular interest, serving as arylating agents in various transformations,17 including transition-metal-free reactions. Here, we used them as an aryl source at room-temperature couplings with in-situ generated sulfenates to give aryl sulfoxides (Scheme 1, route g). The initial reactivity search and subsequent optimization study were carried out using β-sulfinyl ester 1a and diphenyliodonium triflate (2a) as representative substrates. To our disappointment, none of the expected product, p-tolyl phenyl sulfoxide (3aa), was observed in toluene with Cs2CO3 as base (Table 1, entry 1). However, the reaction proceeded well after replacing Cs2CO3 by KOH, providing 3aa in 84% yield (Table 1, entry 2). This result could further be improved by performing the coupling in a 1:1 solvent mixture of toluene and water leading to 3aa in 98% yield (Table 1, entry 3). Under these conditions, NaOH was less effective as base than KOH, and the addition of tetra-n-butylammonium bromide (TBAB) had no apparent impact on the reaction efficiency (Table 1, entries 4 and 5).
Scheme 1. Access to Diaryl Sulfoxides from Sulfenates
work in this field stemmed from Poli, Madec, and co-workers, who realized a smooth generation of the required anions by base-mediated degradation of β-sulfinyl esters6 under biphasic conditions (Scheme 1, route a).7 Alternatively, allyl sulfoxides proved to be suitable sulfenate precursors (Scheme 1, route b).8 In 2013, Nolan and co-workers used a well-defined Pd− NHC complex for the formation of diaryl sulfoxides starting from methyl aryl sulfoxides and aryl bromides or chlorides (Scheme 1, route c).9 In the same year, Walsh and co-workers applied aryl benzyl sulfoxides for palladium-catalyzed preparations of diaryl sulfoxides via the corresponding sulfenates (Scheme 1, route d).10 Furthermore, tert-butyl sulfoxides in combination with K3PO4 at elevated temperature (Scheme 1, © 2018 American Chemical Society
Received: September 24, 2018 Published: October 29, 2018 7104
DOI: 10.1021/acs.orglett.8b03046 Org. Lett. 2018, 20, 7104−7106
Letter
Organic Letters Table 1. Optimization of Reaction Conditionsa
Scheme 3. Substrate Scope: Diaryliodonium Saltsa
entry
base
solvent
additive
yield (%)
1 2 3 4 5
Cs2CO3 KOH KOH NaOH KOH
toluene toluene toluene/H2Ob toluene/H2Ob toluene/H2Ob
TBABc
--84 98 83 98
a
Reaction conditions: 1a (0.20 mmol), 2a (0.22 mmol, 1.1 equiv); for entry 1: Cs2CO3 (0.8 mmol, 4.0 equiv), for entries 2, 3, and 5: KOH (50% aq. 20.0 equiv), and for entry 4: NaOH (30% aq, 20.0 equiv). b Ratio of 1:1. cUse of 1.0 equiv. a Reaction conditions: 1a (0.20 mmol), 2 (0.22 mmol, 1.1 equiv), KOH (50% aq, 20.0 equiv), 1:1 toluene/H2O, at rt under argon for 24 h.
Scheme 2 describes the scope of the arylation reaction with respect to β-sulfinyl esters 1. For S-aryl derivatives, the Scheme 2. Substrate Scope: β-Sulfinyl Estersa
results for p-tert-butyl-containing derivative 3ac, which was isolated in 97% yield. Applying halo-substituted iodine reagents led to slightly lower yields, and thus, sulfoxides 3ae, 3af, and 3ag with p-fluoro, p-chloro, and p-bromo aryl groups were obtained in only 86%, 72%, and 66% yield, respectively. Product 3ah with two methyl substituents in the ortho and para position was isolated in 80% yields. In general, however, the presence of ortho substituents seemed to hamper the reaction as indicated by the moderate yields for 3ai (50%) and 3aj (40%). The aryl transfer from di(2-thienyl) iodonium salt 2k was sluggish providing sulfoxide 3ak in only 19% yield. A mechanistic proposal for the aforereported transitionmetal-free sulfoxide synthesis is presented in Scheme 4. Key Scheme 4. Proposed Mechanism
a Reaction conditions: 1 (0.20 mmol), 2a (0.22 mmol, 1.1 equiv), KOH (50% aq, 20.0 equiv), 1:1 toluene/H2O, at rt under argon for 24 h. bIn parentheses: use of 1.0 mmol of 1a.
substitution pattern of the arene had no apparent influence on the yield of the corresponding sulfoxides. In general, the yields were high to excellent reaching up to 98%, with the exceptions of products 3da, 3ha, and 3la, which were isolated in 82%, 80%, and 82% yield, respectively. Probably, the steric demand of the aryl substituents (o-ethyl, p-tert-butyl, and o-aryl) affected the reaction outcome, although this assumption can be questioned considering the excellent results obtained in the formation of ortho-substituted products 3ca and 3ja (98% yield each). Also, sulfoxides with heteroatom-containing S-aryl groups could be prepared as exemplified by the formation of 3ma and 3na, which were isolated in 98% and 95% yield, respectively. β-Sulfinyl esters with aliphatic S substituents led to sulfoxides in lower yields as observed in the synthesis of Sisopropyl-bearing 3oa (42%) and S-benzyl-substituted 3pa (70%). The scope of this reaction was further examined by testing a range of diaryliodonium salts (Scheme 3). The coupling partner was β-sulfinyl ester 1a. In this series, the yields of the resulting sulfoxides varied significantly (19−97%). Parasubstituted diaryliodonium salts reacted well with the best
steps, which proceed in sequence, are: First, a base-mediated sulfenate formation by retro-Michael reaction of deprotonated β-sulfinyl esters 1. Second, a ligand exchange at the diaryliodonium salt with loss of triflate.18 Third, an aryl− sulfenyl coupling with concomitant elimination of aryl iodide to give the observed product. While every individual step in this reaction path is supported by literature evidence,6−13,18 the structural details of the newly formed iodine(III) intermediate A remain unknown and shall be determined in future work. To conclude, we developed a transition-metal-free sulfoxide synthesis via in-situ generated sulfenates and their coupling with diaryliodonium salts. The reaction conditions are mild, and the functional group tolerance is broad. Considering the accessibility of both reagents, we foresee applications in agricultural and medicinal chemistry. 7105
DOI: 10.1021/acs.orglett.8b03046 Org. Lett. 2018, 20, 7104−7106
Letter
Organic Letters
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2011, 13, 3170. (e) Gelat, F.; Gaumont, A. C.; Perrio, S. J. Sulfur Chem. 2013, 34, 596. (f) Zong, L.; Ban, X.; Kee, C. W.; Tan, C.-H. Angew. Chem., Int. Ed. 2014, 53, 11849. (6) Maitro, G.; Prestat, G.; Madec, D.; Poli, G. J. Org. Chem. 2006, 71, 7449. (7) (a) Maitro, G.; Vogel, S.; Prestat, G.; Madec, D.; Poli, G. Org. Lett. 2006, 8, 5951. (b) Maitro, G.; Vogel, S.; Sadaoui, M.; Prestat, G.; Madec, D.; Poli, G. Org. Lett. 2007, 9, 5493. For selected recent examples of palladium-catalyzed enantioselective arylations of sulfenate anions, see: (c) Jia, T.; Zhang, M.; McCollom, S. P.; Bellomo, A.; Montel, S.; Mao, J.; Dreher, S. D.; Welch, C. J.; Regalado, E. L.; Williamson, R. T.; Manor, B. C.; Tomson, N. C.; Walsh, P. J. J. Am. Chem. Soc. 2017, 139, 8337. (d) Wang, L.; Chen, M.; Zhang, P.; Li, W.; Zhang, J. J. Am. Chem. Soc. 2018, 140, 3467. (8) Bernoud, E.; Le Duc, G.; Bantreil, X.; Prestat, G.; Madec, D.; Poli, G. Org. Lett. 2010, 12, 320. (9) Izquierdo, F.; Chartoire, A.; Nolan, S. P. ACS Catal. 2013, 3, 2190. (10) (a) Jia, T.; Bellomo, A.; Montel, S.; Zhang, M.; El Baina, K.; Zheng, B.; Walsh, P. J. Angew. Chem., Int. Ed. 2014, 53, 260. (b) Jia, T.; Zhang, M.; Sagamanova, I. K.; Wang, C. Y.; Walsh, P. J. Org. Lett. 2015, 17, 1168. (11) Gelat, F.; Lohier, J.-F.; Gaumont, A.-C.; Perrio, S. Adv. Synth. Catal. 2015, 357, 2011. (12) (a) Foucoin, F.; Caupène, C.; Lohier, J. F.; de Oliveira Santos, J. S.; Perrio, S.; Metzner, P. Synthesis 2007, 2007, 1315. (b) Jia, T.; Zhang, M.; Jiang, H.; Wang, C. Y.; Walsh, P. J. J. Am. Chem. Soc. 2015, 137, 13887. (13) Jiang, H.; Jia, T.; Zhang, M.; Walsh, P. J. Org. Lett. 2016, 18, 972. (14) For reviews on transition-metal-free reactions, see: (a) Bhunia, A.; Yetra, S. R.; Biju, A. T. Chem. Soc. Rev. 2012, 41, 3140. (b) Mehta, V. P.; Punji, B. RSC Adv. 2013, 3, 11957. (c) Zhu, C.; Falck, J. R. Adv. Synth. Catal. 2014, 356, 2395. (d) Roscales, S.; Csákÿ, A. G. Chem. Soc. Rev. 2014, 43, 8215. (e) Sun, C.; Shi, Z. Chem. Rev. 2014, 114, 9219. (f) Rossi, R.; Lessi, M.; Manzini, C.; Marianetti, G.; Bellina, F. Adv. Synth. Catal. 2015, 357, 3777. (g) Narayan, R.; Matcha, K.; Antonchick, A. P. Chem. - Eur. J. 2015, 21, 14678. (h) Qin, Y.; Zhu, L.; Luo, S. Chem. Rev. 2017, 117, 9433. (15) For a recent thematic issue on hypervalent iodine compounds, see: Zhdankin, V. V.; Muniz, K. J. Org. Chem. 2017, 82, 11667. (16) For reviews, see: (a) Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2016, 116, 3328. (b) Wang, X.; Studer, A. Acc. Chem. Res. 2017, 50, 1712. (c) Muniz, K. Acc. Chem. Res. 2018, 51, 1507. (d) Li, X.; Chen, P.; Liu, G. Beilstein J. Org. Chem. 2018, 14, 1813. (e) Grelier, G.; Darses, B.; Dauban, P. Beilstein J. Org. Chem. 2018, 14, 1508. (f) Boelke, A.; Finkbeiner, P.; Nachtsheim, B. J. Beilstein J. Org. Chem. 2018, 14, 1263. (g) Ghosh, S.; Pradhan, S.; Chatterjee, I. Beilstein J. Org. Chem. 2018, 14, 1244. (17) For reviews, see: (a) Deprez, N. R.; Sanford, M. S. Inorg. Chem. 2007, 46, 1924. (b) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299. (c) Merritt, E. A.; Olofsson, B. Angew. Chem., Int. Ed. 2009, 48, 9052. (d) Aradi, K.; Tóth, B. L.; Tolnai, G. L.; Novák, Z. Synlett 2016, 27, 1456. (e) Fañanás-Mastral, M. Synthesis 2017, 49, 1905. (18) (a) Dohi, T.; Ito, M.; Yamaoka, N.; Morimoto, K.; Fujioka, H.; Kita, Y. Angew. Chem., Int. Ed. 2010, 49, 3334. (b) Dey, C.; Lindstedt, E.; Olofsson, B. Org. Lett. 2015, 17, 4554.
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b03046. General methods and analytical data including NMR spectra (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Carsten Bolm: 0000-0001-9415-9917 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS H.Y. thanks the China Scholarship Council for a predoctoral stipend. REFERENCES
(1) (a) Suwanborirux, K.; Charupant, K.; Amnuoypol, S.; Pummangura, S.; Kubo, A.; Saito, N. J. Nat. Prod. 2002, 65, 935. (b) Kim, S.; Kubec, R.; Musah, R. A. J. Ethnopharmacol. 2006, 104, 188. (c) Dini, I.; Tenore, G. C.; Dini, A. J. Nat. Prod. 2008, 71, 2036. (d) El-Aasr, M.; Fujiwara, Y.; Takeya, T.; Tsukamoto, S.; Ono, M.; Nakamo, D.; Okawa, M.; Kinjo, J.; Yoshimitsu, H.; Nohara, T. J. Nat. Prod. 2010, 73, 1306. (e) Wyche, T. P.; Piotrowski, J. S.; Hou, Y.; Braun, D.; Deshpande, R.; McIlwain, S.; Ong, I. M.; Myers, C. L.; Guzei, I. A.; Westler, W. M.; Andes, D. R.; Bugni, T. S. Angew. Chem., Int. Ed. 2014, 53, 11583. (f) Nohara, T.; Fujiwara, Y.; Komota, Y.; Kondo, Y.; Saku, T.; Yamaguchi, K.; Komohara, Y.; Takeya, M. Chem. Pharm. Bull. 2015, 63, 117. (2) (a) Block, E. Garlic and Other Alliums; Royal Society of Chemistry: Cambridge, 2009. (b) Nohara, T.; Fujiwara, Y.; El-Aasr, M.; Ikeda, T.; Ono, M.; Nakano, D.; Kinjo, J. Chem. Pharm. Bull. 2017, 65, 209. (c) McKeage, K.; Blick, S. K.; Croxtall, J. D.; LysengWilliamson, K. A.; Keating, G. M. Drugs 2008, 68, 1571. (d) Salgado, V. L.; Schnatterer, S.; Holmes, K. A. Modern Crop Protection Compounds; Krämer, W., Schirmer, U., Eds.; Wiley-VCH: Weinheim, 2007; Vol. 3, Chapter 29.5, p 1048. (e) Schillheim, B.; Jansen, I.; Baum, S.; Beesley, A.; Bolm, C.; Conrath, U. Plant Physiol. 2018, 176, 2395. (3) (a) Mellah, M.; Voituriez, A.; Schulz, E. Chem. Rev. 2007, 107, 5133. (b) Mariz, R.; Luan, X.; Gatti, M.; Linden, A.; Dorta, R. J. Am. Chem. Soc. 2008, 130, 2172. (c) Jiang, C.; Covell, D. J.; Stepan, A. F.; Plummer, M. S.; White, M. C. Org. Lett. 2012, 14, 1386. (d) Trost, B. M.; Rao, M. Angew. Chem., Int. Ed. 2015, 54, 5026. (e) Sipos, G.; Drinkel, E. E.; Dorta, R. Chem. Soc. Rev. 2015, 44, 3834. (f) Otocka, S.; Kwiatkowska, M.; Madalinska, L.; Kielbasinski, P. Chem. Rev. 2017, 117, 4147. (4) (a) Bolm, C. Coord. Chem. Rev. 2003, 237, 245. (b) Legros, J.; Dehli, J. R.; Bolm, C. Adv. Synth. Catal. 2005, 347, 19. (c) Wojaczyńska, E.; Wojaczyński, J. Chem. Rev. 2010, 110, 4303. (d) O’Mahony, G. E.; Kelly, P.; Lawrence, S. E.; Maguire, A. R. ARKIVOC 2011, i, 1. (e) O’Mahony, G. E.; Ford, A.; Maguire, A. R. J. Sulfur Chem. 2013, 34, 301. (f) Zhu, J.; Yang, W.-C.; Wang, X-d.; Wu, L. Adv. Synth. Catal. 2018, 360, 386. (5) For reviews, see: (a) O’Donnell, J. S.; Schwan, A. L. J. Sulfur Chem. 2004, 25, 183. (b) Maitro, G.; Prestat, G.; Madec, D.; Poli, G. Tetrahedron: Asymmetry 2010, 21, 1075. (c) Schwan, A. L.; Söderman, S. C. Phosphorus, Sulfur Silicon Relat. Elem. 2013, 188, 275. For sulfenate anions in enantioselective alkylation, see: (d) Gelat, F.; Jayashankaran, J.; Lohier, J. F.; Gaumont, A. C.; Perrio, S. Org. Lett. 7106
DOI: 10.1021/acs.orglett.8b03046 Org. Lett. 2018, 20, 7104−7106
