Stereoconvergent Chiral Inductive Diastereodivergent

Letter Cite This: Org. Lett. 2018, 20, 7057−7061

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Stereoconvergent Chiral Inductive Diastereodivergent Sulfonamidation of Diastereomixtures of Diarylmethanols with Sulfonylamine Catalyzed by Lewis Acids Hiroshi Yamamoto and Kenya Nakata* Department of Chemistry, Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu Matsue, Shimane 690-8504, Japan

Org. Lett. 2018.20:7057-7061. Downloaded from pubs.acs.org by UNIV PARIS-SUD on 11/16/18. For personal use only.

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ABSTRACT: Diastereodivergent sulfonamidation of diastereomixtures of diarylmethanols bearing a chiral auxiliary using a sulfonylamine was achieved by use of SnCl2 and FeCl3 as the Lewis acid catalysts in nitromethane under mild reaction conditions. Both reaction conditions were applicable to a broad substrate scope, irrespective of the substituents on the aromatic ring of the substrates. The nosyl group and the chiral auxiliary were easily deprotected under the general conditions without any erosion of chirality.

D

Scheme 1. (a) Related Previous Study, (b) Our Previous Study, and (c) This Study

irect dehydrative substitution of alcohols with nucleophiles catalyzed by Lewis acids and Brønsted acids has been widely employed in organic synthesis.1 Since the hydroxyl group is used without transformation into a good leaving group in the reaction, the atom efficiency of the reaction is excellent. Water is ideally the only byproduct, which makes the protocol environmentally friendly. As an example of this class of reactions, sulfonylamidation reaction has recently garnered research interest because sulfonylamide is not only used as a common protective group of amines2 but also frequently encountered in biologically active compounds.3 Thus, various reactions of diarylmethanol 1 with sulfonylamines have so far been reported using Lewis acids,4 Brønsted acids,5 and boric acid/oxalic acid systems6 as catalysts (Scheme 1a). However, since almost all previously reported reactions proceed in an SN1 manner via a carbocation intermediate, expanding this reaction to its asymmetric version is still challenging. Given such research background, we have recently achieved the Lewis acid catalyzed chiral inductive diastereoconvergent reactions of diastereomixtures of diarylmethanol 3, bearing a designed chiral auxiliary, with 2-naphthol derivatives7 or allyltrimethylsilane8 (Scheme 1b). Therefore, herein we attempted to apply sulfonylamines as a nucleophilic agent for extending the reaction to the asymmetric version (Scheme 1c). To the best of our knowledge, this is the first report of a chiral-auxiliarycontrolled stereoconvergent-type diastereodivergent sulfonamidation with sulfonylamines using different Lewis acid catalysts. In order to optimize the reaction conditions, we chose to sulfonamidate the diarylmethanol 3a,7 bearing a designed chiral auxiliary, with p-toluenesulfonamide (p-TsNH2) in MeNO2 at room temperature for 1 h as our model reaction, © 2018 American Chemical Society

and we examined the type of Lewis acid catalyst and the catalyst loading that gave the best results (Table 1). Since SnBr4 had already been reported to function as an efficient Lewis acid catalyst for our related previous study,7 we first performed the reaction using 5 mol % of SnBr4. The reaction Received: September 19, 2018 Published: October 31, 2018 7057

DOI: 10.1021/acs.orglett.8b03008 Org. Lett. 2018, 20, 7057−7061

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substrates under both conditions (Table 2). We first carried out the reaction of 3 under conditions A (entries a1−a19). The reactions of 3b−3d bearing a methyl group at the ortho-, meta-, and para-positions on the aromatic rings of the substrates gave results similar to those for entry a1, irrespective of the substituent position (entries a2−a4). For the reactions of 3e−3g bearing a methoxy substituent, though the reaction of 3f with a meta-methoxy group proceeded smoothly after 1 h to furnish 5Af in 93% yield with 97:3 dr (entry a7), the reactions of the ortho- and para-substituted compounds 3e and 3g gave complex mixtures or low selectivity. Because the corresponding quinone methide carbocation intermediate7 was probably generated in situ, the reactivity was enhanced, and the assumed chelation effect of the chiral auxiliary was inhibited, reducing the stereoselectivity of the process (entries a5 and a8). Thus, when the reactions were performed at a lower temperature (0 °C) to control the reactivity, the reaction of the ortho-substituted compound 3e gave the desired compound 5Ae with low selectivity (entry a6), while the para-substituted compound 3g afforded 5Ag in high yield with good selectivity (entry a9). In contrast, the reactivity tended to decrease for 3h−3j, bearing a chloro substituent, under the standard reaction conditions A, using 5 mol % catalyst (entries a10, a13, and a15). In entry a10, though the starting material was almost completely consumed in 1 h, the target compound 5Ah was not detected; instead, the corresponding homoether,12 derived from two molecules of 3, was observed by thin layer chromatography analysis. However, with increasing catalyst loading amount, the reactivities of 3h and 3i increased to afford good diastereoselectivity (entries a10−a12 and a13− a14, respectively). The reaction of 3j was completed by prolonging the reaction time from 1 to 3 h to afford 5Aj in 89% yield with 98:2 dr (entry a15). The reactions of 3k and 3l, bearing a naphthyl ring, were found to be affected by the position of the naphthyl ring (entries a16−a19). Although the reaction of the 3k α-naphthyl group did not afford the desired compound 5Ak (entry a16), 3l with the β-naphthyl group gave a good result (entry a19). However, in this case, better results were obtained by increasing the catalyst loading up to 30 mol % and lowering the reaction temperature to 0 °C (entries 17 and 18). Similarly, we next carried out the reaction under the conditions B (entries b1−b20). Almost all the reactions proceeded smoothly to afford 5B in preference to 5A by adjusting the reaction conditions. However, the electronic nature and the steric effect of the substrates did have an effect on the outcome. In other words, for highly reactive substrates bearing MeO substituents, the reaction was favored by decreasing the catalyst loading in order to suppress the reactivity (entries b5−b10). For low-reactivity substrates bearing Cl substituents, the reaction was favored by increasing the catalyst loading in order to promote the reactivity (entries b11−b17). To further demonstrate the utility of the present method, deprotection of the chiral auxiliary and tosyl group was examined (Scheme 2). Considering the ease of deprotection of the sulfonyl group, we carried out the reaction of 3a using NsNH2 (2-nitrobenzenesulfonamide), instead of p-TsNH2 under conditions A, catalyzed by SnCl2. The reaction proceeded smoothly to give 6A in 91% yield with 94:6 dr. The major diastereomer of 6A was purified by crystallization as a single diastereomer in 74% yield with 99:1 dr. On the other hand, when the reaction was performed under conditions B, catalyzed by FeCl3, compound 6B was afforded in 44% yield,

Table 1. Examination of the Effect of Lewis Acid on the Sulfonamidation of Diarylmethanol 3a

entry

Lewis acid (n mol %)

yield of 5 (%)a

drb

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17c 18c 19

SnBr4 (5) SnBr4 (10) SnBr4 (20) SnBr4 (30) SnBr2 (5) SnBr2 (30) SnCl2 (5) SnCl2 (30) SnCl4 (5) SnCl4 (30) InCl3 (5) InCl3 (30) Yb(OTf)3 (5) Yb(OTf)3 (30) FeCl3 (5) FeCl3 (10) FeCl3 (20) FeCl3 (30) FeCl3 (50)

96 91 84 70 97 94 98 95 94 67 96 95 89 73 89 90 87 84 44

95:5 89:11 53:47 10:90 96:4 94:6 96:4 97:3 77:23 10:90 97:3 96:4 96:4 97:3 67:33 61:39 17:83 8:92 10:90

a Isolated yield of the diastereomixtures. bThe diastereomeric ratio (dr) was determined by 1H NMR analysis. cAverage of two reactions.

proceeded smoothly to produce (R,S)-5a in 96% yield with 95:5 dr (entry 1). Surprisingly, when the same reaction was performed with increased catalyst loading, the diastereoselectivity was reversed from that of the previous result (entry 1) to afford (S,S)-5a as a major product (entries 2−4). Subsequently, other tin salts such as SnBr2, SnCl2, and SnCl4 were applied as catalysts for the reaction. The reactions using SnBr2 and SnCl2 gave almost the same results to furnish 5a in high yields and diastereoselectivities, irrespective of the catalyst loading amount (entries 5−8).9,10 To further improve the efficiency of the reaction, we investigated the solvent effect under the same conditions as those for entry 7, using CH2Cl2, which we had previously found to be an efficient solvent in some cases.7,8 Under these conditions, the reactivity was found to be low, and 5a was obtained in 28% yield (data not shown in the table). When SnCl4 was used, a similar tendency was observed as the case using SnBr4, and the diastereoselectivity was reversed, depending on the catalyst loading amount (entries 9 and 10).11 We further attempted to apply the commonly used Lewis acids InCl3 and Yb(OTf)3 to the reaction. These catalysts gave results similar to those obtained using SnBr2 and SnCl2 (entries 11−14). Interestingly, although the reaction using 5 mol % FeCl3 gave moderate selectivity (entry 15), the selectivity was gradually reversed upon increasing the catalyst loading (entries 16−19). Eventually, the reaction using 30 mol % FeCl3 gave the highest diastereoselectivity for (S,S)-5a (entry 18). With the optimized reaction conditions in hand, for providing the individual diastereomers separately, i.e. using 5 mol % SnCl2 (conditions A) and 30 mol % FeCl3 (conditions B), we attempted to explore the scope and limitations of the 7058


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Table 2. Stereoconvergent Chiral Inductive Diastereodivergent Sulfonamidation Reactions of a Series of Diarylmethanols

entry

conditiona

Ar

n (mol %)

time (h)

yield of 5 (%)b

dr (5A:5B)c

a1d a2 a3 a4 a5 a6e a7 a8 a9e a10 a11 a12 a13 a14 a15 a16 a17 a18e a19 b1f b2 b3 b4 b5 b6 b7 b8 b9 b10 b11 b12 b13 b14 b15 b16 b17 b18 b19 b20

A A A A A A A A A A A A A A A A A A A B B B B B B B B B B B B B B B B B B B B

Ph (a) o-MeC6H4 (b) m-MeC6H4 (c) p-MeC6H4 (d) o-MeOC6H4 (e) o-MeOC6H4 (e) m-MeOC6H4 (f) p-MeOC6H4 (g) p-MeOC6H4 (g) o-ClC6H4 (h) o-ClC6H4 (h) o-ClC6H4 (h) m-ClC6H4 (i) m-ClC6H4 (i) p-ClC6H4 (j) α-Np (k) α-Np (k) α-Np (k) β-Np (l) Ph (a) o-MeC6H4 (b) m-MeC6H4 (c) p-MeC6H4 (d) o-MeOC6H4 (e) o-MeOC6H4 (e) m-MeOC6H4 (f) m-MeOC6H4 (f) p-MeOC6H4 (g) p-MeOC6H4 (g) o-ClC6H4 (h) o-ClC6H4 (h) o-ClC6H4 (h) m-ClC6H4 (i) m-ClC6H4 (i) p-ClC6H4 (j) p-ClC6H4 (j) α-Np (k) α-Np (k) β-Np (l)

5 5 5 5 5 5 5 5 5 5 30 50 5 30 5 5 30 30 5 30 30 30 30 30 15 30 15 30 15 30 50 80 30 70 30 50 30 50 30

1 1 1 1 1 24 1 1 3 1 24 24 3 3 3 24 3 24 1 1 1 1 1 1 1 1 1 1 1 1 0.5 0.5 1 0.5 1 0.5 1 0.5 1

98 90 97 96 NDg 43 93 93 93 NDg 59 85 51 93 89 NDg 90 94 97 84 75 70 75 NDg 19 35 61 13 85 85 74 39 85 52 84 85 88 75 84

96:4 93:7 95:5 95:5 − 57:43 97:3 38:62 86:14 − 94:6 94:6 98:2 98:2 98:2 − 83:17 88:12 93:7 8:92 30:70 9:91 10:90 − 25:75 7:93 69:31 7:93 12:88 82:18 55:45 10:90 79:21 5:95 25:75 20:80 29:71 26:74 9:91

a

Conditions A: Using SnCl2 as a Lewis acid catalyst. Conditions B: Using FeCl3 as a Lewis acid catalyst. bIsolated yield of the diastereomixtures. The diastereomeric ratio (dr) was determined by 1H NMR analysis. dSame as in Table 1, entry 7. eThe reaction was carried out at 0 °C. fSame as in Table 1, entry 18. gNot detected. c

the reported value.14 The absolute stereochemistry of the other products were also assigned based on these results. The proposed transition states for the two conditions A and B are depicted in Figure 1. Regardless of conditions A and B, the Lewis acid first coordinates to the hydroxy oxygen atom of the diarylmethanol to generate the corresponding dibenzyl carbocation. Under conditions A (transition state (i)), the generated carbocation is stabilized by the formation of a sevenmembered ring by chelation with the cation and the methoxy group on the chiral auxiliary.7,8 Then the nucleophile attacks on the re-face of the diarylmethyl cation, thus avoiding the

with 33:67 dr. During this investigation, the order of deprotection was found to be important. In other words, when the deprotection of the chiral auxiliary was done first, NsNH2 was eliminated via the corresponding ortho-quinone methide. Thus, deprotection of the Ns-group13 of the obtained compound 6A was performed using 4-methoxybenzenethiol and K2CO3 to furnish the denosylated compound 7 in 98% yield with 99:1 dr. We next performed the removal of the chiral auxiliary using BBr3 to furnish the aminophenol 814 in 72% yield with 99% ee. The absolute stereochemistry of 8 was determined by comparing its experimental optical rotation with 7059


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chiral auxiliary with the carbocation. On the other hand, when FeCl3 is used as a Lewis acid, the reaction proceeds via a carbocation intermediate that is stabilized by chelation with the Lewis acid coordinating to two oxygen atoms on the chiral auxiliary. The substituent effect on the aromatic ring of the substrate was systematically evaluated, and various substrates were found to be applicable for both reaction conditions. Deprotection of the nosyl group followed by the removal of the chiral auxiliary could be easily carried out according to general methods without any loss in chirality. Further studies are now in progress in our laboratory to expand the scope of this reaction and to develop novel chiral catalysts for this protocol.

Scheme 2. Chiral Inductive Sulfonamidation Using NsNH2 Followed by Deprotection of Ns Group and the Chiral Auxiliary

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b03008. Experimental procedures and characterization data or all compounds (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Kenya Nakata: 0000-0001-8126-6166 Notes

The authors declare no competing financial interest.

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REFERENCES

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Figure 1. Proposed transition states for the two reaction manners.

steric repulsion of the phenyl ring on the stereogenic center, to afford the product with an R-configuration. On the other hand, under conditions B (transition state (ii)), the Lewis acid coordinates with the two oxygen atoms on the chiral auxiliary and chelates with the carbocation on the diarylmethanol to form the bicyclic intermediate. To form the transition state (ii), more equivalents of Lewis acid must be used, probably because the transition states (i) and (ii) compete with each other. This phenomenon is consistent with the abovedescribed experiment results (Table 1, entries 15−18). Then the nucleophile (Nu) coordinating to the Lewis acid attacks on the si-face of the diarylmethyl cation to afford the product with opposite stereochemistry. In conclusion, we have developed a diastereodivergent sulfonamidation reaction of diastereomixtures of diarylmethanols bearing a chiral auxiliary with sulfonylamine by using different Lewis acid catalysts. Both reactions proceed via carbocation intermediates in a stereoconvergent fashion. Chiral induction, using SnCl2 as the Lewis acid catalyst, is assumed to be caused by the chelation between an oxygen atom on the 7060


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Organic Letters Zhang, Y.; Fan, X.; Zhang, G. RSC Adv. 2014, 4, 4286−4291. (l) Pan, J.; Li, J.-q.; Huang, R.-f.; Zhang, X.-h.; Shen, H.; Xiong, T.; Zhu, X.-m. Synthesis 2015, 47, 1101−1108. (m) Xu, X.; Wu, H.; Li, Z.; Sun, X.; Wang, Z. Tetrahedron 2015, 71, 5254−5259. (5) (a) Sanz, R.; Martínez, A.; Á lvarez-Gutiérrez, J. M.; Rodríguez, F. Eur. J. Org. Chem. 2006, 2006, 1383−1386. (b) Motokura, K.; Nakagiri, N.; Mori, K.; Mizugaki, T.; Ebitani, K.; Jitsukawa, K.; Kaneda, K. Org. Lett. 2006, 8, 4617−4620. (c) Motokura, K.; Nakagiri, N.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Org. Chem. 2007, 72, 6006−6015. (d) Wang, G.-W.; Shen, Y.-B.; Wu, X.-L. Eur. J. Org. Chem. 2008, 2008, 4367−4371. (e) Qureshi, Z. S.; Deshmukh, K. M.; Tambade, P. J.; Dhake, K. P.; Bhanage, B. M. Eur. J. Org. Chem. 2010, 2010, 6233−6238. (f) Trillo, P.; Baeza, A.; Nájera, C. J. Org. Chem. 2012, 77, 7344−7354. (g) Pallikonda, G.; Chakravarty, M. RSC Adv. 2013, 3, 20503−20511. (h) Fu, W.; Shen, R.; Bai, E.; Zhang, L.; Chen, Q.; Fang, Z.; Li, G.; Yi, X.; Zheng, A.; Tang, T. ACS Catal. 2018, 8, 9043−9055. (6) Verdelet, T.; Ward, R. M.; Hall, D. G. Eur. J. Org. Chem. 2017, 2017, 5729−5738. (7) Suzuki, N.; Nakata, K. Eur. J. Org. Chem. 2017, 2017, 7075− 7086. (8) Fujihara, R.; Nakata, K. Eur. J. Org. Chem. 2018, DOI: 10.1002/ ejoc.201801236. (9) When the reaction was carried out using 2 mol % SnCl2, the results were similar to those for entry 7 in Table 1 (93% yield, 96:4 dr). (10) To examine the effect of reaction concentration, we performed the reaction using 0.05 and 0.2 M MeNO2 under the conditions corresponding to entry 7 in Table 1. It was found that the reaction was not affected by the concentration. The former reaction afforded 5Aa in 98% yield with 96:4 dr, and the latter afforded 5Aa in 97% yield with 97:3 dr. (11) With an increase in the catalyst loading to 50 mol %, under the same conditions as those for entry 10 in Table 1, the starting material was completely consumed but a complex mixture was obtained. (12) (a) Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem., Int. Ed. 2006, 45, 793−796. (b) Suzuki, N.; Tsuchihashi, S.; Nakata, K. Tetrahedron Lett. 2016, 57, 1456−1459. (13) (a) Fukuyama, T.; Jow, C.-K.; Cheung, M. Tetrahedron Lett. 1995, 36, 6373−6374. (b) Cranfill, D. C.; Lipton, M. A. Org. Lett. 2007, 9, 3511−3513. (14) Wang, Y.-Q.; Yu, C.-B.; Wang, D.-W.; Wang, X.-B.; Zhou, Y.-G. Org. Lett. 2008, 10, 2071−2074.

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Stereoconvergent Chiral Inductive Diastereodivergent

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