Ni(NIXANTPHOS)-Catalyzed Mono-Arylation of Toluenes with Aryl

Org. Lett. , 2019, 21 (6), pp 1735–1739. DOI: 10.1021/acs.orglett.9b00294. Publication Date (Web): March 6, 2019. Copyright © 2019 American Chemica...
1 downloads 0 Views 948KB Size
Download PDF
Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

pubs.acs.org/OrgLett

Ni(NIXANTPHOS)-Catalyzed Mono-Arylation of Toluenes with Aryl Chlorides and Bromides Hui Jiang, Sheng-Chun Sha, Soo A Jeong, Brian C. Manor, and Patrick J. Walsh* Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States

Downloaded via WASHINGTON UNIV on March 6, 2019 at 15:43:41 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: A nickel-catalyzed cross-coupling of toluene derivatives with both aryl bromides and chlorides using a NIXANTPHOS-ligated nickel(II) complex has been developed. The key factor to success is proposed to be the catalyst activation of toluene by a cation−π complex, enabling methyl arenes (pKa ≈ 43) to be deprotonated with the relatively mild base NaN(SiMe3)2. This method facilitates access to a variety of sterically and electronically diverse hetero- and nonheteroarylcontaining diarylmethanes.

A

toluene, diphenylmethane, benzylic ether, and benzylic amine derivatives.9 In the years after our initial work with (η6-RC6H5)Cr(CO)3 complexes, we made several observations that suggested to us that cation−π interactions10 could act as both directing groups to control selectivity11 and activating groups to increase the acidity of benzylic C−H bonds.12 Prior computational work by Periana, Ess, Cundari and their coworkers implied that cation−π interactions could acidify the benzylic C−H bonds of toluene.13 Very recently we developed a palladium-catalyzed benzylic arylation of toluenes with aryl bromides (Scheme 2).12a

romatic hydrocarbons are common starting materials for the preparation of more functionalized and higher value small molecules with applications in synthesis, materials science, and pharmaceutical chemistry. Recent years have witnessed spectacular advances in transition metal catalyzed C−H functionalizations,1 and a host of new reactions and catalysts have been introduced.2 In the realm of toluene activation at the benzylic position, contributions by Stahl,3 Liu,4 Davies,5 and Kozlowski6 stand out (Scheme 1A−D). Remarkable progress has also been made on use of organocatalysts in enantioselective toluene functionalization reactions.7 We have been interested in the functionalization of weakly acidic C(sp3)−H bonds by a deprotonative cross-coupling process (DCCP). In 2010 we demonstrated that activation of the benzylic C−H bonds by coordination of an arene to the Cr(CO)3 fragment,8 enabling the arylation of η6-coordinated

Scheme 2. Cation−π Interactions in the Benzylic Arylation of Toluenes

Scheme 1. Transition-Metal-Catalyzed C(sp3)−H Arylation

Mechanistic and computational studies support acidification of toluene derivatives by the K+−cation−π interaction. Interestingly, this reaction was only successful with aryl bromides and not aryl chlorides, despite our prior demonstration that the Pd(NIXANTPHOS) catalyst can activate aryl chlorides at rt (in cyclopentyl methyl ether, CPME).14 This observation inspired us to examine the nickel-based analogue. Received: January 23, 2019

© XXXX American Chemical Society

A

DOI: 10.1021/acs.orglett.9b00294 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

approach using van Leeuwen’s NIXANTPHOS.20 Thus, the synthesis of the precatalyst was accomplished by exchange of the triphenylphosphine ligands on (Ph3P)2Ni(2-tolyl)Cl (P1) with NIXANTPHOS in THF at room temperature, resulting in P2 in 78% yield (Scheme 3; see SI for details). The structure of P2 is shown in Figure 1 (see SI for details).

The replacement of the precious metal palladium (Scheme 2) with the first-row, abundant metal nickel for catalytic synthesis of diarylmethanes could significantly reduce the cost of this process. Additionally, due to the high reactivity of nickel toward oxidative addition,15 nickel catalysts often show enhanced catalytic efficiency relative to palladium analogues with substrates that are difficult to oxidatively add, including aryl chlorides16 and fluorides.17 In several cases, nickel precatalysts16c,d,18 have been shown to exhibit significantly enhanced catalytic activity in comparison to Ni(COD)2 and the corresponding phosphine ligand. This observation may be due to the absence of COD, which is known to hinder catalysis in some instances.18e Based on our success with the Ni(COD)2/NIXANTPHOS catalyst system19 and these precedents, we sought to develop an air-stable, highly active NIXANTPHOS-ligated Ni(II) precatalyst for C(sp3)−H arylation of methyl arenes. We initiated our research into the arylation of toluene with 1-bromo-4-tert-butylbenzene, NaN(SiMe3)2, 10 mol % Ni(COD)2, and 15 mol % NIXANTPHOS with toluene as the solvent for 12 h at 110 °C, rendering 3a in 76% assay yield (AY, determined by 1H NMR integration against an internal standard, Table 1, entry 1) (for examination of other nickel precursors, see the Supporting Information (SI)).

Scheme 3. Synthesis of (NIXANTPHOS)Ni(ο-tolyl)Cl (P2)

Figure 1. X-ray crystal structure of (NIXANTPHOS)Ni(2-tolyl)Cl (P2) (from two different angles). Hydrogen atoms are omitted for clarity.

Table 1. Optimization of Ni-Catalyzed Arylation of Toluenea

entry

base

1

NaN(SiMe3)2

2 3 4 5 6 7 8d 9e 10f 11g 12h 13i

NaN(SiMe3)2 LiN(SiMe3)2 KN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2 NaN(SiMe3)2

[Ni] (mol %) Ni(COD)2 (10) P2 (5) P2 (5) P2 (5) P2 (7.5) P2 (10) P2 (7.5) P2 (7.5) P2 (7.5) P2 (7.5) P2 (7.5) P2 (7.5) P2 (7.5)

ligand (mol %)

concn

AYb(%)

15

0.033

76

− − − − − 7.5 − − − − − −

0.033 0.033 0.033 0.033 0.033 0.033 0.033 0.033 0.033 0.1 0.05 0.025

77 8 26 89(84c) 90 84 78 89 18 65 66 72

Performing the toluene arylation using 5 mol % of P2 as the catalyst with NaN(SiMe3)2 as the base in toluene for 12 h at 110 °C resulted in a 77% AY (Table 1, entry 2). LiN(SiMe3)2 and KN(SiMe3)2 as the base led to reduced reactivity, giving the coupled product 3a in 8% and 26% AY, respectively (Table 1, entries 3−4). Increasing the precatalyst loading of P2 resulted in an increase in the yield of coupling product 3a to 89% AY with an 84% isolated yield (Table 1, entry 5). Increasing the catalyst loading to 10 mol % had little impact on the AY (90%, Table 1, entry 6). Addition of an extra 7.5 mol % ligand led to a slight decrease in AY (84%, Table 1, entry 7). Attempts to decrease the equivalents of NaN(SiMe3)2, temperature, or reaction concentration led to a diminished AY of 3a (Table 1, entries 8, 10, and 13). When the dosage of NaN(SiMe3)2 was increased from 4 to 4.5 equiv, we obtained the same AY (entry 5 vs 9). Increasing the reaction concentration from 0.033 to 0.1 M decreased the AY of 3a from 89% to 65% (Table 1, entry 5 vs 11−12). Under the optimized conditions, the scope of the direct arylation of toluene with selected aryl bromides was investigated (Scheme 4). Diphenylmethane (3b) was isolated using 1a and bromobenzene (2b) in 83% yield. Sterically hindered 1-bromonaphthalene (2h) was well tolerated, affording 3h in 85% yield, respectively. The yields with these aryl bromides were 5−9% lower than when the Pd(NIXANTPHOS)-based catalyst was used with KN(SiMe3)2 at the same 110 °C. Next, the scope of the arylation of toluene with various aryl chlorides was investigated (Scheme 4). With the nickel precatalyst, toluene coupled with chlorobenzene (2b′) to give the parent diphenylmethane (3b) in 86% yield under the same conditions used with aryl bromides. Aryl chlorides bearing electron-donating groups at the 4-position, such as tertbutyl, methyl, and methoxy, generated the corresponding diarylmethanes 3a, 3c−3d in good yields (65−87%). Aryl chlorides bearing 3-Me (2e′) and 3-NMe2 (2f′) were also used

a Reactions conducted on a 0.10 mmol scale of 2a with 3 mL toluene at 110 °C for 12 h. bAssay yield (AY) determined by 1H NMR spectroscopy of the crude reaction mixtures. cIsolated yield after chromatographic purification. d3 equiv of NaN(SiMe3)2. e4.5 equiv of NaN(SiMe3)2. f80 °C. g1 mL of toluene. h2 mL of toluene. i4 mL of toluene.

To facilitate the reaction optimization and substrate studies, we desired to prepare a nickel precatalyst bearing the NIXANTPHOS ligand. Nickel(II) aryl halide complexes have been known to be relatively air stable since the work of Chatt and Shaw.18b Inspired by advances from Buchwald’s18g and Jamison’s18d,e laboratories, who successfully developed nickel precatalyst derived from substitution of phosphine ligands on (Ph3P)2Ni(2-tolyl)Cl, we adopted a similar B

DOI: 10.1021/acs.orglett.9b00294 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Scheme 4. Substrate Scope of Aryl Bromides and Chlorides in Ni-Catalyzed Arylation of Toluenea

Scheme 5. Substrate Scope in Ni-Catalyzed Direct Arylation of Toluene Derivativesa,b

a

Reactions conducted on a 0.10 mmol scale of 2b′, ArCH3 (0.5 mL) and cyclohexane (0.5 mL). bIsolated yield after chromatographic purification. c3 mL of toluene derivatives without cycloheaxance. d Yield determined by 1H NMR spectroscopy of the crude reaction mixtures.

a

Reactions conducted on a 0.10 mmol scale of 2 and 2′; for aryl bromides, 4 equiv of NaN(SiMe3)2; for aryl chlorides, 4.5 equiv of NaN(SiMe3)2.

Although product derived exclusively from arylation at the methyl group was observed, the isolated yield was 45%. 3Methyl anisole underwent the coupling reaction and afforded the product 3n in 57% yield. Ethylbenzene was a challenging substrate, with an isolated yield of only 17%. In most cases, these reactions worked better in the methylarene/cyclohexane solvent mixtures. A limitation of this system is that it does not work with electron-withdrawing groups on the toluene derivatives, such as 4-CF3, 4-CN, and 4-F. The reason for this finding is not clear at this time, but consistent with the Pd(NIXANTPHOS)-catalyzed process. Next, we desired to probe cooperativity between the Ni and NIXANTPHOS ligand in this nickel-catalyzed arylation of toluene. Despite the outward similarity of NIXANTPHOS, its N-benzylated analogue (N-Bn-NIXANTPHOS), and the parent XANTPHOS ligand scaffolds (Scheme 6, eq 1), catalysts bearing these ligands showed very different reactivity in the toluene arylation. Using Ni(COD)2 as a precursor, the Ni(NIXANTPHOS)-based catalyst promoted the coupling of

as coupling partners, affording 3e and 3f in 92−95% yield. Sterically hindered 2-chloroanisole (2g′) and 1-chloronaphthalene (2h′) gave desired products 3g and 3h in 54% and 92% yield, respectively. Heterocycle-containing diarylmethanes are valuable targets because of their use in pharmaceuticals. To our delight, under the optimized conditions, 6-chloroindole 2i′ afforded products 3i in 62% yield. To demonstrate the scalability of this approach, we performed the coupling of 6chloroindole (2i′) (1 mmol) with toluene (30 mL) to generate 3i in 53% isolated yield. We were also able to produce a pyrrole-containing diarylmethane 3j from the corresponding aryl chloride, albeit with reduced yield (35%). We then turned our attention to the scope of toluene derivatives using chlorobenzene as the coupling partner (Scheme 5). First, six commonly used solvents [THF, DME (dimethoxyethane), dioxane, 2-MeTHF, cyclohexane, and CPME] were screened with the goal of decreasing the quantity of the toluene derivatives employed (see Supporting Information for details). Cyclohexane was the leading hit in this screen. Next, we examined arylation of toluene derivatives with chlorobenzene under the optimized conditions (see Table S3 for details). As expected, the different xylene isomers exhibited different reactivity under the reaction conditions. For example, para-xylene (1c) underwent arylation in 70% yield with a para-xylene/cyclohexane 1:1. Use of para-xylene alone gave a similar yield (67%). ortho-Xylene (1b) reacted with chlorobenzene to form the desired product 3k in 72% yield. Interestingly, meta-xylene proved to be the best of the xylenes, providing the arylation product in 93% yield. In contrast, orthoxylene provided the arylation product in 72% yield with an ortho-xylene/cyclohexane ratio of 1:1, but jumped to 90% yield in pure ortho-xylene. Mesitylene (1e) proved to be an excellent coupling partner generating the corresponding product 3l in 95% yield. To test the selectivity of the arylation, we examined 4-ethyltoluene.

Scheme 6. Control Experiments of Ni-Catalyzed Arylation of Toluene

C

DOI: 10.1021/acs.orglett.9b00294 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

(c) Johansson, C. C. C.; Colacot, T. J. Angew. Chem., Int. Ed. 2010, 49, 676. (2) For reviews, see: (a) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (b) Davies, H. M. L.; Du Bois, J.; Yu, J.-Q. Chem. Soc. Rev. 2011, 40, 1855. (3) Vasilopoulos, A.; Zultanski, S. L.; Stahl, S. S. J. Am. Chem. Soc. 2017, 139, 7705. (4) Zhang, W.; Chen, P.; Liu, G. J. Am. Chem. Soc. 2017, 139, 7709. (5) Qin, C.; Davies, H. M. L. J. Am. Chem. Soc. 2014, 136, 9792. (6) Curto, J. M.; Kozlowski, M. C. J. Am. Chem. Soc. 2015, 137, 18. (7) Mazzarella, D.; Crisenza, G. E. M.; Melchiorre, P. J. Am. Chem. Soc. 2018, 140, 8439. (8) Hartwig, J. F. Organotransition Metal Chemistry; University Science Books: Sausalito, CA, 2010. (9) (a) McGrew, G. I.; Temaismithi, J.; Carroll, P. J.; Walsh, P. J. Angew. Chem., Int. Ed. 2010, 49, 5541. (b) Zhang, J.; Stanciu, C.; Wang, B.; Hussain, M. M.; Da, C.-S.; Carroll, P. J.; Dreher, S. D.; Walsh, P. J. J. Am. Chem. Soc. 2011, 133, 20552. (c) Mao, J.; Zhang, J.; Jiang, H.; Bellomo, A.; Zhang, M.; Gao, Z.; Dreher, S. D.; Walsh, P. J. Angew. Chem., Int. Ed. 2016, 55, 2526. (10) For a review, see: Kennedy, C. R.; Lin, S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2016, 55, 12596. (11) (a) Li, M.; Gonzalez-Esguevillas, M.; Berritt, S.; Yang, X.; Bellomo, A.; Walsh, P. J. Angew. Chem., Int. Ed. 2016, 55, 2825. (b) Zhang, J.; Sha, S.-C.; Bellomo, A.; Trongsiriwat, N.; Gao, F.; Tomson, N. C.; Walsh, P. J. J. Am. Chem. Soc. 2016, 138, 4260. (12) (a) Sha, S.-C.; Tcyrulnikov, S.; Li, M.; Hu, B.; Fu, Y.; Kozlowski, M. C.; Walsh, P. J. J. Am. Chem. Soc. 2018, 140, 12415. (b) Wang, Z.; Zheng, Z.; Xu, X.; Mao, J.; Walsh, P. Nat. Commun. 2018, 9, 1. (13) Pardue, D. B.; Gustafson, S. J.; Periana, R. A.; Ess, D. H.; Cundari, T. R. Comput. Theor. Chem. 2013, 1019, 85. (14) (a) Zhang, J.; Bellomo, A.; Creamer, A. D.; Dreher, S. D.; Walsh, P. J. J. Am. Chem. Soc. 2012, 134, 13765. (b) Zhang, J.; Bellomo, A.; Trongsiriwat, N.; Jia, T.; Carroll, P. J.; Dreher, S. D.; Tudge, M. T.; Yin, H.; Robinson, J. R.; Schelter, E. J.; Walsh, P. J. J. Am. Chem. Soc. 2014, 136, 6276. (15) For reviews, see: (a) Tasker, S. Z.; Standley, E. A.; Jamison, T. F. Nature 2014, 509, 299. (b) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346. (c) Henrion, M.; Ritleng, V.; Chetcuti, M. J. ACS Catal. 2015, 5, 1283. (d) Glorius, F. Angew. Chem., Int. Ed. 2008, 47, 8347. (e) Cornella, J.; Zarate, C.; Martin, R. Chem. Soc. Rev. 2014, 43, 8081. (f) Balcells, D.; Nova, A. ACS Catal. 2018, 8, 3499. For selected examples, see: (g) Wu, K.; Doyle, A. G. Nat. Chem. 2017, 9, 779. (h) Shimasaki, T.; Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2010, 49, 2929. (i) Ramgren, S. D.; Silberstein, A. L.; Yang, Y.; Garg, N. K. Angew. Chem., Int. Ed. 2011, 50, 2171. (16) For selected examples, see: (a) Zultanski, S. L.; Fu, G. C. J. Am. Chem. Soc. 2011, 133, 15362. (b) Lavoie, C. M.; MacQueen, P. M.; Rotta-Loria, N. L.; Sawatzky, R. S.; Borzenko, A.; Chisholm, A. J.; Hargreaves, B. K. V.; McDonald, R.; Ferguson, M. J.; Stradiotto, M. Nat. Commun. 2016, 7, 11073. (c) Ge, S.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 16330. (d) Ge, S.; Green, R. A.; Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 1617. (17) For reviews, see: (a) Clot, E.; Eisenstein, O.; Jasim, N.; MacGregor, S. A.; McGrady, J. E.; Perutz, R. N. Acc. Chem. Res. 2011, 44, 333. (b) Braun, T.; Perutz, R. N. Chem. Commun. 2002, 2749. For selected examples, see: (c) Johnson, S. A.; Huff, C. W.; Mustafa, F.; Saliba, M. J. Am. Chem. Soc. 2008, 130, 17278. (d) Bohm, V. P. W.; Gstottmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem., Int. Ed. 2001, 40, 3387. (18) For reviews, see: (a) Standley, E. A.; Tasker, S. Z.; Jensen, K. L.; Jamison, T. F. Acc. Chem. Res. 2015, 48, 1503. For a pioneering work, see: (b) Chatt, J.; Shaw, B. L. J. Chem. Soc. 1960, 1718. For selected examples, see: (c) Zhang, N.; Hoffman, D. J.; Gutsche, N.; Gupta, J.; Percec, V. J. Org. Chem. 2012, 77, 5956. (d) Standley, E. A.; Smith, S. J.; Muller, P.; Jamison, T. F. Organometallics 2014, 33, 2012. (e) Standley, E. A.; Jamison, T. F. J. Am. Chem. Soc. 2013, 135, 1585.

1-bromo-4-tert-butylbenzene with toluene to afford the diarylmethane product in 78% AY. In contrast, under identical reaction conditions, the N-Bn-NIXANTPHOS- and the parent XANTPHOS-based catalysts exhibited 15% and 0% AY, respectively. These results indicate the importance of the deprotonated NIXANTPHOS ligand for efficient arylation of toluene. We then decided to investigate the cation effect in the presence of additives (Scheme 6, eq 2). Addition of 4 equiv of 15-crown-5 to the arylation of toluene caused a dramatic drop in the reactivity, furnishing only a 7% yield of the arylation product, compared to 78% in the absence of crown ether (Scheme 6, eq 1). Addition of 8 equiv of 15-crown-5 shut down the reaction. These results provide circumstantial evidence for cooperativity between the main group metals Na and K with the Ni or Pd centers, respectively, in these heterobimetallic catalysts. In summary, we have developed a versatile nickel-catalyzed C−H functionalization of toluene and its derivatives with aryl bromides and chlorides to generate diarylmethanes. The difference between the Pd(NIXANTPHOS)- and Ni(NIXANTPHOS)-based catalysts is that the nickel catalysts introduced herein function with aryl chlorides, whereas the palladium catalysts do not. Furthermore, the optimal main group element for nickel is sodium, whereas potassium forms a more active heterobimetallic with the palladium derivative.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b00294. Procedures, characterization data for all new compounds (PDF) Accession Codes

CCDC 1890453 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Hui Jiang: 0000-0001-6431-3004 Patrick J. Walsh: 0000-0001-8392-4150 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS P.J.W. thanks the National Science Foundation [CHE1464744], and H.J. thanks the China Scholarship Council [201406350156] for financial support.

■

REFERENCES

(1) For reviews, see: (a) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234. (b) Bellina, F.; Rossi, R. Chem. Rev. 2010, 110, 1082. D

DOI: 10.1021/acs.orglett.9b00294 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters (f) Shields, J. D.; Gray, E. E.; Doyle, A. G. Org. Lett. 2015, 17, 2166. (g) Park, N. H.; Teverovskiy, G.; Buchwald, S. L. Org. Lett. 2014, 16, 220. (h) Miyakoshi, R.; Yokoyama, A.; Yokozawa, T. J. Am. Chem. Soc. 2005, 127, 17542. (i) Leowanawat, P.; Zhang, N.; Safi, M.; Hoffman, D. J.; Fryberger, M. C.; George, A.; Percec, V. J. Org. Chem. 2012, 77, 2885. (j) Lanni, E. L.; McNeil, A. J. J. Am. Chem. Soc. 2009, 131, 16573. (k) Ge, S.; Hartwig, J. F. Angew. Chem., Int. Ed. 2012, 51, 12837. (l) Bronstein, H. A.; Luscombe, C. K. J. Am. Chem. Soc. 2009, 131, 12894. (19) Cao, X.; Sha, S.-C.; Li, M.; Kim, B.-S.; Morgan, C.; Huang, R.; Yang, X.; Walsh, P. J. Chem. Sci. 2016, 7, 611. (20) (a) van Leeuwen, P. W. N. M.; Kamer, P. C. J. Catal. Sci. Technol. 2018, 8, 26. (b) Van der Veen, L. A.; Keeven, P. H.; Schoemaker, G. C.; Reek, J. N. H.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M.; Lutz, M.; Spek, A. L. Organometallics 2000, 19, 872.

E

DOI: 10.1021/acs.orglett.9b00294 Org. Lett. XXXX, XXX, XXX−XXX