Silyloxyarenes as Versatile Coupling Substrates Enabled by Nickel

Letter pubs.acs.org/acscatalysis

Silyloxyarenes as Versatile Coupling Substrates Enabled by NickelCatalyzed C−O Bond Cleavage Eric M. Wiensch,‡ David P. Todd,‡ and John Montgomery* Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, Michigan 48109-1055, United States S Supporting Information *

ABSTRACT: Silyloxyarenes are demonstrated to be a versatile substrate class in a variety of nickel-catalyzed coupling processes. The C(sp2)−O bond of aryl silyl ethers is directly transformed into C−H or C−Si bonds using Ti(O-i-Pr)4 or trialkylsilanes as reagents using nickel catalysts with N-heterocyclic carbene (NHC) ligands. Paired with the useful characteristics of silyl protecting groups, these methods enable protected hydroxyls to directly participate in high-value bond-forming steps rather than requiring deprotection-activation strategies that conventional approaches require. These processes of silyloxyarenes provide reactivity complementary to widely used phenol derivatives such as aryl pivalates, carbamates, and methyl ethers, thus enabling a powerful strategy for sequential chemoselective derivatization of complex substrates without protecting group and activating group manipulations. KEYWORDS: nickel, catalysis, silyloxyarenes, cross-coupling, C−O bond activation, silane

C

reagents required, ease of installation, and stability during multistep synthetic procedures. A notable omission among the substrate classes commonly employed in cross-couplings is silyloxyarenes. Trialkylsilyl groups make up a highly versatile class of protecting groups for masking the reactivity of hydroxyl functional groups.2 Large numbers of silyl protecting groups have been developed for this purpose, and they typically may be chemoselectively installed and removed through well-established reactivity patterns that enable their use in a broad variety of complex settings with polyfunctional molecules.3 Their ease of installation and removal, paired with the ability to readily tune their stability and reactivity, make silyl ethers exceptionally attractive as a potential substrate class in cross-coupling methods. Additionally, the strong nature of the silicon−oxygen bond and accompanying unique leaving group ability of silanolates suggests that the properties of silyl ethers might effectively modulate reactivity of the adjacent carbon−oxygen bond in a manner that enables reactivity differences compared with other widely used derivatives of phenols. Despite this potential, silyloxyarenes are very rarely utilized in cross-coupling methods that involve activation of an C(sp2)−O bond.4 In this study, we demonstrate methods for the conversion of silyloxyarenes to Ar−Si or Ar−H products through nickel-catalyzed coupling processes. The unique reactivity of silyloxyarenes compared with widely used phenol derivatives is demonstrated, and a unique reactivity pattern with silane reductants to afford aryl silane products is described. The direct reductive removal of aromatic substituents using nickel catalysis with silane reductants is well documented with

ross-couplings of phenol derivatives are widely used catalytic processes, wherein changes in the identity of the activating group on oxygen lead to reactivity differences in the proximal carbon−oxygen bond. Many classes of phenol derivatives have been utilized, given their wide availability, structural variety, and low cost. For example, triflates, tosylates, phosphates, pivalates, carbamates, sulfamates, and methyl ethers are among the many classes of phenol derivatives that have each been extensively developed in palladium- and/or nickel-catalyzed coupling processes (Scheme 1).1 By carefully Scheme 1. Substrate Classes for Metal-Catalyzed Couplings

matching the activating group on oxygen with the catalyst employed, clear reactivity differences among these groups lead to opportunities for chemoselective addition processes. These reactivity differences provide a powerful strategy for sequencing two or more cross-coupling reactions in a streamlined manner, starting from a polyfunctional starting material.1a The choice of O-activation method often depends not only on the efficiency in a desired cross-coupling application but also on the cost of © XXXX American Chemical Society

Received: June 21, 2017 Revised: July 18, 2017 Published: July 20, 2017 5568

DOI: 10.1021/acscatal.7b02025 ACS Catal. 2017, 7, 5568−5571

Letter

ACS Catalysis

along with product 2a. However, in an experiment with the exceptionally bulky ligand IPr*OMe,7b the production of aryl silane 2b was observed in 97% yield when Et3SiH was employed (Table 1, entry 5; more complete Table S2 is available in the Supporting Information). While not commonly employed in cross-coupling procedures, triethylsilylarenes were recently demonstrated to be useful substrates in palladiumcatalyzed cross couplings.8 This outcome is highly surprising considering the vast number of silane-mediated reductions of other aromatics, where hydrogen installation is uniformly observed.1d,f,4b,5 For example, studies from Martin and Chatani have described methods where aryl methyl ethers were reduced to simple Ar−H products using silane reductants. Furthermore, studies from Nakao described reduction of silyloxyarenes (forming Ar−H products) using trialkylsilanes with less hindered nickel NHC complexes rather than the formation of arylsilanes described herein. The direct conversion of phenol derivatives to aryl silanes using simple trialkylsilane reductants thus complements alternate methods for installation of C(sp2)−Si functionality and represents an unusual reactivity pattern for silane-based reductions with nickel catalysts.9 The above experiments thus uncovered efficient methods for the conversion of substrate 1 to either arene product 2a using Ti(O-i-Pr)4 as reductant (Table 1, entry 4), or to aryl silane product 2b using a trialkylsilane as reductant (Table 1, entry 5). The above outcome with TBS ethers was then compared with other types of silyl ethers as well as more conventional substrate classes. Using the bulkier Si(i-Pr)3 (TIPS) ether of the starting phenol led to the formation of reduction product 2a in high yield, whereas aryl silane 2b was obtained with poorer conversion using Et3SiH (Table 1, entry 6). In contrast, the smaller SiEt3 (TES) ether of the starting phenol was an efficient substrate for formation of the aryl silane 2b, while formation of reduction product 2a using Ti(O-i-Pr)4 was less efficient than the corresponding reactions with bulkier silyl ethers (Table 1, entry 7). Reactions of widely used methyl ethers, aryl pivalates, and aryl triflates in either reaction with Et3SiH or Ti(O-i-Pr)4 as reductant were markedly less efficient and less selective in the formation of 2a and 2b than the corresponding reactions of silyloxyarene substrates, thus demonstrating synthetic utility of the siloxyarene substrate class (Table 1, entries 8−10). On the basis of the promising outcomes of entries 4 and 5, TBS ethers were routinely used in the remainder of our studies. With promising procedures in hand for the reductive conversion of silyloxyarene substrates to either Ar−H or ArSiEt3 products, the scope and chemoselectivity of both procedures were explored (Table 2). The use of Ti(O-i-Pr)4 to produce reduced arenes was examined in toluene at 120 °C using Ni(acac)2 as the precatalyst in combination with IPrMe· HCl as ligand because this air-stable precatalyst generally provided excellent results. Similar conditions with IPr*OMe as ligand were employed in silyl transfer using silane reagents, but the more sensitive precatalyst Ni(COD)2 provided superior results than air stable Ni(II) sources. Under these conditions, simple naphthol derivatives were cleanly reduced or silylated (3a-b and 4a-b), and an arylsilane functionality was tolerated in the process (5a-b). Additionally, benzyl silyl ethers, free phenols, and methoxyarenes were similarly unaffected in substrates in which silyloxyarenes were cleanly reduced or silylated (6a-b, 7a-b, 8a-b). Alternatively, a substrate possessing two silyloxy groups underwent bis-reduction or bis-silylation (9a-b). A variety of nitrogen-containing substrates were tolerated, as evidenced by examples with a quinoline, carbazole,

many substrate/catalyst/ligand combinations. Whereas silane reductants are commonly used with nickel catalysis,1d,f,4b,5 recent studies from our lab illustrated that Ti(O-i-Pr)4 displays complementary and sometimes synergistic behavior compared with silanes in reductive processes.6 Given this precedent, the reduction of silyloxyarenes was compared with silanes and with titanium alkoxides using nickel catalysts derived from phosphines or NHC ligands (Table 1; more complete Table Table 1. Optimization of Nickel-Catalyzed Reductions of Phenol Derivativesa

a

Experiments with Ti(O-i-Pr)4 use Ni(acac)2 as precatalyst, and experiments with Et3SiH use NiCOD)2 as precatalyst. In entries 6−10, IPrMe·HCl was used with Ti(O-i-Pr)4, IPr*OMe was used with Et3SiH. Piv = pivalate, Tf = trifluoromethanesulfonate. Conditions for entries 6−10, using Ti(O-i-Pr)4: Ni(acac)2 (5 mol %), IPrMe·HCl (10 mol %), Ti(O-i-Pr)4 (1.1 equiv), NaO-t-Bu (2.5 equiv), toluene (0.5 M) at 120 °C for 6 h. Conditions for entries 6−10, using Et3SiH: Ni(COD)2 (10 mol %), IPr*OMe (10 mol %), triethylsilane (6 equiv), NaO-t-Bu (2.5 equiv), toluene (0.5 M) at 120 °C for 6 h. Major product for entries 9 and 10 was 4-phenylphenol. All yields determined by GCFID with tridecane as internal standard.

S1 is available in the Supporting Information). Given the excellent stability and protecting group characteristics of the tbutyldimethylsilyl (TBS) protecting group, an initial ligand screen focused on TBS-protected phenol derivative 1. Whereas catalysts derived from PCy3 were ineffective with both triethylsilane and with Ti(O-i-Pr)4 (Table 1, entry 1), the use of NHC ligands provided good turnover at 120 °C. The NHC ligand IMes led to poor reactivity in all cases, but the bulkier NHC ligands IPr and IPrMe provided good yields of reduction product 2a derived from reductive replacement of the silyloxy group using a titanium reductant (Table 1, entries 2−4). The IPrMe ligand,7a in particular, provided a highly efficient process, with direct reductive removal of the t-butyldimethylsilyloxy group being observed in 94% yield. In the above experiments using Et3SiH, aryl silane 2b was commonly seen in low yield 5569

DOI: 10.1021/acscatal.7b02025 ACS Catal. 2017, 7, 5568−5571

Letter

ACS Catalysis

The above studies demonstrate that silyloxyarenes are versatile substrates for nickel-catalyzed reduction procedures. Additionally, both of the procedures possesses high chemoselectivity in reactions of the silyloxyarene unit when other potentially reactive functional groups are present. These features suggest that silyloxyarenes may hold an important place in sequential reactions of polyfunctional substrates when used in combination with other widely used classes of crosscoupling substrates. Expanding the repertoire of substrate classes that enable highly chemoselective cross couplings avoids the interchange of protecting groups that often accompanies derivatization of polyfunctional substrates.1a To explore this potential, we opted to examine the use of silyloxyarenes in multistep sequences that utilize C(sp2)-Br, C(sp2)-OPiv, C(sp2)-O(CO)NR2, and C(sp2)-OMe functional groups. This effort began from a common substrate 4-bromo-3methoxyphenol, which was converted to carbamate derivative 20 and pivalate derivative 21 (Scheme 2). A palladiumcatalyzed Suzuki coupling of these substrates with TBSprotected boronic acid derivative 22 cleanly afforded intermediates 23 and 24,5b in a process where chemoselective coupling of the boronic acid and bromoaryl functional groups proceeded in the presence of the carbamate, methoxy, and silyloxy groups. Derivatives 23 and 24 then cleanly underwent nickel-catalyzed Buchwald-Hartwig aminations with morpholine to produce 25,11 in a process where the carbamate or pivalate undergoes chemoselective amination in the presence of methoxy and silyloxy functional groups. With silyl substrate 25 in hand, following procedures described herein, the chemoselective silylation with triethylsilane generated product 26. This reaction further demonstrates the utility of the higher reactivity of silyloxyarenes in the presence of methoxyarene and aniline functional groups. Finally, the methoxyarene of product 26 underwent nickel-catalyzed coupling with (trimethylsilyl)methyllithium to afford product 27.12 The sequence leading to 27 notably illustrates four sequential cross coupling procedures, with no protecting group manipulations or functional group interconversions required. The sequence relies on the sequential and selective couplings of a bromide, a carbamate or pivalate group, a silyloxy group, and finally a methoxy group. These examples are illustrative of the manner in which these new couplings of silyloxyarenes may be paired with known chemoselective cross couplings to enable streamlined multistep synthetic operations. In summary, this work illustrates a number of new coupling processes utilizing silyloxyarene substrates as versatile precursors for nickel-catalyzed bond formations. The direct reduction of silyloxyarenes with Ti(O-i-Pr)4 enables the chemoselective removal of silyloxy groups from arenes, whereas silane-mediated production of C−Si bonds allows the buildup of complexity from this widely accessible functional group class. The remarkable versatility of silyl groups provides considerable value to the methods, because hydroxyls protected as their silyl ethers can directly participate in high-value bond-forming steps, circumventing two-step deprotection/activation sequences that conventional approaches require. Furthermore, the reactivity trends of silyl ethers complement other classes of C(sp2)-OR derivatives that have been widely exploited in the crosscoupling literature. This complementarity enables multistep sequential couplings that avoid the installation and removal of protecting groups as part of a synthetic sequence.

Table 2. Scope of Nickel-Catalyzed Reductions and Silylations of Silyloxyarenesa

a Conditions for reactions using Ti(O-i-Pr)4 as reductant: Ni(acac)2 (5 mol %), IPrMe·HCl (10 mol %), Ti(O-i-Pr)4 (1.1 equiv), NaO-t-Bu (2.5 equiv), toluene (0.5 M) at 120 °C for 3−6 h. Conditions for reactions using HSiEt3 as reductant: Ni(COD)2 (10 mol %), IPr*OMe (10 mol %), triethylsilane (6 equiv), NaO-t-Bu (2.5 equiv), toluene (0.5M) at 120 °C for 16 h. See Supporting Information for variations from standard conditions. Isolated yields are shown except compounds 3a, 4a, 9a, 13a, 14a, 15a, and 16a which were determined by GCFID with tridecane as internal standard.

or pyridyl functionality on the silyloxy arene (10a-b, 11a-b, 12a-b). In contrast, morpholino- and N-acylamino derivatives were sluggish substrates in the Ti(O-i-Pr)4-mediated reduction, leading to modest conversion after extended reaction times (13a, 14a). However, with this substrate class, silylation with Et3SiH remained efficient and high yielding (13b, 14b). A variety of frameworks that possess alkyl substituents on the silyloxyarene were also tolerated in the reductive transformation (15a-b, 16a-b, 17a-b). In the production of aryl silane products, some variation in silane structure is tolerated, as evidenced by the production of dimethylethylsilane and dimethylisopropylsilane derivatives (18a-b). However, benzyldimethylsilane underwent addition only in modest yields (18c). To confirm that Ti(O-i-Pr)4 serves as the terminal reductant in the reductive process, reduction of a substrate possessing a trifluoroaryl substrate with d28-Ti(O-i-Pr)4 led to 89% deuterium incorporation (19). As expected, the site of deuteration was exclusively localized at the ipso carbon where the silyloxy group was positioned in the starting substrate.10 5570

DOI: 10.1021/acscatal.7b02025 ACS Catal. 2017, 7, 5568−5571

Letter

ACS Catalysis Scheme 2. Four-Step Sequential Cross Coupling Utilizing Silyloxyarenes

■

T.; Miyamoto, K.; Wang, C.; Uchiyama, M. Chem. - Eur. J. 2016, 22, 15693−15699. (5) (a) Alvarez-Bercedo, P.; Martin, R. J. Am. Chem. Soc. 2010, 132, 17352−17353. (b) Tobisu, M.; Yamakawa, K.; Shimasaki, T.; Chatani, N. Chem. Commun. 2011, 47, 2946−2948. (c) For a related process using methyl ethers as the internal reductant: Tobisu, M.; Morioka, T.; Ohtsuki, A.; Chatani, N. Chem. Sci. 2015, 6, 3410−3414. (6) Todd, D. P.; Thompson, B. B.; Nett, A. J.; Montgomery, J. J. Am. Chem. Soc. 2015, 137, 12788−12791. (7) (a) Clavier, H.; Correa, A.; Cavallo, L.; Escudero-Adán, E. C.; Benet-Buchholz, J.; Slawin, A. M. Z.; Nolan, S. P. Eur. J. Inorg. Chem. 2009, 2009, 1767−1773. (b) Meiries, S.; Speck, K.; Cordes, D. B.; Slawin, A. M. Z.; Nolan, S. P. Organometallics 2013, 32, 330−339. (8) Komiyama, T.; Minami, Y.; Hiyama, T. Angew. Chem., Int. Ed. 2016, 55, 15787−15791. (9) (a) Zarate, C.; Martin, R. J. Am. Chem. Soc. 2014, 136, 2236− 2239. (b) Zarate, C.; Nakajima, M.; Martin, R. J. Am. Chem. Soc. 2017, 139, 1191−1197. (c) Toutov, A. A.; Liu, W.-B.; Betz, K. N.; Fedorov, A.; Stoltz, B. M.; Grubbs, R. H. Nature 2015, 518, 80−84. (d) Cheng, C.; Hartwig, J. F. Chem. Rev. 2015, 115, 8946−8975. (10) Cornella, J.; Gómez-Bengoa, E.; Martin, R. J. Am. Chem. Soc. 2013, 135, 1997−2009. (11) (a) Mesganaw, T.; Silberstein, A. L.; Ramgren, S. D.; Nathel, N. F. F.; Hong, X.; Liu, P.; Garg, N. K. Chem. Sci. 2011, 2, 1766−1771. (b) Shimasaki, T.; Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2010, 49, 2929−2932. (12) Leiendecker, M.; Hsiao, C.-C.; Guo, L.; Alandini, N.; Rueping, M. Angew. Chem., Int. Ed. 2014, 53, 12912−12915.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.7b02025. Experimental details and copies of spectra (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

John Montgomery: 0000-0002-2229-0585 Author Contributions ‡

(E.M.W., D.P.T.) These authors contributed equally.

Notes

The authors declare no competing financial interest.

■ ■

ACKNOWLEDGMENTS This work was supported by the National Science Foundation (CHE-1565837). REFERENCES

(1) (a) Mesganaw, T.; Garg, N. K. Org. Process Res. Dev. 2013, 17, 29−39. (b) Zeng, H. Y.; Qiu, Z. H.; Dominguez-Huerta, A.; Hearne, Z.; Chen, Z. W.; Li, C. J. ACS Catal. 2017, 7, 510−519. (c) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A. M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346−1416. (d) Tobisu, M.; Chatani, N. Top. Curr. Chem. 2016, 374, 41. (e) Yamaguchi, J.; Muto, K.; Itami, K. Eur. J. Org. Chem. 2013, 2013, 19−30. (f) Cornella, J.; Zarate, C.; Martin, R. Chem. Soc. Rev. 2014, 43, 8081−8097. (g) Yu, D. G.; Li, B. J.; Shi, Z. J. Acc. Chem. Res. 2010, 43, 1486−1495. (2) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190− 6191. (3) Nelson, T. D.; Crouch, R. D. Synthesis 1996, 1996, 1031−1069. (4) (a) Zhao, F.; Yu, D. G.; Zhu, R. Y.; Xi, Z. F.; Shi, Z. J. Chem. Lett. 2011, 40, 1001−1003. (b) Ohgi, A.; Nakao, Y. Chem. Lett. 2016, 45, 45−47. (c) Guan, B. T.; Xiang, S. K.; Wu, T.; Sun, Z. P.; Wang, B. Q.; Zhao, K. Q.; Shi, Z. J. Chem. Commun. 2008, 2, 1437−1439. (d) Dankwardt, J. W. Angew. Chem., Int. Ed. 2004, 43, 2428−2432. (e) Xie, L. G.; Wang, Z. X. Chem. - Eur. J. 2011, 17, 4972−4975. (f) Yang, Z. K.; Wang, D. Y.; Minami, H.; Ogawa, H.; Ozaki, T.; Saito, 5571

DOI: 10.1021/acscatal.7b02025 ACS Catal. 2017, 7, 5568−5571