Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Silylation of Aryl Halides with Monoorganosilanes Activated by Lithium Alkoxide Takumi Yoshida, Laurean Ilies,*,† and Eiichi Nakamura* Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan S Supporting Information *
ABSTRACT: Lithium alkoxide activates a monoorganosilane to generate a transient LiH/alkoxysilane complex, which quickly reacts with aryl and alkenyl halides at 25 °C to deliver a diorganosilane product. Experimental and theoretical studies suggest that the reaction includes nucleophilic attack of LiH on the halogen atom of the organic halide to generate a transient organolithium/alkoxysilane intermediate, which undergoes quick carbon−silicon bond formation within the complex.
L
ong regarded largely as a base, alkali metal hydrides are finding new utility as a reducing agent.1 Our interest2 in mild methods for the generation of reactive metal hydride reagents led us to find a new way to cross-couple a hydrosilane and an aryl and alkenyl halide to produce diorganosilanes, a valuable synthetic intermediate for organic synthesis.3 However, there is a paucity of selective synthetic routes to this class of compounds4 due to the high reactivity of diorganosilanes leading to disproportionation or overreaction.5,6 Herein we describe that a transient LiH/alkoxysilane, which is generated from two air stable reagents, monoorganosilane (R1SiH3) and lithium tert-butoxide (LiOt-Bu),7,8 reacts with an aryl or alkenyl halide (R2X) to produce a diorganosilane (Figure 1). The synthetic merits include simplicity, scalability, and quickness and mildness of the reaction often finishing within 10 min at 25 °C under dry air or argon. The reactive species is rather insensitive to steric hindrance, and the reaction does not produce tri- or tetraorganosilane side products. Experimental
and theoretical studies suggest an intriguing new possibility for generating a metal hydride species, including a LiH/ alkoxysilane complex (A) and a transient LiH (B), which nucleophilically reduces the C−X bond in R2X. The reaction bifurcates into silylation (a) and reduction (b) after a transient R2−Li intermediate (C). Equation 1 shows a typical example of the silylation reaction for 1-iodonaphthalene (1): To a solution of lithium tertbutoxide (20 mmol, 1 M) in THF at 25 °C under argon were added sequentially phenylsilane (20 mmol) and 1-iodonaphthalene (10 mmol), which was followed by hydrogen gas evolution (identified by 1H NMR) and an exothermic reaction for several minutes. As analyzed by GC, GC-MS, and 1H NMR, the reaction produced 1-naphtylphenylsilane (2; 1.18 g, 51% yield, isolated by silica gel chromatography), naphthalene (3; 43%), and di(tert-butoxy)phenylsilane (∼25% based on phenylsilane; this product presumably forms by the reaction of (tert-butoxy)phenylsilane, the formation of which was detected by NMR (SI), and tert-butanol in the presence of lithium tert-butoxide). The reaction under dry air9 took place equally well in 50% yield, while the reaction was slightly sensitive to moisture in air (44% yield). The silylation/ reduction ratio did not change much either by the increase/ decrease of PhSiH3 or by use of PhSiD3 (i.e., lack of kinetic isotope effect; Supporting Information, SI). The choice of the base much affects the reaction (Table 1; additional data in SI). In the absence of a base, 1iodonaphthalene and phenylsilane alone did not react at all (entry 1). Both secondary and tertiary lithium alkoxides reacted equally well in THF (entries 2 and 3), while primary alkoxide and phenoxide were unreactive (entries 4 and 5). 12-Crown-4ether did not significantly affect the reaction rate or product selectivity (entry 6). Potassium and sodium tert-butoxide
Figure 1. Reaction of monoorganosilane with aryl and alkenyl halide.
Received: March 13, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00818 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
Scheme 1. Silylation of Aryl and Alkenyl Bromides or Iodidesa
(entries 7, 8) gave a complex mixture of silylation and reduction products as well as products due to silane disproportionation (silane, diphenylsilane, and triphenylsilane). No reaction took place in diethyl ether, dichloromethane, toluene, and hexane (SI). Control experiments discounted the possibility of catalysis by contaminated transition metals.10 We next investigated the scope of the reaction between aryl and alkenyl halides, and monoorganosilanes (Scheme 1). All reactions underwent 100% conversion (except for 23 (no reaction) and some aryl bromides, 4−7, 9, 11), and the reduction product accounts for the rest of the material balance. The reduction products and alkoxysilane can be easily separated by column chromatography. Iodobenzene and 4iodotoluene underwent silylation in about 50% yield (4 and 5), while the corresponding bromides were unreactive. Radical clock substrate 7 did not give any cyclization product.11 Interestingly, the reaction tolerates ortho-substitution, which even promotes silylation over reduction (cf. 5 vs 6−11 and iodide vs bromide). For instance, 2,4,6-triisopropyl-iodobenzene and mesityl iodide underwent silylation (10 and 11) in higher yield than iodobenzene, although the reaction required a higher temperature (50 °C instead of 25 °C). Here, the intermediacy of benzyne can be discounted. 2,4,6-Tri-tertbutyliodobenzene is apparently too hindered to be silylated, but still underwent smooth C−I bond cleavage to give the reduction product in 90% yield (12). Electron-poor iodoarenes reacted faster but were silylated in low yield (18, 19), while electron-rich iodoarenes reacted slower but were silylated in higher yield (15−17). We discuss further this interesting contrast in the next paragraph. The reaction tolerates the presence of a sulfur group (20 and 25). An alkylsilane also gave the silylated compounds (24, 25) albeit in low yield. A trisubstituted alkenyl bromide reacted well to give a tetrasubstituted alkenylsilane (21), while simple alkenyl halides were very poor yielding. Fluoro, chloro, tosyl, and trifluoromethanesulfonate compounds did not react at all (unreacted substrates are listed in SI).12 The electronegativity of the 4-substituent affects both the reactivity and the silylation/reduction selectivity in an interesting way. Thus, in a competitive reaction, 4-fluoroiodobenzene reacts markedly faster than 4-methoxyiodobenzene (no reaction) with silylation/reduction selectivity as low as 1:4
a
Aryl iodide (0.5 mmol), silane (1.0 mmol), lithium tert-butoxide (1.0 mmol) in tetrahydrofuran (1.0 mL) at 25 °C under argon for 10 min, unless mentioned otherwise. Aryl or alkenyl bromides: aryl bromide (0.5 mmol), silane (1.5 mmol), lithium tert-butoxide (1.5 mmol) in tetrahydrofuran (1.5 mL) at 70 °C under argon for 3 h. b25 °C, 3 h. c Yield determined by 1HNMR with 1,1,2,2-tetrachloroethane as an internal standard. d50 °C, 1 h. e70 °C, 3 h. f1 mmol scale. g10 mmol scale.
(Figure 2a). As mentioned for 15 and 16 vs 18 in (Scheme 1), the 4-fluoro substituent favors reduction, while the 4-alkoxy substituent favors silylation. The ratio of silylation/reduction remained the same during the reaction, excluding protodesilylation of the product. A mechanistic issue is thus whether the C−X bond cleavage includes electron donation directly to C−X σ* or indirectly to π* of the aromatic ring. To probe this issue, we examined competition between a 4-bromostilbene and 4-trifluoromethyl1-bromobenzene13 and found exclusive reaction of the latter
Table 1. Base Effects on Silylation of 1-Iodonaphthalene (1) with Phenylsilanea
a b
entry
base
2 (%)b
3 (%)b
entry
base
2 (%)b
3 (%)b
1 2 3 4
none LiOt-Bu LiOi-Pr LiOEt
0 51 50 0
0 50 40 0
5 6c 7 8
LiOPh LiOt-Bu KOt-Bu NaOt-Bu
0 26 19 3
0 63 44 26
1-Iodonaphthalene (1, 0.20 mmol), phenylsilane (0.40 mmol), base (0.40 mmol) in tetrahydrofuran (0.40 mL) at 25 °C under argon for 10 min. GC yield with tridecane as an internal standard. cWith 2.0 equiv of 12-crown-4-ether. B
DOI: 10.1021/acs.orglett.8b00818 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
Figure 2. Competition experiments as mechanistic probe. (a) Between 4-methoxyiodobenzene and 4-fluoroiodobenzene. (b) Between 4bromostilbene and 4-trifluoromethylbromobenzene. Orbital levels at the B3LYP/6-31++G(d) level of theory, except SDD basis set and ECP46MWB effective core potential for iodine atom. E0 determined by DPV measurement.
Figure 3. Reaction pathway obtained by DFT calculations (M062X/6311++G(d,p)//B3LYP/6-31++G(d)). Gibbs energies (X = I) are shown in kcal/mol. The numbers refer to bond length (Å) and natural charges (underlined). (a) Generation of transient LiH. (b) Ratedetermining step: generation of aryllithiate complex from transient LiH. (c) Product selectivity determining step: silylation vs reduction.
(Figure 2b). Thus, the C−Br bond cleavage is driven by electron donation from LiH to the C−Br σ* bond rather than to the aromatic π* orbital (B in Figure 1). We made additional observations. First, no EPR signals were detected during the reaction, and a radical scavenger (TEMPO) showed no effects on the reaction yield and rate. The tolerance of air attests to the absence of radical species. Second, the reaction rate examined for phenylsilane, lithium tert-butoxide, and 1-iodonaphthalene showed 0.94th, 0.95th, and 0.48th order dependence, respectively, indicating participation of all reactants in the rate limiting transition state and probable involvement of pre-equilibria before the formation of INT3.14 These observations were corroborated by a reaction pathway found by the DFT calculation summarized in Figure 3. The model here is arguably too simplified, yet provides insights into the mechanism of reductive cleavage of the C−X bond. The reaction comprises three stages, generation of a LiH reactive species (a), C−X bond cleavage (b), and C−Si bond formation (c). In Figure 3a, the silane and the alkoxide first form a silicate INT1 and then a LiH/alkoxysilane complex INT2 with energy loss. In agreement with these energetics, we could not detect these species by 29Si NMR or 1H NMR. In Figure 3b, LiH starts donating electrons to the σ* orbital of the C−halide bond (INT3), where a linear H−X−C geometry is characteristic, and accounts for the observed low steric sensitivity of the reaction. There was no sign of aromatic π-orbital participation as suggested by the experiment in Figure 2b. The transition state of the C−X bond cleavage is early and structurally similar to INT3. It goes downhill to INT4, a ternary complex among aryllithium, alkoxysilane, and HX. The −0.666 charge on the H atom in INT3 becomes near zero in INT4, and the negative charge accumulates on the aromatic ring.15 Here we expect that
an electron-donating group destabilized TS1 and, hence, decelerates the C−X bond cleavage as seen experimentally (see above). This expectation was supported by theory; that is, the calculated energy barrier increases in the order of 4-F, 4-H, and 4-MeO as shown in Figure 4a.
Figure 4. Gibbs free energy diagrams for the reaction with 4-fluoro-1iodobenzene, iodobenzene, and 4-methoxy-1-iodobenzene (a) As to TS1. (b) As to TS2.
INT4 is arguably an unstable species and decomposes immediately to stable products in Figure 3c, where the silylation/reduction selectivity is determined. The silylation path via TS2 is an intramolecular substitution on the silicon atom within INT4, and the reduction step via TS3 comprises protonation of the aryllithium moiety of INT4. The calculated C
DOI: 10.1021/acs.orglett.8b00818 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
Chem. Soc. 2007, 129, 14164−14165. (d) Kuninobu, Y.; Yamauchi, K.; Tamura, N.; Seiki, T.; Takai, K. Angew. Chem., Int. Ed. 2013, 52, 1520− 1522. (4) Selected examples using organometallics: (a) Hirone, N.; Sanjiki, H.; Tanaka, R.; Hata, T.; Urabe, H. Angew. Chem., Int. Ed. 2010, 49, 7762−7764. (b) Fridel−Crafts C−H silylation: Bähr, S.; Oestreich, D. Angew. Chem., Int. Ed. 2017, 56, 52−59 and references therein. (c) Marciniec, B. Hydrosilylation: A Comprehensive Review on Recent Advances; Springer Science; 2009, 1−418. (5) Lesbani, A.; Kondo, H.; Yabusaki, Y.; Nakai, M.; Yamanoi, Y.; Nishihara, H. Chem. - Eur. J. 2010, 16, 13519−13527. (6) A review for the silylation reaction: (a) Xu, Z.; Xu, L. W. ChemSusChem 2015, 8, 2176−2179. (b) Sharma, R.; Kumar, R.; Kumar, I.; Singh, B.; Sharma, U. Synthesis 2015, 47, 2347−2366. (c) Xu, Z.; Huang, W. S.; Zhang, J.; Xu, L. W. Synthesis 2015, 47, 3645−3668. (7) Dehydrogenative silylation with solid bases including metal alkoxides and hydrosilanes: (a) Calas, R.; Bourgeois, P. C. R. Acad. Sci., Paris, Ser. C 1969, 268, 3645−3668. (b) Baba, T.; Kato, A.; Ono, Y. Catal. Today 1998, 44, 271−276. (c) Itoh, M.; Iwata, K.; Inoue, K. J. Organomet. Chem. 1994, 476, C30−C31. (d) Ishikawa, J. I.; Inoue, K.; Itoh, M. J. Organomet. Chem. 1998, 552, 303−311. (e) Ishikawa, J. I.; Itoh, M. J. Organomet. Chem. 1998, 552, 303−311. (8) Metal-alkoxide mediated silylation of aryl halides: Dervan, P. B.; Shippey, M. A. J. Org. Chem. 1977, 42, 2654−2655. (9) The reaction vessel was connected to atmospheric air through a column of anhydrous CaCl2. (10) ICP analysis revealed only a trace amount of transition metal contamination. Addition of a catalytic amount of a transition metal did not accelerate the reaction. Use of several lithium tert-butoxides from different sources gave the same results. See SI for details. (11) (a) Pan, X.; Lacote, E.; Lalevée, J.; Curran, P. D. J. Am. Chem. Soc. 2012, 134, 5669−5674. (b) Zhou, B.; Sato, H.; Ilies, L.; Nakamura, E. ACS Catal. 2018, 8, 8−11. (12) For a list of substrates investigated, see SI. (13) (a) Shirakawa, E.; Hayashi, Y.; Itoh, K.; Watabe, R.; Uchiyama, N.; Konagaya, W.; Masui, S.; Hayashi, T. Angew. Chem., Int. Ed. 2012, 51, 218−221. (b) Yamamoto, E.; Ukigai, S.; Ito, H. Chem. Sci. 2015, 6, 2943−2951. (14) For a detailed discussion, see SI. (15) Attempts to trap this anionic species failed, maybe due to its short lifetime. See Scheme S8 in SI. (16) The reactivity difference between different substrates (i.e., bromobenzene vs iodobenzene) is well explained by the proposed mechanism. See Table S1 in the SI. (17) (a) Fedorov, A.; Toutov, A. A.; Swisher, N. A.; Grubbs, R. H. Chem. Sci. 2013, 4, 1640−1645. (b) Toutov, A. A.; Liu, W. B.; Betz, K. N.; Fedorov, A.; Stoltz, B. M.; Grubbs, R. H. Nature 2015, 518, 80−84. (c) Toutov, A. A.; Liu, W. B.; Betz, K. N.; Stoltz, B. M.; Grubbs, R. H. Nat. Protoc. 2015, 10, 1897−1903. Toutov, A. A.; Salata, M.; Fedorov, A.; Shabaker, J. W.; Houk, K. N.; Grubbs, R. H. Nat. Energy 2017, 2, 17008. (18) (a) Liu, W.-B.; Schuman, D. P.; Yang, Y.-F.; Toutov, A. A.; Liang, Y.; Klare, H. F. T.; Nesnas, N.; Oestreich, M.; Blackmond, D. G.; Virgil, S. C.; Banerjee, S.; Zare, R. N.; Grubbs, R. H.; Houk, K. N.; Stoltz, B. M. J. Am. Chem. Soc. 2017, 139, 6867−6879. (b) Banerjee, S.; Yang, Y.-F.; Jenkins, I. D.; Liang, Y.; Toutov, A. A.; Liu, W.-B.; Schuman, D. P.; Grubbs, R. H.; Stoltz, B. M.; Krenske, E. H.; Houk, D. P.; Zare, R. N. J. Am. Chem. Soc. 2017, 139, 6880−6887.
activation energy of the silylation path also shows correlation to the 4-substituent (Figure 4b), indicating that an electronwithdrawing substituent stabilized the aryllithium intermediate and hence retarded the silylation relative to the protonation pathway. This is opposite to the one found for the C−X cleavage. The experimental observation in Figure 2a is thus supported.16 In summary, we have generated a transient LiH species under mild conditions from air stable reagents and discovered its ability to reductively silylate aromatic and alkenyl halides. The silylation reaction reported here shows some resemblance to the C−H silylation reported by Stoltz and Grubbs,17 which proceeds however under markedly different conditions and presumably through different mechanisms.18 Several puzzling reactivity profiles found in the synthetic experiments were reconciled by the mechanism proposed with the aid of theory, which will provide useful guidelines for future development of new alkali metal hydride chemistry.
■
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b00818. Experimental procedures and physical properties of the compounds (PDF)
■
AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. ORCID
Takumi Yoshida: 0000-0001-5006-3075 Laurean Ilies: 0000-0002-0514-2740 Eiichi Nakamura: 0000-0002-4192-1741 Present Address †
RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS We thank MEXT for financial support KAKENHI (15H05754 for E.N. and JP26708011 to L.I.). T.Y. thanks the University of Tokyo’s “Evonik Scholars Fund” Scholarship. This work was partially supported by CREST, JST (Molecular Technology). We thank for Dr. Yasukawa Tomohiro (The University of Tokyo) for assistance with the ICP-AES analysis.
■
REFERENCES
(1) (a) Too, P. C.; Chan, G. H.; Tnay, Y. L.; Hirao, H.; Chiba, S. Angew. Chem., Int. Ed. 2016, 55, 3719−3723. (b) Hong, Z.; Ong, D. Y.; Muduli, S. K.; Too, P. C.; Chan, G. H.; Tnay, Y. L.; Chiba, S.; Nishiyama, Y.; Hirao, H.; Soo, H. S. Chem. - Eur. J. 2016, 22, 7108− 7114. (c) Ong, D. Y.; Tejo, C.; Xu, K.; Hirao, H.; Chiba, S. Angew. Chem., Int. Ed. 2017, 56, 1840−1844. (2) Ilies, L.; Yoshida, T.; Nakamura, E. J. Am. Chem. Soc. 2012, 134, 16951−16954. (3) For example: (a) Corey, J. Y. Adv. Organomet. Chem. 2004, 51, 1−52. (b) Nakajima, Y.; Shimada, S. RSC Adv. 2015, 5, 20603−20616. (c) Fukazawa, A.; Li, Y.; Yamaguchi, S.; Tsuji, H.; Tamao, K. J. Am. D
DOI: 10.1021/acs.orglett.8b00818 Org. Lett. XXXX, XXX, XXX−XXX
