Letter pubs.acs.org/OrgLett
Diastereoselective B(C6F5)3‑Catalyzed Reductive Carbocyclization of Unsaturated Carbohydrates Trandon A. Bender,† Jennifer A. Dabrowski,‡ Hongyu Zhong,† and Michel R. Gagné*,† †
Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States Department of Chemistry, Elon University, Elon, North Carolina 27244, United States
‡
S Supporting Information *
ABSTRACT: A B(C6F5)3-catalyzed method for the selective conversion of unsaturated carbohydrates to cyclopentanes and cyclopropanes is disclosed. Catalyst activation of tertiary silanes generates the ion pair [(C6F5)3B−H][ROSi2] whose components synergistically activate C−O bonds for diastereoselective C−C bond formation. Sila-THF cations are invoked as key intermediates facilitating carbocyclizations. Complex chiral synthons are thereby obtained in a single pot.
R
Prominent recent developments in this area include enantioselective reductions of carbonyls, imines, and enol ethers.2 Much less explored are reactions that reduce C−O single bonds, though these transformations were discovered early.6 In these cases, the combination of B(C6F5)3, a silane, and an ether yields H−B(C6F5)3− paired with a sila-oxonium ion (R2O−Si+). This nucleophile/electrophile pair productively recombine to reduce/cleave the C−O bond. In our own experiments, we have found that competent neighboring groups (e.g., ROSi) can intercept the R2O−Si+ intermediate to yield cyclic intermediates prior to reduction (e.g., Scheme 1).7 Since these intramolecular additions are typically stereospecific, we examined whether tethered alkenes might also be sufficiently nucleophilic to provide carbocycles. Our previous work demonstrating that THFs were preferred intermediates in the C−O activation of polyols led us to first test unsaturated 2-deoxysugars. As Scheme 2 illustrates, 10 mol % of B(C6F5)3 in combination with a tertiary silane efficiently converts gluco-derived 1 into a single diastereomer of cyclopropane 6 (82%), rather than the expected cyclopentane. This outcome is consistent with a chemoselective activation of the homoallylic C−O position,8 though mechanistic studies suggest a more complex mechanism (vide infra). Galactosederived 2 generates the diastereomeric 8 with high efficiency and selectivity (95% yield, >98:2 dr), indicating an insensitivity to existing stereochemistry. The yields and/or diastereoselectivities are moderately silane dependent, and this can be used for condition optimization. Diene derivatives of the 2deoxycarbohydrates were also productive and led to the analogous carbocycles with a readily functionalized alkene substituent (7, 9, and 10, Scheme 2).9 High diastereoselectivity
eactions catalyzed by the strong Lewis acid tris(pentafluorophenyl)borane, B(C6F5)3, are rapidly expanding in scope. As the catalyst is robust, it can be used in substoichiometric quantities (cf. BF3·OEt2), it provides a unique reactivity profile,1 and it can be made chiral for asymmetric catalysis.2 As articulated by Piers (Scheme 1), and in contrast to BF3·OEt2,3,4 B(C6F5)3 heterolytically activates the silane and not the Lewis base,5 which provides a novel mechanism for the hydrosilylative reduction of carbonyls.1a−e Scheme 1. B(C6F5)3-Catalyzed Reductions
Received: July 13, 2016 Published: August 10, 2016 © 2016 American Chemical Society
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DOI: 10.1021/acs.orglett.6b02050 Org. Lett. 2016, 18, 4120−4123
Letter
Organic Letters
be key to controlling which Lewis adducts of the silylium ion are populated and lead to products. In this case, precyclization acts to sequester the silylium ion (in A),7b and this consequently directs C−C bond formation to between the C2 and C4 positions (Scheme 3). In an outcome that more closely aligns with our original hypothesis, inhibiting transient sila-THF cations does lead to cyclopentanes (Scheme 4). Such is the case with ribose-derived
Scheme 2. Formation of Cyclopropanes from Homoallylic Sugar Derivativesa−c
Scheme 4. B(C6F5)3-Catalyzed Cyclopentane Formationa
a
a
The substrates for 6, 8, and 10 were per-Me3Si protected, and those for 7 and 9 were per-Me2EtSi protected; dr of isolated product; average yield from two trials (± 5%); see the Supporting Information. b 75:25 C3 vs C1 hydride addition. c83:17 C3 vs C1 hydride addition.
55:45 C3 vs C1 hydride addition.
12, which could only form strained cyclic ethers. In the absence of cyclic intermediates, monocyclic transition states (B) are viable and the expected cyclopentanediol 13 (60% yield and 90:10 dr) is formed.14 A similar outcome was obtained for diene nucleophiles, though the regioselectivity for allyl cation reduction was poor (Scheme 4). When multiple THF intermediates are possible, as in the allylic alcohol substrates in Table 1, unique reactivity patterns arise. Njardarson has nicely shown that B(C6F5)3−HSiEt3 catalyzes the rapid reduction of cyclic allylic ethers to yield stereodefined alkenols;15 however, as shown in Table 1, allylic polyols demonstrate divergent reactivity en route to carbocyclic products. Substrates 16−19 thus provide a single cyclopentane diastereomer with four contiguous stereocenters, one of which results from a C−C migration (Table 1). The stereoablation of C3 converges the manno- (17) and gluco-derived (18) substrates to cyclopentane 21 (86:14 dr, entries 2 and 3, Table 1). The diene analogues of 16−19 (not shown) follow suit but trap the allyl cation intermediate with poor site selectivity (∼1:1). The structural assignment was secured by Xray study of 23 (Figure 1).16 Mechanistic studies provided insight into the pathway to the tetrasubstituted cyclopentanes. As shown in Scheme 5, lowering the silane loading to 2.2 equiv stopped the reaction at methylcontaining 24 (73%). The analogous experiment with Et3SiD, which yielded 25 and pointed to the relevancy of silyloxycarbenium ion D (Scheme 5), which is doubly reduced to 25, was informative. X-ray diffraction of 26 verified the invertive nature of the vinyl shift.17 As depicted in Scheme 6A, 27 (per-TMS-24, prepared from 16 on 0.5 mmol scale, see the SI) is smoothly converted to a single diastereomer of 20 with 1.5 equiv of Me2EtSiH (83%), indicating the plausibility of both 27 and E on the reaction pathway. The preponderance of precyclization processes also leads us to suggest that D forms from sila-oxonium C (Scheme 5), which is analogous to A (Scheme 3) except that it additionally contains an allylic silyl ether at C3. This oxygen
was observed in all cases, with the hydride delivery yielding the more stable E-alkene. In all cases, no primary bond reduction was observed.10 One plausible mechanism invokes a R3Si+- (or (C6F5)3B)promoted precyclization to sila-oxonium A (Scheme 3), a Scheme 3. Proposed Pathway for Cyclopropane Formation
process that is driven by the generation of a more basic ethereal oxygen for the silylium ion. C−C bond formation then occurs when the alkene attacks σ*C−O to generate a benzylic cation that is subsequently reduced by (C6F5)3B−H−. The geometric constraints of a bicyclic transition state should favor 3- over 5membered ring formation.11 The organization inherent in A may also account for the high diastereoselectivity. The borane itself is sufficiently active to catalyze the (condensative) conversion of 3 to a single diastereomer of 11 (releasing Si−O−Si). This species arises from the nucleophilic attack of C4−OSi onto the activated primary C7 position.12 Under reductive conditions, 11 can be smoothly converted to 8. Under catalytic conditions, the formation of a more basic THF oxygen would also influence which Lewis base site the silylium ion is located on13 and implies that basicity effects may 4121
DOI: 10.1021/acs.orglett.6b02050 Org. Lett. 2016, 18, 4120−4123
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Organic Letters Table 1. Diastereoselective Formation of Cyclopentanesa
Scheme 5. Mechanism of Methyl Group Introduction
a
Reactions performed with per-Me3Si-protected substrates. Stereochemistry assigned by analogy with 23. bAverage isolated yield from two trials (± 5%). cdr of the isolated product.
Scheme 6. Mechanistic Studies Involving Cyclic Intermediates in the Formation of Cyclopentanes
Figure 1. ORTEP representation of 23. 50% probability thermal ellipsoids.
stabilizes the intermediate resulting from vinyl migration (silaoxo-carbenium ion, D). Consistent with this assertion, 2818 smoothly converts to 24 as a single diastereomer. A precyclization-dependent mechanism also rationalizes how a hindered internal secondary position (C4) could be activated on converting 16 to 24 (i.e., the initial activation is actually of the more accessible primary position followed by THF formation). The combination of B(C6F5)3 and a tertiary silane effectively generates transient silylium ion/hydride ion pairs that work synergistically to activate C−O bonds. The resulting silaoxonium ions are susceptible to alkene trapping to form the C− C bonds of cyclopropanes and cyclopentanes prior to hydride reduction. Our experiments additionally establish the role of neighboring group participation in guiding the cyclization/ reductions while also revealing a set of principles that enable the predictive synthesis of new synthons from biorenewables.
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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.6b02050. Experimental data, spectral data, and X-ray data for new compounds (PDF) X-ray data for compound 26 (CIF) X-ray data for compound 23 (CIF) 4122
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(5) Oestreich, M.; Hermeke, J.; Mohr, J. Chem. Soc. Rev. 2015, 44, 2202−2220. (6) (a) Gevorgyan, V.; Liu, J.-X.; Rubin, M.; Benson, S.; Yamamoto, Y. Tetrahedron Lett. 1999, 40, 8919−8922. (b) Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J.-X.; Yamamoto, Y. J. Org. Chem. 2000, 65, 6179− 6186. (c) Nimmagadda, R. D.; McRae, C. Tetrahedron Lett. 2006, 47, 5755−5758. For a recent review, see: (d) Drosos, N.; Ozkal, E.; Morandi, B. Synlett 2016, 27, 1760−1764. (7) (a) Adduci, L. L.; McLaughlin, M. P.; Bender, T. A.; Becker, J. J.; Gagné, M. R. Angew. Chem., Int. Ed. 2014, 53, 1646−1649. (b) Adduci, L. L.; Bender, T. A.; Dabrowski, J. A.; Gagné, M. R. Nat. Chem. 2015, 7, 576−581. (8) For reviews discussing cationic approaches to cyclopropanes, see: (a) Brookhart, M.; Studabaker, W. B. Chem. Rev. 1987, 87, 411−432. (b) Taylor, R. E.; Engelhardt, F. C.; Schmitt, M. J. Tetrahedron 2003, 59, 5623−5634. (c) Chianese, A. R.; Lee, S. J.; Gagné, M. R. Angew. Chem., Int. Ed. 2007, 46, 4042−4059. (d) Archambeau, A.; Miege, F.; Meyer, C.; Cossy, J. Acc. Chem. Res. 2015, 48, 1021−1031. For relevant examples, see: (e) Nagasawa, T.; Handa, Y.; Onoguchi, Y.; Ohba, S.; Suzuki, K. Synlett 1995, 1995, 739−741. (f) Taylor, R. E.; Engelhardt, F. C.; Schmitt, M. J.; Yuan, H. J. Am. Chem. Soc. 2001, 123, 2964−2969. (g) Taylor, R. E.; Engelhardt, F. C.; Schmitt, M. J. Tetrahedron 2003, 59, 5623−5634. (h) Melancon, B. J.; Perl, N. R.; Taylor, R. E. Org. Lett. 2007, 9, 1425−1428. (9) The direct olefination of reducing sugars with nonstabilized Wittig reagents has been unsuccessful; see: Henk, T.; Giannis, A.; Sandhoff, K. Liebigs Ann. der Chemie 1992, 1992, 167−168. (10) Selective primary bond reduction has been observed by utilizing a neighboring group participation strategy: Drosos, N.; Morandi, B. Angew. Chem., Int. Ed. 2015, 54, 8814−8818. (11) Gutierrez, O.; Harrison, J. G.; Felix, R. J.; Guzman, F. C.; Gagné, M. R.; Tantillo, D. J. Chem. Sci. 2013, 4, 3894−3898. (12) Subjecting 11 to catalytic reduction conditions utilizing the less sterically demanding Et3SiH yielded a mixture of primary reduction (hydride addition to C7) and cyclopropane 8. Stereochemical analysis of the primary reduction product (see the SI) confirmed that the dehydrative cyclization is stereoretentive at C3 (i.e., O3 onto C7).) (13) Silylium ions require Lewis base stabilization (in contrast to carbocations); see: (a) Reed, C. A. Acc. Chem. Res. 1998, 31, 325−332. (b) Reed, C. A. Chem. Commun. 2005, 1669−1677. (14) Volatility of the initial silyl product led to low isolated yield of diol 13. (15) Mack, D. J.; Guo, B.; Njardarson, J. T. Chem. Commun. 2012, 48, 7844−7846. (16) CCDC 1477913. See the Supporting Information for detailed crystallographic data. (17) CCDC 1407831. See Supporting Information for detailed crystallographic data. (18) For representative examples of in situ generation of Et3Si+, see: (a) Nava, M.; Reed, C. A. Organometallics 2011, 30, 4798−4800. (b) Reed, C. A. Acc. Chem. Res. 1998, 31, 325−332.
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was exclusively supported by the Department of Energy (Basic Energy Sciences, DE-FG02-05ER15630). T.A.B. is grateful for a UNC Dissertation Completion Fellowship, and H.Z. thanks the UNC SMART Fellowship program.
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REFERENCES
(1) For representative reductions of carbonyls, see: (a) Parks, D. J.; Piers, W. E. J. Am. Chem. Soc. 1996, 118, 9440−9441. (b) Parks, D. J.; Blackwell, J. M.; Piers, W. E. J. Org. Chem. 2000, 65, 3090−3098. (c) Rendler, S.; Oestreich, M. Angew. Chem., Int. Ed. 2008, 47, 5997− 6000. (d) Bézier, D.; Park, S.; Brookhart, M. Org. Lett. 2013, 15, 496− 499. (e) Chadwick, R. C.; Kardelis, V.; Lim, P.; Adronov, A. J. Org. Chem. 2014, 79, 7728−7733. For representative dehydrosilylations, see: (f) Rendler, S.; Oestreich, M. Angew. Chem., Int. Ed. 2008, 47, 5997−6000. (g) Houghton, A. Y.; Hurmalainen, J.; Mansikkamäki, A.; Piers, W. E.; Tuononen, H. M. Nat. Chem. 2014, 6, 983−988. (h) Curless, L. D.; Ingleson, M. J. Organometallics 2014, 33, 7241− 7246. (i) Chen, Q.-A.; Klare, H. F. T.; Oestreich, M. J. Am. Chem. Soc. 2016, 138, 7868−7871. (2) For enantioselective carbonyl reductions, see: (a) Hog, D. T.; Oestreich, M. Eur. J. Org. Chem. 2009, 2009, 5047−5056. (b) Mewald, M.; Fröhlich, R.; Oestreich, M. Chem. - Eur. J. 2011, 17, 9406−9414. (c) Ren, X.; Du, H. J. Am. Chem. Soc. 2016, 138, 810−813. (d) Süsse, L.; Hermeke, J.; Oestreich, M. J. Am. Chem. Soc. 2016, 138, 6940− 6943. For enantioselective imine hydrogenation, see: (e) Blackwell, J. M.; Sonmor, E. R.; Scoccitti, T.; Piers, W. E. Org. Lett. 2000, 2, 3921− 3923. (f) Chen, D.; Klankermayer, J. Chem. Commun. 2008, 2130− 2131. (g) Chen, D.; Wang, Y.; Klankermayer, J. Angew. Chem., Int. Ed. 2010, 49, 9475−9478. (h) Sumerin, V.; Chernichenko, K.; Nieger, M.; Leskelä, M.; Rieger, B.; Repo, T. Adv. Synth. Catal. 2011, 353, 2093− 2110. (i) Stephan, D. W.; Greenberg, S.; Graham, T. W.; Chase, P.; Hastie, J. J.; Geier, S. J.; Farrell, J. M.; Brown, C. C.; Heiden, Z. M.; Welch, G. C.; Ullrich, M. Inorg. Chem. 2011, 50, 12338−12348. (j) Chen, D.; Leich, V.; Pan, F.; Klankermayer, J. Chem. - Eur. J. 2012, 18, 5184−5187. (k) Ghattas, G.; Chen, D.; Pan, F.; Klankermayer, J. Dalton Trans. 2012, 41, 9026−9028. (l) Mewald, M.; Oestreich, M. Chem. - Eur. J. 2012, 18, 14079−14084. (m) Liu, Y.; Du, H. J. Am. Chem. Soc. 2013, 135, 6810−6813. (n) Hermeke, J.; Mewald, M.; Oestreich, M. J. Am. Chem. Soc. 2013, 135, 17537−17546. (o) Wang, X.; Kehr, G.; Daniliuc, C. G.; Erker, G. J. Am. Chem. Soc. 2014, 136, 3293−3303. (p) Zhu, X.; Du, H. Org. Biomol. Chem. 2015, 13, 1013− 1016. For FLP-type hydrogenation of silyl enol ethers, see: (q) Wei, S.; Du, H. J. Am. Chem. Soc. 2014, 136, 12261−12264. (r) Ren, X.; Li, G.; Wei, S.; Du, H. Org. Lett. 2015, 17, 990−993. (3) (a) Piers, W. E.; Marwitz, A. J. V.; Mercier, L. G. Inorg. Chem. 2011, 50, 12252−12262. (b) Houghton, A. Y.; Hurmalainen, J.; Mansikkamäki, A.; Piers, W. E.; Tuononen, H. M. Nat. Chem. 2014, 6, 983−988. (d) Oestreich, M.; Hermeke, J.; Mohr, J. Chem. Soc. Rev. 2015, 44, 2202−2220. (4) Metal-catalyzed hydrosilylation has also been investigated, see: (a) McLaughlin, M. P.; Adduci, L. L.; Becker, J. J.; Gagné, M. R. J. Am. Chem. Soc. 2013, 135, 1225−1227. (b) Cheng, C.; Brookhart, M. Angew. Chem., Int. Ed. 2012, 51, 9422−9424. (c) Cheng, C.; Brookhart, M. J. Am. Chem. Soc. 2012, 134, 11304−11307. (d) Yang, J.; White, P. S.; Brookhart, M. J. Am. Chem. Soc. 2008, 130, 17509−17518. (e) Park, S.; Brookhart, M. Organometallics 2010, 29, 6057−6064. (f) Park, S.; Brookhart, M. Chem. Commun. 2011, 47, 3643−3645. (g) Metsänen, T. T.; Hrobárik, P.; Klare, H. F. T.; Kaupp, M.; Oestreich, M. J. Am. Chem. Soc. 2014, 136, 6912−6915. 4123
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