Subscriber access provided by United Arab Emirates University | Libraries Deanship
Letter
NHC-Catalyzed Enantioselective Dearomatizing Hydroacylation of Benzofurans and Benzothiophenes for the Synthesis of Spirocycles Daniel Janssen-Müller, Mirco Fleige, Danny Schluens, Marco Wollenburg, Constantin G. Daniliuc, Johannes Neugebauer, and Frank Glorius ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b01852 • Publication Date (Web): 26 Jul 2016 Downloaded from http://pubs.acs.org on July 28, 2016
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 6
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ACS Catalysis
NHC-Catalyzed Enantioselective Dearomatizing Hydroacylation of Benzofurans and Benzothiophenes for the Synthesis of Spirocycles Daniel Janssen-Müller†, Mirco Fleige†, Danny Schlüns†,‡, Marco Wollenburg†, Constantin G. Daniliuc†, Johannes Neugebauer†,‡,* and Frank Glorius†,* †
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraβe 40, 48149 Münster, Germany ‡ Center for Multiscale Theory and Computation, Westfälische Wilhelms-Universität Münster, Corrensstraβe 40, 48149 Münster, Germany ABSTRACT: Benzofurans and benzothiophenes have been efficiently employed as substrates in an enantioselective intramolecular hydroacylation. Breaking aromaticity in a 5-exo-trig cyclization of easily accessible heteroarenes by NHCcatalyzed hydroacylation gives access to a simple class of mainly unexplored spirocycles with up to 99% ee. The formed product class bears interesting 3-dimensional pseudo-axial chirality and shows typical ketone reactivity. DFT-calculations reveal erosion of the ee via a stepwise mechanism bearing a hetero Wheland intermediate. Theoretical data is in agreement with deuterium-labelling studies and a linear correlation between electronics (σ) and the ee. KEYWORDS:
carbenes
•
organocatalysis
•
aromaticity
1
The use of N-heterocyclic carbenes (NHCs) as organocatalysts2 for the hydroacylation of unactivated olefins is an emerging field that enables the C–C bond formation between aldehydes and olefins. The reaction is generally based on a concerted Conia-ene type mechanism and has been successfully applied to various olefin (and few alkynes & benzynes) substrates.3 Noteworthy in this context is the first successful hydroacylation of enol-ethers, which was developed by She et al.3b and later rendered enantioselective by our group.3g Going from olefins to arenes, the reactivity towards addition reactions diminishes significantly, due to resonance stabilization energy (40 kJ/mol for benzofuran and 48 kJ/mol for benzothiophene),4a which needs to be overcome to achieve dearomatization, rendering these transformations challenging.4 During a dearomatization reaction, several stereocenters are often formed in one step and complex 3-dimensional products are formed from simple 2-dimensional, easily accessible and stable starting materials. Therefore, new methodologies for the enantioselective dearomatization of arenes are highly desirable.
•
enantioselectivity
•
spiro
compounds
The enantioselective synthesis of spirocyclic compounds is an important field, due to the unique structure, rigidity and related properties of the spirocyclic scaffold.8 Prominent applications are organic optoelectronics,9a drugdiscovery9b or use as chiral building-blocks for enantioselective catalysis.9c Herein, we report the NHC-catalyzed intramolecular hydroacylation/dearomatization of benzofurans and benzothiophenes (Scheme 1). The reaction reveals a new reactivity of these heteroarenes, which have to date not been used as substrates for hydroacylation, introducing a new tool for the enantioselective functionalization of heteroarenes. Scheme 1. Influence of different NHC structures on the reaction.a
There are several approaches for the dearomatization of phenols or nitrogen-containing heteroarenes, such as indole- or pyridine-derivatives.4 The latter was recently applied in the field of NHC catalysis by our group, using N-iminopyridinium ylides as preactivated arenes for annulation with NHC-generated homoenolates or enolates.5a Noteworthy is also the annulation of tropone as a partly aromatic species, which is reported to undergo annulation with NHC-generated homoenolates.5b To our knowledge, there is no enantioselective catalytic method for the dearomatization of benzofurans or benzothiophenes6 with the exception of their hydrogenation.7
ACS Paragon Plus Environment
ACS Catalysis a
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
1
The yield of 2a and 2r was determined by H NMR spectroscopy with CH2Br2 as internal standard. The ee value was determined by HPLC using a chiral stationary phase.
We started our investigation by subjecting benzofuran 1a to catalytic amounts of triazolium salt 3a. and K2CO3. The product 2a formed in full conversion and 98% ee. The yield dropped significantly using stronger bases such as DBU, which led to several decomposition products. Variations of the catalyst led to inferior yield and ee. Interestingly, the N-2,6-dimethoxyphenyl substituent at the triazole core was crucial for this challenging transformation, a continuation of a trend regarding this newly designed class of highly active NHCs.10 Catalyst and base loading could be reduced to 10 mol% each. Product 2a could be isolated in 81% yield and 99% ee on a 2 mmol scale. Remarkably, the reaction could be extended to the dearomatization of benzothiophenes. However, while the corresponding spirocyclic product 2r could be isolated in 74% yield, only 51% ee were obtained. Such a large decrease in enantioselectivity compared to benzofurans is surprising, since the transition-states of the two heteroarenes should have a similar geometry with steric influences of the chiral catalyst being similar. We screened different chiral NHC precursors, revealing 3d (79% ee) and 3e (89% ee) as promising candidates, but only 3d gave satisfactory yields and was used for the substrate scope. Table 1. Scope of benzofurans and benzothiophenes.a
Page 2 of 6
and electron-withdrawing substituents, either directly attached to the benzofuran ring (2e-q), providing the products in satisfying yields and excellent enantioselectivities. The structure and absolute stereochemistry of product 2e was confirmed by single-crystal X-ray diffraction analysis. We tested a range of benzothiophene substrates 1r-1z for this transformation with both catalysts 3a and 3d and found that with 3a, the ee correlates to the electronics of the employed benzothiophene. Using catalyst 3d, the ee was quite robust against electronic influences on the benzothiophenes, leading to 70-84% ee for benzothiophenes and 38% ee for thienopyridine 1t. With catalyst 3a, an inverse electronic trend was observed for benzothiophenes, compared to benzofurans, where the electronpoor substrates (in particular 1x and 1z) were converted to the product in higher ee than the more electron-rich substrates 1u-w (Figure 1).12 100 Me 80
OCF3 CF3 OCF3
OMe
H
CN
60 % ee 40
OMe
CF3
H Me
20 σmeta
0 -0.1
0.1
0.3
Catalyst 3a
0.5
Catalyst 3d
Figure 1. Enantioselectivity of benzothiophene dearomatization plotted against σmeta of aryl substituents X shows differ12 ent behaviour of 3a and 3d.
O
N R N N O
(24.4) -29.1
O R=
Bn H
O
X
a: X = O r: X = S
O O N R N
N Bn
N R N
(18.7) -35.5
O Bn
OH
X
(-86.5) -91.9 a
Conditions: 0.3 mmol 1a-z, 10 mol% 3a/d, 10 mol% K2CO3, 1,4-dioxane (0.5 M), 80 °C, 16 h. Yields given are isolated yields after column chromatography. The ee was determined b by HPLC using a chiral stationary phase. Catalyst and base c 11 loading 20 mol% each. Molecular structure of 2e.
Investigation of the scope of the reaction (Table 1) revealed various substitutions of the benzaldehyde moiety were well tolerated (2b-d). Substitutions of the benzofuran moiety gave good results, with both electron-donating
∆ E = 62.8 (110.9) ∆ E = 59.8 (108.0)
(-89.3) -95.3
X
(-27.9) -64.5
O
N Bn OH H
TS1a/r
(-34.5) -64.4
(-94.6) -81.2
O N R N
S
4a/r
N
5r
N R N
N Bn O
(-94.0) -93.7
S
TS2r
6a/r
Figure 2. Calculated relative energies [TPSS-D3(BJ)/def2-1 TZVP, M06-2X in parentheses] in kJmol : Reaction pathways for substrates 1a (red) and 1r (orange) with structures of 11 transition states and intermediates.
ACS Paragon Plus Environment
Page 3 of 6
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ACS Catalysis
Based on the interesting effects between electronics and ee found with catalyst 3a, we expected this reaction to be an exciting test case to elucidate the mechanism. We performed DFT-calculations to gain a deeper understanding into why the enantioselectivities for benzothiophene substrates were lower compared to the benzofurans (Figure 2).11 Starting from the (E)-Breslow intermediates (4a and 4r) derived from substrates 1a and 1r, a transition-state (TS1) for both reactions was found, which corresponds to the previously postulated3d proton transfer from the OH to the 3-position of the heterocycles. In the case of benzofuran (1a), the C–C bond formation occurs subsequently without a second transition-state to give the NHC adduct of the product (6a), similar to the hydroacylation of olefins.3d Conversely, the benzothiophene was found to form zwitterionic intermediate (5r) following proton transfer, without the formation of a C–C bond (dC-C = 2.126 Å) and a second transition-state (TS2r) with a small energy barrier for the C–C bond formation. Taking into account the observed experimental electronic influence of the arene on the ee value, we postulate that the lowered ee is a result of a possible rotation of the protonated arene to give the minor enantiomer. The more electron-rich benzothiophenes, which should give a more stable intermediate 5r, would make a rotation and loss of enantiocontrol more likely. This mechanistic proposal is supported by the reaction of deuterated benzothiophene substrate 7 (Scheme 2): The corresponding product 8 was isolated as a mixture of deuterium/hydrogen diastereomers resulting from synand anti-hydroacylation (syn/anti mixture, determined by NMR). The (R):(S) ratio (regarding the quarternary stereocenter, determined by HPLC using a chiral stationary phase) was interestingly the same ratio as the deuterium syn/anti ratio (77:23 for 3a, 84:16 for cat. 3d).
highly selective, as supported by the DFT-calculations (TS1r to 5r), while the C–C bond formation (TS2r to 6r), which sets the enantioselectivity of the product, is less selective. Substrate 9 also supports this hypothesis, only leading to syn-hydroacylation product 10 in 97% ee, without any of the anti-diastereomers detected. We investigated the reactivity of ketone 2a (Scheme 3): The formation of oxime 11 was achieved in almost quantitative yield. Reduction of the carbonyl group using NaBH4 led to a diastereoselective formation of alcohol 12 and, using standard Baeyer-Villiger oxidative conditions, formation of the spirocyclic isochromanone derivative 13 was achieved. All follow-up reactions proceeded with retention of the stereogenic center. Scheme 3. Derivatizations of 2a: Oxime formation, reduction and Baeyer-Villiger oxidation.
We investigated the hydroacylation of the analogous indole substrate 14, which unfortunately didn’t lead to the desired product under the developed reaction conditions (Scheme 4). Unprotected indole substrates could not be synthesized so far. Scheme 4. Attempted indole hydroacylation.
Scheme 2. Substituents at the 3-position reveal highly selective proton transfer with less selective C–C bond formation for benzothiophenes for both catalyst 3a and 3d. In conclusion, we have developed the first organocatalyzed enantioselective dearomatization of benzofurans and benzothiophenes via hydroacylation, allowing the formation of a new class of chiral spirocycles.13 Results from DFT-calculations and experimental data both suggest that there is a qualitative difference between the mechanisms of the hydroacylation of benzofurans and benzothiophenes, where benzofurans react in a concerted, highly enantioselective fashion and benzothiophenes react stepwise, which accounts for a loss of enantiocontrol with catalyst 3a.
AUTHOR INFORMATION After recrystallization from hexanes (enrichment of the major enantiomer), the syn/anti ratio increased in the same magnitude as the enantiomeric ratio for both reactions with 3a and 3d, suggesting that out of the four possible diastereomers, the isomers resulting from proton transfer to the Si face of the benzothiophene are formed
Corresponding Authors
[email protected] [email protected] Notes The authors declare no competing financial interests.
ACS Paragon Plus Environment
ACS Catalysis Funding Sources
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Generous financial support by the Deutsche Forschungsgemeinschaft (SPP 1179, IRTG2027, Leibniz Award, SFB858) are gratefully acknowledged. The research of F.G. is supported by the Alfried Krupp Prize for Young University Teachers of the Alfried Krupp von Bohlen and Halbach Foundation.
ASSOCIATED CONTENT Supporting Information. Experimental procedures, spectroscopic data, mechanistic experiments and computational studies. This material is available free of charge via the Internet at http://pubs.acs.org.
ACKNOWLEDGMENT We thank Theresa Olyschläger for synthesizing compounds S2-8. We are grateful to Karin Gottschalk for skillful technical assistance and thank Dr. Chang Guo, Dr. Lisa Candish and Dr. Michael Schedler for helpful discussions.
REFERENCES (1) Selected references: (a) Herrmann, W. A.; Köcher, C. Angew. Chem. Int. Ed. Engl. 1997, 36, 2162−2187. (b) Bourissou, D.; Guerret, O.; Gabbaï, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39– 92. (c) Hahn, F. E.; Jahnke, M. C. Angew. Chem. Int. Ed. 2008, 47, 3122–3172. (d) Díez-González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612–3676. (e) Dröge, T.; Glorius, F. Angew. Chem. Int. Ed. 2010, 49, 6940–6952. (f) Nelson, D. J.; Nolan, S. P. Chem. Soc. Rev. 2013, 42, 6723–6753. (g) Hopkinson, M. N.; Richter, C.; Schedler, M.; Glorius, F. Nature 2014, 510, 485–496. (2) For reviews on NHC organocatalysis, see: (a) Zeitler, K. Angew. Chem. Int. Ed. 2005, 44, 7506–7510. (b) Marion, N.; DíezGonzález, S.; Nolan, S. P. Angew. Chem. Int. Ed. 2007, 46, 2988– 3000. (c) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606–5655. (d) Rovis, T. Chem. Lett. 2008, 37, 2–7. (e) Phillips, E. M.; Chan, A.; Scheidt, K. A. Aldrichimica Acta 2009, 42, 55–66. (f) Moore, J. L.; Rovis, T. Top. Curr. Chem. 2010, 291, 77– 144. (g) Vora, H. U.; Rovis, T. Aldrichimica Acta 2011, 44, 3–11. (h) Hirano, K.; Piel, I.; Glorius, F. Chem. Lett. 2011, 40, 786–791. (i) Chiang, P.-C.; Bode, J. W. TCI Mail 2011, 149, 2–17. (j) Nair, V.; Menon, R. S.; Biju, A. T.; Sinu, C. R.; Paul, R. R.; Jose, A.; Sreekumar, V. Chem. Soc. Rev. 2011, 40, 5336–5346. (k) Biju, A. T.; Kuhl, N.; Glorius, F. Acc. Chem. Res. 2011, 44, 1182–1195. (l) Cohen, D. T.; Scheidt, K. A. Chem. Sci. 2012, 3, 53–57. (m) Grossmann, A.; Enders, D. Angew. Chem. Int. Ed. 2012, 51, 314– 325. (n) Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012, 41, 3511–3522. (o) Izquierdo, J.; Hutson, G. E.; Cohen, D. T.; Scheidt, K. A. Angew. Chem. Int. Ed. 2012, 51, 11686–11698. (p) Mahatthananchai, J.; Bode, J. W. Chem. Sci. 2012, 3, 192–197. (q) Vora, H. U.; Wheeler, P.; Rovis, T. Adv. Synth. Catal. 2012, 354, 1617–1639. (r) Fèvre, M.; Pinaud, J.; Gnanou, Y.; Vignolle, J.; Taton, D. Chem. Soc. Rev. 2013, 42, 2142–2172. (s) Ryan, S. J.; Candish, L.; Lupton, D. W. Chem. Soc. Rev. 2013, 42, 4906–4917. (t) Mahatthananchai, J.; Bode, J. W. Acc. Chem. Res. 2014, 47, 696–707. (u) Jin, Z.; Chen, S.; Wang, Y.; Zheng, P.; Yang, S.; Chi, Y. R. Angew. Chem. Int. Ed. 2014, 53, 13506–13509. (v) Flanigan, D. M.; RomanovMichailidis, F.; White, N. A.; Rovis, T. Chem. Rev. 2015, 115, 9307– 9387. (w) Menon, R. S.; Biju, A. T.; Nair, V. Chem. Soc. Rev. 2015, 44, 5040–5052. (x) Yetra, S. R.; Patra, A.; Biju, A. T. Synthesis 2015, 47, 1357–1378. (3) For intramolecular NHC-catalyzed hydroacylation, see: (a) He, J.; Zheng, J.; Liu, J.; She, X.; Pan, X. Org. Lett. 2006, 8, 4637– 4640. (b) He, J.; Tang, S.; Liu, J.; Su, Y.; Pan, X.; She, X. Tetrahe-
Page 4 of 6
dron 2008, 64, 8797–8800. (c) Hirano, K.; Biju, A. T.; Piel, I.; Glorius, F. J. Am. Chem. Soc. 2009, 131, 14190–14191. (d) Piel, I.; Steinmetz, M.; Hirano, K.; Fröhlich, R.; Grimme, S.; Glorius, F. Angew. Chem. Int. Ed. 2011, 50, 4983–4987. (e) Biju, A. T.; Wurz, N. E.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 5970–5971. (f) Padmanaban, M.; Biju, A. T.; Glorius, F. Org. Lett. 2011, 13, 5624– 5627. (g) Janssen-Müller, D.; Schedler, M.; Fleige, M.; Daniliuc, C. G.; Glorius, F. Angew. Chem. Int. Ed. 2015, 127, 12671–12675. h) Lu, H.; Lin, J.-B.; Liu, J.-Y.; Xu, P.-F. Chem. Eur. J. 2014, 20, 11659– 11663. i) Ghosh, A; Walker Jr., J. A.; Ellern, A.; Stanley, L. M. ACS Catal. 2016, 6, 2673–2680. For intermolecular hydroacylation of alkenes and alkynes see: (j) Biju, A. T.; Glorius, F. Angew. Chem. Int. Ed. 2010, 49, 9761–9764. (k) Bugaut, X; Liu, F; Glorius, F. J. Am. Chem. Soc. 2011, 133, 8130–8133. (l) Liu, F.; Bugaut, X.; Schedler, M.; Fröhlich, R.; Glorius, F. Angew. Chem. Int. Ed. 2011, 50, 12626–12630. (m) Schedler, M.; Wang, D.-S.; Glorius, F. Angew. Chem. Int. Ed. 2013, 52, 2585–2589. (4) For resonance-stabilization energies of heterocycles; see: (a) Agostinha, M.; Matos, R.; Liebman, J. F. Top. Heterocycl. Chem. 2009, 19, 1–26. For reviews on dearomatization reactions, see: (b) Roche, S. P.; Porco, J. A. Angew. Chem. Int. Ed. 2011, 50, 4068–4093. (c) Pouysegu, L.; Deffieux, D.; Quideau, S. Tetrahedron 2010, 66, 2235–2261. (d) Ortiz, F. L.; Iglesias, M. J.; Fernandez, I.; Sanchez, C. M. A.; Gomez, G. R. Chem. Rev. 2007, 107, 1580–1691. (e) Pape, A. R.; Kaliappan, K. P.; Kündig, E. P. Chem. Rev. 2000, 100, 2917–2940. (f) Zhuo, C. X.; Zhang, W.; You, S. L. Angew. Chem. Int. Ed. 2012, 51, 12662–12686. (g) Zhuo, C. X.; Zheng, C.; You, S. L. Acc. Chem. Res. 2014, 47, 2558–2573. (h) Ding, Q. P.; Zhou, X. L.; Fan, R. H. Org. Biomol. Chem. 2014, 12, 4807–4815. (i) Roche, S. P.; Tendoung, J. J. Y.; Treguier, B. Tetrahedron 2015, 71, 3549–3591. (j) James, M. J.; O'Brien, P.; Taylor, R. J. K.; Unsworth, W. P. Chem. Eur. J. 2016, 22, 2856–2881. (k) Liang, X.-W.; Zheng, C.; You, S. L. Chem. Eur. J. 2016, doi: 10.1002/chem.201600885. (5) For NHC-catalyzed dearomatization, see: a) Guo, C.; Fleige, M.; Janssen-Müller, D.; Daniliuc, C. G.; Glorius, F. Nat. Chem. 2015, 7, 842–847. b) Nair, V.; Poonoth, M.; Vellalath, S.; Suresh, E.; Thirumalai, R. J. Org. Chem., 2006, 71, 8964–8965. (6) For pioneering work on the catalytic dearomatization of benzofurans see: (a) Hata, K.; He, Z. H.; Daniliuc, C. G.; Itami, K.; Studer, A. Chem. Commun. 2014, 50, 463–465. (b) James, M. J.; Cuthbertson, J. D.; O'Brien, P.; Taylor, R. J. K.; Unsworth, W. P. Angew. Chem. Int. Ed. 2015, 54, 7640–7643. For uncatalyzed dearomatization reactions see: (c) Chopin, N.; Gérard, H.; Chataigner, I.; Piettre, S. R. J. Org. Chem. 2009, 74, 1237–1246. (d) Grandclaudon, P.; Lablachecombier, A. J. Org. Chem. 1978, 43, 4379–4381. (e) Yoshida, K.; Miyoshi, K. J. Chem. Soc., Perkin Trans. 1, 1992, 333–335. (f) Wang, M. L.; Liu, X. X.; Zhou, L.; Zhu, J. D.; Sun, X. Org. Biomol. Chem. 2015, 13, 3190–3193. (7) For reviews on hydrogenations of arenes see: (a) Dyson, P. J. Dalton Trans. 2003, 2964–2974. (b) Glorius, F. Org. Biomol. Chem. 2005, 3, 4171–4175. (c) Zhou, Y.-G. Acc. Chem. Res. 2007, 40, 1357–1366. (d) Kuwano, R. Heterocycles 2008, 76, 909–922. (e) Wang, D.-S.; Chen, Q.-A.; Lu, S.-M.; Zhou, Y.-G. Chem. Rev. 2012, 112, 2557–2590. (f) Yu, Z.; Jin, W.; Jiang, Q. Angew. Chem. Int. Ed. 2012, 51, 6060–6072. (g) He, Y.-M.; Song, F.-T.; Fan, Q.-H. Top. Current Chem. 2014, 343, 145–190. For selected examples of hydrogenations of benzofurans and benzothiophenes see: (h) Kaiser, S.; Smidt, S. P.; Pfaltz, A. Angew. Chem. Int. Ed. 2006, 45, 5194–5197. (i) Ortega, N.; Urban, S.; Beiring, B.; Glorius, F. Angew. Chem. Int. Ed. 2012, 51, 1710–1713. (j) Ortega, N.; Beiring, B.; Urban, S.; Glorius, F. Tetrahedron 2012, 68, 5185–5192. (k) Pauli, L.; Tannert, R.; Scheil, R.; Pfaltz, A. Chem. Eur. J. 2015, 21, 1482– 1487. (l) Urban, S.; Beiring, B.; Ortega, N.; Paul, D.; Glorius, F. J. Am. Chem. Soc. 2012, 134, 15241–15244. (8) For the synthesis of spiro compounds, see: (a) Rosenberg, S.; Leino, R. Synthesis 2009, 2651–2673. (b) Rios, R. Chem. Soc.
ACS Paragon Plus Environment
Page 5 of 6
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ACS Catalysis
Rev. 2012, 41, 1060–1074. (c) Franz, A. K.; Hanhan, N. V.; BallJones, N. R. ACS Catal. 2013, 3, 540–553. (9) For applications of spiro compounds, see: (a) Saragi, T. P. I.; Spehr, T.; Siebert, A.; Fuhrmann-Lieker, T.; Salbeck, J. Chem. Rev. 2007, 107, 1011–1065. (b) Zheng, Y. J.; Tice, C. M.; Singh, S. B. Bioorg. Med. Chem. Lett. 2014, 24, 3673–3682. (c) Ding, K. L.; Han, Z. B.; Wang, Z. Chem. Asian J. 2009, 4, 32–41. (10) Schedler, M.; Fröhlich, R.; Daniliuc, C. G.; Glorius, F. Eur. J. Org. Chem. 2012, 4164–4171.
(11) See the supporting information for more details. (12) We plotted ee against σmeta instead of σpara because the functionalized phenyl group is in meta position with respect to the aromatic olefin. (13) For a 3-(2-oxopropyl) derivative of 2a see: Hu, J.; Liu, D.; Xu, W.; Zhang, F.; Zheng, H. Tetrahedron 2014, 70, 7511–7517.
ACS Paragon Plus Environment
ACS Catalysis
Page 6 of 6
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 ACS Paragon Plus Environment
6
