Chiral-at-Metal Rh(III) Complex Catalyzed Asymmetric Conjugate

Letter pubs.acs.org/OrgLett

Chiral-at-Metal Rh(III) Complex Catalyzed Asymmetric Conjugate Addition of Unactivated Alkenes with α,β-Unsaturated 2‑Acyl Imidazoles Kuan Li,†,‡ Qian Wan,‡ and Qiang Kang*,‡ †

College of Chemistry, Fuzhou University, Fuzhou 350108, China Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou 350002, China

‡

S Supporting Information *

ABSTRACT: A newly prepared chiral-at-metal Rh(III) complex catalyzed highly efficient asymmetric conjugate addition of para-vinylanilines with α,β-unsaturated 2-acyl imidazoles is developed, affording the corresponding adducts in 67−95% yields with 86−95% ee. Remarkably, employing as low as 0.05 mol % of Rh(III) complex as catalyst, a gram-scale reaction still affords the desired product in 81% yield with 92% ee.

A

Scheme 1. Catalytic Asymmetric Conjugate Addition of Nucloephilic Alkene

symmetric Michael addition of vinyl anion synthons (alkenyl nucleophiles) to Michael acceptors is a powerful synthetic protocol that allows for construction of enantiomerically enriched chiral centers adjacent to an alkenyl moiety.1 Despite the great synthetic value of this kind of double bond,2 the catalytic asymmetric addition of alkenyl nucleophiles remains insufficiently explored. Typical protocols to install a vinyl group onto α,β-unsaturated carbonyl compounds require stoichiometric vinyl organometallic reagents, such as alkenyl boronic acids3 or boronates,4 alkenylaluminums,5 alkenylsilanes,6 alkenylzirconiums,7 alkenylstannanes,8 and alkenyl Grignard reagents9 (Scheme 1a). Simple alkenes have rarely been utilized in asymmetric conjugate addition reactions due to the low nucleophilicity and uncontrolled side reactions.10 Recently, only the Luo group realized the first example of the asymmetric conjugate addition of para-vinylanilines11 to enones catalyzed by chiral primary amines (Scheme 1b).12 Despite these impressive advances,13 development of efficient and highly enantioselective protocols for conjugate addition of unactivated alkenyl nucleophiles is still in great demand. We envisioned combining simple alkenes and chiral-at-metal rhodium complex in asymmetric conjugate addition reaction. Herein, we report an enantioselective addition of para-vinylanilines with α,β-unsaturated 2-acyl imidazoles catalzyed by chiral-at-metal Rh(III) complexes (Scheme 1c).14,15 Our studies were initiated by an exploration of the reaction of α,β-unsaturated 2-acyl imidazole16 1a with para-vinylaniline 2a catalyzed by chiral-at-metal Rh(III) complexes (Table 1). In the presence of 2 mol % of Λ-Rh115a in 1,2-dichloroethane (DCE) at © 2017 American Chemical Society

50 °C, the reaction gave the conjugate addition product 3a in 93% yield with 75% ee (entry 1). Encouraged by these promising results, we examined different chiral Rh(III) complexes ΛRh2,15k Λ-Rh3, and Λ-Rh415m in the title reaction. Gratifyingly, Λ-Rh3 was the best one in terms of enantioselectivity, resulting in 3a in 92% yield with 88% ee (entry 3). In the absence of catalyst, the reaction could not afford any product, which showed that the presence of Λ-Rh3 is mandatory (entry 5). Various solvents such as CHCl3, CH2Cl2, toluene, THF, and MeCN were Received: May 13, 2017 Published: June 8, 2017 3299

DOI: 10.1021/acs.orglett.7b01456 Org. Lett. 2017, 19, 3299−3302

Letter

Organic Letters Table 1. Optimization of the Reaction Conditionsa

Table 2. Substrate Scope: α,β-Unsaturated 2-Acyl Imidazolesa

entry

Λ-Rh (x)

solvent

temp (°C)

time (h)

yieldb (%)

eec (%)

1 2 3 4 5 6 7 8 9 10 11 12

Λ-Rh1 (2) Λ-Rh2 (2) Λ-Rh3 (2) Λ-Rh4 (2)

DCE DCE DCE DCE DCE CHCl3 toluene THF MeCN DCM DCE DCE

50 50 50 50 50 30 30 30 30 30 30 30

1 3 1 1 12 6 9 5 5 4 2 4

93 92 92 91 trace 87 90 93 84 95 89 87

75 76 88 85

Λ-Rh3 (2) Λ-Rh3 (2) Λ-Rh3 (2) Λ-Rh3 (2) Λ-Rh3 (2) Λ-Rh3 (2) Λ-Rh3 (1)

75 34 83 87 91 92 92

entry

R1

R2

time (h)

product

yieldb (%)

eec (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Me Pr Ph i Pr i Pr i Pr i Pr i Pr i Pr i Pr i Pr i Pr i Pr i Pr i Pr Me i Pr i Pr

C6H5 C6H5 C6H5 4-Me-C6H4 3-Me-C6H4 4-MeO-C6H4 4-Br-C6H4 3-Br-C6H4 4-Cl-C6H4 3-Cl-C6H4 2-Me-C6H4 1-naphyl 2-furyl 2-thienyl Me Et i Pr CO2Et

4 5 4 2 3 5 2 2 3 2 2 2 2 3 2 9 5 6

3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n 3o 3p 3q 3r

87 93 90 95 94 80 95 86 92 95 95 82 92 90 82 80 84 67

92 95 86 93 90 87 93 94 94 94 93 88 88 88 95 95 95 93

i

Reaction conditions: 1 (0.25 mmol), 2a (0.3 mmol), Λ-Rh3 (1 mol %) in DCE (0.5 mL) at 30 °C under argon atmosphere. bIsolated yields. cDetermined by chiral HPLC analysis. a

Reaction conditions: 1a (0.25 mmol), 2a (0.3 mmol), Λ-Rh (x mol %), solvent (0.5 mL) under argon atmosphere. bIsolated yields. c Determined by chiral HPLC analysis. a

conditions to give desired products in good yields with slightly decreased enantioselecvivities (entries 13 and 14). In addition to aromatic substituents, the aliphatic variants of α,β-unsaturated 2-acyl imidazoles (Me, Et, iPr, CO2Et) were also examined, affording the corresponding vinylated adducts 3o−3r in 67−84% yields with 93−95% ee (entries 15−18). The absolute configuration of product 3k was determined and confirmed by a single-crystal X-ray analysis (Figure 1; for details, see the Supporting Information).17

screened at 30 °C (entries 6−11). This investigation led to the finding that DCE is optimal for the process in terms of reactivity and enantioselectivity, delivering desired adduct 3a in 89% yield with 92% ee within 2 h (entry 11). Further decreasing the catalyst loading to 1 mol % under similar reaction conditions exhibited significant reactivity without decreasing enantioslectivity, affording 3a in 87% yield with 92% ee (entry 12). With the optimized reaction conditions in hand (entry 12, Table 1), the substrate scope of the enantioselective conjugate addition of para-vinylaniline 2a with α,β-unsaturated 2-acyl imidazoles 1 was investigated, and the results are summarized in Table 2. The bulkiness of the substituent on the imidazole ring (R1) had a slight influence on enantioselecivity as the sterically hindered isopropyl-substituted imidazole delivered the corresponding adduct 3b in 95% ee (entry 2, Table 2). The α,βunsaturated 2-acyl imidazoles bearing electron-donating groups on the phenyl ring had little impact on the outcome, leading to the corresponding products 3d−3f with good to excellent enantioselectivies (entries 4−6). Substrates with electronwithdrawing groups, such as Br or Cl, on the phenyl ring were also tolerable, affording the desired products with comparable enantioselectivities (entries 7−10). The ortho-substituted substrate 1k was also compatible to afford the desired product 3k in 95% yield with 93% ee (entry 11). Sterically hindered substrate such as 1-naphyl-substituted 2-acyl imidazole was tolerated in the optimal reaction conditions, resulting in the corresponding adduct 3l in 82% yield with 88% ee (entry 12). Moreover, heterocycle-substituted α,β-unsaturated 2-acyl imidazoles (1m, 1n) worked smoothly in the optimal reaction

Figure 1. X-ray derived ORTEP of 3k with thermal ellipsoids shown at the 35% probability level.

Then we evaluated the scope of nucleophilic alkenes (Scheme 2). In general, replacing the N,N-dimethyl with N,N-diethyl or piperidinyl of alkenes had no influence on enantioselectivities. The corresponding adducts were obtained in good yields with 95% ee (3s and 3t, Scheme 2). However, methoxyl-substituted alkene 1u and other alkyl-substituted alkenes19 could not give any conjugate addition product in the optimal reaction 3300

DOI: 10.1021/acs.orglett.7b01456 Org. Lett. 2017, 19, 3299−3302

Letter

Organic Letters Scheme 2. Substrate Scope: Alkenes 2a

a Reaction conditions: 0.25 mmol of 1o, 0.3 mmol of 2, and 1 mol % of Λ-Rh3 in DCE (0.5 mL) at 30 °C under an argon atmosphere. Yields of isolated products 3 are shown. Enantiomeric excesses were determined via HPLC analysis on a chiral stationary phase.

conditions, probably due to low nucleophilicity of these substrates. To demonstrate the practicality of the current methodology, a gram-scale reaction of α,β-unsaturated 2-acyl imidazole 1k (0.89 g, 3.5 mmol) with para-vinylaniline 2a (1.12 g, 4.2 mmol) was conducted under the optimal reaction conditions, affording 3k in 88% yield with 92% ee within 4 h.18 Notably, when as low as 0.05 mol % of Λ-Rh3 (2.3 mg) was used, the asymmetric conjugate addition of 1k on 3.93 mmol scale (1.0 g) with 2a (1.2 equiv) could deliver the desired product 3k in 81% yield (1620 catalyst turnovers) with 92% ee (Scheme 3, eq 1). In addition, the alkenyl

Figure 2. Proposed mechanism.

affording the corresponding adducts in good yields with excellent enantioselectivities. This protocol features wide substrate scope, mild reaction conditions, and an operationally simple procedure. Moreover, this process exhibits remarkable reactivity and enantioselectivity, given the fact that the title reaction can be conducted on a gram scale using as low as 0.05 mol % of Λ-Rh3 as catalyst with comparable enantioselectivity. Further research on the new design type of chiral Rh(III) complexes and its application in asymmetric synthesis is ongoing in our laboratory.

Scheme 3. Gram-Scale Experiments and Synthetic Transformation of Product 3k

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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.7b01456. X-ray data for compound 3k, experimental procedures, characterization data, and copies of 1H and 13C NMR spectra and HPLC chromatograms for obtained compounds (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. moiety of product 3k (>99% ee) could be easily hydrogenated to afford saturated product 4 in 86% yield without loss in enantiomeric excess (Scheme 3, eq 2). The proposed mechanism for this reaction is depicted in Figure 2. The 2-acyl imidazole substrate 1b is activated by the Rh(III) complex through bidentate N,O-coordination to form intermediate A. Excellent shielding of the Si face of A by the bulky t Bu group of achiral ligand leads to Re facial nucleophilic attack by 2a, resulting in the iminium cation (intermediate B) with dearomatization of the phenyl ring. The driving force of rearomatization helps to lose the proton of B to form intermediate C with α-carbanion, which undergoes subsequent protonation to generate vinylated intermediate D. Finally, desired product 3b is released from the coordinated intermediate D by ligand exchange with 1b. In conclusion, we have developed a highly efficient asymmetric conjugate addition of para-vinylanilines with α,β-unsaturated 2acyl imidazoles catalyzed by a chiral-at-metal Rh(III) complex,

ORCID

Qiang Kang: 0000-0002-9939-0875 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank Prof. Daqiang Yuan (Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences) for his kind help with X-ray analysis. This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, Grant No. XDB20000000, and 100 Talents Programme of the Chinese Academy of Sciences.

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REFERENCES

(1) For some reviews, see: (a) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829−2844. (b) Alexakis, A.; Bäckvall, J. E.; Krause, N.; Pàmies, O.; Diéguez, M. Chem. Rev. 2008, 108, 2796−2823. 3301

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Letter

Organic Letters

D.; Bergman, R. G. J. Am. Chem. Soc. 2011, 133, 10787−10789. (d) Okamoto, K.; Tamura, E.; Ohe, K. Angew. Chem., Int. Ed. 2013, 52, 10639−10643. (11) Cui, L.; Zhu, Y.; Luo, S.; Cheng, J.-P. Chem. - Eur. J. 2013, 19, 9481−9484. (12) Cui, L.; Zhang, L.; Luo, S.; Cheng, J.-P. Eur. J. Org. Chem. 2014, 2014, 3540−3545. (13) Patel, H. H.; Sigman, M. S. J. Am. Chem. Soc. 2016, 138, 14226− 14229. (14) Recent reviews on chiral-at-metal complexes in catalysis: (a) Brunner, H. Angew. Chem., Int. Ed. 1999, 38, 1194−1208. (b) Knight, P. D.; Scott, P. Coord. Chem. Rev. 2003, 242, 125−143. (c) Fontecave, M.; Hamelin, O.; Ménage, S. Top. Organomet. Chem. 2005, 15, 271. (d) Bauer, E. B. Chem. Soc. Rev. 2012, 41, 3153−3167. (e) Gong, L.; Chen, L.-A.; Meggers, E. Angew. Chem., Int. Ed. 2014, 53, 10868−10874. (f) Cao, Z.-Y.; Brittain, W. D. G.; Fossey, J. S.; Zhou, F. Catal. Sci. Technol. 2015, 5, 3441−3451. (15) Examples of chiral-at-metal Rh(III) complex catalyzed reactions: (a) Wang, C.; Chen, L.-A.; Huo, H.; Shen, X.; Harms, K.; Gong, L.; Meggers, E. Chem. Sci. 2015, 6, 1094−1100. (b) Tan, Y.; Yuan, W.; Gong, L.; Meggers, E. Angew. Chem., Int. Ed. 2015, 54, 13045−13048. (c) Huo, H.; Harms, K.; Meggers, E. J. Am. Chem. Soc. 2016, 138, 6936− 6939. (d) Ma, J.; Harms, K.; Meggers, E. Chem. Commun. 2016, 52, 10183−10186. (e) Ma, J.; Shen, X.; Harms, K.; Meggers, E. Dalton. Trans. 2016, 45, 8320−8323. (f) Shen, X.; Harms, K.; Marsch, M.; Meggers, E. Chem. - Eur. J. 2016, 22, 9102−9105. (g) Zheng, Y.; Harms, K.; Zhang, L.; Meggers, E. Chem. - Eur. J. 2016, 22, 11977−11981. (h) Wang, C.; Harms, K.; Meggers, E. Angew. Chem., Int. Ed. 2016, 55, 13495−13498. (i) Huang, X.; Webster, R. D.; Harms, K.; Meggers, E. J. Am. Chem. Soc. 2016, 138, 12636−12642. (j) Gong, J.; Li, K.; Qurban, S.; Kang, Q. Chin. J. Chem. 2016, 34, 1225−1235. (k) Sun, G.-J.; Gong, J.; Kang, Q. J. Org. Chem. 2017, 82, 796−803. (l) Deng, T.; Thota, G. K.; Li, Y.; Kang, Q. Org. Chem. Front. 2017, 4, 573−577. (m) Li, S.-W.; Gong, J.; Kang, Q. Org. Lett. 2017, 19, 1350−1353. (16) Examples employing α,β-unsaturated 2-acyl imidazoles as substrates in catalytic asymmetric conjugated additions: (a) Evans, D. A.; Fandrick, K. R.; Song, H. J. J. Am. Chem. Soc. 2005, 127, 8942−8943. (b) Evans, D. A.; Song, H. J.; Fandrick, K. R. Org. Lett. 2006, 8, 3351− 3354. (c) Boersma, A. J.; Feringa, B. L.; Roelfes, G. Org. Lett. 2007, 9, 3647−3650. (d) Evans, D. A.; Fandrick, K. R.; Song, H. J.; Scheidt, K. A.; Xu, R. J. Am. Chem. Soc. 2007, 129, 10029−10041. (e) Zheng, L.; Marcozzi, A.; Gerasimov, J. Y.; Herrmann, A. Angew. Chem., Int. Ed. 2014, 53, 7599−7603. (f) Drissi-Amraoui, S.; Morin, M. S.; Crévisy, C.; Baslé, O.; Marcia de Figueiredo, R.; Mauduit, M.; Campagne, J. M. Angew. Chem., Int. Ed. 2015, 54, 11830−11834. (g) Rout, S.; Das, A.; Singh, V. K. Chem. Commun. 2017, 53, 5143−5146. (17) CCDC 1548640 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/ data_request/cif. (18) With >99% ee of desired product 3k obtained in 61% yield by a single recrystallization. (19) Alkyl-substituted alkenes 5a−5c employed in the title reaction could not afford desired adducts in the optimal reaction conditions due to low nucleophilicities.

(c) Defieber, C.; Grützmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482−4502. (d) Csákÿ, A. G.; Herrán, G.; Murcia, M. C. Chem. Soc. Rev. 2010, 39, 4080−4102. (2) Application in total synthesis: (a) Lalic, G.; Corey, E. J. Org. Lett. 2007, 9, 4921−4923. (b) König, C. M.; Gebhardt, B.; Schleth, C.; Dauber, M.; Koert, U. Org. Lett. 2009, 11, 2728−2731. (c) Hickmann, V.; Alcarazo, M.; Fürstner, A. J. Am. Chem. Soc. 2010, 132, 11042− 11044. (d) May, T. L.; Dabrowski, J. A.; Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133, 736−739. (e) Hickmann, V.; Kondoh, A.; Gabor, B.; Alcarazo, M.; Fürstner, A. J. Am. Chem. Soc. 2011, 133, 13471−13480. (3) (a) Takaya, Y.; Ogasawara, M.; Hayashi, T. J. Am. Chem. Soc. 1998, 120, 5579−5580. (b) Hayashi, T.; Senda, T.; Ogasawara, M. J. Am. Chem. Soc. 2000, 122, 10716−10717. (c) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584−13585. (d) Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. M. Org. Lett. 2004, 6, 3873−3875. (e) Mauleón, P.; Carretero, J. C. Chem. Commun. 2005, 4961−4963. (f) Mauleón, P.; Alonso, I.; Rivero, M. R.; Carretero, J. C. J. Org. Chem. 2007, 72, 9924− 9935. (g) Zigterman, J. L.; Woo, J. C. S.; Walker, S. D.; Tedrow, J. S.; Borths, C. J.; Bunel, E. E.; Faul, M. M. J. Org. Chem. 2007, 72, 8870− 8876. (h) Tokunaga, N.; Hayashi, T. Adv. Synth. Catal. 2007, 349, 513− 516. (i) Konno, T.; Tanaka, T.; Miyabe, T.; Morigaki, A.; Ishihara, T. Tetrahedron Lett. 2008, 49, 2106−2110. (j) Gendrineau, T.; Chuzel, O.; Eijsberg, H.; Genet, J.-P.; Darses, S. Angew. Chem., Int. Ed. 2008, 47, 7669−7672. (k) Okamoto, K.; Hayashi, T.; Rawal, V. H. Org. Lett. 2008, 10, 4387−4389. (l) Defieber, C.; Grützmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482−4502. (m) Shintani, R.; Ichikawa, Y.; Takatsu, K.; Chen, F.-X.; Hayashi, T. J. Org. Chem. 2009, 74, 869− 873. (n) Pattison, G.; Piraux, G.; Lam, H. W. J. Am. Chem. Soc. 2010, 132, 14373−14375. (o) Wang, Y.; Hu, X.; Du, H. Org. Lett. 2010, 12, 5482−5485. (p) Brown, M. K.; Corey, E. J. Org. Lett. 2010, 12, 172− 175. (q) Chen, G.; Gui, J.; Li, L.; Liao, J. Angew. Chem., Int. Ed. 2011, 50, 7681−7685. (r) Thaler, T.; Guo, L.-N.; Steib, A. K.; Raducan, M.; Karaghiosoff, K.; Mayer, P.; Knochel, P. Org. Lett. 2011, 13, 3182−3185. (s) Trost, B. M.; Burns, A. C.; Tautz, T. Org. Lett. 2011, 13, 4566−4569. (4) (a) Takaya, Y.; Ogasawara, M.; Hayashi, T. Tetrahedron Lett. 1998, 39, 8479−8482. (b) Pucheault, M.; Darses, S.; Genêt, J.-P. Eur. J. Org. Chem. 2002, 2002, 3552−3557. (c) Duursma, A.; Boiteau, J.-G.; Lefort, L.; Boogers, J.; de Vries, A. H. M.; de Vries, J. G.; Minnaard, A. J.; Feringa, B. L. J. Org. Chem. 2004, 69, 8045−8052. (d) Lalic, G.; Corey, E. J. Tetrahedron Lett. 2008, 49, 4894−4896. (5) (a) Alexakis, A.; Albrow, V.; Biswas, K.; d'Augustin, M.; Prieto, O.; Woodward, S. Chem. Commun. 2005, 2843−2845. (b) Hawner, C.; Li, K.; Cirriez, V.; Alexakis, A. Angew. Chem., Int. Ed. 2008, 47, 8211−8214. (c) Hawner, C.; Alexakis, A. Chem. Commun. 2010, 46, 7295−7306. (d) Müller, D.; Hawner, C.; Tissot, M.; Palais, L.; Alexakis, A. Synlett 2010, 2010, 1694−1698. (e) Müller, D.; Tissot, M.; Alexakis, A. Org. Lett. 2011, 13, 3040−3043. (f) Müller, D.; Alexakis, A. Org. Lett. 2012, 14, 1842−1845. (6) (a) Oi, S.; Taira, A.; Honma, Y.; Inoue, Y. Org. Lett. 2003, 5, 97−99. (b) Otomaru, Y.; Hayashi, T. Tetrahedron: Asymmetry 2004, 15, 2647− 2651. (c) Nakao, Y.; Chen, J.; Imanaka, H.; Hiyama, T.; Ichikawa, Y.; Duan, W.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 9137− 9143. (d) Shintani, R.; Ichikawa, Y.; Hayashi, T.; Chen, J.; Nakao, Y.; Hiyama, T. Org. Lett. 2007, 9, 4643−4645. (e) Lee, K.; Hoveyda, A. H. J. Org. Chem. 2009, 74, 4455−4462. (7) (a) Oi, S.; Sato, T.; Inoue, Y. Tetrahedron Lett. 2004, 45, 5051− 5055. (b) Nicolaou, K. C.; Tang, K.; Dagneau, P.; Faraoni, R. Angew. Chem., Int. Ed. 2005, 44, 3874−3879. (c) Hargrave, J. D.; Allen, J. C.; Frost, C. G. Chem. - Asian J. 2010, 5, 386−396. (8) Mahoney, S. J.; Dumas, A. M.; Fillion, E. Org. Lett. 2009, 11, 5346− 5349. (9) (a) Ahn, K.−H.; Klassen, R. B.; Lippard, S. J. Organometallics 1990, 9, 3178−3181. (b) Robert, T.; Velder, J.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2008, 47, 7718−7721. (10) Examples of nonasymmetric direct conjugate addition reactions of alkenes to enones: (a) Ho, C.-Y.; Ohmiya, H.; Jamison, T. Angew. Chem., Int. Ed. 2008, 47, 1893−1895. (b) Ogoshi, S.; Haba, T.; Ohashi, M. J. Am. Chem. Soc. 2009, 131, 10350−10351. (c) Zhao, C.; Toste, F. 3302

DOI: 10.1021/acs.orglett.7b01456 Org. Lett. 2017, 19, 3299−3302