Enantioselective Palladium-Catalyzed Decarboxylative Allylation of β-Keto Esters Assisted by a Thiourea

^‡ These two authors contributed equally to this work

Abstract

Enantioselective intramolecular decarboxylative allylation of β-keto esters catalyzed by a palladium bis(phosphine)-thiourea complex is reported. This procedure is not only effective for β-keto esters, but also effective for β-keto amides. An intermolecular variant of the asymmetric decarboxylative allylation is also established. DFT calculations indicate that an outer-sphere mechanism is viable for the decarboxylative allylation of β-keto esters.

Key words

asymmetric synthesis - β-keto esters - decarboxylative allylation - thioureas - palladium catalysis

• References and Notes

• 1a Fuji K. Chem. Rev. 1993; 93: 2037
• 1b Corey EJ. Guzman-Perez A. Angew. Chem. Int. Ed. 1998; 37: 388
• 1c Christoffers J. Mann A. Angew. Chem. Int. Ed. 2001; 40: 4591
• 1d Douglas CJ. Overman LE. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 5363
• 1e Baro A. Christoffers J. Adv. Synth. Catal. 2005; 347: 1473
• 1f Trost BM. Jiang C. Synthesis 2006; 369
• 1g Bella M. Gasperi T. Synthesis 2009; 1583
• 1h Das JP. Marek I. Chem. Commun. 2011; 4593
• 1i Quasdorf KW. Overman LE. Nature 2014; 516: 181
• 2a Weaver JD. Recio III A. Grenning AJ. Tunge JA. Chem. Rev. 2011; 111: 1846
• 2b Mohr JT. Stoltz BM. Chem. Asian J. 2007; 2: 1476
• 3a Trost BM. Xu J. J. Am. Chem. Soc. 2005; 127: 2846
• 3b Trost BM. Xu J. J. Am. Chem. Soc. 2005; 127: 17180
• 3c Trost BM. Xu J. Schmidt T. J. Am. Chem. Soc. 2009; 131: 18343
• 3d Trost BM. Schäffner B. Osipov M. Wilton DA. A. Angew. Chem. Int. Ed. 2011; 50: 3548
• 4a Zheng W.-H. Zheng B.-H. Zhang Y. Hou X.-L. J. Am. Chem. Soc. 2007; 129: 7718
• 4b Lei B.-L. Ding C.-H. Yang X.-F. Wan X.-L. Hou X.-L. J. Am. Chem. Soc. 2009; 131: 18250
• 5a Liu W.-B. Reeves CM. Virgil S. Stoltz BM. J. Am. Chem. Soc. 2013; 135: 10626
• 5b Liu W.-B. Reeves CM. Stoltz BM. J. Am. Chem. Soc. 2013; 135: 17298
• 5c Hethcox JC. Shockley SE. Stoltz BM. Angew. Chem. Int. Ed. 2016; 55: 16092
• 6 Burger EC. Tunge JA. Org. Lett. 2004; 6: 4113
• 7 Pupo G. Properzi R. List B. Angew. Chem. Int. Ed. 2016; 55: 6099

For examples of asymmetric intermolecular allylation of β-keto esters with allyl acetate, see:
• 8a Trost BM. Radinov R. Grenzer EM. J. Am. Chem. Soc. 1997; 119: 7879
• 8b Yoshida M. Yano S. Hara S. Synthesis 2017; 49: 1295
• 8c Hayashi T. Kanehira K. Hagihara T. Kumada M. J. Org. Chem. 1988; 53: 113
• 9a Behenna DC. Stoltz BM. J. Am. Chem. Soc. 2004; 126: 15044
• 9b Keith JA. Behenna DC. Mohr JT. Ma S. Marinescu SC. Oxgaard J. Stoltz BM. Goddard III WA. J. Am. Chem. Soc. 2007; 129: 11876
• 9c McDougal NT. Virgil SC. Stoltz BM. Synlett 2010; 1712
• 9d Keith JA. Behenna DC. Sherden N. Mohr JT. Ma S. Marinescu SC. Nielsen RJ. Oxgaard J. Stoltz BM. Goddard WA. J. Am. Chem. Soc. 2012; 134: 19050
• 9e Behenna DC. Mohr JT. Sherden NH. Marinescu SC. Harned AM. Tani K. Seto M. Ma S. Novák Z. Krout MR. McFadden RM. Roizen JL. Enquist JA. White DE. Levine SR. Petrova KV. Iwashita A. Virgil SC. Stoltz BM. Chem. Eur. J. 2011; 17: 14199
• 9f Reeves CM. Eidamshaus C. Kim J. Stoltz BM. Angew. Chem. Int. Ed. 2013; 52: 6718
• 9g Reeves CM. Behenna DC. Stoltz BM. Org. Lett. 2014; 16: 2314
• 9h Craig II R. A. Loskot SA. Mohr JT. Behenna DC. Harned AM. Stoltz BM. Org. Lett. 2015; 17: 5160
• 10 An enantioselective Claisen rearrangement of O-allyl β-keto esters catalyzed by thiourea has been reported, see: Uyeda C. Rötheli AR. Jacobsen EN. Angew. Chem. Int. Ed. 2010; 49: 9753
• 11 Dong X.-Q. Zhao Q. Li P. Chen C. Zhang X. Org. Chem. Front. 2015; 2: 1425
• 12a Zhao Q. Wen J. Tan R. Huang K. Metola P. Wang R. Anslyn EV. Zhang X. Angew. Chem. Int. Ed. 2014; 53: 8467
• 12b Wen J. Tan R. Liu S. Zhao Q. Zhang X. Chem. Sci. 2016; 7: 3047
• 13a Zhao Q. Li S. Huang K. Wang R. Zhang X. Org. Lett. 2013; 15: 4014
• 13b Li P. Zhou M. Zhao Q. Wu W. Hu X. Dong X.-Q. Zhang X. Org. Lett. 2016; 18: 40
• 14a Li P. Hu X. Dong X.-Q. Zhang X. Chem. Commun. 2016; 11677
• 14b Wen J. Jiang J. Zhang X. Org. Lett. 2016; 18: 4451
• 15a Han Z. Li P. Zhang Z. Chen C. Wang Q. Dong X.-Q. Zhang X. ACS Catal. 2016; 6: 6214
• 15b Han Z. Wang R. Gu G. Dong X.-Q. Zhang X. Chem. Commun. 2017; 4226
• 16 General procedure for decarboxylative allylation of β-keto esters: A Schlenk tube containing Pd₂(dba)₃ (7 mg, 0.0076 mol), ZhaoPhos (16 mg, 0.0184 mmol) and K₂CO₃ (42 mg, 0.30 mmol) in degassed anhyd CH₂Cl₂ (5 mL) was stirred for 15 min under Ar. Substrate (0.30 mmol) was added last. The resulting mixture was stirred at r.t. under Ar for 24 h and was concentrated under vacuum. The residue was then purified by chromatography with petroleum ether/EtOAc to afford enantioenriched product. For 2a: Yield: 58 mg (92%); colorless oil; 89% ee. ¹H NMR: δ = 5.83–5.67 (m, 1 H), 5.04 (d, J = 13.3 Hz, 2 H), 4.19 (q, J = 7.1 Hz, 2 H), 2.61 (dd, J = 14.0, 6.9 Hz, 1 H), 2.47 (dt, J = 14.9, 4.3 Hz, 3 H), 2.34 (dd, J = 14.0, 7.8 Hz, 1 H), 2.07–1.97 (m, 1 H), 1.82–1.71 (m, 3 H), 1.50–1.43 (m, 1 H), 1.26 (t, J = 7.1 Hz, 3 H). ¹³C{¹H} NMR: δ = 207.5, 171.4, 133.3, 118.2, 61.2, 60.8, 41.1, 39.3, 35.7, 27.5, 22.4, 14.1. HPLC (Daicel Chiralpak) AD-H column; hexanes/i-PrOH = 99.5:0.5; flow rate = 0.5 mL/min; UV detection at 210 nm): t _R = 10.512 (t _minor), 12.371 (t _major) min.

For selected examples on asymmetric allylation of β-keto esters with cinnamyl acetate or cinnamyl carbonates, see:
• 17a Gavrilov KN. Zheglov SV. Novikov IM. Lugovsky VV. Zimarev VS. Mikhel I. Tetrahedron: Asymmetry 2016; 27: 1260
• 17b Savoia D. Alvaro G. Fabio RD. Fiorelli C. Gualandi A. Monari M. Piccinelli F. Adv. Synth. Catal. 2006; 348: 1883
• 17c Gavrilov KN. Shiryaev AA. Zheglov SV. Bochelyuk MS. Chuchelkin IV. Tafeenko VA. Chernyshev VV. Zamilatskov IA. Mikhel IS. Tetrahedron Lett. 2015; 56: 4756
• 17d Nemoto T. Masuda T. Matsumoto T. Hamada Y. J. Org. Chem. 2005; 70: 7172

For asymmetric allylation of β-keto esters with cinnamyl alcohols, see:
• 18a Zhou H. Zhang L. Xu C. Luo S. Angew. Chem. Int. Ed. 2015; 54: 12645
• 18b Kita Y. Kavthe RD. Oda H. Mashima K. Angew. Chem. Int. Ed. 2016; 55: 1098
• 19 Cinnamyl methyl carbonates were the limiting reagents in the intermolecular asymmetric allylation reaction.
• 20a Bai D.-C. Yu F.-L. Wang W.-Y. Chen D. Li H. Liu Q.-R. Ding C.-H. Chen B. Hou X.-L. Nat. Commun. 2016; 7: 11806
• 20b Huo X. Yang G. Liu D. Liu Y. Gridnev ID. Zhang W. Angew. Chem. Int. Ed. 2014; 53: 6776
• 20c Patil M. Thiel W. Chem. Eur. J. 2012; 18: 10408
• 20d Chen J.-P. Peng Q. Lei B.-L. Hou X.-L. Wu Y.-D. J. Am. Chem. Soc. 2011; 133: 14180
• 20e Meletis P. Patil M. Thiel W. Frank W. Braun M. Chem. Eur. J. 2011; 17: 11243
• 21 Considering the Pd-O distance of 2.602 Å, TS-RE-O2-Si can be classified as a quasi-outer-sphere pathway (with some inner-sphere character).
• 22a Legault CY. Garcia Y. Merlic CA. Houk KN. J. Am. Chem. Soc. 2007; 129: 12664
• 22b Ess DH. Houk KN. J. Am. Chem. Soc. 2007; 129: 10646