Diastereoselective Palladium-Catalyzed Conjugate Addition of Arylboronic Acids to α-Substituted Cyclic Enones

This paper is dedicated to Professor Victor Snieckus on the occasion of his 80^th birthday.

Abstract

A palladium-catalyzed conjugate addition of arylboronic acids to α-substituted cyclic enones was developed to give α,β-disubstituted ketones with high diastereoselectivity. Mechanistic investigation showed that the high diastereoselectivity was realized through epimerization.

Key words

palladium - conjugate addition - boronic acid - cyclic enone - diastereoselectivity

• References and Notes

• 1a Rosiak A. Rössle M. Synthesis 2007; 1279
• 1b Hawner C. Alexakis A. Chem. Commun. 2010; 7295
• 1c Gutnov A. Eur. J. Org. Chem. 2008; 4547
• 1d Christoffers J. Koripelly G. Liu Y. Han S.-J. Liu W.-B. Stoltz BM. Acc. Chem. Res. 2015; 48: 740
• 2a Hird AW. Hoveyda AH. J. Am. Chem. Soc. 2005; 127: 14988
• 2b Alexakis A. Bäckvall JE. Krause N. Pàmies O. Diéguez M. Chem. Rev. 2008; 108: 2796
• 2c Harutyunyan SR. den Hartog T. Geurts K. Minnaard AJ. Feringa BL. Chem. Rev. 2008; 108: 2824
• 3a Takaya Y. Ogasawara M. Hayashi T. Sakai M. Miyaura N. J. Am. Chem. Soc. 1998; 120: 5579
• 3b Hayashi T. Yamasaki K. Chem. Rev. 2003; 103: 2829
• 3c Hayashi T. Ueyama K. Tokunaga N. Yoshida K. J. Am. Chem. Soc. 2003; 125: 11508
• 3d Paquin J.-F. Defieber C. Stephenson CR. J. Carreira EM. J. Am. Chem. Soc. 2005; 127: 10850
• 3e Shintani R. Duan W.-L. Hayashi T. J. Am. Chem. Soc. 2006; 128: 5628
• 3f Wang Z.-Q. Feng C.-G. Zhang S.-S. Xu M.-H. Lin G.-Q. Angew. Chem. Int. Ed. 2010; 49: 5780
• 4a Nishikata T. Yamamoto Y. Miyaura N. Angew. Chem. Int. Ed. 2003; 42: 2768
• 4b Lu X. Lin S. J. Org. Chem. 2005; 70: 9651
• 4c Gini F. Hessen B. Minnaard AJ. Org. Lett. 2005; 7: 5309
• 4d Nishikata T. Yamamoto Y. Miyaura N. Adv. Synth. Catal. 2007; 349: 1759
• 4e Nishitaka T. Kiyomura S. Yamamoto Y. Miyaura N. Synlett 2008; 2487
• 4f Lin S. Lu X. Org. Lett. 2010; 12: 2536
• 4g Xu Q. Zhang R. Zhang T. Shi M. J. Org. Chem. 2010; 75: 3935
• 4h Kikushima K. Holder JC. Gatti M. Stoltz BM. J. Am. Chem. Soc. 2011; 133: 6902
• 4i Gottumukkala AL. Matcha K. Lutz M. de Vries JG. Minnaard AJ. Chem. Eur. J. 2012; 22: 6907
• 4j Holder JC. Zou L. Marziale AN. Liu P. Lan Y. Gatti M. Kikushima K. Houk KN. Stoltz BM. J. Am. Chem. Soc. 2013; 135: 14996
• 4k Gerten AL. Stanley LM. ­Tetrahedron Lett. 2016; 57: 5460
• 5a Sim TB. Choi J. Joung MJ. Yoon NM. J. Org. Chem. 1997; 62: 2357
• 5b Prabagaran N. Sundararajan G. Tetrahedron: Asymmetry 2002; 13: 1053
• 5c Jang DO. Cho DH. Synlett 2002; 631
• 5d Lee PH. Seomoon D. Lee K. Heo Y. J. Org. Chem. 2003; 68: 2510
• 5e Shen Z.-L. Cheong H.-L. Loh T.-P. Tetrahedron Lett. 2009; 50: 1051
• 5f Taber DF. Guo P. Pirrot MT. J. Org. Chem. 2010; 75: 5737
• 5g Tian X. Cassani C. Liu Y. Moran A. Urakawa A. Galzerano P. Arceo E. Melchiorre P. J. Am. Chem. Soc. 2011; 133: 17934
• 5h Shrestha R. Dom SC. M. Weix DJ. J. Am. Chem. Soc. 2013; 135: 751
• 6a Vuagnoux-d’Augustin M. Kehrli S. Alexakis A. Synlett 2007; 2057
• 6b Vuagnoux-d’Augustin M. Alexakis A. Chem. Eur. J. 2007; 13: 9647
• 6c Ngoc DT. Albicker M. Schmeider L. Cramer N. Org. Biomol. Chem. 2010; 8: 1781
• 6d Gärtner M. Qu J. Helmchen G. J. Org. Chem. 2012; 77: 1186
• 6e Silva AL. Toscano RA. Maldonado LA. J. Org. Chem. 2013; 78: 5282
• 6f Pan J.-L. Chen T. Zhang Z.-Q. Li Y.-F. Zhang X.-M. Zhang F.-M. Chem. Commun. 2016; 2382
• 7a Germain N. Guénée L. Mauduit M. Alexakis A. Org. Lett. 2014; 16: 118
• 7b Calvo BC. Madduri AV. R. Harutyunyan SR. Minnaard AJ. Adv. Synth. Catal. 2014; 356: 2061
• 7c Germain N. Alexakis A. Chem. Eur. J. 2015; 21: 8597
• 8a Zhang T.-K. Mo D.-L. Dai L.-X. Hou X.-L. Org. Lett. 2008; 10: 3689
• 8b Ding C.-H. Hou X.-L. Bull. Chem. Soc. Jpn. 2010; 83: 992
• 8c Huang X.-J. Mo D.-L. Ding C.-H. Hou X.-L. Synlett 2011; 943
• 8d Li H. Gao A. Liu X.-Y. Ding C.-H. Xu B. Hou X.-L. Synthesis 2017; 49: 159
• 9a Ohmiya H. Yorimitsu H. Oshima K. J. Am. Chem. Soc. 2006; 128: 1886
• 9b DeTitta GT. Langs DA. Edmonds JW. Biochemistry 1979; 18: 3387
• 9c Bellavance É. Luu-The V. Poirier D. J. Med. Chem. 2009; 52: 7488
• 10 Oxidative Heck reaction of cyclohexanone with phenylboronic acid was reported to proceed in the presence of Pd(OAc)₂ and 2,9-dimethyl-1,10-phenanthroline under an oxygen balloon. For details, see: Yoo KS. Yoon CH. Jung KW. J. Am. Chem. Soc. 2006; 128: 16384
• 11 Typical experimental procedure: To a flame-dried 25 mL Schlenk tube were added Pd(TFA)₂ (4.2 mg, 0.0125 mmol), ligand L2 (2.3 mg, 0.015 mmol), and anhydrous DMAc (1.0 mL). The resulting mixture was stirred for 60 min. Arylboronic acid 2b (68.0 mg, 0.5 mmol) and ketone 1a (24.0 mg, 0.25 mmol) were added subsequently. The resulting reaction mixture was stirred at 80 °C for 24 h. Water (10 mL) was added and the aqueous phase was extracted with ethyl acetate (2 × 10 mL). The combined organic phase was washed with water (3 × 10 mL) and brine (10 mL). The organic phase was dried over anhydrous Na₂SO₄ and filtered. After the volatile materials were removed in vacuo, the ratio of two diastereoisomers was determined by GC chromatography. The resulting residue was then subjected to flash chromatography on silica gel with petroleum ether and ethyl acetate as eluent to give product 3b (39.9 mg, 85%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.33–7.01 (m, 5 H), 3.10 (td, J = 12.1, 5.2 Hz, 1 H), 2.61–2.48 (m, 1 H), 2.43–2.17 (m, 7 H), 1.87–1.71 (m, 1 H), 1.01 (dd, J = 6.8, 1.3 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 219.7, 140.3, 136.4, 130.6, 126.5, 126.4, 124.7, 51.0, 46.0, 37.6, 29.1, 19.8, 12.1. IR (neat): 2962, 1738, 1492, 1459, 1406, 1260, 1147, 1090, 1021, 798, 761, 732. MS (EI): m/z (%) = 187 (60) [M⁺], 132 (90), 114 (100), 90 (50). HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₆O: 188.1201; found: 188.1199.
• 12 Han X. Wang X. Pei T. Widenhoefer RA. Chem. Eur. J. 2004; 10: 6333