Hopping of Palladium: Access to Original Polycyclic Structures Containing Three-, Four-, Five- and Six-Membered Rings

Abstract

The syntheses of new scaffolds containing small strained rings are described via an original domino reaction. The process works efficiently and selectively via 4-exo-dig/5- or 6-exo-trig/3-exo-trig cyclocarbopalladations followed by a β-hydride elimination. During this cascade, the palladium moves several times along the carbon structure for the creation of three new C–C bonds and three new rings.

Key words

cyclocarbopalladation - cyclopropanation - domino reaction - palladium - fused bicycles - small strained cycles

• References and Notes

• 1 Tietze LF. Chem. Rev. 1996; 96: 115
• 2 Applications of Domino Transformations in Organic Synthesis 2 . Snyder SA, Carreira EM. Science of Synthesis. Georg Thieme Verlag KG; Stuttgart New York: 2015
• 3 Düfert A, Werz DB. Chem. Eur. J. 2016; 22: 16718 ; and references inside
• 4 Bour C, Blond G, Salem B, Suffert J. Tetrahedron 2006; 62: 10567
• 5 Charpenay M, Boudhar A, Blond G, Suffert J. Angew. Chem. Int. Ed. 2012; 51: 4379
• 6 Charpenay M, Boudhar A, Hulot C, Blond G, Suffert J. Tetrahedron 2013; 69: 7568
• 7 Charpenay M, Boudhar A, Siby A, Schigand S, Blond G, Suffert J. Adv. Synth. Catal. 2011; 353: 3151
• 8 Hulot C, Blond G, Suffert J. J. Am. Chem. Soc. 2008; 130: 5046
• 9 Blouin S, Gandon V, Blond G, Suffert J. Angew. Chem. Int. Ed. 2016; 55: 7208
• 10 Hulot C, Amiri S, Blond G, Schreiner PR, Suffert J. J. Am. Chem. Soc. 2009; 131: 13387
• 11 Blond G, Bour C, Salem B, Suffert J. Org. Lett. 2008; 10: 1075
• 12 Petrignet J, Boudhar A, Blond G, Suffert J. Angew. Chem. Int. Ed. 2011; 50: 3285
• 13 Nandi S, Ray JK. Tetrahedron Lett. 2009; 50: 6993
• 14 Grigg R, Sakee U, Sridharan V, Sukirthalingam S, Thangavelauthum R. Tetrahedron 2006; 62: 9523
• 15 Ohno H, Takeoka Y, Miyamura K, Kadoh Y, Tanaka T. Org. Lett. 2003; 5: 4763
• 16 Böhmer J, Grigg R, Marchbank JD. Chem. Commun. 2002; 768
• 17 Schweizer S, Song Z.-Z, Meyer FE, Parsons PJ, de Meijere A. Angew. Chem. Int. Ed. 1999; 38: 1452
• 18 Henniges H, Meyer FE, Schick U, Funke F, Parson PJ, de Meijere A. Tetrahedron 1996; 52: 11545
• 19 Grigg R, Rasul R, Redpath J, Wilson D. Tetrahedron Lett. 1996; 37: 4609
• 20 Brown A, Grigg R, Ravishankar T, Thornton-Pett M. Tetrahedron Lett. 1994; 35: 2753
• 21 Meyer FE, Parsons PJ, De Meijere A. J. Org. Chem. 1991; 56: 6487
• 22 Grigg R, Sridharan V, Sukirthalingam S. Tetrahedron Lett. 1991; 32: 3855
• 23 Zhang Y, Negishi E. J. Am. Chem. Soc. 1989; 111: 3454
• 24 Torri S, Okumoto H, Ozaki H, Nakayasu S, Tadokoro T, Kotani T. Tetrahedron Lett. 1992; 33: 3499
• 25 Owczarczyk Z, Lamaty F, Vawter EJ, Negishi E. J. Am. Chem. Soc. 1992; 114: 10091
• 26 Feutren S, McAlonan H, Montgomery D, Stevenson PJ. J. Chem. Soc., Perkin Trans. 1 2000; 1129
• 27 For examples of three- and four-membered rings in natural products, see: Kleinnijenhuis RA, Timmer BJ. J, Lutteke G, Smits JM. M, de Gelder R, van Maarseveen JH, Hiemstra H. Chem. Eur. J. 2016; 22: 1266
• 28 Example of three- and four-membered rings on the structure of natural product: Wan L.-S, Nian Y, Ye C.-J, Shao L.-D, Peng X.-R, Geng C.-A, Zuo Z.-L, Li X.-N, Yang J, Zhou M, Qiu M.-H. Org. Lett. 2016; 18: 2166
• 29 Solvent effect on the chemoselectivity endo/exo: Oh CH, Rhim CY, Hwang SK. Chem. Lett. 1997; 26: 777
• 30 General Procedure A mixture of solvents PhH/MeOH/Et₃N (4.5 mL) with a ratio of 6:2:1 was added to a mixture of compound 5 (0.13 mmol, 1.0 equiv) and Pd(PPh₃)₄ (0.013 mmol, 0.1 equiv) in a 2–5 mL microwave vial at r.t. The vial was sealed with a Teflon cap, and the mixture was stirred under MW irradiation for 30 min at 100 °C. The reaction mixture was cooled to r.t. and was filtered through a small pad of Celite^® to eliminate traces of metal. The filtrate was concentrated under reduced pressure and purified by flash column chromatography on silica gel. Following the reported procedure, 6a was obtained in 82% (29 mg) yield as colorless liquid. R_f = 0.43 (heptane–Et₂O, 7:3). ¹H NMR (400 MHz, CDCl₃): δ = 6.18 (dd, J = 2.4, 9.6 Hz, 1 H), 6.10 (dt, J = 2.4z, 6.0 Hz, 1 H), 4.87 (s, 1 H), 3.89 (q, J = 8.0 Hz, 2 H), 3.80 (d, J = 8.4 Hz, 1 H), 3.57 (d, J = 8.4 Hz, 1 H), 2.56–2.43 (m, 1 H), 2.28 (td, J = 5.6, 18.8 Hz, 1 H), 2.10 (dd, J = 5.2z, 12.8 Hz, 1 H), 1.87 (dt, J = 6.0, 12.4 Hz, 1 H), 1.49 (s, 3 H), 1.42 (s, 3 H), 1.29 (s, 3 H), 1.08 (d, J = 4.4 Hz, 1 H), 0.94 (d, J = 4.4 Hz, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 141.3, 139.3, 134.2, 119.4, 114.7, 83.7, 74.4, 71.3, 33.3, 32.1, 29.5, 29.0, 28.8, 23.5, 20.7, 14.5. IR (neat): ν_max = 2928, 2847, 1438, 1366, 1230, 1199, 1094, 1040 cm^–1. ESI-HRMS: m/z calcd for C₁₇H₂₂NaO₃ [M + Na]⁺: 297.1467; found: 297.1452. Following the reported procedure, 6e was obtained in 80% (30 mg) yield as white solid. R_f = 0.28 (heptane–Et₂O, 4:1); mp 49–50 °C. ¹H NMR (400 MHz, CDCl₃): δ = 6.24 (dd, J = 2.4z, 9.6 Hz, 1 H), 6.0 (dt, J = 1.6, 6.0 Hz, 1 H), 4.80 (s, 1 H), 3.90 (d, J = 10.8 Hz, 1 H), 3.85 (d, J = 11.2 Hz, 1 H), 3.75–3.65 (m, 1 H), 3.28–3.22 (m, 1 H), 2.55–2.42 (m, 1 H), 2.27 (td, J = 6.0, 18.8 Hz, 1 H), 2.10 (dd, J = 5.6, 13.0 Hz, 1 H), 1.96–1.77 (m, 2 H), 1.58 (td, J = 3.2 Hz, 14.0 Hz, 1 H), 1.49 (s, 3 H), 1.41 (s, 3 H), 1.19 (s, 3 H), 1.03 (d, J = 4.0 Hz, 1 H), 0.84 (d, J = 4.0 Hz, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 142.5, 142.2, 134.2, 119.8, 114.8, 84.7, 83.0, 68.5, 64.6, 30.9, 29.5, 29.0, 28.9, 25.5, 24.3, 24.1, 23.6, 23.2. IR (neat): ν_max = 2919, 2860, 1366, 1256, 1230, 1195, 1113, 1029 cm^–1. ESI-HRMS: m/z calcd for C₁₈H₂₄NaO₃ [M + Na]⁺: 311.1623; found: 311.1613.
• 31 Castanheiro T, Donnard M, Gulea M, Suffert J. Org. Lett. 2014; 16: 3060 ; and references inside