Total Synthesis of (+)-Dodoneine

Abstract

An eight-step synthesis of (+)-dodoneine was achieved from methyl 3-(4-hydroxyphenyl)propionate.

Key words

total synthesis - dodoneine - allyltitanation - cross­metathesis - 1,4-addition

References and Notes

• 1 Ouedraogo M. Carreyre H. Vandebrouck C. Bescond J. Raymond G. Guissou I.-P. Cognard C. Becq F. Potreau D. Cousson A. Marrot J. Coustard J.-M. J. Nat. Prod.  2007,  70:  2006 
• 2 The allyltitanium complex (S,S)-Ti-I was prepared according to: Hafner A. Duthaler RO. Marti R. Rihs G. Rothe-Streit P. Schwarzenbach F. J. Am. Chem. Soc.  1992,  114:  2321 
• The ee of 3 and its S absolute configuration were determined by ^¹H NMR after derivatization with (S)- and (R)-methoxyphenylacetic acids. See:
• 3a Dale JA. Mosher HS. J. Am. Chem. Soc.  1973,  95:  512 
• 3b Trost BM. Belletire JL. Godleski S. McDougal PG. Balkovec JM. J. Org. Chem.  1986,  51:  2370 
• 3c Seco JM. Quiňoà E. Riguera R. Tetrahedron: Asymmetry  2001,  12:  2915 
• 4 Evans DA. Gauchet-Prunet JA. J. Org. Chem.  1993,  58:  2446 
• 5 Cossy J. BouzBouz S. Hoveyda AH. J. Organomet. Chem.  2001,  624:  327 
• 6 Kingsbury JS. Harrity JPA. Bonitatebus PJ. Hoveyda AH. J. Am. Chem. Soc.  1999,  121:  791 
• 7 Still WC. Gennari C. Tetrahedron Lett.  1983,  24:  4405 

8

Compound 9: R _f = 0.23 (PE-EtOAc, 2:8); [α] _d ^²0 +48.1
(c = 0.34, CHCl₃) {Lit. [¹] [α] _d ^²0 +40.2 (c = 0.40, CHCl₃)}. IR (neat): 3311, 2920, 1698, 1515 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.05 (app dt, J = 8.5, 2.5 Hz, 2 H), 6.88 (app dt, J = 9.5, 4.1 Hz, 1 H), 6.76 (app dt, J = 8.5, 2.5 Hz, 2 H), 6.02 (dt, J = 9.8, 1.9 Hz, 1 H), 5.32 (br s, 1 H), 4.65 (dddd, J = 7.7, 7.7, 7.7, 5.3 Hz, 1 H), 3.87 (m, 1 H), 2.67 (m, 2 H), 2.38 (m, 2 H), 2.00 (dt, J = 15.7, 8.2 Hz, 1 H), 1.90 (br s, 1 H, OH), 1.79 (m, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 164.6 (s), 154.3 (s), 145.8 (d), 133.9 (s), 129.8 (2 × d), 121.5 (d), 115.7 (2 × d), 77.4 (d), 69.0(d), 42.4 (t), 39.7 (t), 31.2 (t), 29.8 (t). MS (EI, 70 eV): m/z (%) = 262 (5), 150 (2), 133 (10), 120 (9), 108 (27), 107 (100), 94 (14), 77 (49), 67 (23), 53 (22). HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₈O₄Na: 285.10987; found: 285.10973.