Efficient and Stereoselective Synthesis of Precursors for Epoxypolyene Cyclizations via Allylic Substitutions

Abstract

A catalytic and highly stereoselective approach to precursors for epoxypolyene cyclizations based on copper-catalyzed allylic substitutions is described. The method allows introduction of various aromatic, benzyl, and alkyl groups without affecting ­epoxides. The compounds obtained are valuable starting materials for the synthesis of natural products and biologically active substances.

catalysis - cuprates - epoxides - Grignard reagent - epoxypolyene cyclization

References

<A NAME="RG12905ST-1A">1a</A> Abe I. Rohmer M. Prestwich GD. Chem. Rev.  1993,  93:  2189 

<A NAME="RG12905ST-1B">1b</A> Wendt KU. Schulz GE. Corey EJ. Liu DR. Angew. Chem. Int. Ed.  2000,  39:  2812 

<A NAME="RG12905ST-2">2</A> Justicia J. Rosales A. Buñuel E. Oller-López JL. Valdivia M. Haïdour A. Oltra JE. Barrero AF. Cárdenas DJ. Cuerva JM. Chem.-Eur. J.  2004,  10:  1778 

<A NAME="RG12905ST-3A">3a</A> Gansäuer A. Bluhm H. Chem. Rev.  2000,  100:  2771 

<A NAME="RG12905ST-3B">3b</A> Gansäuer A. Lauterbach T. Narayan S. Angew. Chem. Int. Ed.  2003,  42:  5556 

<A NAME="RG12905ST-4">4</A> Justicia J. Oltra JE. Cuerva JM. J. Org. Chem.  2004,  69:  5803 

<A NAME="RG12905ST-5">5</A> Review: Krause N. Gerold A. Angew. Chem., Int. Ed. Engl.  1997,  36:  186 

<A NAME="RG12905ST-6">6</A> Whitesell JK. Lawrence RM. Chen HH. J. Org. Chem.  1986,  51:  4779 

<A NAME="RG12905ST-7A">7a</A> Johnson CR. Herr RW. Wieland DM. J. Org. Chem.  1973,  38:  4263 

<A NAME="RG12905ST-7B">7b</A> Sirat HM. Thomas EJ. Wallis JD. J. Chem. Soc., Perkin Trans. 1  1982,  2885 

<A NAME="RG12905ST-8">8</A>

Typical Experimental Procedures.Preparation of Compound 3.
To a solution of 2 (2.120 g, 10 mmol) in dry THF (90 mL) a 0.1 M solution of Li₂CuCl₄ (5.4 mL, 0.5 mmol) was added dropwise after cooling to 0 °C. Then a solution of BuMgCl (7 mL, 2 M, 14 mmol) was added dropwise over 20 min. The mixture was stirred at 0 °C for 3 h and then at r.t. overnight. Then sat. aq NH₄Cl was added and the mixture extracted with EtOAc, dried over MgSO₄ and the solvent was removed in vacuo. The residue was purified by SiO₂ chromatography (cyclohexane-EtOAc, 97:3) to yield 3 (1520 mg, 72%): colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 5.17 (t of app. sext, J = 7.0, 1.1 Hz, 1 H), 2.69 (t, J = 6.3 Hz, 1H), 2.04-2.19 (m, 2 H), 1.97 (q, J = 7.0 Hz, 2 H), 1.54-1.70 (m, 2 H), 1.60 (s, 3 H), 1.25-1.36 (m, 6 H), 1.29 (s, 3H), 1.25 (s, 3 H), 0.88 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃, DEPT): δ = 133.9, 125.6, 64.3, 58.4, 36.5, 31.7, 29.6, 28.0, 27.6, 25.0, 22.7, 18.9, 16.1, 14.2. IR (film): 2925, 1460, 1375, 1120 cm^-1. HRMS (EI): m/z calcd for C₁₄H₂₆O: 210.1984; found: 210.1986.
Preparation of Compound 14. To a vigorously stirred suspension of Mg (29 mg, 1.2 mmol) in THF (2 mL) was added 2-bromoanisol (225 mg, 1.2 mmol). The mixture was stirred at reflux until dissolution of the metal and added dropwise to a solution of 2 (85 mg, 0.4 mmol) and Li₂CuCl₄ (0.20 mL of a 0.1 M solution in THF, 0.02 mmol) in THF (2 mL) at 0 °C. Stirring was continued for 4 h at r.t. After addition of a sat. solution of NH₄Cl the mixture was extracted with EtOAc, dried over MgSO₄, and the solvent was removed in vacuo. Purification by SiO₂ chromatography (cyclohexane-EtOAc, 95:5) yielded 14 (72 mg, 69%): colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.17 (td, J = 7.7, 1.5 Hz, 1 H), 7.12 (dd, J = 7.4, 1.5 Hz, 1 H), 6.87 (td, J = 7.4, 1.1 Hz, 1 H), 6.77 (br d, 1 H), 5.36 (tq, J = 7.3, 1.2 Hz, 1 H), 3.82 (s, 3 H), 3.34 (d, J = 7.3 Hz, 2 H), 2.70 (t, J = 6.2 Hz, 1 H), 2.31-2.05 (m, 2 H), 1.73 (s, 3 H), 1.71-1.57 (m, 2 H), 1.26 (s, 3 H), 1.24 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃, DEPT): δ = 157.5, 135.1, 130.0, 129.5, 127.1, 123.4, 120.6, 110.4, 64.4, 58.5, 55.5, 36.5, 28.5, 27.6, 25.0, 18.9, 16.2. IR (film): 2970, 2930, 1720, 1600, 1490, 1460, 1380, 1290 cm^-1. HRMS (EI): m/z calcd for C₁₇H₂₄O₂: 260.1776; found: 260.1782.

<A NAME="RG12905ST-9">9</A> Tamura M. Kochi J. Synthesis  1971,  303 

<A NAME="RG12905ST-10">10</A> Knochel P. Dohle W. Gommermann N. Kneisel FF. Kopp F. Sapountzis I. Vu VA. Angew. Chem. Int. Ed.  2003,  42:  4302 

<A NAME="RG12905ST-11">11</A> Jarvis BB. Phytochemistry  2003,  64:  53 

<A NAME="RG12905ST-12A">12a</A> Azevedo DA. Aquino Neto FR. Simoneit BRT. Org. Mass. Spectrom.  1990,  25:  475 

<A NAME="RG12905ST-12B">12b</A> Brandt CW. Neubauer LG. J. Chem. Soc.  1939,  103 

<A NAME="RG12905ST-13">13</A> Raldugin VA. Demenovka LI. Pentegova VA. Khim. Prir. Soedin.  1978,  3:  345