Highly Regioselective and Diastereoselective Photooxygenation of α-Cyclogeranyl Derivatives

Abstract

Methylene blue-sensitized photooxygenation of several α-cyclogeranyl derivatives affords the exocyclic allylic hydroperoxides in 94-99% regioselectivity, while the diastereoselectivity varies from 50-97% de in favor of the cis isomer, depending on the substituents. By contrast, the ene reaction with N-phenyltriazol­inedione affords significantly different regioselectivity and diastereoselectivity.

singlet oxygen - ene reaction - allylic hydroperoxides - regioselectivity - diastereoselectivity

References

1a Stratakis M. Orfanopoulos M. Tetrahedron  2000,  56:  1595 

1b Clennan EL. Tetrahedron  2000,  56:  9151 

For some recent selected applications of ¹O₂ ene reactions in organic synthesis, see:

2a Nakano M. Furuichi N. Mori H. Katsumura S. Tetrahedron Lett.  2001,  42:  7307 

2b Griesbeck AG. El-Idreesy TT. Fiege M. Brun R. Org. Lett.  2002,  4:  4193 

2c Vassilikogiannakis G. Stratakis M. Angew. Chem. Int. Ed.  2003,  42:  5465 

2d Fröhlich L. Linker T. Synlett  2004,  2725 

2e Cordova A. Sunden H. Engqvist M. Ibrahem I. Casas J. J. Am. Chem. Soc.  2004,  126:  8914 

3 Stratakis M. Curr. Org. Synth.  2005,  2:  281 

4 Prein M. Adam W. Angew. Chem., Int. Ed. Engl.  1996,  108:  519 

5 Linker T. Fröhlich L. J. Am. Chem. Soc.  1995,  117:  2694 

6a Compounds 1 and 3-5 were prepared by trivial organic methodology from α-cyclogeranyl acetate (2), which was obtained by cyclization of geranyl acetate promoted by zeolite NaY. See: Tsangarakis C. Stratakis M. Adv. Synth. Catal.  2005,  in press 

6b

Compound 6 (dihydro-α-ionone) is commercially available, while 7 was prepared from 6 by LiAlH₄ reduction followed by mesylation and subsequent reduction by LiAlH₄.

7

Selected NMR data of the allylic hydroperoxides. Compound 1a: ¹H NMR: δ = 9.92 (br s, 1 H), 5.25 (d, 1 H, J = 1.5 Hz), 5.08 (d, 1 H, J = 1.5 Hz), 4.43 (m, 1 H), 3.93 (t, 1 H, J = 10.0 Hz), 3.86 (dd, 1 H, J ₁ = 10.0 Hz, J ₂ = 7.0 Hz), 2.23 (dd, 1 H, J ₁ = 10.0 Hz, J ₂ = 7.0 Hz), 1.82 (m, 2 H), 1.69 (m, 1 H), 1.04 (m, 1 H), 0.92 (s, 3 H), 0.88 (s, 3 H). ¹³C NMR: δ = 143.13, 120.08, 84.52, 62.48, 54.29, 33.43, 29.49, 27.61, 27.54, 26.15.
Compound 2a: ¹H NMR: δ = 8.97 (s, 1 H), 5.19 (d, 1 H, J = 1.5 Hz), 4.99 (d, 1 H, J = 1.5 Hz), 4.46 (dd, 1 H, J ₁ = 10.5 Hz, J ₂ = 5.5 Hz), 4.40 (br t, 1 H, J = 3.5 Hz), 4.34 (t, 1 H, J = 10.5 Hz), 2.35 (dd, 1 H, J ₁ = 10.5 Hz, J ₂ = 5.5 Hz), 2.06 (s, 3 H), 1.85 (m, 2 H), 1.61 (m, 1 H), 1.12 (m, 1 H), 0.96 (s, 3 H), 0.93 (s, 3 H). ¹³C NMR: δ = 170.69, 142.38, 118.90, 84.40, 64.74, 50.68, 33.20, 30.26, 30.16, 27.44, 27.17, 26.02.
Compound 3a (as alcohol): ¹H NMR: δ = 5.31 (br s, 1 H), 4.88 (br s, 1 H), 4.11 (m, 1 H), 3.73 (dd, 1 H, J ₁ = 10.0 Hz, J ₂ = 3.5 Hz), 3.61 (t, 1 H, J = 10.0 Hz), 2.21 (dd, 1 H, J ₁ = 10.0 Hz, J ₂ = 3.5 Hz), 1.90 (m, 1 H), 1.57 (m, 2 H), 1.36 (m, 1 H), 1.03 (s, 3 H), 0.81 (s, 3 H). ¹³C NMR: δ = 147.32, 110.39, 72.91, 54.54, 36.54, 34.50, 31.72, 31.20, 28.98, 22.45.
Compound 3b (as alcohol; representative signals): ¹H NMR: δ = 5.22 (br s, 1 H), 4.86 (br s, 1 H), 4.24 (m, 1 H), 3.73 (dd, 1 H, J ₁ = 10.0 Hz, J ₂ = 3.5 Hz), 3.38 (t, 1 H, J = 10.0 Hz), 2.58 (dd, 1 H, J ₁ = 10.0 Hz, J ₂ = 3.5 Hz), 1.05 (s, 3 H), 0.87 (s, 3 H). Compound 5a: ¹H NMR: δ = 10.04 (s, 1 H), 7.27-7.35 (m, 5 H), 5.23 (d, 1 H, J = 2.0 Hz), 5.13 (d, 1 H, J = 2.0 Hz), 4.61 (d, 1 H, J = 11.5 Hz), 4.52 (d, 1 H, J = 11.5 Hz), 4.44 (br t, 1 H, J = 4.0 Hz), 4.04 (dd, 1 H, J ₁ = 12.0 Hz, J ₂ = 9.5 Hz), 3.64 (dd, 1 H, J ₁ = 9.5 Hz, J ₂ = 7.0 Hz), 2.45 (dd, 1 H, J ₁ = 12.0 Hz, J ₂ = 9.5 Hz), 1.65-1.85 (m, 3 H), 1.03 (m, 1 H), 0.93 (s, 3 H), 0.87 (s, 3 H).
Compound 5b: ¹H NMR: δ = 9.10 (br s, 1 H), 7.27-7.37 (m, 5 H), 5.20 (br s, 1 H), 4.98 (br s, 1 H), 4.54 (d, 1 H, J = 12.0 Hz), 4.49 (d, 1 H, J = 12.0 Hz), 4.43 (br t, 1 H, J = 4.0 Hz), 3.73 (dd, 1 H, J ₁ = 9.5 Hz, J ₂ = 3.5 Hz), 3.64 (t, 1 H, J = 9.5 Hz), 2.51 (dd, 1 H, J ₁ = 9.5 Hz, J ₂ = 3.5 Hz), 1.60-1.85 (m, 3 H), 1.21 (m, 1 H), 1.02 (s, 3 H), 0.76 (s, 3 H). Compound 6a: ¹H NMR: δ = 8.63 (br s, 1 H), 5.18 (br s, 1 H), 4.82 (br s, 1 H), 4.34 (br t, 1 H, J = 4.5 Hz), 2.55 (m, 1 H), 2.43 (m, 1 H), 2.17 (s, 3 H), 1.60-1.85 (m, 6 H), 1.18 (m, 1 H), 0.92 (s, 3 H), 0.87 (s, 3 H). ¹³C NMR: δ = 211.52, 145.35, 119.57, 85.54, 52.46, 42.10, 34.71, 31.54, 30.40, 28.09, 26.88, 26.26, 25.80, 21.78. Compound 6b: ¹H NMR: δ = 8.27 (br s, 1 H), 5.16 (br s, 1 H), 4.77 (br s, 1 H), 4.44 (br t, 1 H, J = 4.0 Hz), 2.47 (m, 1 H), 2.42 (m, 1 H), 2.15 (s, 3 H), 1.60-1.85 (m, 6 H), 1.30 (m, 1 H), 1.01 (s, 3 H), 0.79 (s, 3 H).
Compound 7a (selected signals): ¹H NMR: δ = 8.02 (br s, 1 H), 5.14 (br s, 1 H), 4.83 (br s, 1 H), 4.32 (dd, 1 H, J ₁ = 8.5 Hz, J ₂ = 7.0 Hz).
Compound 7b (selected signals): ¹H NMR: δ = 7.89 (br s, 1 H), 5.11 (br s, 1 H), 4.83 (br s, 1 H), 4.45 (br t, 1 H, J = 5.0 Hz).

8 Adam W. Griesbeck AG. Wang X. Liebigs Ann. Chem.  1992,  193 

9 Stratakis M. Orfanopoulos M. Tetrahedron Lett.  1995,  36:  4291 

10 Snowden RL. Eichenberger J.-C. Linder SM. Sonnay P. Vial C. Schulte-Elte KH. J. Org. Chem.  1992,  57:  955 

11a Fehr C. Angew. Chem. Int. Ed.  1998,  37:  2407 

11b Washington I. Houk KN. Angew. Chem. Int. Ed.  2001,  40:  4485 

12 Vougioukalakis GC. Orfanopoulos M. Synlett  2005,  713 

13

Selected NMR data of the major ene PTAD-adducts.
Compound 1 + PTAD: ¹H NMR: δ = 7.38-7.57 (m, 5 H), 4.64 (t, 1 H, J = 6.0 Hz), 4.16 (d, 1 H, J = 11.5 Hz), 4.03 (d, 1 H, J = 11.5 Hz), 1.92 (m, 2 H), 1.80 (s, 3 H), 1.66 (m, 1 H), 1.47 (m, 1 H), 1.07 (s, 3 H), 0.98 (s, 3 H).
Compound 2 + PTAD: ¹H NMR: δ = 9.45 (br s, 1 H), 7.37-7.53 (m, 5 H), 4.72 (t, 1 H, J = 6.5 Hz), 4.57 (d, 1 H, J = 12.0 Hz), 4.51 (d, 1 H, J = 12.0 Hz), 2.01 (s, 3 H), 1.93 (m, 2 H), 1.69 (s, 3 H), 1.61 (m, 1 H), 1.52 (m, 1 H), 1.00 (s, 3 H), 0.99 (s, 3 H). ¹³C NMR: δ = 171.08, 153.43, 151.72, 140.78, 131.23, 130.85, 128.99, 128.09, 125.27, 60.59, 56.52, 35.97, 34.18, 27.73, 26.87, 23.20, 20.86, 15.97.
Compound 5 + PTAD: ¹H NMR: δ = 7.32-7.58 (m, 10 H), 4.68 (t, 1 H, J = 6.5 Hz), 4.89 (s, 2 H), 3.94 (d, 1 H, J = 10.0 Hz), 3.91 (d, 1 H, J = 10.0 Hz), 1.92 (m, 2 H), 1.72 (s, 3 H), 1.65 (m, 1 H), 1.51 (m, 1 H), 1.04 (s, 3 H), 1.02 (s, 3 H).
Compound 6 + PTAD: ¹H NMR: δ = 9.17 (br s, 1 H), 7.36-7.53 (m, 5 H), 4.63 (t, 1 H, J = 6.0 Hz), 2.45 (m, 2 H), 2.29 (t, 2 H, J = 8.0 Hz), 2.04 (s, 3 H), 1.92 (m, 2 H), 1.63 (m, 1 H), 1.61 (s, 3 H), 1.48 (m, 1 H), 1.00 (s, 3 H), 0.99 (s, 3 H). ¹³C NMR: δ = 208.38, 153.35, 151.52, 146.03, 131.34, 129.03, 128.16, 125.52, 123.24, 56.50, 43.26, 35.92, 35.12, 29.71, 27.87, 27.24, 23.68, 22.81, 16.36.
Compound 7 + PTAD (selected peaks): ¹H NMR: δ = 8.55 (br s, 1 H), 7.35-7.55 (m, 5 H), 4.64 (t, 1 H, J = 6.0 Hz), 1.63 (s, 3 H), 1.02 (s, 3 H), 1.00 (s, 3 H).

14 Elemes Y. Stratakis M. Orfanopoulos M. Tetrahedron Lett.  1997,  38:  6437