Synthetic Studies towards Cembranoids via the Heck Reaction

Abstract

The Heck reaction was employed for the construction of the macrocyclic cembranoid skeleton.

Key words

palladium - Heck reaction - ring closure - macrocycles - cembranoids

References and Notes

• For reviews, see:
• 1a Tius MA. Chem. Rev.  1988,  88:  719 
• 1b Mulzer J. Altenbach H.-J. Braun M. Krohn K. Reissig H.-U. Organic Synthesis Highlights   VCH; Weinheim: 1990.  p.286 
• For some recent reports, see:
• 2a Marshall JA. Andersen MW. J. Org. Chem.  1992,  57:  2766 
• 2b Petasis NA. Bzowej EI. Tetrahedron Lett.  1993,  34:  1721 
• 2c Paquette LA. Astles PC. J. Org. Chem.  1993,  58:  165 
• 2d Pattenden G. Smithies AJ. J. Chem. Soc., Perkin Trans. 1  1996,  57 
• 2e Marshall JA. Van Devender EA. J. Org. Chem.  2001,  66:  8037 
• 2f Peng L. Zhang F. Mei T. Zhang T. Li Y. Tetrahedron Lett.  2003,  44:  5921 
• 2g Gurjar MK. Nayak S. Ramana CV. Tetrahedron Lett.  2005,  14:  1881 ; and references therein
• For recent reviews, see:
• 3a Link JT. Org. React. (N.Y.)  2002,  60:  157 ; and references therein
• For examples, see:
• 3b Ziegler FE. Chakraborty UR. Weisenfeld RB. Tetrahedron  1981,  37:  4035 
• 3c Akaji K. Teruya K. Akaji M. Aimoto S. Tetrahedron  2001,  57:  2293 
• 3d Li J. Jeong S. Esser L. Harran PG. Angew. Chem. Int. Ed.  2001,  40:  4765 
• 3e Dyker G. Kadzimirsz D. Henkel G. Tetrahedron Lett.  2003,  44:  7905 
• 3f Gibson SE. Mainolfi N. Kalindjian SB. Wright PT. White AJP. Chem. Eur. J.  2005,  11:  69 
• 3g Byk G. Cohen-Ohara M. Raichman D. Pept. Sci.  2006,  84:  274 
• The stereochemical aspect of the Heck Reaction was discussed in relation to rearrangement or isomerization:
• 4a Jeffery T. J. Chem. Soc., Chem. Commun.  1984,  1287 
• 4b Abelman MM. Oh T. Overman LE. J. Org. Chem.  1987,  52:  4130 
• 4c Abelman MM. Overman LE. J. Am. Chem. Soc.  1988,  110:  2328 
• 4d Torii S. Okumoto H. Kotani T. Nakayasu S. Ozaki H. Tetrahedron Lett.  1992,  33:  3503 
• 4e Nagasawa K. Zako Y. Ishihara H. Shimizu I. Tetrahedron Lett.  1991,  32:  4937 
• 4f Nagasawa K. Zako Y. Ishihara H. Shimizu I. J. Org. Chem.  1993,  58:  2523 
• 4g Mascarenas JL. Garcia AM. Castedo L. Mourino A. Tetrahedron Lett.  1992,  33:  4365 
• 4h Yokoyama H. Miyamoto K. Hirai Y. Takahashi T. Synlett  1997,  187 
• 7 Still WC. Gennari C. Tetrahedron Lett.  1983,  24:  4405 
• 8a Jeffery T. Tetrahedron Lett.  1985,  26:  2667 
• 8b Jeffery T. Synthesis  1987,  70 
• 8c Jeffery T. Tetrahedron  1996,  52:  10113 
• Cyclopropanation was suggested; for reports, see:
• 10a Torii S. Okumoto H. Ozaki H. Nakayasu S. Tadokoro T. Kotani T. Tetrahedron Lett.  1992,  33:  3499 
• 10b Owczarczyk Z. Lamaty F. Vawter EJ. Nagishi E. J. Am. Chem. Soc.  1992,  114:  10091 
• 10c Yokoyama H. Takahashi T. Tetrahedron Lett.  1997,  38:  595 

5

The ketone 3 was synthesized in 15 steps from geraniol according to usual methods.

6

Data for 10: IR (neat): 1716 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 6.21 (d, 1 H, J = 15.6 Hz), 6.15 (d, 1 H, J = 15.6 Hz), 5.72 (s, 1 H), 5.02-4.98 (m, 2 H), 4.17 (q, 2 H, J = 7.2 Hz), 2.92-2.74 (m, 2 H), 2.35-1.81 (m, 10 H), 1.61 (s, 3 H), 1.57 (s, 3 H), 1.31-1.29 (m, 6 H), 0.92 (s, 9 H), 0.10 (s, 3 H), 0.08 (s, 3 H); an NOE of 4.3% was observed between H₁ and H₂ (Figure [3] ). EIMS: m/z = 446 (M⁺).

Figure 3

9

Data for 12: IR (neat): 1722 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.60 (d, 1 H, J = 16.4 Hz), 6.19 (d, 1 H, J = 16.4 Hz), 5.65 (s, 1 H), 5.18-5.05 (m, 1 H), 5.04-4.95 (m, 1 H), 4.17 (q, 2 H, J = 7.2 Hz), 2.82-2.65 (m, 2 H), 2.51-1.75 (m, 8 H), 1.56 (s, 6 H), 1.61 -1.48 (m, 2 H), 1.35-1.19 (m, 6 H), 0.95-0.80 (m, 9 H), 0.08-0.04 (m, 3 H). EIMS: m/z = 389 [M⁺ - t-Bu].