Towards the Synthesis of the Cornexistins

Abstract

A concise synthetic route to the carbocyclic core of the cornexistins is reported. The route is highlighted by a Diels-Alder cycloaddition/oxidative cleavage strategy to generate the central highly functionalized nine-member ring. A silyl-tethered ring-closing metathesis strategy is utilized to control trisubstituted alkene geometry.

Key words

Diels-Alder - oxidative cleavage - natural products - ring expansion - ring-closing metathesis - carbocycle

References

• 1 Nakajima M. Itoi K. Takamatsu Y. Sato S. Furukawa Y. Furuya K. Honma T. Kadotani J. Kozasa M. Haneishi T. J. Antibiot.  1991,  44:  1065 
• 2 Fields SC. Mireles-Lo L. Gerwick BC. J. Nat. Prod.  1996,  59:  698 
• 3 Barton DHR. Sutherland JK. J. Chem. Soc.  1965,  1769 
• 4a Spiegel DA. Njardarson JT. McDonald IM. Chem. Rev.  2003,  103:  2691 
• 4b Hayashi Y. Itoh T. Fukuyama T. Org. Lett.  2003,  5:  2235 
• 5 Stork G. Tabak JM. Blount JF. J. Am. Chem. Soc.  1972,  94:  4735 
• 6a White JD. Kim J. Drapela NE. J. Am. Chem. Soc.  2000,  122:  8665 
• 6b White JD. Dillon MP. Butlin RJ. J. Am. Chem. Soc.  1992,  114:  9673 
• 7 Clark JS. Marlin F. Nay B. Wilson C. Org. Lett.  2003,  5:  89 
• 8 Wender PA. Lechleiter JC. J. Am. Chem. Soc.  1977,  99:  267 
• 10 The syn-relationship of 8 was determined by removal of the protecting groups, formation of the acetonide and Rychnovsky ¹³C analysis: Rychnovsky SD. Ryan BN. Richardson TI. Acc. Chem. Res.  1998,  31:  9 
• 11 Mitsunobu O. Synthesis  1981,  1 
• 12 Trost BM. Lee DC. J. Am. Chem. Soc.  1988,  110:  7255 
• 14a Pine SH. Kim G. Lee V. Org. Synth.  1990,  69:  72 
• 14b Renneberg D. Pfander H. Leumann CJ. J. Org. Chem.  2000,  65:  9069 
• 15a Gauthier DR. Zandi KS. Shea KJ. Tetrahedron  1998,  54:  2289 
• For an elegant example of the use of a temporary tether to control olefin geometry, see:
• 15b Evans DA. Carreira EM. Tetrahedron Lett.  1990,  31:  4703 
• Inspired by our initial results, this strategy has recently been successfully applied to total synthesis, see,
• 15c Li F. Miller MJ. J. Org. Chem.  2006,  71:  5221 
• 16 Scholl M. Ding S. Lee CW. Grubbs RH. Org. Lett.  1999,  1:  953 
• 17 Tamao K. Ishida N. Kumada M. Org. Synth.  1990,  69:  96 

9

Aldehyde 5 was derived from the monoprotection of propane-1,3-diol (BuLi, TBSCl, THF, -78 °C to reflux) and TEMPO/bleach oxidation.

13

Crystal data, selected bond lengths and angles for 3: Formula: C₃₀H₄₄O₇Si, MW = 544.74, a = 10.3090(4) Å, b = 12.2193(5) Å, c = 13.9422(5) Å, α = 70.593(2)°, β = 78.609(2)°, γ = 74.217(2)°, P1, V = 1582.90(11) ų, Z = 2, R ₁ = 0.0588, wR ₂ = 0.1815. Data collection: 0.5° φ and ω scans, CCD area detector. Solved by direct methods and refined by full-matrix least-squares refinement against F ². Selected bond lengths (Å): O2-C1: 1.429(4), C2-C3: 1.497(4), C8-C9: 1.525(5), C1-C2: 1.499(4), C3-C28: 1.542(4). Selected bond angles (°): C1-O2-C16: 112.5(3), O2-C1-C2: 111.2(3), O2-C1-C9: 113.5(3), C2-C1-C9: 102.5(3), C2-C3-C4: 110.5(2), C2-C3-C28: 112.6(2), C4-C3-C28: 112.6(2). Details of the crystal structure determination have been deposited with the Cambridge crystallographic Data Centre and may be retrieved at www.ccdc.cam.ac.uk by citing CCDC 642483.