Synthesis of Highly Functionalized δ-Lactone-Fused Cyclopentanoids

Abstract

A short and efficient route to δ-lactone-fused cyclopentanoids starting from the easily accessible Diels-Alder adducts between homoallylic alcohol acetates and 1,2,3,4-tetrachloro-5,5-dimethoxycyclopenta-1,3-diene is reported. Since homoallyl alcohols were derived from the corresponding aldehydes RCHO (R = alkyl, aryl) through allyl metal addition, the methodology is broad in scope with regard to the choice of R group. The initially formed 1:1 diastereomeric mixture of adducts were subjected to ruthenium-catalyzed oxidation followed by acid-mediated hydrolysis of the acetate groups to obtain the hemiacetals 6a-e. Alkaline H₂O₂-mediated cleavage of the hemiacetals led, after esterification with diazomethane, to a chromatographically separable diastereomeric mixture of 7 and 8 in high overall yield (54-68%).

Key words

δ-lactones - Diels-Alder reactions - α-diketones - α-keto hemiacetals - diastereomers

References

• For selected examples of δ-lactone-containing natural products, see:
• 1a Hanessian S. Total Synthesis of Natural Products: The Chiron Approach   Pergamon; Oxford: 1983. 
• 1b Scott JW. In Asymmetric Synthesis   Vol. 4:  Morrison JD. Scott JW. Academic Press; New York: 1984.  p.1-226  
• 1c Devon TK. Scott AI. In Handbook of Naturally Occurring Compounds   Vol. 1:  Academic Press; New York: 1975. 
• 1d Braun M. In Organic Synthesis Highlights   Vol. 1:  Mulzer J. Altenbach H.-J. Braun M. Krohn K. Reissig H.-U. VCH; Weinheim: 1991.  p.309-322  
• 1e Dhotare B. Goswami D. Chattopadhyay A. Tetrahedron Lett.  2005,  46:  6219 
• 1f Chakraborty TK. Goswami RK. Tetrahedron Lett.  2004,  45:  7637 
• 1g Dias LC. Steil LJ. Vasconcelos VdA. Tetrahedron: Asymmetry  2004,  15:  147 
• 1h Meresse P. Monneret C. Bertounesque E. Tetrahedron  2004,  60:  2657 
• 2a Paquette LA. Wang TZ. Vo Nha H. J. Am. Chem. Soc.  1993,  115:  1676 
• 2b Borrelly S. Paquette LA. J. Am. Chem. Soc.  1996,  118:  727 
• 2c Murga J. García-Fortanet J. Carda M. Marco JA. J. Org. Chem.  2004,  69:  7277 
• 2d Sato K. Akai S. Sugita N. Ohsawa T. Kogure T. Shoji H. Yoshimura J. J. Org. Chem.  2005,  70:  7496 
• 2e Kagawa N. Ihara M. Toyota M. J. Org. Chem.  2006,  71:  6796 
• 2f Sawant KB. Jennings MP. J. Org. Chem.  2006,  71:  7911 
• 3a Eaton PE. Or YS. Branca SJ. Shankar BKR. Tetrahedron  1986,  42:  1621 
• 3b Ohta H. Kobori T. Fujisawa T. J. Org. Chem.  1977,  42:  1231 
• 3c Lee J. Lewin NE. Blumberg PM. Marquez VE. Bioorg. Med. Chem. Lett.  1994,  4:  2405 
• 3d Lee J. Marquez VE. Blumberg PM. Krausz KW. Kazanietz MG. Bioorg. Med. Chem.  1993,  1:  119 
• 4a Aplander K. Hidestal O. Katebzadeh K. Lindström UM. Green Chem.  2006,  8:  22 
• 4b Brandänge S. Färnbäck M. Leijonmarck H. Sundin A. J. Am. Chem. Soc.  2003,  125:  11942 
• 4c Cateni F. Zilic J. Zacchigna M. Bonivento P. Frausin F. Scarcia V. Eur. J. Med. Chem.  2006,  41:  192 
• 4d Lin L. Fan Q. Qin B. Feng X. J. Org. Chem.  2006,  71:  4141 
• 4e Tiecco M. Testaferri L. Temperini A. Terlizzi R. Bagnoli L. Marini F. Santi C. Synlett  2006,  587 
• 4f Dieter RK. Guo F. Org. Lett.  2006,  8:  4779 
• For some applications of norbornyl α-diketones, see:
• 5a Khan FA. Dash J. Eur. J. Org. Chem.  2004,  2692 
• 5b Khan FA. Dash J. Sudheer Ch. Chem. Eur. J.  2004,  10:  2507 
• 5c Khan FA. Dash J. Sahu N. Sudheer Ch. J. Org. Chem.  2002,  67:  3783 
• 5d Khan FA. Dash J. Rout B. Tetrahedron Lett.  2004,  45:  9285 
• 5e Khan FA. Satapathy R. Dash J. Savitha G. J. Org. Chem.  2004,  69:  5295 
• 5f Khan FA. Dash J. Sudheer Ch. Sahu N. Parasuraman K. J. Org. Chem.  2005,  70:  7565 
• 5g Khan FA. Dash J. J. Am. Chem. Soc.  2002,  124:  2424 
• 5h Khan FA. Rout B. Tetrahedron Lett.  2006,  47:  5251 
• 5i Khan FA. Satapathy R. Sudheer Ch. Rao CN. Tetrahedron Lett.  2005,  46:  7193 
• 6a Khan FA. Prabhudas B. Dash J. Sahu N. J. Am. Chem. Soc.  2000,  122:  9558 
• 6b Khan FA. Sahu N. J. Catal.  2005,  231:  438 
• 7a Takaya H. Ohta T. Noyori R. In Catalytic Asymmetric Synthesis   Ojima I. VCH; Weinheim: 1993. 
• 7b Denmark SE. Fu J. Chem. Rev.  2003,  103:  2763 
• 7c Mathre D. Thompson A. Douglas A. Hoogsteen K. Carroll J. Corley E. Grabowski E. J. Org. Chem.  1993,  58:  2880 
• 7d Wilson SR. Guazzaroni ME. J. Org. Chem.  1989,  54:  3087 
• 7e Keck GE. Krishnamurthy D. Org. Synth.  1998,  75:  12 
• 8 For a review on synthetic applications of Diels-Alder adducts of 1,2,3,4-tetrachloro-5,5-dimethoxy cyclopenta-1,3-diene (3), see: Khan FA. Prabhudas B. Dash J.
  J. Prakt. Chem.  2000,  342:  512 
• 9a Das B. Reddy MR. Reddy KR. Ramu R. Thirupathi P. J. Mol. Catal. A: Chem.  2006,  248:  185 
• 9b Cahiez G. Chavant PY. Tetrahedron Lett.  1989,  30:  7373 
• 9c Boaretto A. Marton D. Tagliavini G. J. Organomet. Chem.  1985,  288:  283 ; and references cited therein
• 9d Tan X.-H. Shen B. Deng W. Zhao H. Liu L. Guo Q.-X. Org. Lett.  2003,  5:  1833 
• 10 Khan FA. Sahu N. Dash J. Prabhudas B. J. Indian Inst. Sci.  2000,  81:  325 ; Chem. Abstr. 2004, 140, 76960

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CCDC-618880 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.