title: endo/exo stereoselectivity in Diels-Alder reactions of α,β-dialkylated conjugated enals to cyclic 1,3-dienes: intermediates in the synthesis of (-)-β-santalol and its analogs.
abstract: Highly exo-selective [4+2] cycloadditions of cyclopenta-1,3-diene 2a to α,β-dialkyl conjugated enals 5 are compared with the analogous endo-favored Diels-Alder reaction of cyclohexa-1,3-diene 7. The exo-stereoselectivity is lower in the homologous case of methylcyclopenta-1,3-diene 9. This diastereoselectivity is discussed either in terms of a retro-homo-Diels-Alder reaction, associated with thermodynamic control, or with respect to either a competing hetero-Diels-Alder/Claisen or Cope domino pathway, or retro-Claisen/retro-hetero-Diels-Alder of the endo-homo-cycloadducts. These hypothetical mechanisms have been examined by DFT calculations at the MPW1K(CH2 Cl2 )/6-31+G** level of theory for the AlCl3 -mediated cycloadditions of 5d to 2a and 7. Application of Corey's methodology to the γ-halogeno-α-methyl-substituted dienophiles 5a and 5b allowed an enantioselective preparation of known and useful intermediates for the synthesis of either the naturally occurring (-)-β-santalol or its potentially olfactive structural analogs.
authors.affiliation: Firmenich SA, Synthesis Department, Corporate R & D Division, P. O. Box 239, CH-1211 Geneva 8, (phone: +41-22-7803610; fax: +41-22-7803334). christian.chapuis@firmenich.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Chapuis
authors.forename: David
authors.initials: D
authors.lastname: Skuy
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: de Saint Laumer
authors.forename: Robert
authors.initials: R
authors.lastname: Brauchli
mesh_terms: D002384:Catalysis; D003500:Cyclization; D061565:Cycloaddition Reaction; D008958:Models, Molecular; D015394:Molecular Structure; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C043206:santalol
keywords: Claisen rearrangement; Cope rearrangement; DielsAlder reaction; β-Santalol