Chapuis Christian, Skuy David, de Saint Laumer Jean-Yves, Brauchli Robert
Firmenich SA, Synthesis Department, Corporate R & D Division, P. O. Box 239, CH-1211 Geneva 8, (phone: +41-22-7803610; fax: +41-22-7803334).
Chem Biodivers. 2014 Oct;11(10):1470-516. doi: 10.1002/cbdv.201400060.
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.
将环戊-1,3-二烯2a与α,β-二烷基共轭烯醛5进行高度外选择性的[4+2]环加成反应，并与环己-1,3-二烯7类似的内型优势狄尔斯-阿尔德反应进行比较。在甲基环戊-1,3-二烯9的同系物情况下，外型立体选择性较低。这种非对映选择性要么根据与热力学控制相关的逆同型狄尔斯-阿尔德反应来讨论，要么根据竞争的杂狄尔斯-阿尔德/克莱森或科普多米诺途径，或者内型同型环加成产物的逆克莱森/逆杂狄尔斯-阿尔德反应来讨论。这些假设的机理已通过在MPW1K(CH2Cl2)/6-31+G**理论水平上的DFT计算，对AlCl3介导的5d与2a和7的环加成反应进行了研究。将科里方法应用于γ-卤代-α-甲基取代的亲双烯体5a和5b，能够对已知的、用于合成天然存在的(-)-β-檀香醇或其潜在具有嗅觉活性的结构类似物的有用中间体进行对映选择性制备。
