Wróblewski Andrzej E, Verkade John G
Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, USA.
J Org Chem. 2002 Jan 25;67(2):420-5. doi: 10.1021/jo010648+.
Although P(CH(3)NCH(2)CH(2))(3)N (1) was found to be less effective than 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the removal of hydrogen bromide from vitamin A intermediates 13-cis-10-bromo-9,10-dihydroretinyl acetates (6) and 14-bromo-9,14-dihydroretinyl acetate (11) when the reaction was carried out in refluxing benzene, in acetonitrile at room temperature it was superior to DBN and DBU. A (31)P NMR study of this reaction suggests that the carbanion generated from acetonitrile-d(3) in the presence of 1 is the basic species that initiates the elimination step. Diastereoselectivity of the nucleophilic addition of (Z)-HC triple bond C(CH(3))=CHCH(2)OH to the carbonyl group of (E)-2-methyl-4-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-3-butenal (2) was only moderate (20%), and (9R,10S)-13-cis-11,12-didehydro-9,10-dihydro-10-hydroxyretinol (3b) predominated. The LiAlH(4) reduction of the C triple bond C bond in the diastereoisomeric diols 3 afforded 13-cis-9,10-dihydro-10-hydroxyretinols 4a and 4b as major products together with 11-cis-13-cis-isomers and the deoxygenated compound (3EZ,5EZ,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5,8-nonatetraene (9). Reaction of 15-acetates of the pure diastereoisomeric allylic alcohols 4a and 4b with PBr(3) occurred with significant but not identical retention of configuration, and with concomitant formation of the rearranged bromide 11.
尽管在回流苯中进行反应时，发现三（2 - 甲基氮丙啶基）胺（1）在从维生素A中间体13 - 顺式 - 10 - 溴 - 9,10 - 二氢视黄基乙酸酯（6）和14 - 溴 - 9,14 - 二氢视黄基乙酸酯（11）中脱除溴化氢方面不如1,5 - 二氮杂双环[4.3.0]壬 - 5 - 烯（DBN）或1,8 - 二氮杂双环[5.4.0]十一 - 7 - 烯（DBU）有效，但在室温乙腈中它优于DBN和DBU。对该反应的³¹P NMR研究表明，在1存在下由氘代乙腈 - d₃产生的碳负离子是引发消除步骤的碱性物种。（Z） - HC≡C（CH₃）=CHCH₂OH对（E） - 2 - 甲基 - 4 - （2',6',6' - 三甲基 - 1' - 环己烯 - 1' - 基） - 3 - 丁烯醛（2）羰基的亲核加成的非对映选择性仅为中等（20%），且（9R,10S） - 13 - 顺式 - 11,12 - 二脱氢 - 9,10 - 二氢 - 10 - 羟基视黄醇（3b）占主导。非对映异构二醇3中碳 - 碳三键的LiAlH₄还原得到13 - cis - 9,10 - 二氢 - 10 - 羟基视黄醇4a和4b作为主要产物，同时还有11 - 顺式 - 13 - 顺式异构体和脱氧化合物（3EZ,5EZ,8E） - 3,7 - 二甲基 - 9 - （2,6,6 - 三甲基 - 1 - 环己烯 - 1 - 基） - 1,3,5,8 - 壬四烯（9）。纯非对映异构烯丙醇4a和4b的15 - 乙酸酯与PBr₃反应时，构型保持显著但不完全相同，同时伴有重排溴化物11的形成。
