Bew Sean P, Hiatt-Gipson Glyn D, Mills Graham P, Reeves Claire E
School of Chemistry, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
Centre for Ocean and Atmospheric Science, School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
Beilstein J Org Chem. 2016 May 27;12:1081-95. doi: 10.3762/bjoc.12.103. eCollection 2016.
Here we report the chemoselective synthesis of several important, climate relevant isoprene nitrates using silver nitrate to mediate a 'halide for nitrate' substitution. Employing readily available starting materials, reagents and Horner-Wadsworth-Emmons chemistry the synthesis of easily separable, synthetically versatile 'key building blocks' (E)- and (Z)-3-methyl-4-chlorobut-2-en-1-ol as well as (E)- and (Z)-1-((2-methyl-4-bromobut-2-enyloxy)methyl)-4-methoxybenzene has been achieved using cheap, 'off the shelf' materials. Exploiting their reactivity we have studied their ability to undergo an 'allylic halide for allylic nitrate' substitution reaction which we demonstrate generates (E)- and (Z)-3-methyl-4-hydroxybut-2-enyl nitrate, and (E)- and (Z)-2-methyl-4-hydroxybut-2-enyl nitrates ('isoprene nitrates') in 66-80% overall yields. Using NOESY experiments the elucidation of the carbon-carbon double bond configuration within the purified isoprene nitrates has been established. Further exemplifying our 'halide for nitrate' substitution chemistry we outline the straightforward transformation of (1R,2S)-(-)-myrtenol bromide into the previously unknown monoterpene nitrate (1R,2S)-(-)-myrtenol nitrate.
在此,我们报道了几种重要的、与气候相关的异戊二烯硝酸盐的化学选择性合成,使用硝酸银介导“卤化物换硝酸盐”取代反应。利用易得的起始原料、试剂以及霍纳-沃兹沃思-埃蒙斯反应,通过廉价的“现货”材料实现了易于分离、具有多种合成用途的“关键结构单元”(E)-和(Z)-3-甲基-4-氯丁-2-烯-1-醇以及(E)-和(Z)-1-((2-甲基-4-溴丁-2-烯氧基)甲基)-4-甲氧基苯的合成。利用它们的反应活性,我们研究了它们进行“烯丙基卤化物换烯丙基硝酸盐”取代反应的能力,结果表明该反应能以66%-80%的总收率生成(E)-和(Z)-3-甲基-4-羟基丁-2-烯基硝酸盐以及(E)-和(Z)-2-甲基-4-羟基丁-2-烯基硝酸盐(“异戊二烯硝酸盐”)。通过NOESY实验确定了纯化后的异戊二烯硝酸盐中碳-碳双键的构型。进一步举例说明我们的“卤化物换硝酸盐”取代化学,我们概述了(1R,2S)-(-)-桃金娘烯醇溴化物向先前未知的单萜硝酸盐(1R,2S)-(-)-桃金娘烯醇硝酸盐的直接转化。