School of Chemical Sciences , The University of Auckland , Symonds Street , Auckland 1010 , New Zealand.
School of Chemical and Physical Sciences , Victoria University of Wellington , Kelburn Parade , Wellington 6012 , New Zealand.
Org Lett. 2020 Feb 7;22(3):1022-1027. doi: 10.1021/acs.orglett.9b04567. Epub 2020 Jan 28.
2-Bromo-1,3-butadienes are demonstrated to be effective substrates for tandem Diels-Alder/transition metal cross-coupling reaction sequences. Intermolecular cycloaddition of a 2-bromo-1,3-diene with activated dienophiles proceeded under Lewis acid catalysis in generally high yields with good to excellent diastereoselectivity. The resulting vinyl bromide cycloadducts underwent subsequent Stille and Suzuki cross-couplings under standard conditions in good yields. Both the Diels-Alder and cross-coupling steps were highly tolerant of a range of functionalities and protecting groups. The use of the bromine substituent as both a cycloaddition directing group and cross-coupling nucleofuge avoids extra steps required to install and remove the more commonly used silyl enol ethers and enol sulfonates for each transformation and gives full control of the alkene regiochemistry throughout the reaction sequence. The 2-bromo-1,3-dienes were conveniently prepared in three steps from readily available aldehydes and established as hydrolytically stable and practical synthetic intermediates.
2-溴-1,3-丁二烯被证明是串联 Diels-Alder/过渡金属交叉偶联反应序列的有效底物。在路易斯酸催化下，2-溴-1,3-二烯与活化的双烯进行分子间环加成，通常以高产率和良好到优异的非对映选择性进行。所得的乙烯基溴环加成产物在标准条件下进行随后的 Stille 和 Suzuki 交叉偶联，产率良好。Diels-Alder 和交叉偶联步骤都高度耐受一系列官能团和保护基。溴取代基既作为环加成导向基团，又作为交叉偶联离去基团，避免了在每个转化中安装和去除更常用的硅基烯醇醚和烯醇硫酸盐所需的额外步骤，并在整个反应序列中完全控制烯烃区域化学。2-溴-1,3-二烯可以方便地通过三步从易得的醛制备，并且被证明是水解稳定且实用的合成中间体。
