In(OTf)₃-Catalyzed Cascade Cyclization for Construction of Oxatricyclic Compounds

Abstract

A highly diastereoselective cascade cyclization reaction has been developed for establishing a series of oxatricyclic compounds using Chan's diene and simple keto alkynal substrates with only 1 mol % of In(OTf) 3 as the catalyst in 82−92% yields. The potential utility of this synthetic strategy has been demonstrated in model studies for the construction the core structures of 1α,8α:4α,5α-diepoxy-4,5-dihydroosmitopsin and cortistatin A.

Synthesis of Framework Structure of Guaiane

“…该化合物的主体环系结构由五元环并七元 氧桥环组成, 其中五元环和七元环结构呈反式稠合关 系, 乙氧酰基与氧桥呈反式关系. 13 C NMR (100 MHz, CDCl 3 ) δ: 174.84, 168.97, 161.11, 134.29, 118.20, 106.70, 96.23, 82.48, 60.96, 60.79, 41.09, 36.77, 35.54, 30.18, 25.26, 25.04, 18.84, 14.26 [17] 合成化合物 14.…”

“…2,2-二甲基-4- 羰基-4,5,6,8,9,10-六氢-5,9a-环氧薁 [5,6-d][1,3]-二噁英-6a(7H)-甲酸乙酯( 14 175.46, 163.53, 159.43, 106.78, 106.67, 94.77, 72.39, 61.80, 61.31, 46.92, 40.69, 37.09, 34.83, 26.15, 24.23, 23.90, 14.16;FTIR (KBr, thin film) ν: 3425, 2984, 2949, 1723, 1657, 1441, 1238, 1100 3.2.2 (5R,6aR,7S,9aR)-2,2,7-三甲基-5,6a,7,8,9,10-六 氢-5,9a-环氧薁 [5,6-d] 16), 淡黄色油状液体, 产率 97%. 1 H NMR (400 MHz, CDCl 3 ) δ: 5.66～5.53 (m, 1H), 5.12～5.08 (m, 1H), 5.06 (t, J＝1.1 Hz, 1H), 4.17 (dq, J＝ 10.8, 7.1 Hz, 1H), 4.09 (dq, J＝10.8, 7.1 Hz, 1H), 2.63 (ddt, J＝14.2, 6.3, 1.4 Hz, 1H), 2.57～2.43 (m, 2H), 2.30 (dq, J＝12.0, 6.7 Hz, 1H), 2.17～1.98 (m, 2H), 1.86～1.72 (m, 1H), 1.23 (t, J＝7.1 Hz, 3H), 1.02 (d, J＝6.9 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ: 216.22, 170.51, 133.33, 119.49, 62.94, 61.09, 39.01, 38.65, 35.70, 28.32, 15.45, 14.32;FTIR (KBr, thin film) ν: 2968, 1741, 1454, 1227, 1115, 1019 (d, J＝6.4 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ: 169.32, 161.07, 138.44, 116.01, 106.70, 95.84, 82.23, 55.95, 44.86, 38.34, 38.04, 32.87, 30.93, 25.33, 25.27, 20.41;FTIR (KBr, thin film) ν: 2953, 2356, 1720, 1628, 1386, 1275, 1009…”

“…2018 年, 李志成研究组 [13] 发展了一种快速构建 [5,7] 本研究组一直进行 dioxinone 化合物的研究及其在 合成中的应用 [14] . Dioxinone 化合物在常温下能够稳定 存在, 且具有一定的耐酸性, 方便进行结构修饰, 酯化 和酰胺化反应都能够得到较好的收率, 操作和应用起来 十分方便.…”

A Paal–Knorr agent for chemoproteomic profiling of targets of isoketals in cells

“…S2 † ) in chemical reactivity and bioactivities is likely attributed to the substitution of γ-dicarbonyls at positions 2 and 3, the “clickable” alkyne handle needs to be rationally implemented onto the 4-methyl group in order to minimize the biases when competing with IsoKs in target engagement. Interestingly, we reasoned that 4-oxonon-8-ynal, a previously reported Paal–Knorr agent used as an intermediate for synthesizing fatty acid probes 35 or oxa-tricyclic compounds, 36 could be repurposed for the γ-dicarbonyl-directed ABPP application. With this chemical in hand (herein termed ONAyne, Fig.…”

Synthesis of Oxa-Bridged Medium-Sized Carbocyclic Rings via Prins Cyclization

“…In 1991, Molander’s group reported an elegant vinylogous aldol-addition/Prins-cyclization annulative approach , toward the synthesis of oxa-bridged seven- and eight-membered ring systems via the reaction of a β-dicarbony1-l,3-dianionic equivalent, normally bis­(trimethylsilyl) enol ether, with 1,4- or 1,5-dielectrophiles under the catalysis of Lewis acids (Scheme , eq 1). The asymmetric version for the synthesis of seven- and eight-membered rings based on this annulation was also developed by using chiral substrates (Scheme , eq 2).…”