Catalytic Asymmetric [4+2]‐Cycloadditions Using Tropolones: Developments, Scope, Transformations, and Bioactivity

Abstract

An organocatalyzed asymmetric [4+2]-cycloaddition between tropolones and electron-deficient dienophiles is presented. Complex and biologically interesting dihydrohomobarrelenone scaffolds are formed through a Diels-Alder reaction utilizing bifunctional Brønsted-base catalysis, affording the corresponding bridged bicyclic cycloadducts in up to quantitative yields with good enantio- (up to 92 % ee) and diastereoselectivity (up to >20:1 d.r.). The synthetic value of the obtained products is explored by downstream transformations, including photoisomerizations, and their biological relevancy by in vivo testing in MCF-7 cancer cells.

Antiaromaticity Gain Activates Tropone and Nonbenzenoid Aromatics as Normal-Electron-Demand Diels–Alder Dienes

“…But examples of converting tropones into electron-rich dienes for normal-electron-demand Diels–Alder reactions are limited to their donor-substituted derivatives. For example, tropolones have been activated with use of silica gel and triethylamine as base catalysts or with the use of bifunctional Brønsted base catalysts . In both cases, the tropolone hydroxyl group is deprotonated to generate an anion, thereby raising the HOMO energy of the diene.…”

“…For example, tropolones have been activated with use of silica gel and triethylamine as base catalysts 7 or with the use of bifunctional Brønsted base catalysts. 8 In both cases, the tropolone hydroxyl group is deprotonated to generate an anion, thereby raising the HOMO energy of the diene.…”

Novel Methodologies for Chemical Activation in Organic Synthesis under Solvent-Free Reaction Conditions

“…Presently, organocatalysis continues to be a rapidly developing research area, as shown by the large number of publications that have appeared since 2000 [36]. Some recent examples are highlighted in references [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56].…”

The Solid-State Structures of Cyclic NH Carboximides

“…Twenty structures exhibit a linear ribbon type of hydrogen bonding (C(4)) in pattern B. These are compounds 133 [122], 134 [124], 135 [120], 136 [125], 137 [126], 138 [126], 139 [127], 140 [128], 130 [121], 141 [129], 142 [124], 143 [130,131], 144 [132], 145 [132], 146 [119], 147 [119], 148 [113], 149 [133] and 150 [134] (Figure 45).…”

“…128 [119], 129 [120], 130 [121], 131 [122] and 132 [123] (Figure 44) exist as simple R Twenty structures exhibit a linear ribbon type of hydrogen bonding (C(4)) in pattern B. These are compounds 133 [122], 134 [124], 135 [120], 136 [125], 137 [126], 138 [126], 139 [127], 140 [128], 130 [121], 141 [129], 142 [124], 143 [130,131], 144 [132], 145 [132], 146 [119], 147 [119], 148 [113], 149 [133] and 150 [134] (Figure 45). One structure, compound 151 [135] (Figure 46) exhibits the square hydrogen bonding R 4 4 (16) pattern G involving four molecules.…”