Furans cycloaddition

The cycloaddition of some nitrile oxides to trani-l,2-disubstituted alkenebor-onates afforded the respective isoxazoline-4-boronates with high regioselectivity. These products were then used to prepare the 4-hydroxy derivatives (139) complementing earlier approaches that took advantage of 4-modification (140,141) of furan cycloaddition products (20,21) (see Section 6.4.4). 

High pressures are especially effective in furan cycloadditions since the desirable forward reaction is accelerated and the undesirable retro reaction, which is especially easy in furan cycloadducts, is also suppressed, although in this case the catalysed 1 bar reaction would probably be the reaction chosen for large-scale synthesis. 

Efforts to isolate the initial alkyne oxazole [4 + 2] cycloadducts have been unsuccessful, and only the furan cycloaddition products have been detected in the reaction mixtures. The Diels-Alder reaction of alkyl- or aryl-substituted oxazoles with neutral, conjugated, or electron-deficient al-kynes displays little regioselectivity whereas polarized, electron-rich oxazoles (e.g., 1, = OEt) do participate in regioselective, intermolecu-... 

During the course of the total synthesis of rubromycins, Reipig and coworkers have employed an aryne-furan cycloaddition to construct the key building block naphthaldehyde 120 (Scheme 12.39) [71]. 

In order to control the regiochemistry of the aiyne-furan cycloadditions, removable silicon tethCTs have been used and this methodology has been applied in total synthesis. This concept is exemplified with the regioselective preparation of naphthol 18 (Schane 12.12) [20]. 

The application of the TBCP furan cycloaddition chemistry to the platen-simycin system highlights the ability to directly access the oxa-bridged core foxmd in these natural products. In a second application, we describe how opening of the oxa-bridge can lead to the highly substituted cycloheptane ring found in the marine natural product frondosin A. 

Molar equivalent of furan substrate is important for the reaction outcome, as multiple furan cycloadditions could occur by the increase of furan molarity, elongation of reaction time and pressure (Scheme 1) [llj. Synthesis of up to tetra-adducts were reported in the literature [12]. 

An example of an acetylenic furan cycloaddition reaction was reported by Ho and Wong [14]. While in some cases, the reaction of furans with dimethyl acetylenedicarboxylate (DMAD) leads to ring opening and aromatization (see below), the addition of 3,4-bis(trimethylsilyl)furan to DMAD at 75 °C gave furan-3,4-dicarboxylate 13, presumably by extrusion of bis(trimethylsilyl)acetylene from the initially formed cycloadduct 12. Stable [47t-l-27i] furan cycloadducts were also obtained using the highly reactive bis(terf-butylsulfonyl)acetylene [15], as well as nitro(trime thylsilyl)acetylene (Scheme 13.5) [16]. 

Furans are also useful 4ti components for tandem Ugi condensation/intramolecular Diels-Alder cascade reactions. For example, stirring a methanolic mixture of compounds 131-133 and benzylamine at room temperature gave the Ugi condensation product 134 that underwent a subsequent intramolecular Diels-Alder furan cycloaddition (IMDAF) to furnish 135 in 70-90% yield (Scheme 13.35) [69,70]. This methodology also allowed for a solid-phase synthesis by using an ArgoGel-Rink resin as the amine component, thereby providing cycloadducts 135 (after cleavage from the resin) in 90-95% yields. 

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