Boronic acids intramolecular Diels-Alder reactions

In order to introduce functionality at key positions, an intramolecular Diels-Alder reaction with furan as the diene component was planned. Suzuki coupling of the previously mentioned 105 with furan-3-boronic acid 106 gave compound 107, which was N-tosylated to 108. Construction of the dienophile portion was performed as in the previous case, by addition of vinylmagne-sium bromide to give 109, followed by MnC>2 oxidation to give the cyclization precursor, which was immediately heated at 120 °C in toluene and afforded compound 110, which incorporates an oxygen atom at both the ketone and vinyl chloride positions of welwistatin (Scheme 24). 

In order to prepare the cyclohexenaldehyde 8, 3-hydroxy-2-pyrone 14 and ethyl 4-hydroxy-2-methyl-2-butenoate 15 are subjected to a Diels-Alder reaction in the presence of phenylboronic acid which arranges both reactants to the mixed boro-nate ester 19 as a template to enable a more efficient intramolecular Diels-Alder reaction with optimal control of the regiochemical course of the reaction. Refluxing in benzene affords the tricyclic boronate 20 as primary product. This liberates the intermediate cycloadduct 21 upon transesterification with 2,2-dimethylpropane-l,3-diol which, on its part, relaxes to the lactone 22. Excessive i-butyldimethyl-silyltriflate (TBSTf) in dichloromethane with 2,6-lutidine and 4-7V,A-dimethyl-aminopyridine (DMAP) as acylation catalysts protects both OH goups so that the primary alcohol 23 is obtained by subsequent reduction with lithiumaluminum-hydride in ether. 

The Diels-Alder reactions of -deficient 2//-pyran-2-ones with vinyl moiety containing dienophiles under microwave and high pressures have been extensively reviewed. The microwave-initiated intramolecular Diels-Alder reaction of an alkynol with a furan (80) formed a cycloadduct (81) that readily converted to 3,4-disubstituted 5-hydroxyindoles (82) in 15-74% yields in a one-pot reaction (Scheme 23). ° The treatment of < rt/io-(trifluoromethanesulfonyloxy)aryl boronic acid pinacol ester (83) with t- or i-butyllithium generates arynes (85) via boronate intermediate (84) at... 

The Baccatin III synthesis by K. C. Nicolaou and co-workers is summarized in Scheme 13.54. Diels-Alder reactions are prominent in forming the early intermediates. In Step A the pyrone ring served as the diene. This reaction was facilitated by phenyl-boronic acid, which brings the diene and dienophile together as a boronate, permitting an intramolecular reaction. 

He and his students developed C-alkylation with quaternary ammonium salts and nucleophilic displacements on such salts, including the stereochemistry. His name is immediately associated with important innovations in the use of polyphosphoric acid for inter- and intramolecular condensations, cyclizations, and functional conversions in organic chemistry. He pioneered the use of boron trifluoride as an efficient catalyst in the Fischer indole synthesis and discovered new reactions of anils, including Diels-Alder reactions. He and his students delineated the requirements for disproportionation of tertiary amines. He developed the synthesis and chemistry of arylboranic acids. One of his fundamental ideas was for the incorporation of sufficient boron into organ-specific drugs that they could then be... 

The use of a boron atom as a covalent template for intramolecularizing the Diels-Alder reaction has been relatively little investigated [20-22]. However Narasaka et al. have reported the use of a boronate template to control regio- and stereoselectivity in an IMDA reaction between anthrone 50 and methyl 4-hydroxybut-2-enoate 3 [20a]. Formation of the boronate tether was achieved by simply heating an equimolar mixture of phenylboronic acid with the diene and dienophile at reflux in pyridine with azeotropic removal of water. After 5 h, a single cycloadduct 51 was obtained in 81% yield. The tether was readily removed oxidatively affording the corresponding diol 52 in excellent yield (Scheme 10-19). 

In recent years, the concept of tethered intramolecular reactions has become popular. The basis of this concept is that the diene and alkene units are linked together by a species that allows an intramolecular Diels-Alder but can be chemically removed later. In the work of Batey et al., reaction of boronic acid (231) with... 

The synthesis commences with alkylation of oxindole 120 with spiroaziri-dinium triflate 109, providing the 3,3-disubstituted 121 in 53% yield (cf. Scheme 2.17). Treatment of 121 with boron trifluoride etherate at 100°C in toluene initiates the tandem retro Diels-Alder/intramolecular aza Diels-Alder process, leading to spiro-tetracyclic oxindoles 122 and 123 (1.5/1) in 61% yield. Addition of 2-lithio-l,l-diethoxy-2-propene to oxindole 122 provides carbinolamine 124 (95%). Exposure of 124 to p-toluenesulfonic acid in acetone-water followed by treatment with excess triethylamine in acetonitrile at 80°C effects the biomimetic transformation to adduct 126, which possesses the pentacyclic carbon framework of pseudotabersonine. This unique two-step one-pot transformation generates the inherently unstable dihydropyridine portion of dehydrosecodine 125, which participates in an intramolecular reverse electron-demand Diels-Alder reaction, providing 126 in 50% yield. The total synthesis is completed by transformation of the formyl group into the requisite carbomethoxy unit followed by N-benzyl deprotection (Scheme 2.19). 

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