Boron compounds natural products synthesis

Heterocyclic aromatic boronic acids, in particular pyridinyl, pyrrolyl, indolyl, thienyl, and furyl derivatives, are popular cross-coupling intermediates in natural product synthesis and medicinal chemistry. The synthesis of heterocyclic boronic acids has been reviewed recently [222], and will not be discussed in detail here. In general, these compounds can be synthesized using methods similar to those described in the above section for arylboronic acids. Of particular note, all three isomers of pyridineboronic acid have been described, including the pinacol ester of the unstable and hitherto elusive 2-substituted isomer, which is notorious for its tendency to pro-todeboronate [223]. Improvements and variants of the established methods for synthesizing heterocyclic boronic acids have been constantly reported [13, 182]. For example, a Hg-to-B transmetallation procedure was recently employed to synthesize a highly functionalized indolylboronic acid (entry 19, Table 1.3) [187]. 

Cyclopropanes and their derivatives are versatile building blocks in organic synthesis. They are also present in many natural products and frequently included as substituents in the structure of new biologically active substances. While cydopropylbo-ranes have long been described [34], it is only since an efficient access to the boronic esters was reported that they really attracted chemist s interest. In 1989, the first additions of carbenes, generated from diazo compounds and palladium acetate, to pina-col alkenylboronic esters were reported to give racemic mixtures of cyclopropyl-boronates (Scheme 9.15) [35]. 

Cyclic acetals are useful and common protecting groups for aldehydes and ketones, especially during the course of a total synthesis [8]. The successful synthesis of acetals frequently relies on the removal of water, a by-product of the reaction between the carbonyl compound and the corresponding diol. A Dean-Stark trap is often used for the removal of water as an azeotrope with benzene, but this method is not suitable for small-scale reactions. In addition, the highly carcinogenic nature of benzene makes it an undesirable solvent. Many of the reported catalysts for acetal synthesis such as p-toluenesulfonic acid and boron trifluoride etherate are toxic and corrosive. 

Some insight into the nature of these catalyzed cyclizations is provided by the synthesis of benzobicyclo[3.1.0]hexene 17. Intramolecular cycloaddition under base catalysis (from the tosylhydrazone 14) or by heating compound 18 gave the [3.3.0] bicyclic product 16 but, in the boron trifluoride catalyzed reaction, the [3.2.1] bicyclic product 13 was formed. In the base-catalyzed reaction the intermediate 4,5-dihydro-3//-pyrazole 16 suffered tautomerization (to give 19). The diazo compound 13 cannot tautomerize, and gave a quantitative yield of benzobicyclohexene 17 when heated. These boron trifluoride catalyzed addition reactions do not involve the free diazo compound and in this particular case the cyclic A -tosyl intermediate 12 could be isolated from the reaction mixture. ... 

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