Synthesis of Six-Membered Rings

Dipolar cycloaddUions. Interest in 1,3-dipolar cycloadditions increased dramatically during the past 20 years, largely because of the pioneering studies of Huisgen [7, 2] The versatility of this class of pericychc reactions in the synthesis of five-membered-ring heterocyclic compounds is comparable with that of the Diels-Alder reaction in the synthesis of six-membered-ring carbocyclic systems (equation 1)... 

The extrapolation of the vinylcyclopropane-cyclopentene rearrangement to a vinyl-cyclobutaiie-cyclohexene synthesis begins to create new insights into the synthesis of six membered ring natural products. The eudesmane sesquiterpene (—)-P-selinene, 217 illustrates such a strategy as summarized in Scheme 14 80). A suitable cyclohexene... 

Because the Diels-Alder reaction allows the construction of six-membered rings with the introduction of up to four new stereocenters in a stereocontrolled fashion in one single step, it is a very important tool for the synthesis of six-membered rings containing natural compounds and derivatives. In many synthetic strategies toward these types of compounds, the Diels-Alder reaction is a crucial step, as illustrated by the following examples. 

As six-membered heterocycles are present in a number of natural products and biologically important molecules, solid-phase synthesis of these has been reported very often (Fig. 3.9). Solid-phase synthesis for nearly every six-membered ring including one nitrogen atom are known piperidines (272) [376], tetrahydropyridines (273) [377, 378], dihydropyridines (274) [219, 379, 380], pyridines (275) [349, 381-386], (Scheme 3.37), piperidinones (276) [387], dihydropyridones (277-279) [313, 378, 388-390], pyridinones (280-281) [328, 329] and piperidindiones (282) [391] derivatives. In contrast, the synthesis of six-membered rings with one single oxygen is rarely described. Nevertheless, solid-phase synthesis of dihydropyrans (283-284) [392-394] and tetrahydropyrans (285) [335, 336] has been reported. 

---