Heteroaromatic compounds Michael addition

Heteroaromatic compounds are also suitable nucleophiles in the Michael additions to enals catalysed by prolinol silyl ethers. Hayashi and coworkers demonstrated that oxazolinones can add effectively to enals (Scheme S.lSa)." Indole also added effectively to a,p-unsaturated aldehydes (Scheme 8.13b). Also, enantioselective Michael addition of simple 3(2H)-furanones to a,(3-unsaturated aldehydes has been described (Scheme 8.13c). ... 

The Friedel-Crafts alkylation is one of the oldest synthetic methodologies known. The catalytic asymmetric version of the reaction [311] enables the preparation of important chiral building blocks. Electron-rich aromatic and heteroaromatic compounds have been productively used in organocatalyzed enantioselective inter- and intramolecular Friedel-Craft-[312] type conjugate additions over different Michael acceptors such as, a,p-unsaturated aldehydes, a,P-unsaturated ketones, nitroole-fins, and a,p-unsaturated acyl phosphonates. 

The reaction of 11 with ordinary alkenes with a Cu(OTf)2 catalyst gave 1,2-dihydronaphthalenes. However, reaction with p-methoxystyrene 8 afforded the naphthalene derivative 12 in 83% yield. Probably, retro-Michael addition occurred and the methoxy group was eliminated as methanol [24], This protocol can be applied to the formation of benzo-fused heteroaromatic compounds such as indols 35 and benzofuranes (Scheme 15.13) [25]. 

As a different family of heteroaromatic-substituted organocatalysts, imidazole-and triazole-based compounds have been known to be quite effecbve for asymmetric aldol and Michael addition reacbons. Figure 1.6 lists representative examples of these catalysts. 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

---