Diastereoselective Spiroannulation of Phenolic Substrates: Advances Towards the Asymmetric Formation of the Manumycin m-C7N Core Skeleton

Abstract

Abstract:The asymmetric syntheses of two new spirolactones prepared in optically pure form from L-3-nitrotyrosine are described. The key step, an oxidative spiroannulation, was carried out on the optically active phenols 11a and 11b and afforded the new spirolactones 5a and 5b in 85% and 83% yields, respectively, as mixtures (3:1 dr) of diastereomers. The major diastereomers from these mixtures could be isolated in optically pure form by trituration using acetone-hexanes as the solvent. Thus, the optically active spirolactones (+)-5a (+ 92.8 o , c=0.125 acetone) and (+)-5b (+112.0 o , c= 0.125 acetone) were obtained after four synthetic steps from L-3-nitrotyrosine in 41% and 43% yield, respectively.

Total Synthesis of TK‐57‐164A, Isariotin F, and Their Putative Progenitor Isariotin E

“…With the desired monoprotected resorcinol tyrosine analogue in hand, we were poised to test the oxidative dearomatization of the dissymmetric resorcinol 8. 9 We hoped that the methoxy and amine residues would emerge being positioned on opposite sides of the conjoined spirocyclic molecule in a diastereoselective manner, reminiscent of a reaction developed by Wardrop et al. for the production of spiroamides from nitrenes 10.…”

Diastereoselective Spiroannulation of Phenolic Derivatives: Effect of Steric Hindrance on the Diastereoselectivity

“…2003c). Other studies have also shown the importance of the presence of electron donating groups (EDG) such as methoxy or amide ortho to the phenolic hydroxyl as shown in compounds 1-3 in Figure 1 (Plourde et al, 2005;Plourde et al, 2007;Plourde et al, 2008). Such groups not only increase the overall chemical yield of the spiroannulation reaction, but also appear to favour a higher diastereoselectivity as well.…”

Total Synthesis of TK‐57‐164A, Isariotin F, and Their Putative Progenitor Isariotin E

“…With the desired monoprotected resorcinol tyrosine analogue in hand, we were poised to test the oxidative dearomatization of the dissymmetric resorcinol. [8,9] We hoped that the methoxy and amine residues would emerge being positioned on opposite sides of the conjoined spirocyclic molecule in a diastereoselective manner, reminiscent of a reaction developed by Wardrop et al for the production of spiroamides from nitrenes. [10] To our delight, sequential exposure of the acid 5 to hypervalent iodine and DBN provided the spirocyclic lactone 4 as the major diastereomer (61 % overall yield, > 12:1 d.r.…”