Stereochemical Study of a Transannular Michael Reaction Cascade

Abstract

We systematically explored a transannular Michael reaction cascade for stereoselective synthesis of polycyclic systems. Both E,Z- and E,E-1,7-bis-enones in the form of 14-membered macrocyclic lactones underwent transannular cyclization to give polycyclic products with high efficiency and excellent diastereoselectivity. In contrast, Z,E- and Z,Z-macrocyclic lactones did not cyclize under similar reaction conditions. Our study revealed similarities and subtle stereochemical differences between this transannular cyclization process and transannular Diels-Alder reactions. An acyl ketene approach was developed for efficient synthesis of macrocyclic lactones. This investigation also illuminated the scope and limitation of macrocyclization by intramolecular Reformatsky reaction to prepare macrocyclic lactones.

4-Step Total Synthesis of (−)-Pavidolide B

“…13,14 The strategy of tandem intramolecular Michael addition, termed as TIMA, blends the two biosynthetic processes, through cascade reactions of oxygenstabilized carbanions with oxygen-polarized C-C double bonds. Through literature survey, we have identified precedent that has demonstrated the similar concept, 15,16 and our work reported here supports TIMA to be a highly efficient synthetic methodology for building complex ring systems in organic synthesis.…”

Addition of Vinylmetallic Reagents to Chiral 2‐Formyltetrahydrofuran

“…Additives such as MgBr 2 ·(OEt) 2 and Yb(OTf) 3 [26] (OTf = trifluoromethanesulfonate) were employed, but the desired product was not obtained (see Table 1, Entries 2 and 3). The employment of AlMe 3 [27] and ZnMe 2 [28] led to an epimeric mixture of alcohols 3a and 3b in low yields with low stereoselectivity, and alkene 5 was again the major product (see Table 1, Entries 4-6).…”

Total Synthesis of Diocollettines A via an Acid-Promoted Oxa-Michael–Aldol–Acetalization Cascade

“…Fortunately, when the reaction was quenched with wet silica gel, the clean and nearly quantitative formation of an equilibrium mixture consisting of the cyclic hemiacetal 8 (produced as a single diastereomer) and its ring-opened form 13 ( Z -form) was observed by 1 H NMR analysis of the crude reaction product, which showed the latter to be significantly predominant ( 13 / 8 = ca. 12:1) . Upon exposure to prolonged silica gel column chromatography, the mixture gradually changed into a more complicated product mixture, which made us decide to treat the mixture of 13 and 8 in situ with acidic methanol to bring about the oxa-Michael reaction.…”