Asymmetric Synthesis of (+)-Polyanthellin A

Abstract

A concise and convergent route to (+)-polyanthellin A is presented. This synthesis features a diastereoselective cyclopropane/aldehyde [3+2] cycloaddition to install the hydroisobenzofuran core. The use of MADNTf(2) as a potent, bulky Lewis acid was essential to allow a labile beta-silyloxy aldehyde to be used in the cycloaddition. Other key steps include a ring-closing metathesis and a selective olefin oxidation.

Metalltriflimidate sind bessere Katalysatoren für die organische Synthese als Metalltriflate – der Effekt eines stark delokalisierten Gegenions

“…-Cyclobutanen veranschaulicht. [45,46] Das durch Protonolyse aus MAD [108] (Methylaluminium-bis(2,6-di-tert-butyl-4-methylphenoxid) mit HNTf 2 in situ gebildete MADNTf 2 schien der beste Katalysator für diese Reaktionen zu sein, da sich die aliphatischen Aldehyde mit vielen anderen Lewis-Säuren zersetzten. Dieses Triflimidatreagens wurde erfolgreich in einer asymmetrischen Totalsynthese von (+)-Polyanthellin A zum Aufbau eines Tetrahydrofuran-Schlüsselintermediats eingesetzt (Schema 12).…”

Organocatalysis in Total Synthesis

“…Moreover, organocatalytic Michael addition is other main C-C bond-forming strategy widely used in natural product synthesis. Illustrative examples are the syntheses of (+)-polyanthellin A [25], (+)-simplactone B [26], biyouyanagin A [27], ()-oseltamivir [28,29], and ABT-341 [29,30] (Fig XII.2). As an application of this enamine activation we describe the organocatalytic step in the construction of ()-bitungolide F (2) skeleton recently published by Cossy and co-workers (Scheme XII.1) [31].…”

Organocatalytic Conjugate Addition in Stereoselective Synthesis

“…[45][46][47][48] Using commercially available catalyst 55, above 90% ee could be obtained for this valuable synthon using particularly simple procedures. In a typical manner, the methyl vinyl ketone just needed to be added to a 0 C solution of the aldehyde with the catalyst and acidic co-catalyst present.…”