A radical cyclization approach to the formal total syntheses of platencin

Abstract

Two different strategies leading to formal total syntheses of platencin are described. The first strategy involving Claisen rearrangement and radical cyclization provides a rapid access to the core structure of platencin, and also use minimum protective-group operations. The second strategy, a protecting group-free route, utilizes a 6-exo-trig radical cyclization and aldol condensation as key steps leading to the formal synthesis of platencin.

Recent advances in the synthesis of natural multifunctionalized decalins

“…24 Intramolecular aldol reaction has proved to be a powerful tool for the elaboration of this late intermediate. [70][71][72] Accordingly, from aldehyde 143, the cyclization is efficiently carried out under basic conditions in 99% yield. Interestingly, the precursor 146 is obtained by Nicolaou through an asymmetric intermolecular Diels-Alder reaction (144) followed by a radical rearrangement (145 / 146) (Scheme 36).…”

Synthesis of platencin core structures via twist-brendane

“…This was achieved by refluxing 8 in NaOH/MeOH for 12 h followed by diazomethane workup which provided a separable mixture of diastereomers 9a/9b in 1:1 exo/endo ratio of methyl ester (Scheme 2). Reduction enone 9a was carried out using Raney nickel 33,37 in THF to obtain the keto ester 10 as a single diastereomer in 83% yield. Several two-step protocols are available in the literature for the conversion of ketone to enone moiety.…”

“…17 Platencin core structure constitutes tricyclic system with a bicyclic octane ring having exomethylene group, fused with a cyclohexenone ring. Many synthetic strategies have been developed for the construction of platencin core structure involving key steps like homoallyl radical rearrangement of bicyclo[3.2.1]octane to bicyclo[2.2.2]octane, [18][19][20][21][22] intramolecular DielsAlder reaction, [22][23][24] intramolecular Michael addition, 25 Michael addition followed by aldol condensation, 26 ring closing metathesis reaction, 27,28 pinacol coupling reaction, 29 radical cyclization reactions [30][31][32][33] and intramolecular aldol reaction. 34 Although nor-platencin is less potent than its parent molecule, but serves as a convenient target as it lacks the acid-sensitive exo-methylene group present in platencin which is also responsible for the decrease in the metabolic stability of platencin.…”

Short Route to Platencin

“…The major problem in Robinson reaction with MVK is anionic polymerization, and polyalkylation which led to poor yields. 18 We optimized this reaction with a new procedure which produced excellent yield for Robinson product (Scheme 2). The cyclohexanone 11 was treated with methyl vinyl ketone in the presence of a catalytic amount of t-BuOK and anhydrous Na 2 SO 4 in dry t-BuOH at room temperature to provide the tricyclic enone 7 in 90% yield.…”

“…Spectral data of the resulted olefin was compared and found to be identical to that of the previously reported data. 10,11,17,18 Thus, the synthesis of 5 constituted a formal synthesis of platencin 2 as this carbon skeleton has been converted to platencin previously by other groups. 10,11,17,18 In our next attempt (Scheme 5), we tried to convert the minor isomer cis-decolone (8a) to the tetracyclic ketone 10 which was achieved from trans-decalone and elaborated to the target enone 5.…”