Seiichi Nakamura

We have developed a facile method for the transformation of a tricyclo[4.3.0.05,7]nonane derivative to a diastereomeric mixture of suitably oxygenated hydrindan isomers, wherein oxidative ring-opening, proton transfer, and deethoxycarbonylation sequentially proceeded in a single operation upon heating with Ni(OTf)2 in the presence of DABCO in DMSO at 150 °C.

We have developed a facile method for the transformation of a tricyclo[4.3.0.0 ^5,7 ]nonane derivative to a diastereomeric mixture of suitably oxygenated hydrindan isomers, wherein oxidative ring-opening, intramolecular proton transfer, and deethoxycarbonylation sequentially proceeded in a single operation upon heating with Ni(OTf) ₂ in the presence of DABCO in DMSO at 150 °C.

A tandem oxidation/Diels-Alder reaction of phthalans was investigated. It was found that phthalans can be oxidized with DDQ to provide isobenzofurans, which immediately undergo Diels-Alder reaction with dienophiles such as benzoquinone, affording oxygen-bridged polycycles in modest to good yields. The reaction was rendered catalytic by the use of Mn(OAc)₃ as a co-oxidant. A portionwise addition of DDQ proved to be effective when using reactive phthalans as IBF precursors.

We describe an intramolecular double Michael addition reaction using 1,3-cyclopentanediones with a Michael acceptor at the C3' position of the C2 side chain through the formal umpolung of the 1,3-cyclopentanedione moiety. Silylation of the reactants generates 1,4-bis(silyloxy)cyclopentadienes, a silyloxy-substituted carbon which attacks the Michael acceptor to afford bicyclic scaffolds. Appropriate selection of the Michael acceptor induces further cyclization toward the activated cyclopentenone moiety to form a cyclobutane ring, affording cyclobuta[cd]pentalenes.

A tandem oxidation/Diels−Alder reaction of phthalans was investigated. It was found that phthalans can be oxidized with DDQ to provide isobenzofurans, which immediately undergo Diels−Alder reaction with dienophiles such as benzoquinone, affording oxygen-bridged polycycles in modest to good yields. The reaction was rendered catalytic by the use of Mn(OAc)3 as a co-oxidant. A portionwise addition of DDQ proved effective when using reactive phthalans as IBF precursors.

Treatment of phthalan derivatives with p-chloranil in dodecane in the presence of molecular sieves at 160–200 °C allowed the generation of unstabilized isobenzofurans, which underwent intramolecular Diels–Alder reaction to give endo cycloadducts exclusively. The cycloaddition turned out to be reversible, providing an equilibrium mixture of endo adducts when heating a substrate with a stereocenter on the tether. We also demonstrated the regioselective allylation of an oxygen-bridged cycloadduct upon exposure to EtAlCl₂ in the presence of allyltrimethylsilane, and the conversion to Rice's intermediate completed a formal synthesis of (±)-morphine.

A stereoselective synthesis of the DE ring portion of kadcoccilactone A, triterpenoid isolated from Kadsura coccinea, has been achieved starting from a chiral building block, utilizing a photocatalytic decarboxylative addition/cyclization/fragmentation sequence to construct the five‐membered ring and intramolecular alkylation to create the quaternary stereocenter as key steps.

The scope and limitations of the diastereoselective 1,4-addition reaction of primary alcohols to γ-alkoxy-α,β-unsaturated esters were investigated. We found that a variety of sodium alkoxides, generated from the corresponding primary alcohols with NaH, underwent 1,4-addition reactions with (E)-enoates in CH₂Cl₂ at –23 °C to give β-alkoxy esters in modest yields with good to excellent syn-selectivity, whereas stereoselectivity was not observed with the use of glycerol derivatives as nucleophiles. Cyclic acetal protection was found to play a pivotal role for the reaction to proceed. Received: 03 July 2020 Accepted after revision: 07 August 2020 Publication Date: 22 September 2020 (online) © 2020. Thieme. All rights reserved Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Total syntheses of the labdane diterpene lactones marrubiin, marrulibacetal, desertine, marrulibacetal A, marrubasch F, cyllenine C, marrulanic acid, and marrulactone are described. The trans-decalin moiety of these molecules was constructed in a stereoselective manner by a Pauson-Khand reaction, and the resultant cyclopentenone was oxidatively cleaved for formation of the lactone ring. Elongation of the side chain at C9 was achieved by an epoxide-opening reaction with a variety of nucleophiles, and the functional group manipulations completed the syntheses of these natural products. Stereochemistries of desertine could be established by the transformations.

Ikeguchi M, et al. Ann Hepatobiliary Pancreat Surg. 2019 Nov;23(4):372-376. https://doi.org/10.14701/ahbps.2019.23.4.372