Recent advances in the synthesis of ent-kaurane diterpenoids.

Covering: 2015 to 2020The ent-kaurane diterpenoids are integral parts of tetracyclic natural products that are widely distributed in terrestrial plants. These compounds have been found to possess interesting bioactivities, ranging from antitumor, antifungal and antibacterial to anti-inflammatory activities. Structurally, the different tetracyclic moieties of ent-kauranes can be seen as the results of intramolecular cyclizations, oxidations, C-C bond cleavages, degradation, or rearrangements, starting from their parent skeleton. During the past decade, great efforts have been made to develop novel strategies for synthesizing these natural products. The purpose of this review is to describe the recent advances in the total synthesis of ent-kaurane diterpenoids covering the period from 2015 to date.

Palladium-Catalyzed Decarbonylative Iodination of Aryl Carboxylic Acids Enabled by Ligand-Assisted Halide Exchange.

We report an efficient and broadly applicable palladium-catalyzed iodination of inexpensive and abundant aryl and vinyl carboxylic acids via in situ activation to the acid chloride and formation of a phosphonium salt. The use of 1-iodobutane as iodide source in combination with a base and a deoxychlorinating reagent gives access to a wide range of aryl and vinyl iodides under Pd/Xantphos catalysis, including complex drug-like scaffolds. Stoichiometric experiments and kinetic analysis suggest a unique mechanism involving C-P reductive elimination to form the Xantphos phosphonium chloride, which subsequently initiates an unusual halogen exchange by outer sphere nucleophilic substitution.

CO- and HCl-free synthesis of acid chlorides from unsaturated hydrocarbons via shuttle catalysis.

The synthesis of carboxylic acid derivatives from unsaturated hydrocarbons is an important process for the preparation of polymers, pharmaceuticals, cosmetics and agrochemicals. Despite its industrial relevance, the traditional Reppe-type carbonylation reaction using pressurized CO is of limited applicability to laboratory-scale synthesis because of: (1) the safety hazards associated with the use of CO, (2) the need for special equipment to handle pressurized gas, (3) the low reactivity of several relevant nucleophiles and (4) the necessity to employ different, often tailor-made, catalytic systems for each nucleophile. Herein we demonstrate that a shuttle-catalysis approach enables a CO- and HCl-free transfer process between an inexpensive reagent, butyryl chloride, and a wide range of unsaturated substrates to access the corresponding acid chlorides in good yields. This new transformation provides access to a broad range of carbonyl-containing products through the in situ transformation of the reactive acid chloride intermediate. In a broader context, this work demonstrates that isodesmic shuttle-catalysis reactions can unlock elusive catalytic reactions.

Catalytic Reductive Pinacol-Type Rearrangement of Unactivated 1,2-Diols through a Concerted, Stereoinvertive Mechanism.

A catalytic pinacol-type reductive rearrangement reaction of internal 1,2-diols is reported herein. Several scaffolds not usually amenable to pinacol-type reactions, such as aliphatic secondary-secondary diols, undergo the transformation well without the need for prefunctionalization. The reaction uses a simple boron catalyst and two silanes and proceeds through a concerted, stereoinvertive mechanism that enables the preparation of highly enantiomerically enriched products. Computational studies have been used to rationalize the preference for migration over direct deoxygenation.