Intermolecular Diels-Alder Cycloaddition/Cross-Coupling Sequences of 2-Bromo-1,3-butadienes.

2-Bromo-1,3-butadienes are demonstrated to be effective substrates for tandem Diels-Alder/transition metal cross-coupling reaction sequences. Intermolecular cycloaddition of a 2-bromo-1,3-diene with activated dienophiles proceeded under Lewis acid catalysis in generally high yields with good to excellent endo diastereoselectivity. The resulting vinyl bromide cycloadducts underwent subsequent Stille and Suzuki cross-couplings under standard conditions in good yields. Both the Diels-Alder and cross-coupling steps were highly tolerant of a range of functionalities and protecting groups. The use of the bromine substituent as both a cycloaddition directing group and cross-coupling nucleofuge avoids extra steps required to install and remove the more commonly used silyl enol ethers and enol sulfonates for each transformation and gives full control of the alkene regiochemistry throughout the reaction sequence. The 2-bromo-1,3-dienes were conveniently prepared in three steps from readily available aldehydes and established as hydrolytically stable and practical synthetic intermediates.

A biomimetic approach towards phorone sesterterpenoids.

We report an investigation towards a unified total synthesis of the Korean sponge derived sesterterpenoids, phorones A (1) and B (2), via a biomimetic strategy. This work has established a new synthetic strategy to the parent ansellane sesterterpenoid skeleton with unanticipated diversion to a biogenetically related pathway.

Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids.

Pyruvic acid and other α-keto acids are frequently encountered as intermediates in metabolic pathways, yet their application in total synthesis has met with limited success. In this work, we present a bioinspired strategy that utilizes highly functionalized OBO (oxabicyclo[2.2.2]octyl) orthoester masked α-ketoacids as key intermediates for the construction of both type I and II lamellarin alkaloids. Lamellarin D was synthesized, via a key 1,4-dicarbonyl, in 7 steps and 22% yield from pyruvic acid. Key steps in the synthesis involve one-pot double enolate functionalisation of 1 followed by double annulation to form the target pyrrole/N-vinyl pyrrole core and late-stage direct C-H arylation. Lastly, a novel OBO-masked ß-cyano ketone, synthesized from 1, proved to be a valuable intermediate for construction of the type II lamellarin core via HBr-mediated cyclisation. In this way, lamellarin Q was synthesized in 7 steps and 20% yield from pyruvic acid.

A new family of sesterterpenoids isolated around the Pacific Rim.

Covering: 2009 up to the end of 2017 There has been a recent eruption in the number of known marine sesterterpenoids which have been isolated from Pacific Rim marine organisms. These compounds have novel and unusual structures that exhibit incredibly potent and varied bioactivities. This review details the isolation, biological testing and prospects for this exciting new family with discussion of their potential biogenetic origins.

Unexpected Direct Synthesis of N-Vinyl Amides through Vinyl Azide-Enolate [3+2] Cycloaddition.

The unexpected synthesis of industrially important N-vinyl amides directly from aldehydes and α,ß-unsaturated N-vinyl amides from esters is reported. This reaction probably proceeds through an initial [3+2] azide-enolate cycloaddition involving a vinyl azide generated in situ. A survey of the reaction scope and preliminary mechanistic findings supported by quantum computational analysis are reported, with implications for the future development of atom-efficient amide synthesis. Intriguingly, this study suggests that (cautious) reevaluation of azidoethene as a synthetic reagent may be warranted.