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Transition metal catalysed allylic substitution is one of the most powerful and frequently used methods in organic synthesis. In particular, palladium-catalysed allylic functionalization has become a well-established strategy for constructing carbon–carbon or carbon–heteroatom bonds, and its utility has been demonstrated in natural product synthesis, drug discovery and materials science. Several methods have been developed to generate π-allylpalladium complexes through ionic mechanisms; however, these methods typically require either prefunctionalized starting materials or stoichiometric oxidants, which naturally limits their scope. Here, we show a radical approach for the generation of π-allylpalladium complexes by employing N-hydroxyphthalimide esters as bifunctional reagents in combination with 1,3-dienes. Using this strategy, we report the 1,4-aminoalkylation of dienes. The remarkable scope and functional group tolerance of this redox-neutral and mild protocol was demonstrated across >60 examples. The utility of this strategy was further demonstrated in radical cascade reactions and in the late-stage modification of drugs and natural products. Palladium-catalysed allylic substitution is a widely used method in organic synthesis, although it requires prefunctionalized starting materials or stoichiometric oxidants. Here the authors report a radical route to form π-allylpalladium complexes, and develop a 1,4-aminoalkylation of dienes under redox-neutral conditions.

(Carbo) nucleoside derivatives constitute an important class of pharmaceuticals, yet there are only few convergent methods to access new analogues. Here, we report the first synthesis of thymine-, uracil-, and 5-fluorouracil-substituted diester donor-acceptor cyclopropanes and their use in the indium-and tin-catalyzed [3+2] annulations with aldehydes, ketones, and enol ethers. The obtained diester products could be easily decarboxylated and reduced to the corresponding alcohols. The method gives access to a broad range of new (carbo) nucleoside analogues in only four or five steps and will be highly useful for the synthesis of libraries of bioactive compounds.

In this Letter, we describe the synthesis of new donor-acceptor substituted cyclopropanes bearing various imido groups and their use in [3+2]-annulation reactions. A sequence of palladium-catalyzed vinylation and rhodium-catalyzed cyclopropanation gave access to the required cyclopropanes in only two steps and high overall yields. The obtained compounds were used successfully in the tin-catalyzed [3+2] annulation with enol ethers to give cyclopentylamine derivatives in 22–95% yield.

The sustainable utilization of available feedstock materials for preparing valuable compounds holds great promise to revolutionize approaches in organic synthesis. In this regard, the implementation of abundant and inexpensive carbon dioxide (CO2) as a C1 building block has recently attracted considerable attention. Among the different alternatives in CO2 fixation, the preparation of carboxylic acids, relevant motifs in pharmaceuticals and agrochemicals, is particularly appealing, thus providing a rapid and unconventional entry to building blocks that are typically prepared via waste-producing protocols. While significant advances have been realized, the utilization of simple unsaturated hydrocarbons as coupling partners in carboxylation events is undoubtedly of utmost academic and industrial relevance, as two available feedstock materials can be combined in a catalytic fashion. This review article aims to describe the main achievements on the direct carboxylation of unsaturated hydrocarbons with CO2 by using cheap and available Ni or Fe catalytic species.

Improving the synthesis of complex organic molecules is essential for progress in many fields such as medicine, agrochemicals or materials. Since 2007, our laboratory has been focusing on the development of non-classical bond disconnections based on the use of small, energy-loaded organic molecules: hypervalent iodine reagents and strained rings. In this overview article, we report our progress since 2011 in these areas. The use of cyclic hypervalent iodine reagents has been extended to the C2-selective alkynylation of indoles, the domino cyclization alkynylation of allenes, the alkynylation of thiols and the azidation of carbonyl compounds. Amino-substituted aminocyclopropanes and aminocyclobutanes were used in [3+2] and [4+2] annulations to access nitrogen-rich building blocks, including nucleoside analogues. The first example of dynamic kinetic [3+2] annulation of aminocyclopropanes with both enol ethers and aldehydes was also reported.

In this Letter, we describe the synthesis of new donor-acceptor substituted cyclopropanes bearing various imido groups and their use in [3+2]-annulation reactions. A sequence of palladium-catalyzed vinylation and rhodium-catalyzed cyclopropanation gave access to the required cyclopropanes in only two steps and high overall yields. The obtained compounds were used successfully in the tin-catalyzed [3+2] annulation with enol ethers to give cyclopentylamine derivatives in 22–95% yield.

(Carbo) nucleoside derivatives constitute an important class of pharmaceuticals, yet there are only few convergent methods to access new analogues. Here, we report the first synthesis of thymine-, uracil-, and 5-fluorouracil-substituted diester donor-acceptor cyclopropanes and their use in the indium-and tin-catalyzed [3+2] annulations with aldehydes, ketones, and enol ethers. The obtained diester products could be easily decarboxylated and reduced to the corresponding alcohols. The method gives access to a broad range of new (carbo) nucleoside analogues in only four or five steps and will be highly useful for the synthesis of libraries of bioactive compounds.

The title reaction proceeds with both enol ethers and aldehydes using Cu and a commercially available bisoxazoline ligand.

We report the first example of a dynamic kinetic asymmetric [3 + 2] annulation reaction of aminocyclopropanes with both enol ethers and aldehydes. Using a Cu catalyst and a commercially available bisoxazoline ligand, cyclopentyl- and tetrahydrofurylamines were obtained in 69-99% yield and up to a 98:2 enantiomeric ratio using the same reaction conditions. The method gives access to important enantio-enriched nitrogen building blocks for the synthesis of bioactive compounds.

The stereodivergent synthesis of natural product frameworks via a single transformation using simple starting materials is a significant challenge. The prevalence of γ-butyrolactones in biologically active natural products has long motivated the development of enantioselective strategies towards their synthesis. Herein, we report an enantio- and diastereodivergent [3 + 2] annulation reaction for the synthesis of α,β-disubstituted γ-butyrolactones through cooperative N-heterocyclic carbene organocatalysis and iridium catalysis. This method overcomes the challenges of merging N-heterocyclic carbene organocatalysis with iridium catalysis by the appropriate choice of ligands. The use of two chiral catalysts allowed control over the relative and absolute configuration of the two formed stereocentres, thereby providing selective access to all four possible stereoisomers of the γ-lactone products. The transformation could be extended to the synthesis of δ-lactams via [4 + 2] annulation. The synthetic utility of this methodology was illustrated in the concise synthesis of the naturally occurring lignan (−)-hinokinin. Methods to allow access to all isomers of a product are both valuable and challenging to achieve. Here the authors report a catalytic system comprised of an N-heterocyclic carbene and an iridium complex, and show that it can be used for the asymmetric, diastereodivergent synthesis of γ-butyrolactones.

Improving the synthesis of complex organic molecules is essential for progress in many fields such as medicine, agrochemicals or materials. Since 2007, our laboratory has been focusing on the development of non-classical bond disconnections based on the use of small, energy-loaded organic molecules: hypervalent iodine reagents and strained rings. In this overview article, we report our progress since 2011 in these areas. The use of cyclic hypervalent iodine reagents has been extended to the C2-selective alkynylation of indoles, the domino cyclization alkynylation of allenes, the alkynylation of thiols and the azidation of carbonyl compounds. Amino-substituted aminocyclopropanes and aminocyclobutanes were used in [3+2] and [4+2] annulations to access nitrogen-rich building blocks, including nucleoside analogues. The first example of dynamic kinetic [3+2] annulation of aminocyclopropanes with both enol ethers and aldehydes was also reported.