Ilan Marek’s research while affiliated with Technion – Israel Institute of Technology and other places

We report a method for the direct palladium-catalyzed cross coupling reactions of cyclopropenyl esters bearing a variety of substitution patterns with Csp² iodides. This reaction is largely insensitive to the electronic nature of the coupling partner. Tetramethylammonium acetate, a halide sequestrant, was exceptionally effective as an organic base. An observed KIE of 2.5 revealed C–H bond cleavage to be involved in the turnover-limiting step. This method enables the rapid assembly of cyclopropenes whose preparation previously required the use of toxic tin and arsenic reagents.

We present a stereoretentive nucleophilic substitution of homoallylic tertiary alcohols via the formation of a nonclassical cyclopropyl carbinyl (CPC) carbocation intermediate. This strategy enables the creation of highly congested tertiary centers with preserved stereocontrol, addressing the typical challenges of carbocation instability and reactivity in SN1 mechanisms. The stabilization of the CPC intermediate is crucial for achieving precise regio- and stereoselectivity, significantly enhancing the utility of SN1-type mechanisms in complex molecule synthesis.

Here we describe a Fe‐catalyzed stereospecific intramolecular Friedel–Crafts‐type reaction of polysubstituted stereodefined fluoroalkyl cyclopropyl carbinols. This transformation provides access to a series of fluoroalkyl group‐substituted dihydro‐1H‐indenols bearing three continuous stereogenic centers including two congested tetra‐substituted stereocenters. The key to the realization of this reaction relies on the electronic destabilizing effect of fluoroalkyl group to tune the stability and reactivity of non‐classical cyclopropyl‐carbinyl cation intermediate. Functional group interconversions of the obtained diastereomerically pure dihydro‐1H‐indenols further demonstrated the synthetic utility of this rationally designed reaction.

Nucleophilic substitution at tetravalent (sp³) carbon is a fundamental transformation in organic synthesis, essential for creating carbon–carbon and carbon–heteroatom bonds. While the mechanism of the SN2 reaction is well understood, achieving stereochemical control in SN1-type reactions remains extremely challenging due to the complexity of successive carbocation intermediates. Here we present a strategy for preparing complex molecular skeletons via stereospecific SN1 at a quaternary stereocentre in acyclic systems. By leveraging neighbouring group participation, we facilitate the selective formation of a unique cyclopropylcarbinyl cation intermediate that undergoes selective nucleophilic substitution with high diastereoselectivity and complete inversion of configuration at a distant position from the original carbocation via molecular rearrangement. This methodology has been applied to generate homoallylic tertiary fluorides, bromides, chlorides, ethers, thiocyanates and azides, demonstrating its applicability in accessing diverse functional groups with exceptional diastereoselectivities. This transformation opens new avenues for constructing complex molecular architectures through precise stereocontrol of C–C bond cleavage at a quaternary stereocentre in acyclic systems.

Disclosed herein is the reaction of silyllithium reagents with quaternary‐substituted arylbicyclobutanes to diastereoselectively form polysubstituted cyclobutylsilanes by C−C bond cleavage. The bicyclobutanes are generated in situ, by lithium‐halogen exchange, from readily accessible (bromomethyl)iodocyclopropane precursors, rendering this a one‐pot transformation. The trapping of a generated cyclobutyllithium intermediate with an electrophile was also demonstrated, providing a cyclobutane product with vicinal quaternary stereocenters. The utility of the cyclobutylsilane products was showcased by Tamao−Fleming oxidation to prepare a quaternary‐substituted cyclobutanol.

Disclosed herein is the reaction of silyllithium reagents with quaternary‐substituted arylbicyclobutanes to diastereoselectively form polysubstituted cyclobutylsilanes by C–C bond cleavage. The bicyclobutanes are generated in situ, by lithium‐iodine exchange, from readily accessible (bromomethyl)iodocyclopropane precursors, rendering this a one‐pot transformation. The trapping of a generated cyclobutyllithium intermediate with an electrophile was also demonstrated, providing a cyclobutane product with vicinal quaternary stereocenters. The utility of the cyclobutylsilane products was showcased by Tamao–Fleming oxidation to prepare a quaternary‐substituted cyclobutanol.

We report a fully stereocontrolled synthesis of previously unknown unsaturated polyacetals through an iteration of two steps: (1) Pd-catalyzed hydroalkoxylation of alkoxyallenes; and (2) base-mediated isomerization of propargyl ethers into alkoxyallenes. Site- and stereoselective alkene isomerization of the capping allyl group initiates a domino-Coates–Claisen rearrangement, which completely rearranges the iteratively assembled backbone with the stereochemistry of the newly formed stereocentres controlled by the configuration of the acetal centres in the starting materials. The resulting products feature multiple stereocentres in a 1,3-relationship, which map onto a broad range of bioactive natural products, including deoxypropionates.

We report a highly diastereoselective protocol for the synthesis of 1,4‐ and 1,5‐dicarbonyl compounds from densely substituted cyclopropanols. The methodology involves a palladium‐catalyzed ring opening reaction followed by a “metal‐walk” and oxidation of a remote hydroxyl group. The methodology represents a new application of cyclopropanols as initiation sites for chain walking remote functionalization. Importantly, this approach provides a straightforward access to highly valuable succinaldehyde derivatives bearing vicinal quaternary and tertiary stereocenters as single diastereomers.

We report a highly diastereoselective protocol for the synthesis of 1,4‐ and 1,5‐dicarbonyl compounds from densely substituted cyclopropanols. The methodology involves a palladium‐catalyzed ring opening reaction followed by a “metal‐walk” and oxidation of a remote hydroxyl group. The methodology represents a new application of cyclopropanols as initiation sites for chain walking remote functionalization. Importantly, this approach provides a straightforward access to highly valuable succinaldehyde derivatives bearing vicinal quaternary and tertiary stereocenters as single diastereomers.