Rafael Gramage-Doria

Enantioselective hydroformylation by a Rh-catalyst entrapped in a supramolecular metallocage

Regio- and enantioselective hydroformylation of styrenes is attained upon embedding a chiral Rh complex in a nonchiral supramolecular cage formed from coordination-driven self-assembly of macrocyclic dipalladium complexes and tetracarboxylate zinc porphyrins. The resulting supramolecular catalyst converts styrene derivatives into aldehyde products with much higher chiral induction in comparison to the nonencapsulated Rh catalyst. Spectroscopic analysis shows that encapsulation does not change the electronic properties of the catalyst nor its first coordination sphere. Instead, enhanced enantioselectivity is rationalized by the modification of the second coordination sphere occurring upon catalyst inclusion inside the cage, being one of the few examples in achieving an enantioselective outcome via indirect through-space control of the chirality around the catalyst center. This effect resembles those taking place in enzymatic sites, where structural constraints imposed by the enzyme cavity can impart stereoselectivities that cannot be attained in bulk. These results are a showcase for the future development of asymmetric catalysis by using size-tunable supramolecular capsules.

Confining Phosphanes Derived from Cyclodextrins for Efficient Regio- and Enantioselective Hydroformylation**

Two confining phosphane ligands derived from either α- or β-cyclodextrin produce singly P(III) -ligated metal complexes with unusual coordination spheres. High-pressure NMR studies have revealed that rhodium hydride complexes of the same type are also formed under hydroformylation conditions. This unique feature strongly favors the formation of the branched aldehyde at the expense of the linear one with high enantioselectivity in the rhodium-catalyzed hydroformylation of styrene.

Gold(I) Catalysis at Extreme Concentrations Inside Self‐Assembled Nanospheres

Homogeneous transition-metal catalysis is a crucial technology for the sustainable preparation of valuable chemicals. The catalyst concentration is usually kept as low as possible, typically at mM or μM levels, and the effect of high catalyst concentration is hardly exploited because of solubility issues and the inherent unfavorable catalyst/substrate ratio. Herein, a self-assembly strategy is reported which leads to local catalyst concentrations ranging from 0.05 M to 1.1 M, inside well-defined nanospheres, whilst the overall catalyst concentration in solution remains at the conventional mM levels. We disclose that only at this high concentration, the gold(I) chloride is reactive and shows high selectivity in intramolecular CO and CC bond-forming cyclization reactions.

Regioselective Double Capping of Cyclodextrin Scaffolds

Four different regioselective double capping reactions were applied either to α- or β-cyclodextrin (CD) scaffolds. The first, which relied on the use of a rigid, bulky dialkylating reagent containing two trityl-like subunits, gave access to an A,B,D,E-tetrafunctionalised β-CD regioisomer in large scale reactions. Two further capping reactions, involving the dianions PhP(2-) and S(2- , led to the synthesis of new C(1)-symmetrical β-cyclodextrins in which pairs of neighbouring glucose units are linked by very short spacers. The last double capping reaction described allowed the high-yield preparation of unprecedented α- and β-cyclodextrins containing two sulfate handles. Proximal capping turned out to be favoured for each of the above difunctional reagents. The structural characterisation of the capped species was achieved by thorough NMR investigations as well as by single-crystal X-ray diffraction studies.

Remotely Controlled Iridium-Catalyzed Asymmetric Hydrogenation of Terminal 1,1-Diaryl Alkenes

The presence of a remote directing group on terminal 1,1-diaryl and 1,1-dialkyl alkenes led to high and unprecedented enantioselectivity in iridium-catalyzed asymmetric hydrogenation (see scheme). This strategy offers efficient synthetic pathways towards valuable enantiomerically enriched 1,1-diaryl and 1,1-dialkyl alkanes. Moreover, the directing group can be further functionalized.

Supramolecular Ligands in Gold(I) Catalysis

A supramolecular ligand-template strategy is applied to gold(I) catalysis. The supramolecular ligands, formed from a phosphoramidite backbone and two templates, display different regioselectivity in the hydroalkoxylation of allenes compared to non-supramolecular analogues. Based on these findings, the catalytic activity of gold(I) complexes could be tunable at a

Regioselective opening of proximally sulfato-capped cyclodextrins.

Sulfato groups capping one or two pairs of adjacent glucose units in methylated cyclodextrin (CD) derivatives have been found to undergo regioselective opening with various nucleophiles; the reported methodology opens the way to the efficient synthesis of tridifferentiated α- and β-cyclodextrins that constitute key starting materials for the preparation of heteropolydentate cavitands.

TRANSDIP: a trans-chelating ligand tailor-made for probing unusual Pd0 and PdII intermediates.

Forty years after Venanzis seminal studies on trans-spanning diphosphines, a cavity-shaped trans chelator (TRANSDIP) has been used to monitor the stepwise formation of a carbon-carbon bond on a palladium centre. Furthermore, the ligand, which incorporates a cyclodextrin subunit, enabled the synthesis of the first η(2)-dioxygen complex in which the M-O(2) unit is entrapped within a cavity.

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon–carbon bond forming reactions

Summary The capacity of two cavity-shaped ligands, HUGPHOS-1 and HUGPHOS-2, to generate exclusively singly phosphorus-ligated complexes, in which the cyclodextrin cavity tightly wraps around the metal centre, was explored with a number of late transition metal cations. Both cyclodextrin-derived ligands were assessed in palladium-catalysed Mizoroki–Heck coupling reactions between aryl bromides and styrene on one hand, and the rhodium-catalysed asymmetric hydroformylation of styrene on the other hand. The inability of both chiral ligands to form standard bis(phosphine) complexes under catalytic conditions was established by high-pressure NMR studies and shown to have a deep impact on the two carbon–carbon bond forming reactions both in terms of activity and selectivity. For example, when used as ligands in the rhodium-catalysed hydroformylation of styrene, they lead to both high isoselectivity and high enantioselectivity. In the study dealing with the Mizoroki–Heck reactions, comparative tests were carried out with WIDEPHOS, a diphosphine analogue of HUGPHOS-2.

Organocatalysis in Confined Spaces

Organocatalysis can often give rise to unprecedented selectivities by encapsulation of the catalytic active site in an analogous manner as enzymes. Catalyst encapsulation can be considered as a powerful strategy for achieving unique transformations in a very efficient way.