The Szabó Research Group

Thank you for your interest in our research activities. Below, pls find a summary of the current research interest of the Szabó group.

The research of the group is focused on development of new synthetic transformations. The main area is transition metal catalysis for organic synthesis but we also develop new metal-free transformations with allylboronates. The main methodology involves functional group transformations and C-H functionalization methods. Currently, the most important synthetic targets are organoboronates and organofluorine compounds.

Keywords: Homogenous catalysis, Metal catalysis (Pd, Cu, Rh, Ir, Zn, Ag), Organocatalysis (BINOLs), Asymmetric catalysis (allylation reactions), Organoboron chemistry, Allylboronic acids, Organofluorine chemistry, Oxyfluorination, Iodofluorination, Difluorination, Trifluoromethylation, 18F labelling for PET, Fluoro-iodoxoles.
 
Synthesis and application of organoboronates
The group has developed several efficient methods for synthesis of allylboronates from allyl alcohols and diboronates as boron source (see recent JACS Perspective).
 
Recently, we developed a new method for synthesis of allylboronic acids from allylic alcohols.
Surprisingly, the isolated allylboronic acids readily react with ketones, imines and hydrazones in a "self-catalyzed" process without any additives. Using commercially available chiral organocatalysts (BINOL derivatives) asymmetric allylation reactions can be performed. In case of application of 3,3'-disubstituted allylboronic acids (geranyl or neryl boronic acids) with ketones homoallylic alcohols bearing adjacent quaternary stereocenters could be obtained with excellent stereo and enantioselectivity.
The allylation reaction could also be employed for functionalisation of indoles and dihydro-isoquinolines.In case of skatol three stereocenters could be created with high selectivity in a single step.
Allylboronic acids undergo cross-coupling reaction with diazo-ketones. In case of Cu-catalyzed reaction the branched allylic product is formed, while using Pd-catalysis the corresponding linear products are formed.

Comprehensive studies were carried out to explore the mechanism of the Pd-catalyzed silylation and borylation of the allylic alcohols.

Recently, our interest has been turned to development of new synthetic methodology for obtaining allenyl boronates.A large number of propargyl substituted strained ring compounds proved to be excellent substrates in these reactions.

We have also explored the possibity of a palladium-catalyzed borylation of propargylic substrates.
 
C-H borylation

Iridium and palladium catalyzed reactions have been successfully used for C-H borylation of alkenes. These reactions are suitable for synthesis of allyl and vinylboronates by selective replacement of a C-H bond in the alkene substrate.

In the presence of PhI(OCOCF3)2 (PIFA) palladium-catalyzed oxidative borylation has been performed.
Efficient allylic C-H borylation could be performed via allyl-palladium intermediates.
 
Fluorination and trifluoromethylation reactions
The group has a vivid researach program on development of new fluorination methods. In these procedures, safe non-toxic fluorinating reagents are employed for selective introduction of the fluorine atom in various organic molecules. Recently, we have developed a number of useful fluorination and trifluoromethylation based difunctionalization reactions. For example, rhodium catalyzed geminal oxyfluorination and trifluoromethylation was developed using diazoketone substrates.
A number of fluorocyclization reactions have been developed using electrophilic fluorobenzoiodoxole derivatives. In a collaborative study with the Himo-group (Stockholm University), we have also investigated the detailed mechanism of the aminofluorination process.
We have also presented an effecient difluorination method, which proceeds via phenonium intermediate.
When this reaction was performed using Pd-catalyst an interesting iodofluorination reaction occured.
Cyclopropane derivatives undego electrophilic ring opening in the presence flouroidines affording 1,3-difluorination or 1,3-oxyfluorination reactions.
We have studied different methodologies to introduce CF3 groups to organic substrates. Studies with hypervalent trifluoromethyl reagents have shown that oxytrifluoromethylation reactions can be performed using alkene or alkyne substrates.
This method could also be extended to the cyano-trifluoromethylation. In this reaction two C-C bonds are created by consecutive functionalization of the adjacent carbon atoms of alkenes.
Under similar reaction conditions quinones undergo C-H trifluoromethylation reaction. This reaction is accelerated in the presence of B2pin2. This acceleration effect and the electronic nature of the oxytrifluoration reaction was also investigated in a mechanistic study.
Using Cu(I)-CF3 reagent nucleophilic trifluoromethylation of propargylic trifluoroacetates and halides could be performed. Trifluoromethylation of chiral propargyl alcohol derivatives proceed stereoselectively providing chiral CF3-allenes.
One of the most recent activities of the Szabó group involves development of new catalytic fluorination methods for life sciences. The group has joint to the Stockholm Brain Institute (see video) with a project entitled: "Development of New Late Stage Fluorination Methods for Synthesis of 18F-labeled Radioligands for PET Imaging". As a part of these studies the Szabó group also entered into the arena of development of new 18F labelling methodology. In collaboration with the Schou group (Karolinska Institutet) we succeeded to develop a new methodology for radiosynthesis of 18F-labelled trifluoroacetamides. We have found that DBU acts as a nucleophilic organomediator in the key [18F] substitution step of this process.