Chemistry of fluorinated phosphonates

We have developed new methodologies for nucleophilic transfer of fluorine-containing groups using fluorinated phosphonates.

• Trifluoromethylation

  Diethyl trifluoromethylphosphonate affects trifluoromethylation of non-enolizable ketones to trifluoromethyl-containing alcohols. It also reacts with aldehydes to give phosphates of trifluormethylated alcohols (Tetrahedron Letters 51: 252–255, 2010).


• Difluoromethylation

  Diethyl difluoromethylphosphonate represents an entry to a range of difluoromethyl, difluoromethylene and fluorovinyl groups containing compounds (Tetrahedron 64: 10977-10985, 2008; Synthesis 957-962, 2009; Journal of Fluorine Chemistry 130: 493-500, 2009; Synlett 331-334, 2011; Journal of Fluorine Chemistry 137: 34-43, 2012; Journal of Fluorine Chemistry 141: 76-82, 2012.


• Fluoromethylation

  Tetraethyl fluoromethylenebisphosphonate serves as precursor to α-alkyl-α-fluoromethylenebisphophonates, α-alkyl-α-fluoro- methylenebisphophonic acids, α-fluorovinylphosphonates and α-fluorophosphonates (Organic & Biomolecular Chemistry 9: 4035-4038, 2011; Synlett 331-334, 2011; Journal of Fluorine Chemistry 132: 363-366, 2011.

  

  The reactivity of McCarthy's reagent with enones and other α,β-unsaturated compounds was investigated (Journal of Organic Chemistry 78: 4573-4579, 2013).

  

  Diethyl fluoronitromethylphosphonate is a new reagent for Horner reaction with aldehydes and nucleophilic fluoroalkylation (submitted).

  

Nucleophilic and radical transfer of tetrafluoroethyl and tetrafluoroethylene groups

Starting from dibromotetrafluoroethane we have synthesized a variety of nucleophilic and radical sulfur-containing compounds, which are now under investigation as reagents for tetrafluoroethyl and tetrafluoroethylene group transfer (European Journal of Organic Chemistry 4528-4531, 2011; Synlett 1187-1190, 2012).

New methodologies for the preparation of (pentafluorosulfanyl)benzenes

Organic compounds with pentafluorosulfanyl (SF₅) groups display a unique set of physicochemical properties. This includes extreme kinetic and hydrolytic stability, very strong electron acceptor capability, and high lipophilicity with high SF₅ electronegativity. A very high dipole moment can be achieved by the introduction of SF₅ group without increasing molecular polarity. These properties make the pentafluorosulfanyl group an increasingly interesting structural motif for the design of bioactive compounds, including agrochemicals and pharmaceuticals as well as functional materials such as polymers or liquid crystals. However, access to SF₅-containing compounds is very limited and their chemistry remains largely unexplored.

In this project we are developing new methodologies towards substituted (pentafluorosulfanyl)benzenes (Organic Letters 13: 1466-1469, 2011; Journal of Organic Chemistry 76: 4781-4786, 2011; Tetrahedron Letters 52: 4392-4394, 2011; Journal of Fluorine Chemistry 143: 130-134, 2012; European Journal of Organic Synthesis 2123-2126, 2012; Beilstein Journal of Organic Chemistry 1185-1190, 2012; Beilstein Journal of Organic Chemistry 9: 411-416, 2013; Synlett 855-859, 2013).

Properties of perfluorocarbon solvents

In this project we exploit extremely inert and hydrophobic properties of perfluorinated hydrocarbons by employing them as reaction media in enzyme-catalyzed processes. We perform biocatalysis (using isolated enzymes or whole cells) in perfluorocarbons. This brings advantages in product separation, modifies substrate and reaction scope, and improves selectivity (Chemical Communications: 1680-1681, 2002).

We also study miscibility of perfluorocarbons with ethers and alcohols (binary and ternary liquid-liquid equilibria) in collaboration with Doc. Řehák from ICT Prague (Journal of Fluorine Chemistry 129: 397-401, 2008).

Synthesis and modifications of plant growth regulators

In 2004, germination promotor of many plant species worldwide has been isolated from the smoke of burning vegetation. This remarkable potent germination stimulant, with effective germination promotion observed at nanomolar concentrations (10^-9M) was identified independently by Flematti and Van Staden as compound 1. Later, other derivatives have been identified in the smoke and this class of bioactive compounds is referred to as karrikins. In 2010, Van Staden discovered in the smoke also 3,4,5-trimethylfuran-2(5H)-one (TMB), the compound that inhibits germination of seeds and significantly reduces effect of karrikins.

This multidisciplinary project involving chemists, plant physiologists and molecular biologists, is focused on the study of mode of action of the above mentioned compounds, their effect to germination of seeds and grow of young plants (Annals of Botany 111: 489-497, 2013) as well as to the study of mutual effect of karrikins and TMB when applied simultaneously (New Phytologist 196: 1060-1073, 2012).

The main objective of the chemical part of this project is the synthesis of analogues of germination inhibitor for the purposes of structure-activity relationship (SAR) study. Modifications are carried out mainly in position C-5 (Journal of Plant Physiology 170: 1235-1242, 2013). Additionally, synthesis of halogen-, alkoxy-, aryloxyderivatives and esters is underway. Structure-activity relationship study of analogues differing in electronic and steric properties identifies the most active candidates that will be used for the synthesis of molecular probes for mode of action investigations.