Roger Salmon

Electrophilic Fluorocyclization of Allyl Silanes

A refreshing cascade: General fluorocyclization reactions will breathe new life into the use of fluorinated hetero- and carbocycles as pharmaceuticals and agrochemicals. Allyl silanes have now been shown to undergo fluorinationcyclization with N-F reagents to give cis- and transsubstituted fluorinated heterocycles selectively (see scheme). The correct choice of silyl group was critical to prevent competitive fluorodesilylation.

Synthesis of Some Arylsulfur Pentafluoride Pesticides and Their Relative Activities Compared to the Trifluoromethyl Analogues

Examples of pesticides containing an arylsulfur pentafluoride group were made and their biological activities compared to the corresponding trifluoromethyl analogues. A phenylsulfur pentafluoride analogue of the insecticide fipronil, screened against a resistant strain of Musca domestica, showed higher activity than the corresponding trifluoromethyl analogue.

Developments in fluorocyclization methodologies

Fluorinated organic compounds constitute a significant proportion of medicines marketed today. Since heterocycles are submotifs frequently encountered in lead compounds, the corresponding fluorinated molecules that possess coupling functional groups to increase structural complexity are sought-after building blocks, especially those with stereogenic elements. To access fluoro-heterocycles, fluorocyclizations constitute an important category of reactions that permit multiple bond construction in one pot. Reactions featuring both nucleophilic and electrophilic sources of fluorine have proved valuable for the delivery of fluorinated carbo- and heterocycles. Mechanistically, two scenarios have been validated with the fluorination occurring either prior to or after the cyclization event. Fluorinated biologically active molecules prepared by employing a fluorocyclization protocol are rare, with two notable exceptions being the synthesis of fluorogypsetin and fluorobrevianamide E. Various levels of diastereocontrol were obtained with best results observed when the cyclization step precedes the fluorination. To date, asymmetric fluorocyclizations have not been explored, with the exception of a Nazarov fluorination process. In essence, this process features a catalytic asymmetric cyclization followed by a diastereoselective fluorination. Asymmetric fluoroheterocyclizations are, however, not known. For this methodology to serve medicinal chemistry, conceptual advances are essential to access fluorinated pharmacophores with programmable stereocontrol as and when necessary.

Cationic rearrangements controlled by the presence of a silyl group

1,1-Disilylcarbinols having two alkyl groups on the adjacent carbon atom react with thionyl chloride in sulfur dioxide to give the product in which one of the alkyl groups has migrated towards the two silyl groups, and one of the silyl groups has been removed from the resultant cation. The reaction is seen in ring-expansion, as in the conversion of cyclohexylbis[dimethyl(phenyl)silyl]carbinol (7) into 1-dimethyl(phenyl)silylcycloheptene (11), and in open chains, as in the conversion of 1,1-bis[dimethyl(phenyl)silyl]-2-methylpropanol (26) into (E)- and (Z)-2-dimethyl(phenyl)silylbut-2-ene (27). Phenyldimethylsilyllithium reacts with pinacolone to give the α-silyl carbinol (44), which rearranges in the same way to give 2,3-dimethylbut-2-ene (46), effectively achieving a pinacolone-to-pinacol rearrangement.