Abstract
We describe a method for the preparation of CF2 -P(V) building blocks and monomers for biological and materials chemistry applications
in multigram quantities based on a formal [2,3]-sigmatropic phospha-Wittig rearrangement
of readily available fluoroallyl bis(amido)phosphites, amido(aryl)phosphonites, and
diarylphosphinites. The proposed intramolecular phosphorylation approach complements
the currently prevailing phosphoryldifluoromethylation methods by providing a straightforward
access to difluoromethylene phosphonate analogues bearing dialkylamino and/or aryl
substituents at the phosphoryl group. An important advantage of the developed method
is that it does not rely on ozone-depleting HCF2 Cl and CF2 Br2 necessary for the preparation of phosphoryldifluoromethylating reagents. 2,3,3-Trifluoroallyloxy
P(III) derivatives substituted with two dialkylamino and/or aryl groups underwent
a facile [2,3]-rearrangement to give difluoromethylene phosphonic and phosphinic amides
and phosphine oxides on up to a 0.15 mol (30 g) scale. The reaction was extended to
P(III) derivatives of 1-substituted 2,3,3-trifluoro- and 3,3-difluoroallylic alcohols
readily available from carbonyl compounds and, respectively, 1,1,1,2-tetrafluoroethane
and O -protected 2,2,2-trifluoroethanols. Products derived from O -(tetrahydropyran-2-yl)-2,2,2-trifluoroethanol were synthesized and deprotected in
a one-pot multistep protocol to give phosphonic and phosphinic amide and phosphine
oxide analogues of α,α-difluoro-β-ketophosphonates on a multigram scale.
Key words phosphonates - phosphinates - phosphine oxides - phosphonic amides - fluoroallyl -
difluoromethylene - ketones - [2,3]-rearrangement
