Solid Supported Synthesis of Phosphinates Via Palladium (0) Catalysed Coupling Reactions

Abstract

In order to gain a broad access to phosphinic acid derivatives, a palladium catalysed coupling reaction of aryl iodides with hypophosphorous acid derivatives has been developed on the solid phase. The resulting arylphosphorous acids (or esters) were derivatised using addition reactions with aldehydes, imines and isocyanates, to give phosphinic acids (or esters) with alpha-hydroxy, alpha-amino or aminoacyl groups attached to the aryl phosphorus moiety. This approach provided a broad chemical entry into a class of polar phosphinates compounds which were rather difficult to handle using normal solution phase synthesis. The synthetic potential of this solid phase based methodology was demonstrated by the synthesis of targeted libraries against the enzyme dihydrodipicolinate synthase (DHDPS).

Combinatorial chemistry in the agrosciences

“…A good agrochemically relevant example has been reported by Haaf who prepared a library of arylphosphinates as potential herbicidal inhibitors of the enzyme dehydropicolinate synthase for biological screening (Scheme 1). 21 The key step involved a palladium catalysed coupling reaction of ethylphosphinate with the resin-bound aryl iodides 1 yielding the resin-bound phosphinates 2 in high yield and purity. The ethyl esters 2 could be cleanly converted to the free phosphinic acids 3 by treatment with diazabicycloundecene (DBU).…”