Abstract
The main objective of the research described in this dissertation was the
preparation of a range of bulky and electron-rich phosphine ligands using the
DoM methodology developed in our labs for this purpose. These ligands would
be employed in the Suzuki cross-coupling reaction of deactivated aryl bromides
and aryl chlorides.
Initially, a range of phosphinic amides was synthesised and tested for DoM
reactivity. TMSCl, MeI and O2 were successfully used as electrophiles,
incorporating TMS, Me and OH groups in the ortho-position of these phosphinic
amide systems. This development was encouraging and provided a route to
incorporate a phosphine on the ortho-position of these phosphinic amide systems
by using Ph2PCl and Cy2PCl as electrophiles to incorporate Ph2P and Cy2P,
respectively.
The route was versatile and a range of electrophiles was used to prepare
phosphine ligands with varying electronic and steric properties. These
electrophiles (of the R2PCl variety) were often specifically prepared from PCl3
and the corresponding Grignard reagent. Phosphine ligands synthesised in this
research project using our DoM (directed ortho metallation) methodology were
tested in Suzuki cross-coupling reactions of deactivated aryl bromides and some
aryl chlorides and showed excellent reactivity, with the advantage that the
ligands of this study are oxidatively and hydrolytically stable.
Efforts were also made to modifying the phosphinic amide-functionalised
phosphine ligands to generate their water-soluble derivatives. One way of
achieving this was by the hydrolysis of the phosphinic amide moiety to the
phosphinic acid analogue. Salts of these phosphinic acid derivatives have
promising activities as water-soluble substrates. This route was successful only
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with less electron-rich systems providing an opening for more research in this
regard.
In an alternative synthetic route to polar water-soluble phosphines it was
envisioned that phosphonate-derivatised phosphines would offer access to
water-soluble phosphine ligands by using milder hydrolysis conditions. These
phosphonate systems were also tested for DoM reactivity and showed promising
reactivity. Phosphonates have not previously being employed as DoM groups,
and this alone expands the application and potential scope of P-based DoM
groups.
Prof. D.B.G. Williams