Abstract
The ortho metallation of some aromatic ring systems has been investigated in
regard to the influence of several types of phosphorus-centred directing groups upon the reactivity, regioselectivity, and utility in later synthetic elaboration.
The metallation step allows derivatisation in several useful ways, offering several
routes to the synthesis of novel chiral ditertiary phosphines. Thus, an ortho lithiation
of N,N,N',N'-tetramethyl-P-phenylphosphonic diamide (10) led to the interesting
primary phosphine, 2-(diphenylphosphino)phenylphosphine (14), after elaboration of
the phosphonic diamide directing group. This primary phosphine undergoes an
unprecedented facile phenyl group exchange process between its two phosphorus
atoms, upon di-lithiation of the primary phosphorus centre.
The primary phosphorus centre of (14) has been elaborated in several ways to
yield new ditertiary phosphines. The alkylation of this centre in the copper(I) chelate
complex has been investigated in several directions.
In another direction, (14) has been chemically elaborated to give a new hybrid
chiral ditertiary phosphine ligand, "SemiPHOS", containing both a chiral phospholane
ring and an adjacent diphenylphosphino group. SemiPHOS has been obtained in
optically pure forms by a stereoselective synthesis and, independently, by a resolution
procedure on its racemate. The molecular design of SemiPHOS was devised such that,
when chelated to a metal atom, a subtle steric interaction appears to allow the chirality
of the phospholane ring to influence the neighbouring diphenylphosphino group to
adopt a complementary chiral conformation. This idea was tested and evaluated by
applying SemiPHOS in catalytic asymmetric hydrogenations of (Z)-a-(Nacylamino)
acrylate substrates to produce the R-amino acid precursors.
Aryl species lithiated ortho to phosphorus-centred directing groups were coupled
oxidatively by a convenient in situ method, to yield biaryl species that could then be
elaborated to give biaryl ditertiary phosphine ligands. This method was used to make
several atropisomeric chiral ditertiary phosphines.