Chemistry Reference
In-Depth Information
R
R
I
HS
S
Et-P2, CuBr (cat.)
+
R'
R'
toluene, reflux
Scheme 5.22
Copper catalysed coupling in the presence of P2
5.2.2.6 Sulfide Formation via S
N
Ar Reaction
In the presence of the phosphazene Et-P2 base as well as DBU the coupling of aryl iodides
with arenethiols only requires catalytic amounts of copper(I) bromide (CuBr). Under these
conditions, the reaction can be performed in refluxing toluene to give biaryl thioethers in
excellent yields [40] (Scheme 5.22).
5.2.3 Use of P4 Base
5.2.3.1 Alkylation of C-Nucleophile
It was shown that monoalkylation of 8-phenylmenthyl phenylacetate using lithiated bases
leads to poor or no diastereoselectivities (50/50 to 69/31) and high yields (75-98%) while
alkylation using
t
Bu-P4 leads to high diastereoselectivities (92/8 to 98/2) and high yields
(65-95%) [41] (Scheme 5.23).
It is postulated that, in the case of phenylacetates, the degree of aggregation of the lithium
enolate is responsible of the poor diastereoselectivities. NMR studies revealed that methyl
phenylacetate enolate generated with the
t
Bu-P4 phosphazene base was 'naked' or tightly
associated with the
t
Bu-P4H
รพ
cation depending on very small variations in solvent
composition. Both forms reacted more rapidly than the corresponding lithium enolate in
a model alkylation experiment using dimethyl sulfate.
Supported
t
Bu-P4 enolate chemistry of phenylacetyloxymethyl polystyrene resin was
investigated using high resolution magic angle spinning (HR-MAS) NMR spectroscopy.
Direct analysis of the crude reaction suspension through the use of a diffusion filter allowed
not only rapid selection of the optimal experimental conditions, but also the characteriza-
tion of the enolate on the solid phase. Comparison with solution experiments and literature
data indicated partially the structure of the enolate. HR-MAS NMR spectra of the enolate
revealed also a tight interaction of
t
Bu-P4 base with the polymer matrix [41].
The structurally novel bicyclic oxazinone was prepared based on D-glucopyranose. The
lithium enolates of these compounds undergo highly diastereoselective alkylation reactions
with reactive alkyl halides, in modest yields. Use of the phosphazene P4 base enhanced the
yields of these processes, suggesting that metal enolate aggregation is at least partly
Me
Me
O
O
Me
Me
RX
Ph
Ph
Ph
Ph
O
O
t
Bu-P4
Me
Me
R
Scheme 5.23
Diastereoselective alkylation in the presence of P4
