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ing bidentate ligands have also been utilised in palla-
dium catalysed asymmetric allylic alkylation reactions.7
a refrigerator under an inert atmosphere for several
months.
As part of an ongoing program of research into poten-
tial ligands for catalytic asymmetric conjugate addition
reactions, we decided to prepare a range of ligands
incorporating both sulfoximide and phosphine moieties,
our rationale for this being that the phosphine would
act as a soft donor ligand and the sulfoximide would
provide a chiral unit with the potential of acting as a
hard donor ligand in certain cases.
Spectroscopic characterisation of (S)-1 served to
confirm the structure,† however, a slight anomaly in the
1H NMR data should be noted: two signals (unequal in
intensity) relating to the S-methyl group were observed.
At first this was thought to be due to a rotameric effect
(possibly resulting from slow rotation about the NꢀP
bond). However, variable temperature NMR studies
seemed to disprove this hypothesis since no variation in
signal intensity or coalescence was observed upon heat-
ing. A second hypothesis was that (S)-1 might exist as
a mixture of cis- and trans-isomers about the SꢁN
bond. Attempts at separation of the two forms were
unsuccessful due to the instability of the compound to
column chromatographic purification and difficulties
with recrystallisation. Despite this we thought it useful
to assess the capability of this novel sulfoximide (even
as a possible mixture of isomers) to act as a ligand in
asymmetric transformations. The reaction chosen for
investigation was the copper-catalysed addition of an
organometallic reagent to an a,b-unsaturated ketone.
To our knowledge no sulfoximide-containing ligands
which also incorporate a phosphine moiety have yet
been reported. Herein, we present the synthesis of
(S)-N-(diphenylphosphinyl)-S-methyl-S-phenyl sulfox-
imide 1 (Scheme 1) and the results of preliminary
investigations into its use as a ligand in copper-
catalysed asymmetric conjugate addition reactions.
2. Results and discussion
In general the best approach to an enantiomerically
pure sulfoximide is via the corresponding sulfoxide,
since imination can be achieved with retention of
configuration at sulfur. Thus, oxidation of commer-
cially available thioanisole using either m-CPBA in
dichloromethane or sodium periodate in methanol/
water gave the corresponding racemic sulfoxide 2 in
good yield. Imination of 2 was then achieved using the
There has been considerable interest, over the past
decade, in the addition of organometallic reagents to
a,b-unsaturated ketones using chiral ligands to enhance
the enantioselectivity in the reaction.13 We chose to
adopt the reaction conditions of Feringa et al.,13b in
which diethylzinc is employed as the organometallic
reagent along with Cu(OTf)2 (converted to Cu(I) in
situ) as the copper source (Scheme 2). The results of
our preliminary studies using a range of enones as
substrates are shown in Table 1.
electrophilic
aminating
agent
O-(mesitylenesul-
fonyl)hydroxylamine (MSH) giving sulfoximide 3 in up
to 92% yield.8 Resolution of ( )-3 was carried out using
(+)-camphorsulfonic acid (CSA) according to the pro-
cedure developed by Gais et al.,9 which resulted in the
isolation of enantiomerically pure (S)-3 in 48% yield.10
Reactions were carried out in either toluene or
dichloromethane at −20°C, giving exclusive formation
of the 1,4-adduct in all cases. The rate of the reaction
was considerably reduced in the case of 4,4-disubsti-
tuted substrates probably due to increased steric hin-
drance at the 4-position. The enantioselectivities
achieved were also much lower in these cases. The best
results were obtained upon reaction of cylohex-2-enone
(23% e.e.) and cyclohept-2-enone (44% e.e.), demon-
strating that the ligand performs best with unhindered
At this point in the synthesis a number of methods for
the introduction of the N-phosphinyl group were
explored. Initial attempts at the reaction of (S)-3 with
chlorodiphenylphosphine in the presence of triethy-
lamine proved unsuccessful due to difficulties encoun-
tered with the removal of triethylamine hydrochloride
from the product. An alternative approach was to
employ N,N-(dimethylamino)diphenylphosphine as the
phosphorus source. This involved heating a 1:1 mixture
of (S)-3 and the amino-phosphine in refluxing toluene
or benzene until evolution of the volatile dimethylamine
(as monitored by the pH of the gas outlet) ceased.
Unfortunately a mixture of phosphorus-containing
products was obtained, as determined by 31P NMR. A
solution to the problem proved to be utilisation of a
procedure developed by Roesky et al.,11 who reported
the synthesis of a similar N-phosphinyl sulfoximide
from dimethyl sulfoxide. The target sulfoximide (S)-1
was successfully prepared by reacting freshly pre-
pared N-TMS protected derivative (S)-412 with
chlorodiphenylphosphine in dry diethyl ether. This
resulted in the formation of (S)-1 as a white precipitate,
which could be isolated from the reaction mixture by
filtration under an inert atmosphere. In our experience
this compound is moisture sensitive but can be stored in
Scheme 2.
† Key data for (S)-1: [h]D=+48.0 (c=1.0 in CHCl3); mp 59–60°C;
wmax cm−1 (DCM) 3154, 2984, 1285 (NꢁSꢁO), 1095 (NꢁSꢁO); lH
(300 MHz; CDCl3), 3.17 (0.5H, s, S-CH3
6
), 3.3 (2.5H, s, S-CH3
6 ),
7.2–8.1 (15H, Ar-H
6
); lc (75.5 MHz; CDCl3) 133.8 (C), 132.5 (d, C,
Jc-p 3.8), 130.6 (d, CH, Jc-p 11.5), 129.5 (CH), 129.3 (CH), 128.9
(CH), 128.7 (CH), 127.9 (CH), 45.4 (CH3); lP (120 MHz; CDCl3)
21.8; m/z (EI); 339 (M+, 28%), 324 (100), 277 (5), 262 (5), 201 (15),
183 (9), 122 (15), 77 (15), 51 (6); HRMS (EI). Found: (M+
339.0831), C19H18NOPS requires 339.0846.
Kinahan, Taryn C.
