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magnesium ate-complex 9, formed through initial coordination of Notes and references
the Cl-anion from CPS. While not strictly necessary for the overall
1
H. J. Cristau and F. Plenat, in The Chemistry of Organophosphorus
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explanation, we believe that it is the more likely reacting species.
The second point about Scheme 4 is related to the fact that
2 (a) I. Gosney and A. G. Rowley, in Organophosphorus Reagents in
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3 P. A. Byrne and D. G. Gilheany, Chem. Soc. Rev., 2013, 42, 6670–6696.
4
5
2
3
Denny and Gross could not authenticate their new reaction.
This is because the combination of phosphine and 12 would
itself lead to QPS via a subsequent independent standard
quaternization after Cl-attack. However, from our own kinetic
studies of phosphine alkylation in conjunction with those by
T. Werner, Adv. Synth. Catal., 2009, 351, 1469–1481.
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327–5331; (b) A. Golandaj, A. Ahmad and D. Ramjugernath, Adv.
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McEwen and co-workers, we can now categorically rule this
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5
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6 A. G. Cairns, S. J. McQuaker, M. P. Murphy and R. C. Hartley, in
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slower than inverse polarity alkylation (see ESI†).
Finally, it was intriguing, of course, to examine the use of
other organometallic reagents, hoping to achieve different
P-selectivity patterns. In reaction with 4, the more reactive
organolithiums strongly favoured Cl-attack regardless of the
7 K. J. Fraser and D. R. MacFarlane, Aust. J. Chem., 2009, 62, 309–321.
8
(a) D. Virieux, J.-N. Volle and J.-L. Pirat, in Science of Synthesis,
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1
R Li type (entries 15/16 vs. 8/13). Conversely, a very pronounced
shift towards P-attack was observed with the less reactive
diethylzinc (entry 17). Reaction of di-n-butyl-magnesium (entry 18)
leads to somewhat less Cl-attack than with the corresponding
Grignard reagent (entries 7 vs. 18).
9
W. A. Henderson and S. A. Buckler, J. Am. Chem. Soc., 1960, 82,
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In conclusion, we have discovered a new high-yielding nucleo- 12 F. Tappe, V. Trepohl and M. Oestreich, Synthesis, 2010, 3037–3062.
1
3 D. G. Gilheany and C. M. Mitchell, in The Chemistry of Organo-
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philic preparation of quaternary phosphonium salts, including
tetraalkyl, and alkyl–aryl series from phosphine oxides via the
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(
b) J. McNulty and P. Das, Eur. J. Org. Chem., 2009, 4031–4035.
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Umpolung strategy, whereby both reacting partners have been
1
5 P. Beck, in Organic Phosphorus Compounds, ed. G. M. Kosolapoff and
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1
7 A. J. Kendall, C. A. Salazar, P. F. Martino and D. R. Tyler, Organo-
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2
0 M. Stankevi ˇc , J. Pisklak and K. Włodarczyk, Tetrahedron, 2016, 72,
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Our new method is a very practical alternative to the existing
8
1
nucleophilic, and therefore readily oxidised, phosphines because it
does not require synthesis/handling of such substrates. The mecha-
nistic complementarity also provides further operational super-
iority, allowing rapid alkylation and arylation offering easy access
to known and new QPS structures as key materials for synthesis.
A primary driver of our study is that this new inversed reactivity
methodology opens the prospect of directly accessing a variety of
QPS – immediate precursors of phosphorus ylides – from phosphine
oxides. This could, in principle, render fully recyclable and reusable
the key phosphorus components in Wittig and Wittig-type reactions.
Work is presently underway on further development of this
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2
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2
5 S. M. Godfrey, C. A. McAuliffe, R. G. Pritchard, J. M. Sheffield and
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approach to Wittig reactions avoiding use of phosphorus(III) 26 K. Nikitin, H. M u¨ ller-Bunz and D. Gilheany, Chem. Commun., 2013,
4
9, 1434–1436.
compounds altogether and will be reported in due course.
This work was supported by Science Foundation Ireland
through the SFI-funded Synthesis & Solid State Pharmaceutical
Centre 12/RC/2275 Grant to D. G. G. We also thank Dr Kamalraj
Rajendran for preliminary studies.
2
7 (a) E. V. Jennings, K. Nikitin, Y. Ortin and D. G. Gilheany, J. Am.
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3
8
Conflicts of interest
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3
There are no conflicts to declare.
Chem. Commun.
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