Lewis acid/base or other properties of a reactive func-
tionality.3,4 More typically, it is desirable that a func-
tionality in a fluorous molecule has reactivity comparable
to that of its nonfluorous parent. In such cases, it is not
important to “completely” insulate a reactive group from
a perfluoroalkyl tag, but it is important to “effectively”
insulate it. By this we mean that the effects of the
perfluoroalkyl group on relative reactivity are small
enough ((10% or so) to be neglected for most preparative
purposes.
Light, Medium, and Heavy Fluorous
Triarylphosphines Exhibit Comparable
Reactivities to Triphenylphosphine in
Typical Reactions of Triarylphosphines
Dennis P. Curran,* Xiao Wang, and Qisheng Zhang
Department of Chemistry, University of Pittsburgh,
Pittsburgh, Pennsylvania 15260
Triphenylphosphine 1a is a staple in organic synthesis,
functioning as a ligand, a reagent, or a catalyst in a
diverse assortment of important transformations.5 Ac-
cordingly, light, medium, and heavy fluorous phosphines
1b-d have been introduced as triphenylphosphine ana-
logues with variable fluorine content suited to different
types of fluorous separations.6 But do phosphines 1b-d
exhibit comparable reactivities to each other and to 1a?
Lindsley and co-workers made the intriguing observation
that phosphine 1b outperformed 1c, 1d, and polymer-
bound phosphines in Staudinger reactions.7 But is the
superiority of 1b due to an inherent reactivity advantage?
The fluorous phosphines 1b-d are often made by the
reactions of aryl anions with aryl phosphorus chlorides,
and phosphine oxides are common byproducts of these
reactions.6c,d Also, Schneider and Bannwarth reported
that a phosphine closely related to 1d was oxidized a little
bit more readily than triphenylphosphine.8 Does this
mean that fluorous phosphines are easily susceptible to
air oxidation?
To answer these questions, we selected representative
transformations of triarylphosphines and conducted a
series of competitive reaction experiments. All the phos-
phines are commercially available,9 and their purities
were checked by 31P NMR prior to use. Competitive
reactions were conducted in THF-d8 to ensure that all
four phosphines were soluble under the reaction condi-
tions, and reaction progress was monitored periodically
Received January 20, 2005
The relative reactivities of triphenylphosphine (PPh3) and
three fluorous triarylphosphines [(p-RF(CH2)2C6H4)nPPh3-n
,
where n ) 1-3] have been compared in internal competition
experiments. Product ratios were determined by 31P NMR
spectroscopy. The four phosphines have about the same
reactivities in oxidation, alkylation, and Staudinger reac-
tions and give comparable yields in a preparative Mitsunobu
reaction. Previously observed rate and yield differences in
Staudinger reactions of the fluorous phosphines are at-
tributed to solubility effects, not reactivity differences. A
light fluorous phosphine [(p-C8F17(CH2)2C6H4)PPh2] outper-
forms a commercially available resin-bound phosphine in a
competitive benzylation experiment by a factor of about 4.
Organic compounds are rendered fluorous by the
attachment of one or more perfluoroalkyl tags, which are
often insulated by an alkylene or other spacer: -(CH2)nRF.
These tags render the tagged molecules susceptible to
convenient fluorous separation techniques such as liquid-
liquid and solid-phase extraction.1 As the use of fluorous
catalysts, reagents, and scavengers in organic synthesis
grows,2 it becomes increasingly important to better
understand the reactivity of fluorous compounds relative
to each other and to suitable nonfluorous models. We and
others often advertise fluorous molecules as having
reactivities comparable to those of their nonfluorous
parents, but detailed spectroscopic and computational
studies by Gladysz and others have shown that “it is very
challenging to ‘completely’ insulate a reactive site from
a perfluoroalkyl group in a fluorous molecule”.3
(4) Retarding spacer effects are evident in the rates of air oxidation
of fluorous arylphosphines bearing perfluoroalkylmethoxy (RFCH2O)
groups. Sinou, D.; Maillard, D.; Pozzi, G. Eur. J. Org. Chem. 2002,
269-275.
(5) Cobb, J. E.; Cribbs, C. M.; Hanke, B. R.; Vehling, D. E.
Encyclopedia of Reagents for Organic Synthesis, Paquette, L. A.; Ed;
Wiley: Chichester; 1995; Vol. 8, pp 5357-5363.
(6) (a) Brief review: Dandapani, S. In ref 1, pp 175-181. (b)
Phosphine 1d was first described by Leitner: Kainz, S.; Koch, D.;
Baumann, W.; Leitner, W. Angew. Chem., Int. Ed. Engl. 1997, 36,
1628-1630. (c) Zhang, Q.; Luo, Z.; Curran, D. P. J. Org. Chem. 2000,
65, 8866-8873. (d) Zhang, Q. Ph.D. Thesis, University of Pittsburgh,
2003.
(7) Lindsley, C. W.; Zhao, Z.; Newton, R. C.; Leister, W. H.; Strauss,
K. A. Tetrahedron Lett. 2002, 43, 4467-4470.
(8) (a) Schneider, S.; Bannwarth, W. Angew. Chem., Int. Ed. 2000,
39, 4142-4145. (b) Schenider, S. Ph.D. Thesis, University of Freiburg,
2000. We thank Professor W. Bannwarth for providing a copy of the
relevant pages of this thesis. In this work, phosphine oxidation
experiments with air were conducted in separate NMR tubes without
For synthetic applications, the perfluoroalkyl group
and the spacer are sometimes purposefully used to tune
(1) Handbook of Fluorous Chemistry; Gladysz, J. A., Curran, D. P.,
Horva´th, I. T., Eds.; Wiley-VCH: Weinheim, 2004.
(2) (a) Curran, D. P. In ref 1, pp 101-127. (b) Curran, D. P. In ref
1, pp 128-156. (c) Zhang, W. Tetrahedron 2003, 59, 4475-4489. (d)
Zhang, W. Arkivoc 2004, 101-109. (e) Zhang, W. Chem. Rev. 2004,
104, 2531-2556.
(3) (a) Gladysz, J. A. In ref 1, pp 41-55. (b) Jiao, H.; LeStang, S.;
Soos, T.; Meier, R.; Kowski, K.; Rademacher, P.; Jafarpour, L.; Hamard,
J. B.; Nolan, S. P.; Gladysz, J. A. J. Am. Chem. Soc. 2002, 124, 1516-
1523.
internal standards.
A fluorous phosphine homologue of 1d [(p-
C8F17C6H4)3P] was suggested to be more readily oxidized than triphen-
ylphosphine. We conducted a single-point internal competition experi-
ment with this phosphine and 1a-c and found that all four oxidized
to the same extent. Thus, (p-C8F17C6H4)3P has about the same
reactivity towards O2 in THF as 1d and triphenylphosphine.
(9) Fluorous phosphines were purchased from Fluorous Technolo-
company.
10.1021/jo050116j CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/02/2005
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J. Org. Chem. 2005, 70, 3716-3719