D
J. Eljo et al.
Letter
Synlett
and tertiary alcohols reacted with these iodanes and PPh3
to give alkyl chlorides, fluorides, acetates, trifluoroacetates,
or 2-iodobenzoates in moderate to good yield. Appel-type
reactivity dominated with iodanes 1 and 3, but acylation
reactions dominated with iodanes 5 and 7, consistent with
an electrophilic acyloxyphosphonium intermediate serving
as the active acylating agents. The chemoselectivity ob-
served with iodane 9 was related to the steric hindrance
and/or nucleophilicity of the alcohol, giving alkyl chlorides
with unhindered alcohols and benzoates with hindered al-
cohols. This study shows various ligands can be transferred
from hypervalent iodine reagents to alcohols and offers a
facile approach to common alcohol derivatives.
Stine, W. R. Tetrahedron Lett. 1967, 2321. (f) Dillon, K. B.; Lynch,
R. J.; Reeve, R. N.; Waddington, T. C. J. Chem. Soc. Dalton 1976,
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(7) (a) Kirk, K. L. Org. Process. Res. Dev. 2008, 12, 305. (b) Bégué, J.-
P.; Bonnet-Delpon, D. Bioorganic and Medicinal Chemistry of Flu-
orine; John Wiley and Sons: Hoboken, NJ, 2008, 365. (c) Ojima, I.
Fluorine in Medicinal Chemistry and Chemical Biology; Wiley-
Blackwell: Chichester, 2009, 624.
(8) For syntheses of Ph3PF2 with various reagents such as XeF2, SF4,
IF5, DAST, COF2, or HgF2, see: (a) Kobayash, Y.; Akashi, C. Chem.
Pharm. Bull. 1968, 16, 1009. (b) Frohn, H. J.; Maurer, H. J. Fluo-
rine Chem. 1986, 34, 73. (c) Holmes, R. R.; Chandrasekhar, V.;
Day, R. O.; Harland, J. J.; Payne, J. S.; Holmes, J. M. Phosphorus
Sulfur Relat. Elem. 1987, 30, 409. (d) Gupta, O. D.; Shreeve, J. M.
J. Chem. Soc., Chem. Commun. 1984, 416. (e) Doxsee, K. M.;
Hanawalt, E. M.; Weakley, T. J. R. Inorg. Chem. 1992, 31, 4420.
(9) Caputo, C. B.; Winkelhaus, D.; Dobrovetsky, R.; Hounjet, L. J.;
Stephan, D. W. Dalton Trans. 2015, 44, 12256.
Funding Information
(10) We believe its increased hydrolytic stability (relative Ph3PCl2) is
due to the increased strength of P–F (490 kJ/mol) over P-Cl (326
kJ/mol) bonds.
(11) Iranpoor, N.; Firouzabadi, H.; Davan, E. E. Tetrahedron Lett. 2013,
54, 1813.
This work was supported by the University of Waterloo and the Natu-
ral Sciences and Engineering Research Council (NSERC) of Canada
(Discovery Grant 418602-2013).
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(12) Gallos, J.; Varvoglis, A. Chim. Chron., New Ser. 1987, 16, 87.
(13) Makowiec, S.; Rachon, J. Heteroat. Chem. 2003, 14, 352.
(14) McNulty, J.; Capretta, A.; Laritchev, V.; Dyck, J.; Robertson, A. J.
Angew. Chem. Int. Ed. 2003, 42, 4051.
(15) Dormoy, J.-R.; Castro, B. Triphenylphosphine Dichloride, In e-
EROS; Wiley: Hoboken, NJ, 2001.
Acknowledgment
We are grateful to Mrs. J. Venne for help with the time-lapse 31P NMR
studies, and we acknowledge Ms. M. Abdinejad for conducting explor-
atory 19F NMR experiments with 3.
(16) Kobayashi, Y.; Akashi, C. Chem. Pharm. Bull. 1968, 16, 1009.
(17) (a) Mohandas, T. P.; Mamman, A. S.; Nair, P. M. Tetrahedron
1983, 39, 1187. (b) Wicha, J.; Zarecki, A.; Kocór, M. Tetrahedron
Lett. 1973, 14, 3635.
Supporting Information
Supporting information for this article is available online at
(18) Taniguchi, T.; Hirose, D.; Ishibashi, H. ACS Catal. 2011, 1, 1469.
(19) Carle, M. S.; Shimokura, G. K.; Murphy, G. K. Eur. J. Org. Chem.
2016, 3930.
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(20) Reacting Ph3PF2 (4, 1.6 equiv) with 4-nitrophenethyl alcohol for
45 min at 160 °C using 10 mol% TiF3 as an activating agent pro-
duced alkyl fluoride 5a in 66% yield.
(21) The major competing reaction pathway in these experiments
was alcohol dimerization, giving the ether. It is proposed that
this arises from the alcohol outcompeting fluoride as the nucle-
ophile. See ref. 16.
(22) Zhang and co-workers reported phenethyl acetate to be the
major byproduct of a reaction between 5, phenethyl alcohol,
hexanoic acid, DMAP, and PPh3. No indication of phenethyl tri-
fluoroacetate was reported for the analogous reaction using
iodane 7. See Table S1 in the supporting information of ref. 1a.
(23) Only trace amounts of 15a or 15b were visible by 1H NMR anal-
ysis of the crude reaction mixtures after 10 min. Prolonging the
reaction times to 2–3 h did not significantly change the product
ratios, suggesting that the reaction pathways are competing, as
opposed to 14 reacting with the benzoate byproduct of the
reaction to give 15. Concentrating the reaction mixtures before
column chromatography appears to have increased the ratio of
the benzoate products.
References and Notes
(1) (a) Tian, J.; Gao, W. C.; Zhou, D. M.; Zhang, C. Org. Lett. 2012, 14,
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(2) Appel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 801.
(3) (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523.
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ments in Organic Synthesis; Springer: Berlin, 2003. (c) Zhdankin,
V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299. (d) Yoshimura, A.;
Zhdankin, V. V. Chem. Rev. 2016, 116, 3328. (e) Zhdankin, V. V.
Hypervalent Iodine Chemistry: Preparation Structure, and Synthetic
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(6) (a) For syntheses of Ph3PCl2 with various reagents such as Cl2,
CCl4, (COCl)2, COCl2, or C2Cl6, see: Michaelis, A.; Michaelis, A.; v.
Soden, H. Justus Liebigs Ann. Chem. 1885, 229, 295. (b) Appel, R.
Angew. Chem., Int. Ed. Engl. 1975, 14, 801. (c) Appel, R.; Geisler,
K.; Scholer, H. Chem. Ber. 1977, 110, 376. For NMR studies on the
synthesis of 2 with C2Cl6, see: (d) Yin, Q.; Ye, Y.; Tang, G.; Zhao,
Y. F. Spectrochim. Acta, Part A 2006, 63, 192. (e) Wiley, G. A.;
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McDonald, R.; Luu, T.; Tykwinski, R. R. J. Org. Chem. 2005, 70,
6484.
(25) Sample Experimental Procedure
Into a conical flask was added the 4-phenyl-2-butanol (0.063 g,
0.42 mmol, 1 equiv) and CH2Cl2 (0.5 mL), and to this was added
PPh3 (1.1 equiv) and [bis(trifluoro-acetoxy)iodo]benzene (1.1
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E