Synthesis of diols using the hypervalent iodine(III) reagent, phenyliodine(III) bis(trifluoroacetate)

Article abstract of DOI:10.1016/j.tetlet.2006.03.137

1,2- and 1,3-Bis(trifluoroacetoxy) alcohols are easily obtained from the one-pot reaction of alkenes with phenyliodine(III) bis(trifluoroacetate) (PIFA) in the absence of any additive or catalyst. The products were converted into the corresponding diols by ammonolysis. The use of bicyclic alkenes has shown that rearranged 1,3-diacetoxy alcohols are mostly formed as the major products.

Full text of DOI:10.1016/j.tetlet.2006.03.137

Tetrahedron Letters 47 (2006) 3659–3663
Synthesis of diols using the hypervalent iodine(III) reagent,
phenyliodine(III) bis(trifluoroacetate)
a
a
Murat C¸ elik,a,b, Cemalettin Alp, Betul Coßskun,
*
¨
M. Serdar Gultekina,b and Metin Balcib,*
¨
aDepartment of Chemistry, Atatu¨rk University, 25240 Erzurum, Turkey
bDepartment of Chemistry, Middle East Technical University, 06530 Ankara, Turkey
Received 6 February 2006; revised 10 March 2006; accepted 22 March 2006
Available online 12 April 2006
Abstract—1,2- and 1,3-Bis(trifluoroacetoxy) alcohols are easily obtained from the one-pot reaction of alkenes with phenyliodine(III)
bis(trifluoroacetate) (PIFA) in the absence of any additive or catalyst. The products were converted into the corresponding diols by
ammonolysis. The use of bicyclic alkenes has shown that rearranged 1,3-diacetoxy alcohols are mostly formed as the major
products.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Alkene oxidation is a subject of general interest, which
profoundly influences the development of synthetic
organic chemistry.1 For example, cis-dihydroxylation2
of alkenes by OsO4 provides an efficient synthetic route
to cis-diols, which are important precursors for a variety
of synthetic applications3 where this functionality is
found in various pharmaceuticals. Due to the high cost
and toxicity of OsO4, there is a need to search for alter-
native metal catalysts for alkene cis-dihydroxylations.4
1,3-Diols have attracted considerable attention in recent
years due to the ubiquitous presence of this moiety in
macrolide antibiotics.5,6 Therefore, the development of
methodologies for the preparation of 1,2- and 1,3-diols
are of considerable interest. We report herein a new pro-
cedure for the synthesis of these diols based on the reac-
tion of olefins with the hypervalent iodine compound,
phenyliodine(III) bis(trifluoroacetate) (PIFA).7
To a solution of cyclohexene dissolved in methylene chlo-
ride, PIFA was added portionwise to give the product 2.
Ammonolysis of cis-1,2-trifluorobisacetoxy-cyclohexane
2a with ammonia afforded cis-1,2-cyclohexanediol 38 in
95% yield (Scheme 1, Table 1, entry 1), which was trans-
formed into diacetate 2b. The cis-geometry in 3 was
confirmed by comparison of the 1H NMR spectrum with
those of authentic cis- and trans-1,2-cyclohexanediol.
Koser et al.9 and Zefirov et al.10 have reported the forma-
tion of cis-1,2-bis(tosyloxy)cyclohexane and cis-1,2-(per-
chloryloxy)cyclohexane upon treatment of cyclohexene
with appropriate hypervalent iodine compounds.
The oxidation of 1,4-cyclohexadiene 4 (entry 2) took
place in 20 h to give bis(trifluoroacetate) 5 as the major
product (59%), which was hydrolyzed to the corre-
sponding cis-diol.11 The tetraacetate 612 was formed as
a minor product in 11% yield. The presence of a cyclo-
propane ring in 5 was established by measuring the cou-
Hypervalent iodine(III) reagents have recently received
much attention due to their low toxicity, easy handling,
and reactivities, which are similar to those of heavy
metal reagents. We focused our studies on the hydroxyl-
ation of various alkenes using PIFA.
1
pling constants JCH = 161.7 and 162.2 Hz for the
cyclopropyl carbons with attached protons. The lack
OH
OH
OR
OR
PIFA
NH3, CH3OH
-25oC, 90%
CH2Cl2, reflux
95%
Keywords: Phenyliodine(III) bis(trifluoroacetate); PIFA; Oxidation;
Rearrangement; 1,2-Diols; 1,3-Diols.
1
3
2a R = COCF3
2b R = COCH3
*
Corresponding authors. Tel.: +90 312 2105140; fax: +90 312 2101280
(M.B.); e-mail addresses: mcelik@atauni.edu.tr; mbalci@metu.
edu.tr
Scheme 1.
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.137

3660
M. C¸ elik et al. / Tetrahedron Letters 47 (2006) 3659–3663
Table 1. Bis(trifluoromethylacetoxy)hydrocarbons from the reaction of alkenes with PIFA
Entry
1
Alkene
Producta
OR
Yield
95%
Conditions
Ref.b
8
CH2Cl2, reflux 36 h
OR
1
4
2a
OR
OR
RO
RO
2
3
70%
(5:1)
CH2Cl2, reflux
20 h
11
12
OR
RO
5
6
OR
OR
98% (55:45)
CH2Cl2, reflux 12 h
13
10
OR
OR
11
12
CHO
4
5
Quantitative
90%
CH2Cl2, reflux 18 h
CH2Cl2, reflux 36 h
13
19
18
20
OH
OH
RO
6
7
95% (97:3) 22:23
92% (95:5) 23.22
CH2Cl2, reflux 11 d
CH2Cl2, reflux 11 d
14
14
OR
21
22
OR
RO
24
23
OR
OR
OR
8
9
90% (6:3:1)
CH2Cl2, reflux 36 h
CH2Cl2, reflux 12 h
CH2Cl2, reflux 24 h
15
OR
OR
OR
25
26
27
28
OR
OR
95%
16
18
29
30
OR
OR
10
94% (3:7)
18
RO
31
32
RO
33
RO
OR
36
35
OR
11
90% (68:22:7:3) 35:36:37:38
CH2Cl2, reflux 36 h
RO
OR
OR
34
OR
37
38
a R = COCF3. The formed trifluoroacetates were transformed into the diols.
b The references are for the corresponding diols and acetates.

M. C¸ elik et al. / Tetrahedron Letters 47 (2006) 3659–3663
3661
PIFA
OCOCF3
SN
OR
2
'
PIFA
Ph
OR
OCOCF3
I
15b
RO
15a
OR
13
+
F3COCO
8
I
14
4
R = COCF3
Ph
OCOCF3
7
CHO
OCOCF3
OR
~H+
Oxidation
OR
18
17
16
Scheme 3.
OCOCF3
-PhI
Ph
OCOCF3
OCOCF3
F3COCO
I
5
9
We next investigated the reactivity of unsaturated bicy-
clic systems such as norbornene 25 and its derivatives
since these compounds have a large tendency to undergo
Wagner–Meerwein-type rearrangement. When norborn-
ene was refluxed in methylene chloride with PIFA, three
products (26–28) were formed, the rearranged product
26 being the major product (54% yield). All three prod-
ucts were transformed into the corresponding diols and
characterized as their acetates (entry 8).15
Scheme 2.
of coupling between the protons J1,2(J4,5) indicated the
cis–syn-configuration of the hydroxyl groups.
For the formation of 5 we suggest the following reaction
mechanism (Scheme 2). The stereochemical outcome is
consistent with the formation of a cyclic organoiodo
intermediate 7. Electrophilic attack of the phenyl(trifluo-
roacetoxy)iodonium ion will generate the intermediate 7,
which can undergo homoallylic substitution reaction
SN20-type substitution to give 8. Nucleophilic displace-
ment of iodobenzene by the trifluoroacetate anion in 9
with inversion of the configuration at carbon would give
the bis(trifluoroacetate) derivative 5.
Benzonorbornadiene 29 reacted with PIFA and pro-
duced the rearranged compound 30 as the sole product
(Scheme 4). The structure of the corresponding 1,3-diol
30a was established by comparison of the spectral data
with those reported in the literature.16 Homo-
benzobarrelene 31 underwent reaction via a different
route and mainly formed the allylic oxidation product
33 in addition to the rearranged product 32 (entry 10).
Finally, we investigated the reaction of benzobarrelene
1,3-Cyclohexadiene 10, in contrast to 1,4-cyclohexadi-
ene 4, underwent 1,4-dihydroxylation resulting in the
formation of the 1,4-bis-trifluoroacetoxycyclohex-2-enes
(11 and 12) (entry 3). To characterize these compounds,
the trifluoroacetyl groups were removed, and the result-
ing diols were then converted into the corresponding
known diacetates.13 Treatment of cycloheptatriene 13
with PIFA at room temperature gave benzaldehyde 18
in quantitative yield. We assume that PIFA first oxidizes
one of the double bonds to form bis(trifluoroacetate) 14,
which undergoes elimination to give 15a. The cyclohepta-
triene derivative 15a exists in equilibrium with its valence
isomer, norcaradiene 15b. Ring opening of norcaradiene
15b followed by oxidation may result in the formation of
benzaldehyde as depicted in Scheme 3.
1
34 with PIFA in methylene chloride. H NMR studies
revealed that the reaction mixture consisted of four
products, which could be isolated by chromatography
on silica gel. The major products 35 and 36 were formed
via endo-attack of PIFA to the double bond. The struc-
tures were determined by comparison of the NMR data
with those of the corresponding dibromo compounds.17
General procedure: To a magnetically stirred solution of
olefin (10 mmol) in methylene chloride (50 mL), PIFA
(13 mmol) was added portionwise over a period of
10 min. After completion of the addition, the solution
was refluxed for the appropriate amount of time (Table
1). The reaction mixture was washed with water and
dried over sodium sulfate. After removal of the solvent,
the residue was chromatographed on silica gel eluting
with hexane/ethyl acetate (95:5) to give the products.
For the hydrolysis of the trifluoroacetate groups, the
product was dissolved in anhydrous methanol (10 mL)
and dry NH3 was bubbled through the solution, with
stirring for 4 h at ꢀ25 ꢁC. Evaporation of the solvent
gave the corresponding diol in quantitative yield.
The reaction of styrene 19 with PIFA followed by
ammonolysis gave 1-phenylethane-1,2-diol 20 in 90%
yield (entry 5). On the other hand, trans-and cis-stilb-
enes 21 and 24 reacted very slowly with PIFA at reflux
in methylene chloride, and formed as the major prod-
ucts, dl- and meso-1,2-diphenylethane-1,2-bis(trifluoro-
acetates)14 22 and 23 in 95% and 92% yields,
respectively (entries 6 and 7).
OCOCF3
OCOCF3
OH
OH
PIFA
NH3, MeOH
-25 oC
CH2Cl2, reflux
29
30
30a
Scheme 4.

3662
M. C¸ elik et al. / Tetrahedron Letters 47 (2006) 3659–3663
13. (a) Ba¨ckvall, J. E.; Gogoll, A. J. Chem. Soc., Chem.
Commun. 1987, 1236–1238; (b) Secen, H.; Gultekin, M. S.;
Sutbeyaz, Y.; Balci, M. Turk. J. Chem. 1993, 17, 108–113.
14. Mukaiyama, T.; Yoshimura, N.; Igarashi, K.; Kagayama,
A. Tetrahedron 2001, 57, 2499–2506.
In conclusion, the reported procedure is easy to carry
out and enables the direct transformation of acyclic as
well as cyclic alkenes to 1,2- and/or 1,3-diacetoxy deriv-
atives using PIFA.
15. (a) Taylor, J. E. Synthesis 1985, 1142–1144; (b) Baird, W.
C., Jr.; Buza, M. J. Org. Chem. 1968, 33, 4105–4111; (c)
Wiberg, K. B.; Saegebarth, K. A. J. Am. Chem. Soc. 1957,
79, 2822–2824.
Acknowledgements
16. (a) Daßstan, A.; Demir, U.; Balci, M. J. Org. Chem. 1994,
59, 6534–6538; (b) Paquette, L. A.; Burke, L. D. J. Org.
Chem. 1987, 52, 2674; (c) Sonawane, H. R.; Sethi, S. C.;
Merchant, S. N. Indian J. Chem. 1984, 23B, 934–939.
17. Dastan, A.; Balci, M.; Hokelek, T.; Ulku, D.; Buyukgun-
gor, O. Tetrahedron 1994, 50, 10555–10578.
The authors are indebted to the Departments of Chem-
istry (Ataturk University and Middle East Technical
¨
University), The Scientific and Technical Research
Council of Turkey (TUBITAK, TBAG 104T314) and
Turkish Academy of Sciences (TUBA) for financial sup-
port of this work.
18. Physical data for selected compounds: 4-(acetyloxy)bi-
cyclo[3.1.0]hex-2-yl acetate (5, R = Ac): 1H NMR (400
MHz, CDCl3) d 5.11 (t, J = 2.9, 2H, H-2 and H-4) 2.07 (s,
6H, –CH3) 2.0 (m, 1H, H-6endo) 1.84 (m, 2H, H-3), 1.72
(dd, J = 8.8 and 4.0 Hz, 2H, H-1 and H-5), 0.67 (dt,
J = 8.8 and 6.2 Hz, 1H, H-6exo). 13C NMR (100 MHz,
CDCl3, coupled) d 170.9 (d, J = 6.9, C@O), 76.2 (d,
J = 157.2 Hz, C-2 and C-4), 36.1 (t, J = 132.0 Hz, C-3),
22.1 (d, J = 161.7 Hz, C-1 and C-5), 21.3 (q, J = 129.7 Hz,
CH3), 6.2 (t, J = 162.2 Hz, C-6). Anal. Calcd for
C10H14O4: C, 60.59; H, 7.12. Found: C, 60.89; H, 7.50.
dl-1,2-Diphenyl-2-[(2,2,2-trifluoroacetyl)oxy]ethyl-2,2,2-
trifluoroacetate (22): 1H NMR (200 MHz, CDCl3) d 7.33–
7.18 (m, 10H, aromatic), 6.27, (s, 2H, OCH). 13C NMR
References and notes
1. (a)Modern Oxidation Methods; Ba¨ckvall, J.-E., Ed.; Wiley-
VCH: Weinheim, 2004; (b) Katsuki, T.. Asymmetric
Oxidation Reactions: A Practical Approach in Chemistry;
Oxford University Press: Oxford, 2001; (c) Singh, H. S. In
Organic Synthesis by Oxidation with Metal Compounds;
Mijs, W. J., De Jonge, C. R. H. I., Eds.; Plenum: New
York, 1986.
2. (a) Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev. 1994, 94, 2483–2547; (b) Schro¨der, M. Chem.
Rev. 1980, 80, 187; (c) Gao, Y. In Encyclopedia of
Reagents for Organic Synthesis; Paquette, L. A., Editor-
in-Chief; Wiley: New York, 1995; Vol. 6, p 3801.
3. (a) Hudlicky, T.; Thorpe, A. J. Chem. Commun. 1996,
1993–2000; (b) Carless, H. A. J. Tetrahedron: Asymmetry
1992, 3, 795–826.
2
(50 MHz, CDCl3) d 158.2 (q, JCH = 43.3 Hz, C@O),
1
134.6, 131,8, 130.8, 129.5, 116,4 (q, JCH = 285.4 Hz,
CF3), 82.3. Anal. Calcd for C18H12F6O4: C, 53.21; H, 2.98.
Found: C, 53.51; H, 3.09.
2-[(2,2,2-Trifluoroacetyl)oxy]bicyclo[2.2.1]hept-7-yl-2,2,2-
1
trifluoroacetate (26): H NMR (200 MHz, CDCl3) d 4.93
(dd, J = 7.6 and 3.6 Hz, 1H, H-2), 4.87 (s, 1H, H-7), 2.70
(d, J = 4.3 Hz, 1H, H-1), 2.50 (m, br s, 1H, H-4), 1.17–
2.12 (m, 6H, CH2). 13C NMR (50 MHz, CDCl3) d 158.5
4. Yip, W. P.; Yu, W. Y.; Zhu, N.; Che, C. M. J. Am. Chem.
Soc. 2005, 127, 14239–14249.
5. (a) Macrolide Antibiotics: Chemistry, Biology, and Prac-
tice; Omura, S., Ed.; Academic Press: New York, 1984; (b)
Rychnovsky, S. D. Chem. Rev. 1995, 95, 2021–2040; (c)
Csaky, G. A.; Maximo, N.; Plumbet, J.; Ramila, A.
Tetrahedron Lett. 1999, 40, 6485–6487.
6. (a) Enders, D.; Hundertmark, T.; Lampe, C.; Jegelka, U.;
Scharfblick, I. Eur. J. Org. Chem. 1998, 2839–2849, and
references cited therein; (b) Feldman, K. S. Synlett 1995,
217–225.
7. (a) Varvoglis, A. Chem. Soc. Rev. 1981, 10, 377–407; (b)
Varvoglis, A. Synthesis 1984, 709–726; (c) Moriarty, R.
M.; Prakash, O. Acc. Chem. Res. 1986, 19, 244–250; (d)
Moriarty, R. M.; Valid, R. K.; Koser, G. F. Synlett 1990,
365–383; (e) Varvoglis, A. The Organic Chemistry of
Polycoordinated Iodine; VCH: New York, 1992; (f) Stang,
P. J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123–1178; (g)
Togo, H.; Katohgi, M. Synlett 2001, 565–581; (h) Mor-
iarty, R. M.; Prakash, O. Org. React. 2001, 57, 327–415; (i)
Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523–
2584.
8. Van Rheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron
Lett. 1976, 27, 1973–1976.
9. Rebrovic, L.;Koser,G. F.J. Org. Chem.1984, 49, 2462–2472.
10. Zhdankin, V. V.; Tykwinski, R.; Berglund, B.; Mullikin,
M.; Caple, R.; Zefirov, N. S.; Kozmin, A. S. J. Org. Chem.
1989, 54, 2609–2612.
11. Theil, F.; Schick, H.; Winter, G.; Reck, G. Tetrahedron
1991, 47, 7569–7582.
12. (a) Tschamber, T.; Backenstrass, F.; Fritz, H.; Streith, J.
Helv. Chim. Acta 1992, 75, 1052–1061; (b) McCasland, G.
E.; Furuta, S.; Johnson, L. F.; Shoolery, J. N. J. Org.
Chem. 1963, 28, 894–900.
2
1
(q, JCH = 42.8 Hz, 2 · C@O), 116.3 (q, JCH = 285.4 Hz,
2 · CF3), 85.5, 82.0, 44.8, 40.3, 38.6, 25.5, 23.3. Anal.
Calcd for C11H10F6O4: C, 41.26; H, 3.15. Found: C, 41.47;
H, 3.17.
11-(Trifluoroacetyloxy)tricyclo[6.2.1.02,7]undeca-2,4,6-
trien-9-yl trifluoroacetate (30): 1H NMR (200 MHz,
CDCl3) d 7.37–7.19 (m, 4H, aromatic), 4.97 (dd, J = 7.0
and 3.8 Hz, 1H, H9), 4.93 (s, 1H, H-11), 3.93 (br s, 1H, H-
8), 3.64 (d, J = 1.6 Hz, 1H, H-1), 2.29–2.24 (m, 2H, CH2).
13C NMR (50 MHz, CDCl3) d158.8 (q), 158.4 (q), 144.4,
1
139.0, 130.6, 129.9, 125.5, 124.2, 116.4, (q, JCH = 286.6),
1
116.3, (q, JCH = 285.8), 86.7, 80.5, 52.6, 47.5, 35.5. Anal.
Calcd for C15H10F6O4: C, 48.93; H, 2.74. Found: C, 49.04;
H, 2.84.
12-(Trifluoroacetyloxy)tricyclo[6.2.2.02,7]dodeca-2,4,6-
trien-9-yl trifluoroacetate (32): 1H NMR (200 MHz,
CDCl3) d 7.36–7.19 (m, 4H, aromatic), 5.05 (dt, J = 9.7
and 3.1 Hz, 2H, H-9 and H-12), 3.87 (t, J = 2.9 Hz, 1H,
H-8), 3.22 (quin., J = 2.4 Hz, 1H, H-1), 2.46–2.30 (ddd, A-
part of AB-system, J = 13.3, 9.7 and 3.0 Hz, 2H, CH2),
1.96–1.86 (dt, B-part of AB-system, J = 13.3, 3.0 Hz, 2H,
CH2). 13C NMR (50 MHz, CDCl3) d 158.2 (q), 144.2,
136.2, 130.7, 129.4, 128.3, 126.2, 116.4 (q,
1JCH = 285.9 Hz, CF3), 77.3, 44.0, 35.7, 35.5. Anal. Calcd
for C16H12F6O4: C, 50.27; H, 3.16. Found: C, 50.04; H,
3.17.
12-(Trifluoroacetyloxy)tricyclo[7.2.1.02,7]dodeca-2,4,6,10-
tetraen-8-yl trifluoroacetate (35, R = COCF3): 1H NMR
(200 MHz, CDCl3) d 7.31–7.1 (m, 4H, aromatic), 6.55
(ddd, J = 6.0, 3.5 and 1.0 Hz, 1H, H-10), 6.02, (br s, 1H,
H-8), 6.0 (ddd, J = 6.0, 4.8 and 2.5 Hz, 1H, H-11), 5.52 (t,

M. C¸ elik et al. / Tetrahedron Letters 47 (2006) 3659–3663
3663
1
J = 4.8 Hz, 1H, H-12), 3.70 (t, J = 4.0 Hz, 1H, H-1), 3.42
(br t, J = 3.2 Hz, 1H, H-9). 13C NMR (50 MHz, CDCl3)
130.3, 129.2 (2C), 116.1 (q, JCH = 285.9 Hz, CF3), 115.8
1
(q, JCH = 279.9 Hz, CF3), 80.2, 73.7, 48.0, 45.6. Anal.
Calcd for C16H10F6O4: C, 50.54; H, 2.65. Found: C, 51.14;
H, 2.75.
d
159.2 (q, 2JCH = 42.8 Hz, C@O), 158.7 (q,
2JCH = 42.1 Hz, C@O), 144.9, 139.9, 132.8, 132.0, 131.0,