A highly chemoselective oxidation of alcohols to carbonyl products with iodosobenzene diacetate mediated by chromium(III)(salen) complexes: Synthetic and mechanistic aspects

Article abstract of DOI:10.1021/ol000142y

The catalytic oxidation of the allylic alcohols 1d-n with iodosobenzene diacetate, mediated by the [Cr^III(salen)]X complex, affords the respective enones in excellent chemoselectivity for Cl^- as counterion [complex A(Cl)], while for the counterions TfO^- [complex A(TfO)] and PF₆^- [complex A(PF₆)] nearly equal amounts of enone and epoxide are observed. This counterion-dependent oxidation of allylic alcohols by Cr^III(salen) complexes is rationalized in terms of Lewis acid catalysis by the complex A(Cl) and redox catalysis for A(TfO) and A(PF₆).

Full text of DOI:10.1021/ol000142y

ORGANIC
LETTERS
2000
Vol. 2, No. 18
2773-2776
A Highly Chemoselective Oxidation of
Alcohols to Carbonyl Products with
Iodosobenzene Diacetate Mediated by
Chromium(III)(salen) Complexes:
Synthetic and Mechanistic Aspects
,†
Waldemar Adam,†,‡ Saumen Hajra,* Markus Herderich,§ and
Chantu R. Saha-Mo1ller†
Institut fu¨r Organische Chemie and fu¨r Lebensmittel Chemie, UniVersita¨t Wu¨rzburg,
Am Hubland, D-97074 Wu¨rzburg, Germany
adam@chemie.uni-wuerzburg.de
Received June 2, 2000
ABSTRACT
The catalytic oxidation of the allylic alcohols 1d−n with iodosobenzene diacetate, mediated by the [CrIII(salen)]X complex, affords the respective
enones in excellent chemoselectivity for Cl- as counterion [complex A(Cl)], while for the counterions TfO- [complex A(TfO)] and PF6- [complex
A(PF )] nearly equal amounts of enone and epoxide are observed. This counterion-dependent oxidation of allylic alcohols by CrIII(salen) complexes
6
is rationalized in terms of Lewis acid catalysis by the complex A(Cl) and redox catalysis for A(TfO) and A(PF ).
6
The oxidation of alcohols to carbonyl products is a pivotal
transformation in organic chemistry, which has received
much attention over the years, especially the search for
versatile and selective reagents in catalytic applications.1
Particularly in the past decade, the oxidizing properties of
hypervalent iodine compounds2 have been of increasing
interest, of which the highly utilized pentavalent iodine
reagents stand out, namely, the Dess-Martin periodinane3
and its direct precursor o-iodoxybenzoic acid.4 Despite their
utility and popularity, a serious disadvantage of such iodine-
(V) oxidants is their explosive nature, which obliges their
impromptu generation, since these potentially dangerous
reagents should not be stocked.5
In contrast, the facile, safe to use, readily available, and
persistent iodine(III) oxidants, e.g., iodosobenzene6,7 and
most notably its diacetate,5,8 have, in comparison, not been
used very much. Consequently, only few selective catalytic
oxidations with iodine(III) reagents are known, especially
† Institut fu¨r Organische Chemie.
‡ Fax: +49-931-888 4756. Internet: http://www-organik.chemie.
uni-wuerzburg.de.
(5) Tohma, H.; Takizawa, S.; Maegawa, T.; Kita, Y. Angew. Chem., Int.
Ed. 2000, 39, 1306-1308.
§ Institut fu¨r Lebensmittel Chemie.
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Org. Chem. 2000, 65, 1915-1918.
(2) (a) Stang, P. J.; Zhdankin, V. V. Chem. ReV. 1996, 96, 1123-1178.
(b) Varvoglis, A. HyperValent Iodine in Organic Synthesis; Academic
Press: London, 1997. (c) Wirth, T.; Hirt, U. H. Synthesis 1999, 1271-
1287. (d) Moriarty, R. M.; Prakash, O. Org. React. 1999, 54, 273-418.
(3) (a) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277-
7287. (b) Meyer, S. D.; Schreiber, S. L. J. Org. Chem. 1994, 59, 7549-
7552.
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1993, 571-572.
(8) (a) Mu¨ller, P.; Godoy, J. Tetrahedron Lett. 1981, 22, 2361-2364.
(b) Mico, A. D.; Margarita, R.; Parlanti, L.; Vescovi, A.; Piancatelli, G. J.
Org. Chem. 1997, 62, 6974-69777.
(9) (a) Samsel, E. G.; Srinivasan, K.; Kochi, J. K. J. Am. Chem. Soc.
1985, 107, 7606-7617. (b) Srinivasan, K.; Kochi, J. K. Inorg. Chem. 1985,
24, 4671-4679. (c) Ryan, K. M.; Bousquet, C.; Gilheany, D. G. Tetrahedron
Lett. 1999, 40, 3613-3616. (d) Khenkin, A. M.; Hill, C. L. J. Am. Chem.
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1995, 36, 3485-3488.
10.1021/ol000142y CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/10/2000

of alcohols to carbonyl products. Transition-metal catalysis9
has been quite effective in the use of the heterogeneous
iodosobenzene: Kochi9a,b employed CrIII(salen) complexes
to epoxidize catalytically olefins by PhIO, which Gilheany9c
recently applied to asymmetric epoxidations. The feasibilty
of oxidizing catalytically allylic alcohols to enones was
demonstrated by Hill9d for cyclohexen-3-ol, who employed
heterotungstate complexes of chromium(III) with PhIO. We
have recently reported6 that quite generally allylic alcohols
may be chemoselectively transformed to the corresponding
enones by the CrIII(salen)/PhIO oxidant under catalytic
conditions.
Table 1. Oxidation of Alcohols 1 with Iodosobenzene
Diacetate, Catalyzed by the [CrIII(salen)]Cl Complexa
The use of iodosobenzene diacetate [PhI(OAc)2] for
selective catalytic oxidations, which is readily soluble in
organic media, is still more limited. In one early report,8a it
was shown that ruthenium catalyzes the oxidation of alcohols
by PhI(OAc)2, as demonstrated for saturated aliphatic and
benzylic alcohols. Very recently,5 an effective and convenient
polymer-supported PhI(OAc)2 reagent was developed for the
oxidation of alcohols catalyzed by KBr in aqueous media,
but primary alcohols were further oxidized to carboxylic
acids. The latter report prompts us to communicate our
preliminary results on the usefulness of PhI(OAc)2 for the
efficient and highly chemoselective oxidation of a variety
of alcohols 1 to their carbonyl products 2 (Scheme 1),
Scheme 1. Chemoselective Oxidation of Alcohols 1 by
Iodosobenzene Diacetate, Catalyzed with CrIII Complex A(Cl)
catalyzed by CrIII(salen) complexes under homogeneous
conditions.
Under the mild homogeneous conditions of ca. 20 °C in
CH2Cl2 and a 1:0.1:1.5 ratio of substrate 1:catalyst A(Cl):
PhI(OAc)2, the corresponding R,â-unsaturated carbonyl
products 2 were obtained from the allylic alcohols 1d-n
essentially exclusively in good to excellent yields (Table 1;
entries 4-16). This procedure is a major improvement over
our previously reported6 heterogeneous procedure using
PhIO. No further oxidation of the aldehydes, derived from
the primary alcohols 1k, 1m, and 1n (entries 13, 15, and
16), to the respective carboxylic acid was observed. Oxida-
tion of the saturated (1a,b) and benzylic (1c) substrates to
the corresponding ketones was also achieved (entries 1-3),
but the saturated substrates showed moderate reactivity and
were converted in only 50-60% even after long (21-24 h)
reaction times. Conspicuous is the fact that no ring-opened
product was observed for the cyclopropyl derivative 1b (entry
2), which implys that cyclopropylcarbinyl radicals do not
intervene.10
a Reaction conditions: PhI(OAc)2 (1.5 equiv), catalyst A(Cl) (0.1 equiv),
1
CH2Cl2,, 20 °C. b Determined by H NMR analysis of the crude reaction
mixture with dimethyl isophthalate as internal standard; error ( 5% of the
stated values. mb stands for mass balance. c Yields of the respective carbonyl
products 2 based on 100% conversion of the alcohol 1; <5% epoxy alcohol
was found. In parentheses are given cis:trans ratios of the respective enone
2 (cf. Supporting Information). d Minor amounts of (ca. 10%) ring-expansion
product (ref 12a) were found. e Observed in 95:5 allylic versus aliphatic
regioselectivity.
To assess whether the counterion of the CrIII(salen)
complex affects the chemoselectivity of the allylic alcohol
(10) Halgren, T. A.; Roberts, J. D.; Horner, J. H.; Martinez, F. N.;
Tronche, C.; Newcomb, M. J. Am. Chem. Soc. 2000, 122, 2988-2994.
2774
Org. Lett., Vol. 2, No. 18, 2000

tion is avoided. Indeed, a good mass balance was obtained
for the 0.5-h run in the presence of PPNO (data not shown).
In addition to these catalytic oxidations (Table 2, entries
1-10), stoichiometric reactions with authentic CrV(salen)-
(O) complexes D(TfO) and D(PF6) were examined (entries
11-14). The triflate [D(TfO)] and hexafluorophosphate
[D(PF6)] derivatives were prepared by oxidation of the
respective CrIII(salen) complexes with PhIO or PhI(OAc)2
(Scheme 2). When the stoichiometric conditions were applied
Table 2. Product Studies for the Catalytic and Stoichiometric
Oxidation of the Allylic Alcohol E-1h by Iodosobenzene and Its
Diacetate, Catalyzed by the [CrIII(salen)]X Complexes
convna mba chemoselectivity
oxidant (equiv) additive
A(Cl) (0.1), none
PhI(OAc)2 (1.5) PPNO
(%)
(%)
2h :3h a,b
1
2
29
22
99
96
>95:05
>95:05
Scheme 2. Reaction of [CrIII(salen)]TfO with Iodosobenzene
and Its Diacetate
3
4
A(Cl) (0.1),
PhIO (1.5)
none
PPNO
17
28
97
94
95:05
94:06
5
A(TfO) (0.1),
none
48
(21)
36
65
(87)
91
96:04
(73:27)
58:42
6
7
PhI(OAc)2 (1.5) PPNO
to the model substrate E-1h, nearly equal amounts of enone
E-2h and epoxide E-3h were obtained in the absence (entries
11 and 13) and the presence of PPNO (entries 12 and 14).
These poor chemoselectivities for the stoichiometric oxida-
tions match those for the catalytic ones in the presence of
the PPNO additive (entries 6, 8, and 10). It may, therefore,
be concluded that in the catalytic oxidations mediated by
the [CrIII(salen)]TfO [A(TfO)] and [CrIII(salen)]PF6 [A(PF6)]
complexes, presumably the [CrV(salen)(O)] species D serves
as the actual oxidant.
A(TfO) (0.1),
none
91
(70)
51
50
(66)
93
89:11
(74:26)
54:46
8
9
PhIO (1.5)
PPNO
A(P F 6) (0.1),
none
PPNO
77
49
59
93
68:32
48:52
10 PhIO (1.5)
11 D(TfO) (1.1)
none
40
(28)
55
83
(94)
86
67:33
(55:45)
51:49
12
PPNO
13 D(P F 6) (1.1)
14
none
PPNO
33
93
75
98
61:39
42:58
Since the complexes [CrV(salen)(O)]X are paramagnetic
and possesses radical character, the present allylic oxidation
may follow C-H insertion by way of the established oxygen-
rebound mechanism.11 To scrutinize this mechanistic pos-
sibilty, oxidation experiments were performed with the 18O-
labeled alcohol 18O-1c (Table 3). In the stoichiometric (first
a Determined as in Table 1. In parentheses are given the values for 0.5
h reaction time. b The diastereomer E-3h was found in a erytro:threo ratio
of ca. 85:15 ((5% of the stated value) as determined by 1H NMR analysis
of the crude reaction mixture.
oxidation, product studies have been carried by employing
the allylic alcohol E-1h as the model substrate. CrIII(salen)
complexes with different counterions under a variety of
reaction conditions were used, and the results (Table 2) show
a very high chemoselectivity (g95:5) in favor of the enone
2h for the complex A(Cl) and PhI(OAc)2 (entries 1 and 2).
The chemoselectivity for PhI(OAc)2 is higher than that for
PhIO (entries 3 and 4), irrespective of whether the additive
4-phenylpyridine N-oxide (PPNO) was employed. For the
triflate complex A(OTf), a high (96: 4) chemoselectivity
was obtained for PhI(OAc)2 without the PPNO additive
(entry 5), but a poor (58:42) chemoselectivity was obtained
with PPNO (entry 6); similar results were found for PhIO
(entries 7 and 8). The diminution in the chemoslectivity is
still more pronounced in the case of PF6- complex and PhIO,
for which a low enone/epoxide ratio was obtained with and
without PPNO (entries 9 and 10).
In the absence of PPNO, the high chemoselectivity after
1 h is accompanied by a low mass balance, while after 0.5
h the mass balance is higher but the chemoselectivity is not
as good (entries 5 and 7). The lower mass balance indicates
that the epoxide is decomposed due to the Lewis acidity of
the Cr(salen) complex, which falsifies the chemoselectivity
results. Presumably, the ligated PPNO reduces the Lewis
acidity of the Cr(salen) complex and the epoxide decomposi-
Table 3. Oxidation of Alcohol 18O-1c by the CrV(salen)(O)
Complexes under Stoichiometric and Catalytic Conditions
time convn 18O content
oxidant (equiv)
(h)
(%)
18O-2cb (%)
[CrV(salen)(O)]TfO (1.1)
[CrIII(salen)]Cl (0.1), PhIO (1.5)
[CrIII(salen)]Cl (0.1), PhI(OAc)2 (1.5)
51
8
6
51
95
95
84
89
90
a The 18O content of the initial alcohol 18O-1c was 90 ( 5%. b The 18
O
content was determined by mass-spectral analysis in terms of the relative
intensities for the respective molecular ions (m/z 122 and 124), error ( 5%
of the stated value.
entry) as well as catalytic (second and third entries) oxida-
tions, the initial 18O content (90 ( 5%) of 18O-1c was
essentially retained (g85%) in the carbonyl product 18O-2c.
These 18O-labeling experiments indicate that this oxidation
is not a C-H insertion; otherwise isotopic dilution would
have had to occur. Moreover, the stoichiometric oxidation
of 18O-1c was very slow (first entry) compared to the catalytic
(11) Hamada, T.; Irie, R.; Mihara, J.; Hamachi, K.; Katsuki, T.
Tetrahedron 1998, 54, 10017-10028.
Org. Lett., Vol. 2, No. 18, 2000
2775

Scheme 3. Mechanism for the CrIII(salen)-Catalyzed Oxidation of Allylic Alcohols by Iodosobenzene Diacetate; Cycle I for the
Redox Chemistry and Cycle II for the Lewis Acid Activation
to rationalize the results for the nucleophilic Cl- counterion;
reactions (second and third entries). This finding suggests
that some species other than the [CrV(salen)(O)]+ complex
may be involved in the catalytic oxidation.
consequently, additional species appear to be involved. It
must be stressed that for the synthesis the CrIII(salen)Cl
complex is the more valuable one, because the enone 2 is
produced exclusively in high yields under mild conditions
To provide a clue as to the nature of the active species,
the reaction mixture from the oxidation of the [CrIII(salen)]X
complex by PhI(OAc)2 without any alcohol was analyzed
by ESI-MS (cf. Supporting Information). Also, the mass
peaks m/z 640.4 (8%) and 377.4 (31%) were found, which
correspond to the ions with the compositions [CrIII(salen)-
{PhI(OAc)2}]+ (B+) and [CrIV(salen)(OAc)]+ (C+), in ad-
dition to the mass peak m/z 333.8 (100%) for [CrV(salen)-
(O)]+ (D+). Their formation (Scheme 3) may be rationalized
in terms of ligation of PhI(OAc)2 with the CrIII(salen)
complex A to afford the adduct B and subsequent electronic
reorganization (Cycle I) with elimination of the PhI(OAc)•
radical to generate the CrIV(salen)(OAc) complex (C).
Electron transfer between the latter and the PhI(OAc)•
radical12 leads to CrV(salen)(O) complex (D), an established
oxidant.
-
(Table 1). In contrast, for the TfO- and PF6 counterions,
the chemoselectivity is poor since under most conditions
nearly equal amounts of enone and epoxide are formed
(Table 2).
To account for this counterion-dependent mechanistic
dichotomy, we propose the Lewis acid activation in Cycle
II (Scheme 3). The pertinent product-branching point is the
CrIII(salen) complex B, for which, in the case where X )
Cl, the chromium metal assists the exchange of an acetate
group in the ligated PhI(OAc)2 for a substrate molecule,
alcohol 1, to generate the complex E. Base-catalyzed
deprotonation of the alcoholate affords carbonyl product 2,
with concurrent elimination of iodobenzene and acetate ion
(shown as AcOH in the Cycle II). In fact, when NaOAc is
added in catalytic amounts (20 mol %) as external base, the
reactivity is significantly enhanced (cf. Supporting Informa-
tion).
Unquestionably, a rather complex mechanism (Scheme 3)
operates in this counterion-dependent catalytic oxidation of
alcohols by the [CrIII(salen)]X complex A with PhIO or PhI-
(OAc)2. Nevertheless, the previously presented chromium
complexes B-D, proposed as potential oxidants in the
catalytic redox chemistry of Cycle I (Scheme 3) for the
Acknowledgment. We thank the DFG (SFB 347) and
the Fonds der Chemischen Industrie for financial support.
S.H. thanks the Alexander-von-Humboldt-Foundation for a
postdoctoral fellowship (1999-2000).
-
nonnucleophilic counterions TfO- and PF6 , are not enough
Supporting Information Available: Experimental de-
tails. This material is available free of charge via the Internet
at http://pubs.acs.org.
(12) (a) Mico, A. D.; Margarita, R.; Piancatelli, G. Tetrahedron Lett.
1995, 36, 3553-3556. (b) Creager, S.; Murray, R. W. Inorg. Chem. 1985,
24, 3824-3828.
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