Baeyer-Villiger oxidation under Payne epoxidation conditions

Article abstract of DOI:10.1016/j.tet.2015.08.037

A novel method for the Baeyer-Villiger oxidation of ketones has been developed and optimized. The transformation involves a transition metal-free activation of hydrogen peroxide under Payne epoxidation conditions. Reaction of a ketone with hydrogen peroxide in the presence of a nitrile under mildly basic reaction conditions leads to the corresponding ester. The transformation has been successfully applied to a range of ketones in moderate to excellent yields (30-91%) and good to excellent regioselectivities (7:1 to 20:1).

Full text of DOI:10.1016/j.tet.2015.08.037

Accepted Manuscript
Baeyer-Villiger oxidation under Payne epoxidation conditions
Tyne Bradley, Andrei Dragan, Nicholas Tomkinson
PII:
S0040-4020(15)01229-6
10.1016/j.tet.2015.08.037
TET 27059
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 25 June 2015
Revised Date: 4 August 2015
Accepted Date: 13 August 2015
Please cite this article as: Bradley T, Dragan A, Tomkinson N, Baeyer-Villiger oxidation under Payne
epoxidation conditions, Tetrahedron (2015), doi: 10.1016/j.tet.2015.08.037.
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Baeyer-Villiger oxidation under Payne
epoxidation conditions
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Tyne Bradley, Andrei Dragan and Nicholas C. O. Tomkinson
WestCHEM, Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde,
295 Cathedral Street, Glasgow, G1 1XL, U.K.

1
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Tetrahedron
journal homepage: www.elsevier.com
Baeyer-Villiger oxidation under Payne epoxidation conditions
Tyne Bradley, Andrei Dragan, and Nicholas Tomkinson
WestCHEM, Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, U.K.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel method for the Baeyer-Villiger oxidation of ketones has been developed and optimized.
The transformation involves a transition metal-free activation of hydrogen peroxide under Payne
epoxidation conditions. Reaction of a ketone with hydrogen peroxide in the presence of a nitrile
under mildly basic reaction conditions leads to the corresponding ester. The transformation has
been successfully applied to a range of ketones in moderate to excellent yields (30 to 91%) and
good to excellent regioselectivities (7:1 to 20:1).
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved
.
Baeyer-Villiger oxidation
Payne epoxidation
Peroxy imidic acid
Urea hydrogen peroxide
Nitrile
———
Corresponding author. Tel.: +44-141-548-2276; fax: +44-141-548-5743; e-mail: Nicholas.Tomkinson@strath.ac.uk

2
Tetrahedron
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Since its discovery in 1899,1 the Baeyer-Villiger (BV)
1. Introduction
oxidation has developed to become a stalwart transformation in
synthesis.2,3 Central to the reaction is a source of peroxide, with
meta-chloroperoxybenzoic acid (mCPBA) being a common
commercial oxidant.4 A more convenient oxidant is hydrogen
peroxide, due to its low cost, high oxygen content, ease of
handling and the generation of water as a byproduct. Hydrogen
peroxide is available either as an aqueous solution or in
anhydrous form as a urea complex,5,6 or a sodium percarbonate
salt,7–9 and each of these have found broad application in
synthesis.
For the BV reaction to proceed with hydrogen peroxide as the
oxidant, the peroxide requires activation.3 Many activation
methods involve the use of abundant Sn catalysts, the most
efficient being Sn-zeolites.10–17 Other metals used for the
activation of hydrogen peroxide in the BV oxidation include Se,18
Re,19 Li and Ca borates,20 Pt,21–23 Pd,24 Si polyoxometalates,25 and
Zr.26 Metal-free methods also exist and make use of enzymes,27
ionic liquids,28 carboxylic acids,29 phosphoric acids,30,31 and
bisflavins32 to activate the peroxide. Of these methods, a few
have been shown to be effective for enantioselective BV
oxidations, which include metals such as Pt, Pd or Zr with chiral
ligands,21,24,26 pro-chiral carboxylic acids,29 phosphoric acids,30,31
and bisflavins.32 While there are a variety of methods of
activating hydrogen peroxide, it is still desirable to develop
methods to broaden the transformation, specifically by defining
new pathways to potential asymmetric oxidations.
Scheme 1. Payne epoxidation.
A recent report by Ji described the discovery of convenient and
novel conditions for the Payne epoxidation of alkenes (Scheme 1;
Conditions B).46 Treatment of an alkene (e.g. 1) with an excess of
hydrogen peroxide urea complex in the presence of benzonitrile
and potassium bicarbonate at 50 °C gave the epoxide 2 in 80%
isolated yield after purification by column chromatography. Of
particular note within this transformation was the practicality of
the procedure using a convenient source of peroxide in the
presence of a catalytic amount of base and the mild conditions
under which the reaction proceeded.
Whilst a substantial amount of work has been devoted to the
development of the Payne epoxidation, relatively little work has
been undertaken in exploiting the oxidation potential of the
peroxy imidic acid intermediates (e.g. 3) in alternative oxidation
processes. This is specifically the case for the BV reaction where
the isolated work of Ruiz investigated specialized heterogeneous
magnesium,47 or magnesium/aluminum hydrotalcite supports as
catalysts for the transformation.48,49 This work showed the
reaction of a ketone (e.g. 4) in benzonitrile solvent with aqueous
hydrogen peroxide, a heterogeneous catalyst and the surfactant
DBS could lead to the corresponding ester or lactone (e.g. 5)
(Scheme 2). Whilst effective, the need to prepare the catalyst
through specific protocols and the use of benzonitrile as the
solvent has limited the uptake of this method by the synthetic
community. Within this current work we develop conditions for
the activation of hydrogen peroxide with a nitrile which can be
applied to the BV oxidation providing a convenient and reliable
method for the preparation of both esters and lactones from the
corresponding ketone.
A simple method using nitriles to activate hydrogen peroxide
under mildly basic reaction conditions was introduced by Payne
in 1961 which resulted in an effective process for the epoxidation
of alkenes (Scheme 1; Conditions A).33,34 Reaction of aqueous
hydrogen peroxide (50%) with alkene 1 in the presence of
benzonitrile at pH 9.5–10 gave the epoxide 2 in 70% isolated
yield. This use of nitriles for the activation of hydrogen peroxide
represents a convenient and simple reaction which has since been
developed to provide an effective and reliable method for alkene
oxidation,35–39 which has been extended to asymmetric
epoxidations,40,41 and the formation of chiral oxaziridines.42,43
Payne proposed the epoxidation proceeded via formation of a
highly reactive peroxy imidic acid intermediate 3. Whilst there
has been overwhelming acceptance of this suggestion, peroxy
imidic acids are highly reactive and have not been isolated due to
decomposition via Radziszewski oxidation leading to the
corresponding amide.44 A study by Vacque et al. using attenuated
total reflectance (ATR) coupled with Fourier transform infrared
(FTIR) and FT Raman spectroscopy provided important
experimental evidence toward the existence of such a peroxy
imidic acid intermediate.45
Scheme 2. Heterogeneous Baeyer-Villiger oxidation
in benzonitrile
2. Results and discussion
2.1. Initial result
.
Our investigations began by the reaction of cyclohexanone 4
with urea hydrogen peroxide complex under conditions reported
by Ji for alkene epoxidation (Scheme 3).46 We were delighted to
discover that ε-caprolactone 5 was formed in 38% conversion by
1H NMR spectroscopy after 48 hours. Repeating the reaction in
the absence of KHCO3, or H2O2·urea, or PhCN resulted in no
product 5 being formed showing that all components added were
necessary to bring about the transformation.

3
hydrogen peroxide complex was an integral part of the process.
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Reducing the stoichiometry of both the nitrile (10%; entry 11)
and the peroxide (25%; entry 7) also proved detrimental to the
transformation. Increasing the amount of base resulted in an
increased consumption of starting material, but this was
accompanied by decomposition of the product as confirmed
against the internal standard (entries 4 and 14).
Scheme 3. Baeyer-Villiger oxidation using benzonitrile
Careful examination of the crude reaction mixtures showed a
small amount of the ε-caprolactone 5 was undergoing solvolysis
with methanol to give the corresponding ε-hydroxy ester. We
therefore considered reducing the nucleophilicity of the alcoholic
solvent to shut down this unwanted side reaction and investigated
the use of fluorinated alcohols as the reaction medium.
Interestingly, it has been shown that fluorinated alcohols can be
used to accelerate reactions involving peroxides.50,51 It has also
been shown that fluorinated alcohols have the ability to activate
hydrogen peroxide,52 which has been specifically exploited in
oxidation reactions. Examination of hexafluoroisopropanol
(HFIP) as an alternative reaction solvent resulted in an equivalent
conversion of cyclohexanone 4 to the ester 5 (42%; entry 12).
Importantly, within this transformation no reaction of 5 with the
for peroxide activation.
2.2. Optimization of the Baeyer-Villiger reaction
Based upon the excellent result outlined in Scheme 3, we
elected to optimize the reaction conditions for this BV
transformation. Table 1 provides a selection of the data obtained
during this optimization process examining the concentration,
base, peroxide source, solvent, reaction stoichiometry and
temperature.
To accelerate the optimization process initial experiments
were conducted in methanol-d4 monitoring by 1H NMR
spectroscopy and using 1,4-dinitrobenzene as an internal
standard. Both increasing (entry 2; 30%) and decreasing (entry 3;
33%) the concentration of the reaction resulted in a lower
conversion under the conditions examined. Reducing the
temperature significantly slowed down the reaction (14%; entry
5), whilst performing the reaction at reflux had negligible effect
on the conversion (44%; entry 6). Altering the peroxide source to
H2O2 (30% v/v aqueous solution) resulted in a considerably
worse transformation (31%; entry 9) suggesting that the urea
1
solvent was observed by H NMR spectroscopy. Changing the
solvent to trifluoroethanol (TFE) showed
a significantly
improved conversion (76%; entry 13) which was confirmed by
isolation of the product after aqueous workup and column
chromatography (70%). Once again, control experiments in the
absence of benzonitrile and/or base (KHCO3) confirmed that both
were necessary for the reaction to proceed efficiently in TFE.

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Tetrahedron
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Table 1. Optimization of the Baeyer-Villiger reaction produced via Scheme 3.a
Entry
H2O2 source
(equiv)
KHCO3
(equiv)
Nitrile
(equiv)
Solvent
(M)
T
(°C)
Conversion
(%)b
1
2
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (3.0)
H2O2•urea (10.0)
H2O2 30% (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
H2O2•urea (6.0)
0.2
0.2
0.2
0.5
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.5
0.1
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
PhCN (3.0)
PhCN (1.1)
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
PhCN (6.0)
MeOH (0.5)
CD3OD (1.0)
CD3OD (0.2)
CD3OD (0.5)
CD3OD (0.5)
CD3OD (0.5)
CD3OD (0.5)
CD3OD (0.5)
CD3OD (0.5)
CD3OD (0.5)
CD3OD (0.5)
HFIP (0.5)
50
50
50
50
25
65
50
50
50
50
50
50
50
50
50
38
30
3
33
4
60c
5
14
6
44
7
25
8
47
9
31
10
11
12
13
14
15
21
10
42
TFE (0.5)
76 (70%)d
95c
37
TFE (0.5)
TFE (0.5)
a Reaction of cyclohexanone (1 mmol) for 48 h.
b Conversion was monitored by 1H NMR against an internal standard (1,4-dinitrobenzene).
c Product decomposition observed.
d Isolated yield after aqueous workup and purification by column chromatography.

5
Table 2. Substrate scope for the Baeyer-Villiger oxidation.
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a Isolated yield.
b Ratio between regioisomeric products (major isomer shown), determined by 1H NMR spectroscopy on crude reaction mixture.
c Conversion to single product monitored by 1H NMR against an internal standard (1,4-dinitrobenzene).
d Average of two runs.
2.3. Substrate scope
giving the expected lactone in an excellent 85% yield in just 18 h
(entry 11). Whilst acyclic ketones were reluctant substrates, it did
prove possible to react pinacolone 28 to give the expected
product 29 after extended reaction times (49%, 144 h; entry 13)
suggesting further optimization would be required to bring about
efficient transformations for this class of substrate.
Having optimized the reaction conditions we examined some
of the scope and limitations of the process (Table 2). The
transformation exhibited typical features of the BV oxidation in
terms of relative reactivity, regioselectivity and stereoselectivity.
Reactions proceeded well and in good yield for a series of
cyclohexanone derivatives (entries 1–9). Control of the
regioselectivity was particularly high with more substituted
groups preferentially migrating (entries 5–7 and 9). Increasing
the steric congestion around the reactive carbonyl slowed down
the reaction, but these transformations remained clean and simply
required a longer reaction time (entries 6 and 9). Retention of
configuration of the migrating carbon was supported by the
optical rotation of the product derived from (–)-menthone 20 as
the substrate (entry 9). Cyclopentanone 22 reacted slower (30%,
72 h; entry 10) when compared to cyclohexanone 4 (70%, 48 h;
entry 1), whereas cyclobutanone 24 reacted substantially quicker,
3. Conclusion
In summary, a novel BV reaction has been developed and
optimized. The transformation uses urea hydrogen peroxide
complex as a convenient source of peroxide which is activated by
benzonitrile and a catalytic amount of base (KHCO3) in a
fluorinated alcohol to form the active peroxy imidic acid in situ.
The reaction proceeds in moderate to good yields, with excellent
and predictable regioselectivity and migration proceeding with
retention of configuration. Given the marked success in
developing asymmetric variants of the Payne epoxidation, we

6
Tetrahedron
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4.4. 5-Methyloxepan-2-one (7)54
believe these results pave the way for exploring novel
asymmetric BV oxidation processes.
Lactone 7 was prepared according to General Procedure 1
4. Experimental section
using 4-methylcyclohexanone 6 (0.49 mL, 4.0 mmol). The title
compound was isolated as a colourless oil (421 mg, 3.3 mmol,
82%). 1H NMR (400 MHz, CDCl3) δ 4.28 (ddd, J = 12.9, 5.7, 1.9
Hz, 1H), 4.17 (dd, J = 12.7, 10.4 Hz, 1H), 2.71–2.56 (m, 2H),
1.98–1.83 (m, 2H), 1.82–1.71 (m, 1H), 1.50 (dtd, J = 15.2, 10.8,
1.8 Hz, 1H), 1.33 (dtd, J = 13.9, 11.5, 2.4 Hz, 1H), 0.99 (d, J =
6.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 176.3, 68.3, 37.4,
35.4, 33.4, 30.9, 22.3; LRMS (CI) m/z 129.0 [M+H]+; HRMS
(SIR-CI) calculated for C7H13O2 [M+H]+ 129.0910, found
129.0910; IR (ATR)/cm–1 2988, 2901, 1717.
4.1. General experimental details
Commercially available solvents and reagents were used
without further purification or drying and all reactions were
performed under an argon atmosphere. Flash chromatography
was carried out using Merck Kieselgel 60 H silica. Analytical
thin layer chromatography was carried out using
aluminum-backed plates coated with Merck Kieselgel 60 GF254
that were visualized under UV light (at 254 nm) or stained using
KMnO4. Nuclear magnetic resonance (NMR) spectra were
4.5. 5-(tert-Butyl)oxepan-2-one (9)55
recorded on a Bruker Avance III or
a Bruker Avance
spectrometer, operating at 400 MHz (1H) and 101 MHz (13C),
respectively. Chemical shifts were reported in parts per million
Lactone 9 was prepared according to General Procedure 1
using 4-tert-butylcyclohexanone 8 (617 mg, 4.0 mmol). The title
compound was isolated as a white solid (554 mg, 3.3 mmol,
81%). m.p. 49–50 °C (lit. 49 °C);55 1H NMR (400 MHz, CDCl3)
δ 4.32 (ddd, J = 12.9, 5.9, 1.8 Hz, 1H), 4.14 (dd, J = 12.9, 10.4
Hz, 1H), 2.69 (ddd, J = 14.3, 7.5, 1.4 Hz, 1H), 2.61–2.51 (m,
1H), 2.13–1.95 (m, 2H), 1.58–1.44 (m, 1H), 1.38–1.28 (m, 2H),
0.88 (s, 9H); 13C NMR (101 MHz, CDCl3) δ 176.5, 68.8, 50.9,
33.6, 33.1, 30.5, 27.6, 23.9; LRMS (CI) m/z 171.1 [M+H]+;
HRMS (FTMS-NSI) calculated for C10H19O2 [M+H]+ 171.1380,
found 171.1377; IR (ATR)/cm–1 2987, 2961, 1717.
1
(ppm) in the scale relative to CHCl3, 7.26 ppm for H NMR and
77.16 for 13C NMR. Multiplicities are abbreviated as: s, singlet;
d, doublet; app d, apparent doublet; t, triplet; app t, apparent
triplet; q, quartet; dd, doublet of doublets; app dd, apparent
doublet of doublets; app dq, apparent doublet of quartets; ddd,
doublet of doublets of doublets; dtd, doublet of triplets of
doublets; t app d, triplet of apparent doublets; m, multiplet.
Coupling constants are measured in Hertz (Hz). Low-resolution
mass spectra (LRMS) were recorded on an Agilent 7890A GC
system, equipped with a 30 m DB5MS column connected to a
5975C inert XL CI MSD with Triple-Axis Detector.
High-resolution mass spectra (HRMS) were obtained courtesy of
the EPSRC National Mass Spectrometry Facility at Swansea
University, U.K. Infrared spectra were recorded on a Shimadzu
IRAffinity-1 equipped with ATR (Attenuated Total Reflectance)
and were reported in cm–1. Melting points were obtained on a
Stuart SMP11 device. In vacuo refers to evaporation under
reduced pressure using a rotary evaporator connected to a
diaphragm pump, followed by the removal of trace volatiles
using a high vacuum (oil) pump.
4.6. 5-Phenyloxepan-2-one (11)56
Lactone 11 was prepared according to General Procedure 1
using 4-phenylcyclohexanone 10 (697 mg, 4.0 mmol). The title
compound was isolated as a white solid (629 mg, 3.3 mmol,
83%). m.p. 95–96 °C (lit. 100–101 °C);56 1H NMR (400 MHz,
CDCl3) δ 7.36–7.29 (m, 2H), 7.26–7.21 (m, 1H), 7.21–7.16 (m,
2H), 4.40 (ddd, J = 13.0, 5.3, 2.3 Hz, 1H), 4.32 (ddd, J = 13.0,
10.0, 1.0 Hz, 1H), 2.90–2.71 (m, 3H), 2.20–1.98 (m, 3H), 1.91–
1.80 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 176.0, 145.1,
128.9, 127.0, 126.7, 68.4, 47.4, 36.9, 33.8, 30.5; LRMS (CI) m/z
191.1 [M+H]+; HRMS (FTMS-NSI) calculated for C12H15O2
[M+H]+ 191.1067, found 191.1064; IR (ATR)/cm–1 2960, 2943,
1740.
4.2. General Baeyer-Villiger procedure (General Procedure 1)
To a flame dried crimp top vial under argon, KHCO3 (80 mg,
0.8 mmol, 0.2 equiv) was weighed, followed by urea hydrogen
peroxide (564 mg, 24 mmol, 6.0 equiv). The ketone (4.0 mmol,
1.0 equiv) was added at this stage if it was a solid. The vial was
then sealed and evacuated, followed by backfilling with argon
(repeated three times). Afterward, the solvent (8.0 mL),
benzonitrile (2.48 mL, 24 mmol, 6.0 equiv) and, if it was a liquid,
the ketone (4.0 mmol, 1.0 equiv), were added via syringe. The
reaction was allowed to run for the specified time at 50 °C, after
which it was cooled down to room temperature. The pressure was
released with a needle, then the vial was opened. The mixture
was diluted with CH2Cl2 (40 mL) and water (20 mL). The layers
were separated and the resulting aqueous solution was extracted
with CH2Cl2 (2 × 40 mL). The combined organic layers were
dried (MgSO4), concentrated in vacuo, and the crude product was
subjected to flash chromatography on silica gel (5:1 petroleum
ether:EtOAc) to afford the corresponding product(s).
4.7. 7-Methyloxepan-2-one (13)53
Lactone 13 was prepared as a 7:1 mixture of regioisomers,
according to General Procedure 1 using 2-methylcyclohexanone
12 (0.49 mL, 4.0 mmol). The title compound was isolated after
column chromatography as a colourless oil (468 mg, 3.7 mmol,
91%, 15:1 mixture of regioisomers). 1H NMR (400 MHz, CDCl3)
δ 4.43 (app dq, J = 8.3, 6.4 Hz, 1H major), 4.31–4.15 (m, 2H
minor), 2.72–2.52 (m, 2H major, 1H minor), 1.99–1.83 (m, 3H
major, 2H minor), 1.72–1.51 (m, 3H major, 4H minor), 1.34 (d, J
= 6.4 Hz, 3H major), 1.18 (d, J = 6.7 Hz, 3H minor); 13C NMR
(101 MHz, CDCl3, major isomer) δ 175.7, 76.9, 36.4, 35.1, 28.4,
23.0, 22.7; LRMS (CI) m/z 129.0 [M+H]+; IR (ATR)/cm–1 2987,
2901, 1716.
4.8. 7-Ethyloxepan-2-one (15)57
4.3. ε-Caprolactone (5)53
Lactone 15 was prepared as a 15:1 mixture of regioisomers,
according to General Procedure 1 using 2-ethylcyclohexanone 14
(0.56 mL, 4.0 mmol). The title compound was isolated after
column chromatography as a colourless oil (410 mg, 2.9 mmol,
72%, 12:1 mixture of regioisomers). 1H NMR (400 MHz, CDCl3)
δ 4.26–4.24 (m, 2H minor), 4.16 (t app d, J = 7.8, 5.3 Hz, 1H
major), 2.71–2.54 (m, 2H major), 2.49–2.39 (m, 1H minor) ,
2.03–1.84 (m, 3H major, 2H minor), 1.80–1.67 (m, 1H major, 2H
minor), 1.66–1.51 (m, 4H major, 2H minor), 1.47–1.37 (m, 2H
Lactone 5 was prepared according to General Procedure 1
using cyclohexanone 4 (0.44 mL, 4.0 mmol). The title compound
was isolated as a colourless oil (321 mg, 2.8 mmol, 70%). H
NMR (400 MHz, CDCl3) δ 4.28–4.17 (m, 2H), 2.71–2.57 (m,
2H), 1.90–1.80 (m, 2H), 1.81–1.69 (m, 4H); 13C NMR (101
MHz, CDCl3) δ 176.3, 69.4, 34.7, 29.4, 29.1, 23.1; LRMS (CI)
m/z 115.0 [M+H]+; IR (ATR)/cm–1 2988, 2901, 1726.
1

7
4.14. Rel-(1R,3R,6S,8S)-4-Oxatricyclo[4.3.1.13,8]undecan-5-
minor) 0.98 (t, J = 7.4 Hz, 3H major), 0.95 (t, J = 7.6 Hz, 3H
minor); 13C NMR (101 MHz, CDCl3, major isomer) δ 175.9, 81.9,
35.1, 34.3, 29.5, 28.5, 23.2, 10.0; LRMS (CI) m/z 143.1 [M+H]+;
HRMS (TOF-EI) calculated for C8H14O2 [M+•] 142.0994, found
142.0997; IR (ATR)/cm–1 2970, 2931, 1721.
ACCEPTED MANUSCRIPT
one (27)61
Lactone 27 was prepared according to General Procedure 1
using 2-adamantanone 26 (600 mg, 4.0 mmol). The title
compound was isolated as a white solid (545 mg, 3.3 mmol,
82%). m.p. >250 °C (lit. 288–290 °C);61 1H NMR (400 MHz,
CDCl3) δ 4.51–4.43 (m, 1H), 3.06 (app t, J = 5.8 Hz, 1H), 2.14–
1.88 (m, 8H), 1.86–1.78 (m, 2H), 1.77–1.70 (m, 2H); 13C NMR
(101 MHz, CDCl3) δ 179.1, 73.3, 41.4, 35.9, 33.9, 31.1, 26.0;
LRMS (CI) m/z 167.0 [M+H]+; HRMS (FTMS-NSI) calculated
for C10H15O2 [M+H]+ 167.1067, found 167.1063; IR (ATR)/cm–1
2988, 2911, 1717.
4.9. 7-Phenyloxepan-2-one (17)58
Lactone 17 was prepared as a 20:1 mixture of regioisomers,
according to General Procedure 1 using 2-phenylcyclohexanone
16 (697 mg, 4.0 mmol). The title compound was isolated after
column chromatography as a white solid (683 mg, 3.6 mmol,
90%, 20:1 mixture of regioisomers). m.p. 68–69 °C (lit. 67–68
°C);58 1H NMR (400 MHz, CDCl3) δ 7.60–7.21 (m, 5H major,
5H minor), 5.29 (app d, J = 9.4 Hz, 1H major), 4.40–4.35 (m, 2H
minor), 3.91–3.86 (m, 1H minor), 2.77 (dd, J = 7.7, 3.7 Hz, 2H
major), 2.18–1.97 (m, 4H major, 4H minor), 1.84–1.64 (m, 2H
major, 2H minor); 13C NMR (101 MHz, CDCl3) δ 175.0, 140.9,
128.7, 128.3, 126.0, 82.3, 37.6, 35.1, 28.8, 23.0; LRMS (CI) m/z
191.1 [M+H]+; HRMS (FTMS-NSI) calculated for C12H15O2
[M+H]+ 191.1067, found 191.1063; IR (ATR)/cm–1 2928, 2868,
1717.
5. Acknowledgements
The authors thank the EPSRC and University of Strathclyde
for financial support and the EPSRC Mass Spectrometry Service,
Swansea for high-resolution spectra.
6. References and notes
1. Baeyer, A.; Villiger, V. Ber. Dtsch. Chem. Ges. 1899, 32, 3625–3627.
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4.10. 1,4,8-Trioxaspiro[4.6]undecan-9-one (19)
Lactone 19 was prepared according to General Procedure 1
using 1,4-dioxaspiro[4.5]decan-8-one 18 (625 mg, 4.0 mmol).
The title compound was isolated as a colourless oil (244 mg, 1.4
1
mmol, 36%). H NMR (400 MHz, CDCl3) δ 4.28–4.19 (m, 2H),
7. McKillop, A.; Sanderson, W. R. Tetrahedron 1995, 51, 6145–6166.
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3.96–3.91 (m, 4H), 2.70–2.60 (m, 2H), 2.00–1.92 (m, 2H), 1.91–
1.81 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 175.5, 107.8, 64.8,
64.3, 39.0, 32.7, 28.8; LRMS (CI) m/z 173.1 [M+H]+; HRMS
(FTMS-NSI) calculated for C8H13O4 [M+H]+ 173.0808, found
173.0804; IR (ATR)/cm–1 2970, 2889, 1729.
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4.11. (4R,7S)-7-Isopropyl-4-methyloxepan-2-one (21)59
Lactone 21 was prepared according to General Procedure 1
using (–)-menthone 20 (0.69 mL, 4.0 mmol). The title compound
was isolated as a colourless oil (344 mg, 2.0 mmol, 51%).
[α]ꢀꢁꢂ –20.6 (c 0.72, CHCl3), lit. –19.7;59 1H NMR (400 MHz,
CDCl3) δ 4.03 (app dd, J = 9.2, 4.5 Hz, 1H), 2.65–2.39 (m, 2H),
2.03–1.77 (m, 4H), 1.66–1.52 (m, 1H), 1.35–1.21 (m, 1H), 1.03
(d, J = 6.7 Hz, 3H), 0.97 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.8 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 175.1, 84.9, 42.7, 37.6, 33.5,
31.1, 30.5, 24.1, 18.5, 17.3; LRMS (CI) m/z 171.1 [M+H]+;
HRMS (FTMS-NSI) calculated for C10H19O2 [M+H]+ 171.1380,
found 171.1376; IR (ATR)/cm–1 2970, 2928, 1722.
18. Zhang, X.; Ye, J.; Yu, L.; Shi, X.; Zhang, M.; Xu, Q.; Lautens, M.
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4.12. Tetrahydro-2H-pyran-2-one (23)60
Lactone 23 was prepared according to General Procedure 1
using cyclopentanone 22 (0.36 mL, 4.0 mmol). The title
compound was isolated as a colourless oil (118 mg, 1.1 mmol,
30%). 1H NMR (400 MHz, CDCl3) δ 4.38–4.29 (m, 2H), 2.54 (t,
J = 7.1 Hz, 2H), 1.97–1.78 (m, 4H); 13C NMR (101 MHz,
CDCl3) δ 171.5, 69.5, 29.9, 22.4, 19.2; LRMS (CI) m/z 104.0
[M+H]+; IR (ATR)/cm–1 2970, 2934, 1724.
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4.13. Dihydrofuran-2(3H)-one (25)60
Lactone 25 was prepared according to General Procedure 1
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compound was isolated as a colourless oil (292 mg, 3.4 mmol,
1
85%). H NMR (400 MHz, CDCl3) δ 4.33 (t, J = 7.0 Hz, 2H),
2.57–2.44 (m, 2H), 2.35–2.18 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 177.8, 68.6, 27.9, 22.3; LRMS (CI) m/z 87.0 [M+H]+;
IR (ATR)/cm–1 2988, 2901, 1763.

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Baeyer-Villiger oxidation under Payne epoxidation conditions
Tyne Bradley,a Andrei Dragan,a and Nicholas C. O. Tomkinsona,*
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WestCHEM, Department of Pure and Applied Chemistry, Thomas Graham Building, University of Strathclyde, 295 Cathedral Street, Glasgow,
G1 1XL, U.K.
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