Visible Light-Mediated Photochemical Reactions of 2-(2′-Alkenyloxy)cycloalk-2-enones

Article abstract of DOI:10.1021/acs.joc.0c01501

The title compounds were prepared, and their reactivity was studied upon sensitized irradiation at λ = 420 nm. Thioxanthen-9-one was employed as the sensitizer at a loading of 10 mol % in small-scale reactions and of 2.5 mol % on a larger scale. Cyclohex-

Full text of DOI:10.1021/acs.joc.0c01501

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Article
Visible Light-mediated Photochemical
Reactions of 2-(2’-Alkenyloxy)cycloalk-2-enones
Raphaela Graßl, Christian Jandl, and Thorsten Bach
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01501 • Publication Date (Web): 27 Jul 2020
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Visible Light-mediated Photochemical Reactions of 2-(2’-
Alkenyloxy)cycloalk-2-enones
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Raphaela Graßl, Christian Jandl, Thorsten Bach*
Department Chemie and Catalysis Research Center (CRC), Technische Universität München,
Lichtenbergstr. 4, 85747 Garching, Germany
Corresponding Author
*Email: thorsten.bach@ch.tum.de
ABSTRACT
R1
O
R1
R2 = H
O
R R
R2
R2
R1
O
O
O O
O
R

R1
R3
O
R
5
6
R2
R3 R3
R3
R1,R2 = Me
R = H
O
H
1R2
O
R
O
h ( = 420nm)
thioxanthen-9-one
(CH Cl )
R
R3
O
R3
O
2R1
R3
2
2
R
R
O
The title compounds were prepared and their reactivity was studied upon sensitized irradiation at
= 420 nm. Thioxanthen-9-one was employed as the sensitizer at a loading of 10 mol% in small

scale reactions and of 2.5 mol% on larger scale. Cyclohex-2-enones substituted by a 2’-
propenyloxy, 2’-butenyloxy, 2’-pentenyloxy, or 2’-methyl-2’-propenyloxy group in 2-position
gave the products of an intramolecular [2+2] photocycloadditon. The reaction proceeded with
high regioselectivity (crossed product) and perfect diastereoselectivity (nine examples, 34%-99%
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yield). If the olefin in the tether was trisubstituted (3’-methyl-2’-butenyloxy) no cycloaddition
was observed. Rather, a cyclization with subsequent hydrogen abstraction occurred (three
examples, 65-86% yield). The results are consistent with a reaction course via a triplet enone
intermediate and the formation of a 1,4-diradical by an initial cyclization. The analogous
cyclopent-2-enones were less prone to an intramolecular reaction. Instead, decomposition or
intermolecular [2+2] photocycloaddition reactions prevailed. In the latter event, two main
products were identified (three examples, 30-43% yield) resulting either from a head-to-head
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[2+2]-photodimerization or from a two-fold [2+2] photocycloaddition of the enone to the olefin.
The latter reaction sequence generated pentacyclic products with a central [1,5]dioxocane ring.
The structure assignment of the two product types was corroborated by single crystal X-ray
analysis.
INTRODUCTION
1
Like most intramolecular cycloadditions, the [2+2] photocycloaddition benefits from an
improved regioselectivity if the two reaction partners are linked by a suitable tether. Cyclic -
2
unsaturated ketones represent the most frequently used chromophores in these reactions and the
3
preferred position for attachment of a tether is the - or the -position. For an -substituted
enone I (Scheme 1) the number m of atoms in the tether governs the regioselectivity. A
preference towards a parallel approach of the two olefins is observed if three or four atoms link
the two olefinic groups (m = 3, 4) and the photocycloaddition products II are frequently referred
to as straight products. If the tether is short (m = 2) photocycloaddition products III prevail in
which the two olefins approach each other in a crossed fashion. The regioselectivity can be
4
understood by the mechanistic course of the reaction which involves an initial attack of the
olefin on the photoexcited enone to a 1,4-diradical intermediate (vide infra). The first step of the
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cycloaddition is consequently a cyclization in which the formation of five-membered rings is
preferred.
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SCHEME 1. Regioselectivity in the Intramolecular [2+2] Photocycloaddition of -Substituted
Enones I and Possible Reaction Pathways of -Allyloxy-substituted Enones IV
3,4
m
O
O
O
2
h
h

m = 3,4
m = 2
II (straight)
I
III (crossed)
O
R1
O
R
O
 [2+2] photodimerization
R2

R1
O

cyclization/intramolecular
hydrogen abstraction
R2
R3
R3
R
IV
V
 crossed [2+2] photocycloaddition
2
-(2’-Alkenyloxy)cycloalk-2-enones with the general structure IV represent a relatively
unexplored compound class in [2+2] photocycloaddition chemistry. Ikeda et al. performed
experiments with three 2-allyloxycyclohex-2-enones as substrates employing a high-pressure
6
mercury lamp as the light source and acetone as the solvent. Crossed products (general structure
V) were obtained in 53-63% yield and subsequent transformations of these products were
intensively studied. We have now looked at an expanded set of substrates with two main
objectives: (a) Instead of UV light it was attempted to perform the photochemical reactions with
visible light. To this end, a suitable sensitizer was required which absorbs in the visible range and
which does not lead to any side reactions. While visible-light mediated, sensitized reactions of
7
styrenes and related compounds have recently received broad attention, studies with cyclic
8
enones have remained scarce. (b) It was expected that other reaction pathways might be feasible
depending on the structure of the chromophore and the substitution pattern of the olefin. Most
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importantly, [2+2] photodimerization and hydrogen abstraction were foreseen as competing
reactions which would in turn lead to intriguing new structures. The results of our experimental
work are summarized in this account.
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RESULTS AND DISCUSSION
Figure 1 provides an overview about the compounds we employed in the present study. With
regard to the olefin component, three 2’-alkenyloxy groups were employed, i.e. a 2’-propenyloxy
(
allyloxy) group (substrates 1), a 2’-methyl-2’-propenyloxy (methallyloxy) group (substrates 2),
and a 3’-methyl-2’-butenyloxy (prenyloxy) group (substrates 3). With regard to the enone
component, some substituted cyclic enones (substrates b, c, d, f) were probed as starting
materials apart from the unsubstituted cyclohex-2-enones (substrates a) and cyclopent-2-enones
(
substrates e). Cyclohex-2-enones with (Z)- and (E)-substituted 2’-alkenyloxy groups were also
prepared but will be discussed in a later section.
O
R
1
2
2
R1
1a R = H
R = Me R , R = H
R , R = H
O
1
2
2
a
2'
R2
1
2
3a R = H
R , R = Me
analogously
O
O
O
O
O
1b-3b
1c-3c
1d-2d
1e-3e
1f-3f
FIGURE 1. Overview about the 2-('-alkenyloxy)cycloalk-2-enones 1-3 employed in this study
Since the synthesis of 2-('-alkenyloxy)-4,4-dimethylcyclohex-2-enones was low yielding only
substrates 1d and 2d were synthesized but not 3d. In general, three approaches towards the [2+2]
photocycloaddition precursors were taken. Starting from cyclic 1,2-diketones the alkenyloxy
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group was introduced either by condensation with the respective allylic alcohol under acidic
conditions (method A: TsOH in cyclohexane, reflux)6,10 or by nucleophilic substitution of an allyl
1
1
bromide via the enolate (method B: K CO in DMF, room temperature). Along these lines, 1,2-
2
3
1
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diketones 4a, 4b, 4e, and 4f (Figure 2) served as precursors for the respective 2-('-
alkenyloxy)cycloalk-2-enones 1a-3a, 1b-3b, 1e-3e, and 1f-3f. For the synthesis of substituted
cyclohexenones 1c-3c and 1d, 2d epoxides 4c and 4d served as starting materials, which
underwent nucleophilic substitution in position C2 when treated with an excess of allylic alcohol
1
2
under basic conditions (method C: NaH or KOH as base). As mentioned above the reaction
gave low yields (6-12%) when applied to epoxide 4d which limited the supply of starting
material. Reasons for the inefficiency of the procedure were (a) difficulties in removing excess
allylic alcohol and (b) formation of a side product (see the SI for further details) by dimerization
of the epoxide. Since the emphasis of the study was on the [2+2] photocycloaddition chemistry
alternative routes to the substituted enones were not pursued. With the exception of compounds
1
a, 2a, and 1c, 2-('-alkenyloxy)cycloalk-2-enones have not been previously employed in
photochemical reactions.
O
O
O
O
O
O
2
2
O
O
O
O
4a
4b
4c
4d
O
S
O
O
4e
4f
5
FIGURE 2. Structure of starting materials 4 for the synthesis of 2-(2’-alkenyloxy)cycloalk-2-
enones and structure of thioxanthen-9-one (5)
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Preliminary photochemical studies were performed with substrate 1a. Its triplet energy was

1
determined from phosphorescence experiments (77 K, CH Cl ) as E = 235 kJ mol . Since a
2
2
T

1
23
wavelength of  = 400 nm corresponds to an energy of ca. 300 kJ Es (1 Es = 6.022 × 10
0
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photons) it seemed feasible to promote the [2+2] photocycloaddition with visible light upon
judicious choice of a sensitizer. In this regard, parent thioxanthen-9-one (5) and its derivatives
represent an excellent option and have been nicely exploited by Booker-Milburn and co-workers
8b
in [2+2] photocycloaddition reactions on large scale. In recent work on visible light-mediated
reactions, we have also seen that catalyst loadings can be as low as 1 mol% for a thioxanthone
1
3
sensitizer. Experiments with a selection of potential sensitizers (see the SI for details)
confirmed the suitability of thioxanthen-9-one (5) as the catalyst in the planned reaction (E =
T

1 14
2
68 kJ mol ). Dichloromethane was established as the preferred solvent and there was no
improvement in selectivity if the reaction was performed at low temperature. The reactions were
run on small scale (50-200 mol substrate, c = 10 mM) at a wavelength of  = 420 nm (16
fluorescent lamps with an emission maximum at  = 420 nm, for the emission spectrum, see the
SI) and yields of product 8a (Scheme 2) were consistently around 70% irrespective of whether
2
.5, 5, or 10 mol% of 5 were used. Indeed, the low molecular weight (212 Da) of thioxanthen-9-
one (5) made it relatively difficult to measure the exact quantity. Iridium catalysts (2.5 mol%)
with a much higher molecular weight performed similar to 5 and there was a correlation between
the reaction time and the triplet energy of the catalyst. Sensitizers with a triplet energy E > 250
T

1
kJ mol led to a complete conversion after 2.5 hours. The reaction time increased with a decrease
1 15
in triplet energy. The reaction with Ir(ppy) (E = 231 kJ mol ) for example required five hours
3
T
before no substrate was detected by TLC. The ruthenium complex Ru(bpy) (PF ) (E = 193 kJ
3
6 2
T

1 16
mol ) did not promote the reaction and there was also no reaction in the absence of a sensitizer.
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SCHEME 2. Mechanistic Proposal for the Course of the Sensitized Intermolecular [2+2]
Photocycloaddition of Cyclohex-2-enone 1a
O
h ( = 420 nm), ISC
5 (T1)
O *
O
O
5
1
1
1
1
1
1
1
1
1
1
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1a
1a (T1)
ET = 237 kJ mol
1
O
O
O
O
O
O
or
H
H
8a
6
7
The formation of crossed product 8a can be easily understood by assuming an energy transfer
from the triplet state T of thioxanthone 5 to substrate 1a. Intermediate 5 (T ) is populated with
1
1
1
7
high efficiency by direct excitation and rapid intersystem crossing (ISC). An exothermic triplet
energy transfer occurs by a spin-allowed, mutual electron-electron exchange process, often
1
8
referred to as sensitization or triplet sensitization. Upon energy transfer, the reactive triplet state
1a (T ) is generated which is * in character and which is prone to undergo double bond
1
4
5
addition. Subsequently, 1,4-diradicals 6 and 7 are formed by five-membered ring closure and
both represent potential precursors to product 8a. The low reduction potentials of -unsaturated
enones (E1/2red  2.0 V) render any single electron transfer (photoredox) processes not viable.
19
Several allyloxy- and methallyloxy-substituted cycloalk-2-enones reacted similar to substrate 1a
and the results are summarized in Scheme 3. In order to secure a reproducible reaction course, 10
mol% of the sensitizer were used for small scale reactions. Some of the reactions were also
performed on larger scale (1 mmol) and at a higher concentration (c = 25 mM). In this case, only
2
.5 mol% of the sensitizer were employed. Despite a longer reaction time, the chemoselectivity
did not suffer and yields were as good as on small scale or even higher.
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SCHEME 3. Intramolecular [2+2] Photocycloaddition of Various 2-('-Alkenyloxy)cycloalk-2-
enones upon Irradiation with Visible Light
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0
O
O
R
h ( = 420 nm)
0 mol% 5 (CH Cl )
O
O
1
2
2
n
n
R3
8, 9
R
R3
1, 2
O
O
O
O
O
O
O
O
H
H
H
H
a (73%,91%a)
9a (91%)
9b (88%,94%a)
8
8b (91%)
O
O
O
O
O
O
O
O
H
H
H
H
H
8c (quant)
9c (90%,92%a)
9d (38%)
9e (34%)
a
Yield if the reaction was performed on 1 mmol scale.
Crossed photocycloadditon products 8a-8c and 9a-9c were isolated cleanly without any
indication for the formation of other side products. Among the 4,4-dimethylcyclohexenones 1d
and 2d, only the latter substrate showed a photochemical reaction. The former substrate did not
react and the starting material was recovered. Since quantities were limited, the low yield of
product 9d might be associated with loss of product during chromatographic purification. Both
compounds 9d and 9e were difficult to detect on TLC which further impaired a quantitative
isolation. Cyclopentenone 1e was converted upon sensitized irradiation (cf. Scheme 3) but no
defined products could be isolated. The same observation was made when the compound was
irradiated directly at  = 350 nm (c = 10 mM, CH Cl ).
2
2
The suspected intermediacy of 1,4-diradicals in the course of the [2+2] photocycloaddition
2
0
implied the possibility to perform stereoconvergent reactions with 1,2-disubstituted olefins in
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the tether. Substrates E-10/Z-10 (Scheme 4) were obtained from an E/Z-mixture (d.r. = 50/50) of
crotyl alcohol (2-butenol) by condensation with 1,2-diketone 4a (method A). Sensitized
irradiation delivered photocycloaddition product 11 as a single diastereoisomer accompanied by
an olefinic impurity which was removed by treatment with 3,6-bis(methoxycarbonyl)-1,2,4,5-
1
1
1
1
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5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
1
tetrazine. The yield of clean isolated product was 78% and its relative configuration was
assigned based on NOESY spectra (see the SI for further details).
SCHEME 4. Stereoconvergent Formation of [2+2] Photocycloaddition Products 11 and 13
O
O
h ( = 420 nm)
O
O
1
0 mol% 2 (CH Cl )
2
2
78%
O
H
H
E-10/Z-10
11
O
O
O
O
R1
O
R2
H
H
E-12 R1 = Et R = H
Z-12 R1 = H R = Et
2
2
13
14
The ethyl-substituted substrates 12 were obtained in diastereomerically pure form from (E)- and
(Z)-3-penten-1-ol and diketone 4a. The compounds were individually subjected to the irradiation
conditions and delivered the same product 13. In this case, the product was not completely
homogenous but was contaminated by compound 14 (yield from E-12: quant., 13/14 = 82/18;
yield from Z-12: 90%, 13/14 = 83/17). By-product formation is likely to occur from the
intermediate 1,4-diradical by intramolecular hydrogen abstraction (vide infra). It was possible to
remove the undesired compound by oxidation and the desired product 13 was obtained in 69%
yield. The outcome of the reactions suggests that 1,4-biradicals related to 6 are the major
intermediates in the [2+2] photocycloaddition to products 11 and 13. Not only do they explain the
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1
1
1
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
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4
5
5
5
5
5
5
5
5
5
5
6
observed stereoconvergence of the reaction but they also account for the formation of the olefinic
side products.
When cyclohexenones 3a-3c with a trisubstituted tethered olefin were employed as starting
materials, a cyclization/reduction pathway became dominant and [2+2] photocycloaddition
products were not detected. The high yields achieved for products 16a-16c (Scheme 5) render
some synthetic utility to this method, which represents formally a conjugate addition to the -
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
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9
0
1
2
3
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5
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8
9
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1
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7
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9
0
1
2
3
4
5
6
7
8
9
0
carbon atom of the -unsaturated enone. The assignment of the relative product configuration
1
was suggested by H-NMR coupling constants and NOESY experiments (see the SI for detail)
and the selectivity of the process is remarkable as it allows to construct three contiguous
stereogenic centers with a defined configuration.
SCHEME 5. Formation of Cyclization Products 16 from 2-Dimethylallyloxy-substituted Enones 3
via 1,4-Diradicals 15
O
O
H
O
O
h ( = 420 nm)
R4
1
0 mol% 5 (CH Cl )
2
2
R4
R4
R3
R3
R4
R3 = H
R4 = H
16a (65%)
16b (79%)
16c (86%)
3a
3b
3c
R3 = Me R4 = H
R3 = H
R4 = Me
via
O
H
O
O
O
R4
R4
R4
R3
R3
R4
15
Mechanistically, the first step of the sequence occurs presumably in analogy to the C-C bond
forming event previously mentioned (1a → 6), i.e. the triplet of 3 undergoes intramolecular
addition to the tethered olefin by a five-membered ring cyclization. However, due to steric
3
hindrance of the substituents (R and CMe ) bond formation occurs in a trans fashion. In the
2
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intermediate bicyclic 1,4-diradical 15 cyclization to a cyclobutane by C-C bond formation is not
9
feasible but an intramolecular hydrogen abstraction can readily occur that generates products 16.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
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9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Like cyclopentenone 1e in the [2+2] photocycloaddition study, the cyclopentenone with a
prenyloxy substituent (3e) showed only decomposition under the conditions successfully
employed for substrate 3a. Also the cyclopentenones 1f-3f with an additional methyl group in -
position displayed a reactivity that did not parallel the reactivity pattern of the comparable six-
membered cyclic enones 1b-3b. In this instance, however, defined products could be isolated
albeit in only low to moderate yields. The preferred reaction pathway of the cyclopentenones 1f-
3
f was a [2+2] photodimerization with the interesting twist that there are two double bonds
available in each component. Along these lines, 2-('-butenyloxy)-3-methylcycloalk-2-enone (1f)
produced a set of [2+2] photocycloaddition products from which two products 17 and 18 could
be isolated (Scheme 6). Product 17 is the [2+2] photodimerization product resulting from
addition of the two enone double bonds in what is commonly referred to as a cis-anti-cis
1
,2
addition. The cis fusion between the five-membered rings and the four-membered ring is to be
expected due to the rigidity of the skeleton while the anti (trans) configuration of the
cyclopentanone rings minimizes their steric repulsion. Based on its NMR data, the second
product 18 was also symmetric and – as confirmed by its crystal structure – it displays an
2
2
inversion center (S symmetry). The crystal structure revealed that the bicyclo[3.2.0]heptane
2
core is cis connected and all substituents within the cyclobutane are positioned in a cis fashion.
The two constitutionally identical bicyclo[3.2.0]heptane fragments possess opposite absolute
configuration. Given the low combined yield for compounds 17 and 18, it is likely that other
dimerization products were formed but could not be isolated in pure form. [2+2]
2
3
Photodimerization in a head-to-head fashion is common for cyclopentenones while the
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2
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2
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6
regioselectivity of the intermolecular head-to-head double bond addition of a monosubstituted
olefin to an enone has less precedence.9d,23d,24
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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9
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1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
SCHEME 6. [2+2] Photodimerization of Cyclopent-2-enone 1f and Crystal Structure of Product
1
8
O
h ( = 420 nm)
O
O
O O
O
1
0 mol% 5 (CH Cl )
2
2
1f
17 (12%)
+
O
O
O
O
18 (18%)
a
Ellipsoids in the ORTEP structure are displayed at the 50% probability level.
The overall product yield achieved in the [2+2] photodimerization of compound 2f was slightly
higher (44%) than observed for 1f. Again two regioisomers were isolated one of which was the
enone dimerization product 19 and the other the product of an enone/olefin addition. The
configuration assignment for the latter product 20 was based on analogy to product 18.
SCHEME 7. [2+2] Photodimerization of Cyclopent-2-enone 2f to Products 19 and 20
h ( = 420 nm)
O
O
10 mol% 5
CH Cl )
O O
O
O
O
O
(
2
2
+
2f
19 (17%)
20 (26%)
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Remarkably, even the prenyloxy-substituted enone 3f did not display the cyclization tendency
observed with cyclohexenones 3a-3c. Instead, the only product isolated from its sensitized
irradiation was the head-to-head regioisomer 21 of a [2+2] photodimerization that was obtained
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
in 34% yield. The C -symmetric compound displayed the same relative configuration as the
2
previously discussed enone dimers 17 and 19 and the structure assignment could in this specific
case be secured by single crystal structure analysis (Figure 3).
O
O
O O
21
FIGURE 3. Structure of the [2+2] photodimerization product 21 (ellipsoids in the ORTEP structure
are displayed at the 50% probability level) obtained by sensitized irradiation of substrate 3f (34%
yield)
The difference between the cyclopentenone and the cyclohexenone chromophore in the
photochemical reactivity of their 2-(2’-alkenyloxy)-substituted derivatives is remarkable. Only in
a single case (product 9e) an intramolecular attack of the tethered olefin occurred while with all
other substrates there was no indication for such an attack, not even for a cyclization to a 1,4-
diradical (in analogy to the formation of intermediate 15). The cyclization seems retarded and
intermolecular [2+2] photocycloaddition reactions become competitive. The observation is
important because it allows to access cyclopentenone dimers without protecting olefinic side
chains.
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1
1
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1
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
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3
3
3
3
4
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
5
5
6
In summary, an array of structurally diverse products has been obtained by irradiation of the title
compounds in the presence of a sensitizer. The photochemical reactions of all cyclohexenone
derivatives proceeded in moderate to excellent yields and with a high degree of
diastereoselectivity. Intramolecular reactions were observed exclusively either as [2+2]
photocycloaddition or as a cyclization/hydrogen abstraction cascade. Up to four stereogenic
centers can be established in a single reaction and the products hold promise as scaffolds which
enable a further functionalization at several positions. The cyclopentenone derivatives were less
prone to intramolecular reactions but underwent preferentially an intermolecular reaction leading
to [2+2] photodimerization products.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
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8
9
0
1
2
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9
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1
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9
0
1
2
3
4
5
6
7
8
9
0
EXPERIMENTAL SECTION
General Methods. All air and moisture sensitive reactions were carried out in flame-dried
glassware under an argon atmosphere using standard Schlenk techniques. For moisture sensitive
reactions, tetrahydrofuran (THF), diethylether (Et
2
O) and dichloromethane (CH
2
Cl ) were dried
2
using a solvent purification system. Cyclohexane was dried over neutral aluminum oxide and
stored over 4 Å molecular sieves. Dry N,N-dimethylformamide (DMF) was obtained in the
highest available purity stored over molecular sieves and used without further purification. For
photochemical reactions, dry dichloromethane was degassed by three freeze-pump-thaw cycles.
Cooling baths used were ice/water (0 °C) and dry ice/ethanol (78 °C). Technical solvents [1,2-
dichloroethane (DCE), pentane (P), Et O, CH Cl , methanol (MeOH), ethyl acetate (EtOAc),
2
2
2
cyclohexane] were distilled prior to use. Flash column chromatography was performed on silica
0 (230-400 mesh) and thin layer chromatography (TLC) was performed on silica coated glass
plates (silica 60 F ) with detection by UV-light (λ = 254 nm) and/or by staining with KMnO
6
2
54
4
solution followed by heat treatment. Infrared spectra (IR) were recorded by attenuated total
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–1
reflection (ATR) technique and are reported as wave numbers ṽ (cm ). The following
abbreviations for intensities were used: vs (very strong), s (strong), m (medium), w (weak). NMR
spectra were recorded at room temperature on either a 300, 400 or 500 MHz nuclear magnetic
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
resonance spectrometer. The H NMR spectra were referenced to the residual solvent peak of
1
3
1
either chloroform (7.26 ppm) or C D (7.16 ppm), and the C{ H} NMR spectra were referenced
6
6
either against the central peak of CDCl (77.16 ppm) or the residual solvent peak of C D
6
3
6
1
(128.06 ppm). H NMR spectra were reported as follows: chemical shift in parts per million
(
ppm), peak shape (s - singlet, d - dublet, t - triplet, q - quartet, quint. - quintet, sept. - septet, m =
multiplet), coupling constant in Hertz (Hz), and integration. Apparent multiplets which occur as a
result of coupling constant equality between magnetically non-equivalent protons are marked as
virtual (virt.). Mass spectra were measured with a mass selective quadrupole detector (EI, 70 eV).
HRMS data were determined at a double-focussing magnetic sector instrument (EI, 70 eV).
UV/Vis Spectra were recorded using a precision cell made of quartz with a pathway of 1 mm.
General procedure 1 (Method A): To a solution of the respective 1,2-cyclohexadione
(
1.0 equiv.) in dry cyclohexane (40 mL/g starting material) was added p-TsOH∙H O (3.0 mol%)
2
and the corresponding allylic alcohol (4.0 equiv.). The reaction mixture was heated at reflux in a
Dean-Stark apparatus for 15 – 17 h. The solution was allowed to cool to room temperature,
washed with brine (2 × 50 mL/g), dried over Na SO , and filtrated. The solvent was removed
2
4
under reduced pressure and the crude product was purified using flash column chromatography
P/Et O).
(
2
General procedure 2 (Method B): To a solution of the respective 1,2-cyclohexadione
1.0 equiv.) in dry DMF (40 mL/g starting material) was added K CO (1.2 equiv.) and the
(
2
3
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
respective allylbromide (1.2 equiv.). The reaction mixture was stirred at room temperature for
4
.5 – 21 h. The reaction was quenched by the addition of H O (20 mL/g). Et O (40 mL/g) was
2 2
added and the layers were separated. The organic layer was washed with H O (4 × 40 mL/g) and
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
brine (1 × 60 mL/g), dried over Na SO , and filtrated. The solvent was removed under reduced
2
4
pressure and the crude product was purified using flash column chromatography (P/Et O).
2
General procedure 3 (Method C): A round bottom flask charged with NaH (60 wt%,
1
.2 equiv.) was cooled to 0 °C and the respective allylic alcohol (30 equiv.) was added dropwise.
The reaction mixture was stirred for 10 min and subsequently the corresponding epoxide
(1.0 equiv.) was added dropwise. The reaction mixture was allowed to warm to room temperature
and stirred for 20 – 24 h. The mixture was diluted with Et O (75 mL/g) and quenched by the
2
addition of H O (35 mL/g). The layers were separated and the organic layer was washed with
2
H O (1 × 35 mL/g) and brine (1 × 75 mL/g), dried over Na SO , and filtrated. The solvent was
2
2
4
removed under reduced pressure and the crude product was purified by flash column
chromatography (P/Et O).
2
General procedure 4 (Method B): To a solution of the respective 1,2-cyclopentadione
(
1.0 equiv.) in dry DMF (40 mL/g starting material) was added K CO (1.2 equiv.) and the
2 3
respective allylbromide (1.2 equiv.). The reaction mixture was stirred at room temperature for 17
– 22 h. The reaction was quenched by the addition of H O (20 mL/g). Et O (40 mL/g) was added
2
2
and the layers were separated. The organic layer was washed with H O (4 × 40 mL/g) and brine
2
(
1 × 60 mL/g), dried over Na SO , and filtrated. The solvent was removed under reduced
2 4
pressure and the crude product was purified using flash column chromatography (P/Et O).
2
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2
-(Allyloxy)cyclohex-2-en-1-one (1a)
According to general procedure 1, compound 1a was synthesized starting from 4a (1.00 g,
8.92 mmol, 1.0 equiv.), allylic alcohol (2.43 mL, 2.07 g, 35.7 mmol, 4.0 equiv.) and
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
p-TsOH∙H O (51.3 mg, 270 µmol, 3.0 mol%). Purification by flash column chromatography
2
(SiO , P/Et O = 5/1, UV) afforded the product (667 mg, 4.38 mmol, 49%) as a colorless oil. TLC
2 2
1
(P/Et O = 3/1): R = 0.18 [UV, KMnO ]. H NMR (400 MHz, CDCl , 300 K): δ = 1.97 (virt.
3
2
f
4
3
3
3
quint. J  J = 6.2 Hz, 2H), 2.41 (td, J = 6.0, 4.7 Hz, 2H), 2.48 – 2.53 (m, 2H), 4.31 (virt. dt
3
4
4
2
3
4
J = 5.5 Hz, J  J = 1.5 Hz, 2H), 5.25 (ddt, J = 1.5 Hz, J = 10.6 Hz, J = 1.5 Hz, 1H), 5.33
2
3
4
3
3
(ddt, J = 1.5 Hz, J = 17.4 Hz, J = 1.5 Hz, 1H), 5.89 (t, J = 4.7 Hz, 1H), 5.98 (ddt, J = 17.4,
13
1
1
0.6, 5.5 Hz, 1H). C{ H} NMR (101 MHz, CDCl
3
, 300 K):  = 23.1 (t), 24.7 (t), 39.0 (t), 68.8
(t), 118.1 (t), 118.7 (d), 133.1 (d), 150.5 (s), 194.5 (s). UV/vis (CH Cl , c = 0.5 mM): λ = 259 nm
2
2
(ε = 3736 cm−1 M ). Data of this compound were in accordance with the literature.6b
−1
2
-(Allyloxy)-3-methylcyclohex-2-en-1-one (1b)
According to general procedure 2, compound 1b12a,25 was synthesized starting from 4a (500 mg,
3
.96 mmol, 1.0 equiv.), allyl bromide (410 µL, 580 mg, 4.76 mmol, 1.2 equiv.) and K CO
2 3
(670 mg, 4.85 mmol, 1.2 equiv.). Purification by flash column chromatography (SiO2,
P/Et O = 9/1, UV) afforded the product (259 mg, 1.56 mmol, 39%) as a colorless oil. TLC
2
1
(P/Et O = 3/1): R = 0.30 [UV, KMnO ]. H NMR (500 MHz, CDCl
3
, 300 K): δ = 1.92 (s, 3H),
2
f
4
3
3
1
.92 – 1.97 (m, 2H), 2.38 (t, J = 6.1 Hz, 2H), 2.41 – 2.47 (m, 2H), 4.34 (virt. dt, J = 6.0 Hz,
2
4
3
2
4
J  J = 1.4 Hz, 2H), 5.18 (virt. dt, J = 10.3 Hz, J  J = 1.4 Hz, 1H), 5.28 (virt. dtd,
3
1
2
4
4
3
J = 17.2 Hz, J  J = 1.6 Hz, J = 1.5 Hz, 1H), 5.99 (ddt, J = 17.0, 10.3, 6.0 Hz, 1H).
3
1
C{ H} NMR (101 MHz, CDCl , 300 K):  = 18.1 (q), 22.3 (t), 31.7 (t), 38.9 (t), 73.0 (t), 117.8
3
(t), 134.5 (d), 146.4 (s), 147.9 (s), 194.9 (s). IR (ATR): ṽ = 2928 (w), 1672 (vs), 1631 (m), 1431
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4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
w), 1379 (w), 1304 (w), 1193 (s), 1153 (s), 985 (s), 926 (s). MS (EI, 70 eV): m/z (%) = 166 (80),
+
1
51 (100), 137 (13), 125 (17), 113 (38), 110 (93), 95 (82), 82 (78). HRMS (EI) m/z: [M] Calcd.
for C H O : 166.0982; Found: 166.0988. UV/vis (CH Cl , c = 0.5 mM): λ = 247 nm
1
0
14
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ε = 8212 cm−1 M ).
−1
(
2
-(Allyloxy)-5,5-dimethylcyclohex-2-en-1-one (1c)
According to general procedure 3, compound 1c12a was synthesized starting from epoxide 4c
(200 mg, 1.43 mmol, 1.0 equiv.), allylic alcohol (3.00 mL, 2.55 g, 43.9 mmol, 31 equiv.) and
NaH (60 wt%, 72.0 mg, 1.80 mmol, 1.3 equiv.). Purification by flash column chromatography
(SiO , P/Et O = 9/1 → 6/1, UV) afforded the product (115 mg, 640 μmol, 45%) as a colorless oil.
2 2
1
TLC (P/Et O = 3/1): R = 0.31 [UV, KMnO ]. H NMR (500 MHz, CDCl , 300 K): δ = 1.06 (s,
3
2
f
4
3
3
2
4
6
H), 2.31 (d, J = 4.6 Hz, 2H), 2.37 (s, 2H), 4.32 (virt. dt, J = 5.8 Hz, J  J = 1.4 Hz, 2H), 5.25
3
2
4
3
2
4
(virt. dq, J = 10.6 Hz, J  J = 1.3 Hz, 1H), 5.33 (virt. dq, J = 17.3 Hz, J  J = 1.5 Hz, 1H),
3
3
13
1
5
.73 (t, J = 4.6 Hz, 1H), 5.98 (ddt, J = 17.2, 10.8, 5.5 Hz, 1H). C{ H} NMR (126 MHz,
, 300 K):  = 28.3 (q), 34.1 (s), 38.6 (t), 52.4 (t), 68.8 (t), 116.1 (d), 118.2 (t), 133.0 (d),
149.8 (s), 194.5 (s). IR (ATR): ṽ = 2959 (m), 1690 (vs), 1629 (m), 1467 (w), 1368 (w), 1165 (m),
CDCl
3
9
9
99 (m). MS (EI, 70 eV): m/z (%) = 180 (100), 165 (10), 151 (10), 127(10), 124 (51), 109 (49),
+
5 (52), 83 (19). HRMS (EI) m/z: [M] Calcd. for C H O : 180.1145; Found: 180.1145. UV/vis
1
1
16
2
−
1
−1
(CH Cl , c = 0.5 mM): λ = 261 nm (ε = 5484 cm M ).
2 2
2
-(Allyloxy)-4,4-dimethylcyclohex-2-en-1-one (1d)
KOH (85 wt%, 94.2 mg, 1.43 mmol, 1.0 equiv.) was dissolved in allylic alcohol (1.00 mL,
854 mg, 14.7 mmol, 10 equiv.). A solution of epoxide 4d (200 mg, 1.43 mmol, 1.0 equiv.) in
allylic alcohol (1.5 mL, 1.28 g, 22.1 mmol, 15 equiv.) was then added dropwise and the reaction
mixture was stirred at room temperature over night. Subsequently the reaction mixture was
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diluted with 15 mL Et O and quenched by the addition of 15 mL H O. The layers were separated
2
2
and the aqueous layer was extracted with Et O (2 × 15 mL). The combined organic layers were
2
washed with brine (1 × 50 mL), dried over Na SO , filtrated and the solvent as well as the
2
4
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
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4
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5
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5
5
6
0
1
2
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4
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0
1
2
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1
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9
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4
5
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7
8
9
0
1
2
3
4
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6
7
8
9
0
remaining allylic alcohol were removed under reduced pressure. After purification by flash
column chromatography (SiO , P/Et O = 20/1 → 6/1, UV) the product 1d (30.5 mg, 169 µmol,
2
2
1
1
2%) was obtained as a colorless oil. TLC (P/Et O = 3/1): R = 0.28 [UV, KMnO ]. H NMR
2 f 4
3
3
(500 MHz, CDCl , 300 K): δ = 1.18 (s, 6H), 1.82 (t, J = 6.5 Hz, 2H), 2.55 (t, J = 6.5 Hz, 2H),
3
3
4
4
3
2
4
4
.27 (virt. dt, J = 5.6 Hz, J  J = 1.5 Hz, 2H), 5.24 (virt. dq, J = 10.4 Hz, J  J = 1.4 Hz,
3
2
4
3
1H), 5.32 (virt. dq, J = 17.2 Hz, J  J = 1.6 Hz, 1H), 5.59 (s, 1H), 5.97 (ddt, J = 17.3, 10.8,
13
1
5
.6 Hz, 1H). C{ H} NMR (126 MHz, CDCl
3
, 300 K):  = 29.2 (q), 33.0 (s), 35.0 (t), 36.0 (t),
6
8.7 (t), 118.2 (t), 128.7 (d), 132.9 (d), 148.1 (s), 194.1 (s). IR (ATR): ṽ = 2958 (m), 1690 (vs),
1619 (s), 1458 (w), 1362 (m), 1261 (m), 1200 (s), 1130 (s), 1107 (s), 1014 (m), 925 (w). MS (EI,
7
0 eV): m/z (%) = 180 (24), 165 (24), 137 (4), 124 (100), 109 (23), 96 (15), 83 (11). HRMS (EI)
+
m/z: [M] Calcd. for C H O : 180.1145; Found: 180.1144. UV/vis (CH Cl , c = 0.5 mM):
1
1
16
2
2
2
λ = 260 nm (ε = 7584 cm−1 M−1).
2
-(Allyloxy)cyclopent-2-en-1-one (1e)
To a solution of 1,2-cyclopentadione (4e) (95.0 mg, 968 μmol, 1.0 equiv.) in 5.0 mL dry
cyclohexane was added p-TsOH∙H O (6.10 mg, 32.1 μmol, 3.0 mol%) and allylic alcohol
2
(210 μL, 178 mg, 3.06 mmol, 3.2 equiv.). The reaction mixture was heated at reflux using a
Dean-Stark apparatus for 23 h. The solution was allowed to cool to room temperature and the
solvent was removed under reduced pressure. After purification by flash column chromatography
25
(
SiO , P/Et O = 3/1, UV) the product 1e (100 mg, 720 μmol, 74%) was obtained as a colorless
2
2
1
oil. TLC (P/Et O = 3/1): R = 0.14 [UV, KMnO ]. H NMR (500 MHz, CDCl
3
, 300 K): δ = 2.38 –
2
f
4
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4
4
2
.48 (m, 2H), 2.52 (ddd, J = 6.4, 4.2, 2.9 Hz, 2H), 4.43 (virt. dt, J = 5.6 Hz, J  J = 1.5 Hz,
3
2
4
3
2
H), 5.28 (virt. dq, J = 10.6 Hz, J  J = 1.4 Hz, 1H), 5.36 (virt. dq, J = 17.3 Hz,
2
4
3
3
J  J = 1.6 Hz, 1H), 5.98 (ddt, J = 17.3, 10.9, 5.6 Hz, 1H), 6.39 (t, J = 2.9 Hz, 1H).
0
1
2
3
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5
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7
8
9
0
1
2
3
4
5
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8
9
0
1
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7
8
9
0
1
2
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5
6
7
8
9
0
1
2
3
4
5
6
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8
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0
1
3
1
C{ H} NMR (126 MHz, CDCl
132.4 (d), 156.4 (s), 202.7 (s). IR (ATR): ṽ = 2925 (w), 1715 (vs), 1624 (m), 1337 (w), 1276 (w),
119 (m), 1027 (w), 934 (w). MS (EI, 70 eV): m/z (%) = 138 (100), 109 (15), 95 (11), 82 (52).
3
, 300 K):  = 22.1 (t), 33.2 (t), 70.8 (t), 118.7 (t), 128.3 (d),
1
+
+
HRMS (EI) m/z: [M] Calcd. for C H O : 138.0675; Found: 138.0677, [M] Calcd. for
8
10
2
1
3
C C H O : 139.0709; Found: 139.0712. UV/vis (CH Cl , c = 0.5 mM): λ = 248 nm
7
1
10
2
2
2
ε = 5180 cm−1 M ).
−1
(
2-(Allyloxy)-3-methylcyclopent-2-en-1-on (1f)
According to general procedure 4, compound 1f12a was synthesized starting from 4f (500 mg,
4.46 mmol, 1.0 equiv.), allyl bromide (460 µL, 650 mg, 5.35 mmol, 1.2 equiv.) and K CO
2
3
(
740 mg, 5.35 mmol, 1.2 equiv.). Purification by flash column chromatography (SiO2,
P/Et O = 3/1, UV) afforded the product (387 mg, 2.54 mmol, 55%) as a colorless oil. TLC
2
1
(
P/Et O = 3/1): R = 0.24 [UV, KMnO ]. H NMR (400 MHz, CDCl
3
, 300 K): δ = 1.98 (s, 3H),
2
f
4
2
3
3
3
2
.30 – 2.39 (m, 2H), 2.43 (virt. dtd, J = 7.1 Hz, J  J = 2.5, J = 1.2 Hz, 2H), 4.67 (virt. dt,
3
2
2
3
2
4
J = 5.9 Hz, J  J = 1.4 Hz, 2H), 5.18 (virt. dq, J = 10.4 Hz, J  J = 1.3 Hz, 1H), 5.29 (virt.
3
2
4
3
13
1
dq, J = 17.2 Hz, J  J = 1.6 Hz, 1H), 5.94 (ddt, J = 17.2, 10.4, 5.8 Hz, 1H). C{ H} NMR
101 MHz, CDCl , 300 K):  = 15.1 (q), 27.6 (t), 33.1 (t), 70.9 (t), 117.9 (t), 134.3 (d), 151.7 (s),
155.6 (s), 203.3 (s). IR (ATR): ṽ = 2917 (w), 1699 (vs), 1643 (m), 1442 (w), 1389 (w), 1333 (m),
(
3
1
1
204 (m), 1094 (s), 984 (m), 928 (m). MS (EI, 70 eV): m/z (%) = 152 (49), 137 (76), 123 (19),
+
12 (9), 96 (22), 84 (16), 81 (8), 69 (26), 67 (15), 55 (19), 41 (100). HRMS (EI) m/z: [M] Calcd.
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for C H O : 152.0827; Found: 152.0832. UV/vis (CH Cl , c = 0.5 mM): λ = 246 nm
9
12
2
2
2
(
ε = 10132 cm−1 M−1).
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
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3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
5
6
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8
9
0
1
2
3
4
5
6
7
8
9
0
2
-[(2-Methylallyl)oxy]cyclohex-2-en-1-one (2a)
According to general procedure 1, compound 2a was synthesized starting from 4a (1.00 g,
.92 mmol, 1.0 equiv.), methallylic alcohol (3.00 mL, 2.57 g, 35.7 mmol, 4.0 equiv.) and
p-TsOH∙H O (52.3 mg, 275 µmol, 3.0 mol%). Purification by flash column chromatography
8
2
(
SiO , P/Et O = 9/1 → 4/1, UV) afforded the product (682 mg, 4.10 mmol, 46%) as a colorless
2 2
1
oil. TLC (P/Et O = 3/1): R = 0.19 [UV, KMnO ]. H NMR (500 MHz, C D , 300 K): δ = 1.36
2
f
4
6
6
3
3
3
(virt. quint. J  J = 6.1 Hz, 2H), 1.66 (s, 3H), 1.74 (td, J = 6.0, 4.6 Hz, 2H), 2.05 – 2.21 (m,
3
13
1
2
H), 3.90 (s, 2H), 4.86 (s, 1H), 5.11 (s, 1H), 5.30 (t, J = 4.6 Hz, 1H). C{ H} NMR (75 MHz,
C D , 300 K):  = 19.8 (q), 23.5 (t), 24.8 (t), 39.6 (t), 71.9 (t), 113.0 (t), 118.1 (d), 141.6 (s),
6
6
−1
−1
1
51.5 (s), 190.4 (s). UV/vis (CH Cl , c = 0.5 mM): λ = 259 (ε = 4518 cm M ). Data of this
2 2
compound were in accordance with the literature.6b
3-Methyl-2-[(2-methylallyl)oxy]cyclohex-2-en-1-one (2b)
According to general procedure 2, compound 2b was synthesized starting from 4b (500 mg,
3
.96 mmol, 1.0 equiv.), methallyl bromide (480 µL, 640 mg, 4.76 mmol, 1.2 equiv.) and K CO
2 3
(0.660 mg, 4.76 mmol, 1.2 equiv.). Purification by flash column chromatography (SiO2,
P/Et O = 9/1, UV) afforded the product (414 mg, 2.29 mmol, 58%) as a colorless oil. TLC
2
1
(
P/Et O = 3/1): R = 0.29 [UV, KMnO ]. H NMR (500 MHz, CDCl3, 300 K): δ = 1.82 (s, 3H),
2
f
4
3
3
1.90 – 1.98 (m, 5H), 2.38 (t, J = 6.1 Hz, 2H), 2.44 (t, J = 6.7 Hz, 2H), 4.22 (s, 2H), 4.90 (virt. t,
2
4
13
1
J  J = 2.0 Hz, 1H), 5.02 (s, 1H). C{ H} NMR (126 MHz, CDCl3, 300 K):  = 18.0 (q), 19.9
(q), 22.3 (t), 31.7 (t), 38.9 (t), 75.7 (t), 112.8 (t), 142.0 (s), 146.1 (s), 148.2 (s), 194.9 (s). IR
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1
1
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
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3
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6
(
ATR): ṽ = 2920 (w), 1673 (vs), 1632 (m), 1433 (w), 1378 (m), 1304 (m), 1193 (s), 1151 (vs),
9
93 (m), 895 (m). MS (EI, 70 eV): m/z (%) = 180 (100), 165 (37), 137 (11), 123 (21), 110 (94),
+
+
95 (74). HRMS (EI) m/z: [M] Calcd. for C H O : 180.1145; Found: 180.1145, [M] Calcd. for
1
1
16
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
C1013C H O : 181.1185; Found: 181.1178. UV/vis (CH Cl , c = 0.5 mM): λ = 248 nm
1 16 2 2 2
(
ε = 7196 cm−1 M−1).
5,5-Dimethyl-2-[(2-methylallyl)oxy]cyclohex-2-en-1-one (2c)
According to general procedure 3, compound 2c was synthesized starting from epoxide 4c
200 mg, 1.43 mmol, 1.0 equiv.), methallylic alcohol (2.40 mL, 2.06 g, 28.6 mmol, 20 equiv.)
(
and NaH (60 wt%, 70.0 mg, 1.75 mmol, 1.2 equiv.). Purification by flash column
chromatography (SiO , P/Et O = 9/1, UV) afforded the product (102 mg, 527 μmol, 37%) as a
2
2
1
colorless oil. TLC (P/Et O = 3/1): R = 0.40 [UV, KMnO ]. H NMR (500 MHz, CDCl
3
, 300 K):
2
f
4
3
δ = 1.06 (s, 6H), 1.76 (s, 3H), 2.29 (d, J = 4.6 Hz, 2H), 2.36 (s, 2H), 4.25 (s, 2H), 4.95 (s, 1H),
3
13
1
5
2
.00 (s, 1H), 5.73 (t, J = 4.6 Hz, 1H). C{ H} NMR (126 MHz, CDCl
3
, 300 K):  = 19.4 (q),
8.3 (q), 34.2 (s), 38.5 (t), 52.4 (t), 71.6 (t), 112.9 (t), 116.3 (d), 140.5 (s), 149.9 (s), 194.3 (s). IR
(ATR): ṽ = 2958 (m), 1691 (vs), 1629 (m), 1455 (w), 1368 (w), 1163 (m), 902 (w). MS (EI,
7
0 eV): m/z (%) = 194 (57), 179 (8), 151 (9), 138 (22), 127 (14), 109 (100), 95 (9), 83 (14).
+
HRMS (EI) m/z: [M] Calcd. for C H O : 194.1301; Found: 194.1302. UV/vis (CH Cl ,
1
2
18
2
2
2
c = 0.5 mM): λ = 261 nm (ε = 4374 cm−1 M−1).
4
,4-Dimethyl-2-[(2-methylallyl)oxy]cyclohex-2-en-1-one (2d)
KOH (85 wt%, 59.9 mg, 908 µmol, 1.0 equiv.) was dissolved in methallylic alcohol (1.00 mL,
8
51 mg, 11.8 mmol, 13 equiv.). A solution of epoxide 4d (127 mg, 908 µmol, 1.0 equiv.) in
methallylic alcohol (1.0 mL, 0.851 mg, 11.8 mmol, 13 equiv.) was then added dropwise and the
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reaction mixture was stirred at room temperature over night. Subsequently the reaction mixture
was diluted with 15 mL Et O and quenched by the addition of 15 mL H O. The layers were
2
2
separated and the aqueous layer was extracted with Et O (2 × 15 mL). The combined organic
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
layers were washed with brine (1 × 50 mL), dried over Na SO , filtrated and the solvent as well
2
4
as the remaining volatiles were removed under reduced pressure. After purification by flash
column chromatography (SiO , P/Et O = 6/1) the product 2d (11.0 mg, 56.6 µmol, 6%) was
2
2
1
obtained as a colorless oil. TLC (P/Et O = 3/1): R = 0.37 [UV, KMnO ]. H NMR (500 MHz,
2
f
4
4
CDCl , 300 K): δ = 1.17 (s, 6H), 1.76 (t, J = 1.2 Hz, 3H), 1.80 – 1.83 (m, 2H), 2.52 – 2.60 (m,
3
2
4
2
2
H), 4.18 (s, 2H), 4.94 (virt. quint., J  J = 1.3 Hz, 1H), 5.00 (virt. dq, J = 2.1 Hz,
4
4
13
1
J  J = 1.2 Hz, 1H), 5.60 (s, 1H). C{ H} NMR (126 MHz, CDCl
3
, 300 K):  = 19.5 (q), 29.2
(q), 33.0 (s), 35.1 (t), 36.0 (t), 71.5 (t), 113.1 (t), 128.9 (d), 140.3 (s), 148.2 (s), 194.1 (s). IR
(ATR): ṽ = 2958 (m), 1692 (vs), 1619 (s), 1455 (w), 1363 (m), 1201 (s), 1130 (s), 1109 (s), 1014
(
(
[
m), 901 (w). MS (EI, 70 eV): m/z (%) = 194 (44), 179 (31), 151 (14), 138 (100), 125 (20), 109
+
37), 97 (22), 83 (10). HRMS (EI) m/z: [M] Calcd. for C H O : 194.1301; Found: 194.1301,
1
2
18
2
+
13
M] Calcd. for C C H O : 195.1335; Found: 195.1350. UV/vis (CH Cl , c = 0.5 mM):
11
1
18
−1
2
2
2
λ = 260 nm (ε = 6300 cm−1 M ), 338 nm (ε = 912 cm M ).
−1 −1
2
-[(2-Methylallyl)oxy]cyclopent-2-en-1-one (2e)
2
3
In analogy to general procedure 4, compound 2e was synthesized starting from 4e (100 mg,
1
.02 mmol, 1.0 equiv.), methallyl bromide (150 µL, 207 mg, 1.53 mmol, 1.5 equiv.) and K CO
2
3
(211 mg, 1.53 mmol, 1.5 equiv.) in 4.0 mL dry DMF. The reaction was quenched by the addition
of 5 mL H O and 10 mL Et O. The organic layer was washed with H O (4 × 10 mL) and brine
2
2
2
(
1 × 20 mL), dried over Na SO , filtrated and the solvent was removed under reduced pressure.
2 4
Purification by flash column chromatography (SiO , P/Et O = 3/1, UV) afforded the product
2
2
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6
(
55.1 mg, 360 μmol, 35%) as a colorless oil. TLC (P/Et O = 1/1): R = 0.30 [UV, KMnO ].
2
f
4
1H NMR (500 MHz, CDCl
, 300 K): δ = 1.78 (s, 3H), 2.40 – 2.44 (m, 2H), 2.50 (dt, J = 6.1,
3
3
3
13
1
2.8 Hz, 2H), 4.34 (s, 2H), 4.98 (s, 1H), 5.03 (s, 1H), 6.40 (t, J = 2.8 Hz, 1H). C{ H} NMR
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(101 MHz, CDCl
3
, 300 K):  = 19.4 (q), 22.1 (t), 33.2 (t), 73.8 (t), 113.7 (t), 128.5 (d, C-3), 140.0
(s), 156.5 (s), 202.6 (s). IR (ATR): ṽ = 2922 (w), 1708 (vs), 1623 (s), 1407 (w), 1336 (w), 1273
(m), 1104 (vs), 1025 (m), 902 (m), 782 (m). MS (EI, 70 eV): m/z (%) = 152 (100), 137 (16), 124
+
(10), 109 (21), 96 (90), 82 (19). HRMS (EI) m/z: [M] Calcd. for C H O : 152.0832; Found:
9
12
2
−
1
−1
1
52.0831. UV/vis (CH Cl , c = 0.5 mM): λ = 248 nm (ε = 6794 cm M ).
2 2
3
-Methyl-2-[(2-methylallyl)oxy]cyclopent-2-en-1-one (2f)
According to general procedure 4, compound 2f was synthesized starting from 4f (500 mg,
.46 mmol, 1.0 equiv.), methallyl bromide (550 µL, 736 mg, 5.46 mmol, 1.2 equiv.) and K CO
4
2
3
(740 mg, 5.35 mmol, 1.2 equiv.). Purification by flash column chromatography (SiO2,
P/Et O = 9/1, UV) afforded the product (621 mg, 3.74 mmol, 84%) as a colorless oil. TLC
2
1
(P/Et O = 3/1): R = 0.28 [UV, KMnO ]. H NMR (300 MHz, C D , 300 K): δ = 1.57 – 1.59 (m,
2
f
4
6
6
3
H), 1.56 – 1.67 (m, 2H), 1.64 – 1.71 (m, 3H), 1.85 – 1.90 (m, 2H), 4.79 – 4.86 (m, 2H), 4.86
2
4
4
4
2
4
4
(virt. ddq, J = 2.3 Hz, J = 1.6, J  J = 0.8 Hz, 1H), 5.11 (virt. dq, J = 2.3 Hz, J  J = 1.1 Hz,
13
1
1
1
H). C{ H} NMR (75 MHz, C D , 300 K):  = 14.4 (q), 19.4 (q), 26.8 (t), 33.1 (t), 73.0 (t),
6
6
12.7 (t), 142.5 (s), 151.8 (s), 152.1 (s), 201.4 (s). IR (ATR): ṽ = 2917 (w), 1700 (vs), 1646 (m),
1448 (w), 1389 (m), 1335 (m), 1204 (m), 1096 (s), 990 (m), 903 (m). MS (EI, 70 eV): m/z (%) =
66 (56), 151 (31), 137 (10), 110 (9), 96 (12), 84 (15), 69 (16), 55 (100), 41 (24). HRMS (EI)
1
+
+
13
m/z: [M] Calcd. for C H O : 166.0988; Found: 166.0985, [M] Calcd. for C C H O :
1
0
14
2
9
1
14
2
−
1
−1
1
67.1022; Found: 167.1026. UV/vis (CH Cl , c = 0.5 mM): λ = 248 nm (ε = 9284 cm M ).
2
2
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2
-[(3-Methylbut-2-en-1-yl)oxy]cyclohex-2-en-1-one (3a)
According to general procedure 2, compound 3a was synthesized starting from 4a (1.00 g,
.92 mmol, 1.0 equiv.), 3,3-dimethylallyl bromide (1.24 mL, 1.60 g, 10.7 mmol, 1.2 equiv.) and
K CO (1.48 g, 10.7 mmol, 1.2 equiv.). Purification by flash column chromatography (SiO ,
8
2
3
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
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3
4
4
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4
4
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4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
P/Et O = 9/1 → 4/1 → 3/1, UV) afforded the product (227 mg, 1.26 mmol, 14%) as a colorless
2
1
oil. TLC (P/Et O = 3/1): R = 0.15 [UV, KMnO ]. H NMR (400 MHz, CDCl
3
, 300 K): δ = 1.64
2
f
4
3
3
(s, 3H), 1.71 (s, 3H), 1.86 – 1.99 (m, 2H), 2.39 (td, J = 6.1, 4.7 Hz, 2H), 2.47 (dd, J = 7.4,
3
3
4
4
6.0 Hz, 2H), 4.23 (d, J = 5.9 Hz, 2H), 5.38 (virt. ddq, J = 8.2, 5.9 Hz, J  J = 1.5 Hz, 1H), 5.85
3
13
1
(t, J = 4.7 Hz, 1H). C{ H} NMR (101 MHz, CDCl
3
, 300 K):  = 18.2 (q), 23.0 (t), 24.6 (t),
2
5.8 (q), 38.9 (t), 64.6 (t), 117.9 (d), 119.6 (d), 137.6 (s), 150.7 (s), 194.5 (s). IR (ATR): ṽ = 2926
(w), 1686 (vs), 1622 (m), 1444 (w), 1375 (w), 1259 (m), 1184 (s), 1148 (vs), 1003 (m), 874 (w).
MS (EI, 70 eV): m/z (%) = 180 (27), 147 (11), 134 (8), 118 (57), 112 (100), 99 (12), 95 (7), 84
+
+
(27). HRMS (EI) m/z: [M] Calcd. for C H O : 180.1148; Found: 180.1145, [M] Calcd. for
11 16 2
C1013C H O : 181.1185; Found: 181.1178. UV/vis (CH Cl , c = 0.5 mM): λ = 261 nm
1
16
2
2
2
ε = 4126 cm−1 M ).
−1
(
3
-Methyl-2-[(3-methylbut-2-en-1-yl)oxy]cyclohex-2-en-1-one (3b)
2
6
According to general procedure 2, compound 3b was synthesized starting from 4b (500 mg,
.96 mmol, 1.0 equiv.), 3,3-dimethylallyl bromide (550 µL, 710 mg, 4.76 mmol, 1.2 equiv.) and
K CO (0.660 mg, 4.76 mmol, 1.2 equiv.). Purification by flash column chromatography (SiO ,
3
2
3
2
P/Et O = 9/1 → 3/1, UV) afforded the product (197 mg, 1.01 mmol, 26%) as a colorless oil. TLC
2
1
(P/Et O = 3/1): R = 0.24 [UV, KMnO ]. H NMR (500 MHz, CDCl
3
, 300 K): δ = 1.68 (s, 3H),
2
f
4
3
1.75 (s, 3H), 1.86 – 2.03 (m, 5H), 2.38 (t, J = 6.1 Hz, 2H), 2.41 – 2.45 (m, 2H), 4.32 (d,
3
3
4
4
13
1
J = 7.4 Hz, 2H), 5.44 (virt. ddq, J = 7.4, 5.9 Hz, J  J = 1.4 Hz, 1H). C{ H} NMR (126
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6
MHz, CDCl
3
, 300 K):  = 18.1 (q), 22.3 (t), 26.0 (q), 31.6 (t), 38.9 (t), 68.3 (t), 120.7 (d), 138.2
(s), 146.5 (s), 148.0 (s), 195.1 (s). IR (ATR): ṽ = 2917 (w), 1673 (vs), 1630 (m), 1433 (w), 1381
(m), 1301 (m), 1191 (s), 1148 (s), 970 (m). MS (EI, 70 eV): m/z (%) = 126 (100), 98 (11), 84
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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0
1
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5
6
7
8
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0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
(23). HRMS (EI) m/z: [M] Calcd. for C H O : 194.1300; Found: 194.1301. UV/vis (CH Cl ,
1
2
18
2
2
2
c = 0.5 mM): λ = 248 nm (ε = 6640 cm−1 M−1).
5
,5-Dimethyl-2-[(3-methylbut-2-en-1-yl)oxy]cyclohex-2-en-1-one (3c)
According to general procedure 3, compound 3c was synthesized starting from epoxide 4c
(
200 mg, 1.43 mmol, 1.0 equiv.), 3,3-dimethylallylic alcohol (4.50 mL, 3.83 g, 44.4 mmol,
1 equiv.) and NaH (60 wt%, 69.0 mg, 1.73 mmol, 1.2 equiv.). Purification by flash column
chromatography (SiO , P/Et O = 9/1, P/Et O = 9/1 → 6/1, UV) afforded the product (45.2 mg,
3
2
2
2
1
2
17 μmol, 15%) as a colorless oil. TLC (P/Et O = 3/1): R = 0.28 [UV, KMnO ]. H NMR
2 f 4
3
(500 MHz, CDCl , 300 K): δ = 1.06 (s, 6H), 1.68 (s, 3H), 1.75 (s, 3H), 2.31 (d, J = 4.6 Hz, 2H),
3
3
3
4
2
.36 (s, 2H), 4.28 (d, J = 7.3 Hz, 2H), 5.42 (ddd, J = 7.3 Hz, J = 4.1, 1.5 Hz, 1H), 5.71 (t,
3
13
1
J = 4.6 Hz, 1H). C{ H} NMR (126 MHz, CDCl
s), 38.6 (t), 52.4 (t), 64.6 (t), 115.3 (d), 119.6 (d), 137.7 (s), 150.1 (s), 194.5 (s). IR (ATR):
ṽ = 2958 (m), 1691 (vs), 1627 (m), 1452 (w), 1368 (w), 1162 (s), 1108 (m), 1003 (w). MS (EI,
0 eV): m/z (%) = 208 (28), 175 (12), 146 (30), 140 (100), 125 (49), 112 (10), 98 (71), 84 (57).
3
, 300 K):  = 18.3 (q), 25.9 (q), 28.3 (q), 34.1
(
7
+
+
HRMS (EI) m/z: [M] Calcd. for C H O : 208.1458; Found: 208.1445, [M] Calcd. for
1
3
20
2
C1213C H O : 209.1491; Found: 209.1482. UV/vis (CH Cl , c = 0.5 mM): λ = 263 nm
1
20
2
2
2
(ε = 4500 cm−1 M−1).
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2
-[(3-Methylbut-2-en-1-yl)oxy]cyclopent-2-en-1-one (3e)
In analogy to general procedure 4, compound 3e was synthesized starting from 4e (170 mg,
1.73 mmol, 1.0 equiv.), 3,3-dimethylallyl bromide (310 µL, 340 mg, 2.68 mmol, 1.5 equiv.) and
K CO (377 mg, 2.73 mmol, 1.6 equiv.) in 7.0 mL dry DMF. The reaction was quenched by the
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
3
addition of 7 mL H O and 15 mL Et O. The organic layer was washed with H O (4 × 15 mL) and
2
2
2
brine (1 × 30 mL), dried over Na SO , filtrated and the solvent was removed under reduced
2
4
pressure. Purification by flash column chromatography (SiO , P/Et O = 3/1, UV) afforded the
2
2
product (60.0 mg, 360 μmol, 21%) as a colorless solid. Mp 42 – 43 °C.TLC (P/Et O = 1/1):
2
1
R = 0.35 [UV, KMnO ]. H NMR (500 MHz, CDCl
3
, 300 K): δ = 1.70 (s, 3H), 1.76 (s, 3H),
f
4
3
3
2.41 – 2.44 (m, 2H), 2.48 – 2.60 (m, 2H), 4.40 (d, J = 6.8 Hz, 2H), 5.43 (t, J = 6.8 Hz, 1H), 6.36
3
4
13
1
(
virt. q, J  J = 2.5 Hz, 1H). C{ H} NMR (126 MHz, CDCl
5.9 (q), 33.2 (t), 66.7 (t), 119.1 (d), 127.6 (d), 138.7 (s), 156.6 (s), 202.9 (s). IR (ATR): ṽ = 2924
(w), 1715 (vs), 1623 (s), 1449 (w), 1342 (w), 1275 (w), 1110 (s), 1026 (w), 964 (w), 782 (m). MS
EI, 70 eV): m/z (%) = 166 (59), 148 (21), 120 (11), 110 (23), 106 (28), 99 (100). HRMS (EI)
3
, 300 K):  = 18.3 (q), 22.2 (t),
2
(
+
+
13
m/z: [M] Calcd. for C H O : 166.0988; Found: 166.0983, [M] Calcd. for C C H O :
1
0
14
2
9
1
14
2
−
1
−1
167.1022; Found: 167.1021. UV/vis (CH Cl , c = 0.5 mM): λ = 250 nm (ε = 5976 cm M ).
2
2
3
-Methyl-2-[(3-methylbut-2-en-1-yl)oxy]cyclopent-2-en-1-one (3f)
2
6
According to general procedure 4, compound 3f was synthesized starting from 4f (500 mg,
.46 mmol, 1.0 equiv.), 3,3-dimethylallyl bromide (620 µL, 800 mg, 5.35 mmol, 1.2 equiv.) and
K CO (750 mg, 5.42 mmol, 1.2 equiv.). Purification by flash column chromatography (SiO ,
4
2
3
2
P/Et O = 9/1, UV) afforded the product (558 mg, 3.09 mmol, 69%) as a colorless oil. TLC
2
1
(P/Et O = 3/1): R = 0.26 [UV, KMnO ]. H NMR (300 MHz, C D , 300 K): δ = 1.55 (dd,
2
f
4
6
6
4J = 1.4, 0.8 Hz, 6H), 1.60 – 1.62 (m, 3H), 1.63 – 1.67 (m, 2H), 1.82 – 1.99 (m, 2H), 4.97 (virt.
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dquint., J = 7.1 Hz, J  J = 0.9 Hz, 2H), 5.52 (virt. ddquint., J = 8.4, 5.6 Hz, J  J = 1.4 Hz,
1
3
1
1
1
1
1
H). C{ H} NMR (75 MHz, C D , 300 K):  = 14.5 (q), 18.0 (q), 25.8 (q), 33.1 (t), 66.4 (t),
6
6
21.9 (d), 137.4 (s), 152.2 (s), 152.7 (s), 201.8 (s). IR (ATR): ṽ = 2915 (w), 1700 (vs), 1645 (m),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
443 (w), 1390 (m), 1338 (m), 1205 (m), 1092 (s), 969 (m), 905 (m). MS (EI, 70 eV): m/z (%) =
+
12 (90), 84 (32), 69 (100), 53 (9), 41 (74). HRMS (EI) m/z: [M] Calcd. for C H O :
11 16
2
−
1
−1
180.1145; Found: 180.1143. UV/vis (CH Cl , c = 0.5 mM): λ = 247 nm (ε = 9532 cm M ).
2
2
3
-Ethoxy-5,5-dimethylcyclohex-2-en-1-one
2
1
According to a modified literature procedure: To a solution of dimedone (2.10 g, 15.0 mmol,
.0 equiv.) in 46 mL dry toluene were added EtOH (3.56 mL, 2.80 g, 61.0 mmol, 4.0 equiv.) and
1
p-TsOH∙H O (139 mg, 0.73 mmol, 5.0 mol%). The reaction mixture was heated at reflux using a
2
water separator for 90 min at which point EtOH (3.00 mL, 2.37 g, 50.3 mmol, 3.4 equiv.) was
added. Subsequently, the solution was refluxed for additional 14 h. It was allowed to cool to
room temperature and the solvent was removed under reduced pressure. The crude product was
then filtered over a short plug of Al O (Et O, UV) and the product (2.52 g, 15.0 mmol, 100%)
2
3
2
1
was obtained as a pale yellow oil. TLC (P/Et O = 3/1): R = 0.17 [UV, KMnO ]. H NMR
2
f
4
3
(
300 MHz, CDCl , 300 K): δ = 1.07 (s, 6H), 1.36 (t, J = 7.0 Hz, 3H), 2.21 (s, 2H), 2.27 (s, 2H),
3
3
13
1
3
2
.90 (q, J = 7.0 Hz, 2H), 5.35 (s, 1H). C{ H} NMR (75 MHz, CDCl
3
, 300 K):  = 14.3 (q),
8.4 (q), 32.6 (t), 43.1 (t), 50.8 (t), 64.4 (t), 101.6 (d), 176.5 (s), 199.8 (s). Data of this compound
were in accordance to the literature.21
5,5-Dimethylcyclohex-2-en-1-one
21
According to a modified literature procedure: To an ice-cooled suspension of LiAlH (138 mg,
4
3
.63 mmol, 0.4 equiv.) in 4.0 mL dry THF a solution of S1 (1.50 g, 8.92 mmol, 1.0 equiv.) in
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.5 mL dry THF was added dropwise. Subsequently, the reaction mixture was allowed to warm
to room temperature and stirred for 3 h. The reaction mixture was then cooled to 0 °C and
quenched by the addition of MeOH (approx. 10 mL) until no further gas evolution was observed.
After addition of 14 mL 1 M HCl the reaction mixture was stirred for 30 min, the layers were
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
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3
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3
3
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3
4
4
4
4
4
4
4
4
4
4
5
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5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
separated and the aqueous layer was extracted with Et O (3 × 30 mL). The combined organic
2
layers were washed with brine (2 × 60 mL), dried over Na SO , filtrated and the solvent was
2
4
removed under reduced pressure. After purification by flash column chromatography (SiO2,
P/Et O = 8/1, UV) the product (663 mg, 5.34 mmol, 60%) was obtained as a colorless oil. TLC
2
1
(P/Et O = 1/1): R = 0.29 [UV, KMnO ]. H NMR (300 MHz, CDCl
3
, 300 K): δ = 1.05 (s, 6H,
2
f
4
3
4
3
CH ), 2.24 (dd, J = 4.1 Hz, J = 2.1 Hz, 2H, H-4), 2.27 (s, 2H, H-6), 6.02 (dt, J = 10.1 Hz,
3
4
3
13
1
J = 2.1 Hz, 1H, H-2), 6.86 (dt, J = 10.1, 4.1 Hz, 1H, H3). C{ H} NMR (75 MHz, CDCl , 300
3
K):  = 28.5 (q), 34.0 (s), 40.0 (t), 51.9 (t), 129.1 (d), 148.5 (d), 200.1 (s). Data of this compound
were in accordance to the literature.21
(1SR,6SR)-4,4-Dimethyl-7-oxabicyclo[4.1.0]heptan-2-one (4c)
According to a modified literature procedure:27 To an ice-cooled solution of 5,5-
21
dimethylcyclohex-2-en-1-one (990 mg, 7.97 mmol, 1.0 equiv.) in 16 mL MeOH were dropwise
added H O (30 wt%, 3.30 mL, 1.10 g, 32.3 mmol, 4.1 equiv.) and 6M NaOH (0.64 mL, 154 mg,
2
2
3
.84 mmol, 0.5 equiv.). The reaction mixture was allowed to warm to room temperature and
stirred for 2 h. Subsequently, the reaction mixture was diluted with 32 mL CH Cl and H O was
2
2
2
added until proper phase separation was achieved. The aqueous layer was extracted with CH Cl
2
2
(3× 30 mL). The combined organic layers were washed with brine (2 × 80 mL), dried over
Na SO , filtrated and the solvent was removed under reduced pressure. After purification by flash
2
4
column chromatography (SiO , P/Et O = 2/1, KMnO ) the product (901 mg, 6.43 mmol, 80%)
2
2
4
ACS Paragon Plus Environment
29