Percarboxylic Acid Oxidation of α-Hydroxy-Substituted Alkoxyallenes: The Unexpected Formation of Acyloxy-Substituted 1,2-Diketones and the Synthesis of Functionalized Quinoxalines

Article abstract of DOI:10.1055/s-0035-1561751

Treatment of α-hydroxy-substituted methoxyallene derivatives with meta-chloroperbenzoic acid provided acyloxy-substituted 1,2-diketones in moderate yields. A mechanism for the formation of these unexpected products is proposed. The configuration of the enantiopure compound (S)-1-(3-methylquinoxalin-2-yl)-1-(4-nitrobenzoyl?oxy)propan-2-yl 3-chlorobenzoate - determined by X-ray crystal structure analysis - indicates the intermediacy of a carbenium ion during formation of the 1,2-diketones. The functionalized 1,2-diketones are valuable starting materials for a variety of products as demonstrated by the synthesis of quinoxalines, an imidazole derivative, and electron-deficient alkenes.

Full text of DOI:10.1055/s-0035-1561751

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2016, 48, A–K
A
paper
Synthesis
R. Klemme et al.
Paper
Percarboxylic Acid Oxidation of α-Hydroxy-Substituted Alkoxy-
allenes: The Unexpected Formation of Acyloxy-Substituted
1
,2-Diketones and the Synthesis of Functionalized Quinoxalines
Robby Klemme
Christoph Bentz
Tomasz Zukowski
Luise Schefzig
NH2
NH2
O
OMe
O
O
Ar
O
N
mCPBA
•
R2
Ar
R2
R1
R1
O
Dieter Lentz
HO
N
O
R2
R1
Hans-Ulrich Reissig*
Reinhold Zimmer*
1
2
6 examples
up to 57% yield
R , R = H, alkyl, aryl
Ar = 3-ClC H
5 examples
up to 72% yield
6
4
Institut für Chemie und Biochemie,
Freie Universität Berlin, Takustr. 3, 14195 Berlin,
Germany
hans.reissig@chemie.fu-berlin.de
rzimmer@zedat.fu-berlin.de
Dedicated to Professor Dieter Enders on the occasion of his 70th birthday
Received: 07.01.2016
Accepted after revision: 05.02.2016
Published online: 01.03.2016
products.2 In contrast to the aforementioned reaction
types, oxidations of alkoxyallenes are relatively little ex-
3
DOI: 10.1055/s-0035-1561751; Art ID: ss-2016-t0011-op
plored. Whereas a few substituted alkoxyallenes have been
4
subjected to ozonolyses providing carboxylic esters, the
Abstract Treatment of α-hydroxy-substituted methoxyallene deriva-
tives with meta-chloroperbenzoic acid provided acyloxy-substituted
epoxidation of electron-rich allenes using oxidizing re-
agents such as meta-chloroperbenzoic acid (mCPBA) or di-
1,2-diketones in moderate yields. A mechanism for the formation of
5
methyldioxirane (DMDO) has been rarely studied. An in-
these unexpected products is proposed. The configuration of the enan-
tiopure compound (S)-1-(3-methylquinoxalin-2-yl)-1-(4-nitrobenzoyl-
oxy)propan-2-yl 3-chlorobenzoate – determined by X-ray crystal struc-
ture analysis – indicates the intermediacy of a carbenium ion during
formation of the 1,2-diketones. The functionalized 1,2-diketones are
valuable starting materials for a variety of products as demonstrated by
the synthesis of quinoxalines, an imidazole derivative, and electron-
deficient alkenes.
teresting reaction outcome of the oxidation of allenyl am-
ides with mCPBA was reported by Hsung and co-workers.
They obtained the corresponding α-keto aminals of type I
bearing a 3-chlorobenzoic ester moiety at the aminal moi-
ety (Scheme 1).6
Stimulated by this result, we were interested to adopt
these reaction conditions to α-hydroxy-substituted alkoxy-
allenes as substrates which might lead to 1,2-diketones
bearing an α-oxy functionality. The motif of vicinal polycar-
bonyl groups, especially 1,2-diketone subunits, represents
Key words allenes, alkoxyallenes, quinoxalines, oxidation, peroxides,
ring closure, rearrangement, 1,2-diketones
7
Donor-substituted allenes constitute a fascinating class
an important class of compounds. 1,2-Diketone moieties
of compounds that have notably contributed to organic
are an integral part of numerous natural products and bio-
logically active compounds. Selected examples having em-
1
8
synthesis as C -building blocks. In particular, alkoxyallenes
3
have been utilized in numerous synthetically useful reac-
tions including hydrolysis, substitution and addition reac-
tions, cross-couplings, multicomponent processes, cycload-
ditions, and cyclizations, transformations that lead to a va-
riety of functionalized acyclic, carbocyclic, and heterocyclic
bedded the 1,2-dicarbonyl moiety as an important struc-
tural element are shown in Figure 1, for instance, the anti-
biotic macrolide (–)-grahamimycin A1 (II), the signaling
molecule for bacterial interspecies communication AI-2
O
O
O
O
Cl
mCPBA, CH2Cl2
O
N
N
–70 °C to r.t.
Ph
Ph
•
O
94%
O
I
Scheme 1 Synthesis of I by oxidation of an allenamide with mCPBA
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

B
Synthesis
R. Klemme et al.
Paper
(
(
III), and its precursor (S)-4,5-dihydroxypentane-2,3-dione
DPD, IV).
and water from the commercially available mCPBA, as re-
ported by Schwartz,11 was quite beneficial. Applying the
pre-treated reagent, the desired product 5a was isolated in
a significantly increased yield of 51% (Table 1, entry 2). To
examine the scope of this oxidation, the reactions were also
carried out with α-hydroxy-substituted methoxyallene de-
rivatives 4b–d under these optimized conditions and the
expected products 5b–d were obtained in moderate yields,
ranging from 32 to 57% (Table 1, entries 3–5).
O
OH
O
O
HO
O
HO
O
B
OH
O
HO
HO
O
O
O
O
O
II [(–)-grahamimycin A1]
III (AI-2)
IV (DPD)
Figure 1 Examples of compounds bearing a 1,2-diketone moiety
O
mCPBA
CH2Cl2, 0 °C
Cl
OMe
O
O
First, before starting our investigation using C-1 substi-
tuted methoxyallene derivatives, we subjected the parent
•
R
R
HO
O
compound 1 to similar reaction conditions as reported by
4
6
5
Hsung. Oxidation of methoxyallene (1) using commercially
available mCPBA at 0 °C in dichloromethane furnished the
ketone 2 containing an adjacent acetal unit as a single prod-
uct in 46% yield (Scheme 2). The oxidation of 1 apparently
occurs in full analogy to that of the allenamide studied by
Hsung.
Scheme 4 Oxidation of aldehyde-derived α-hydroxy-substituted meth-
oxyallenes 4a–d with mCPBA leading to 1,2-diketone derivatives 5a–d
Table 1 Oxidation of α-Hydroxy-Substituted Methoxyallenes 4a–d to
1,2-Diketones 5a–d
mCPBA
CH2Cl2, 0 °C
O
Methoda
Entry
R
4
5
Yield of 5
O
OMe
Cl
O
•
1
2
3
4
cyclohexyl
cyclohexyl
(CH2)10Me
Ph
4a
4a
4b
4c
4d
A
B
B
B
B
5a
5a
5b
5c
5d
20%
51%
57%
47%
32%
46%
OMe
1
2
Scheme 2 Oxidation of methoxyallene (1) leading to acetal 2
5
2
CH OBn
a
Method A: commercial mCPBA was used without pre-treatment. Method
11
The α-hydroxy-substituted methoxyallene derivatives 4
required for this study were prepared from methoxyallene
B: mCBPA was pre-treated with a buffer solution (see Supporting Informa-
tion).
(
1), which is easily converted into the lithiated species 3
and subsequently treated with the corresponding aldehyde
using a well-known standard protocol (Scheme 3).
At this point, it should be mentioned that the moderate
yields of products 5 may be attributed by some unavoidable
side reactions, e.g. over-oxidation or hydrolysis, that could
not completely suppressed despite the optimized reaction
conditions. However, no side-products proving this as-
sumption were isolated.
9
RCHO
nBuLi
OMe
OMe
Li
OMe
Et2O, –78 °C
–78 °C
•
•
•
R
We briefly examined the oxidation protocol employing
HO
1
3
4
ketone-derived α-hydroxy-substituted methoxyallenes 6.
Scheme 3 Synthesis of α-hydroxy-substituted methoxyallene deriva-
tives 4
12
Treatment of 6a (R = Me) and 6b (R = CF ) with mCPBA by
3
using the optimized reaction conditions furnished the ex-
pected 1,2-diketones 7a,b bearing a quaternary center in
moderate yields (Scheme 5).
We initiated our oxidation studies with the screening of
the reaction conditions for the transformation of methoxy-
allene derivatives 4 using mCPBA (Scheme 4). In the first in-
stance, the cyclohexyl-substituted methoxyallene deriva-
tive 4a was treated at 0 °C with commercially available
mCPBA (70%, containing water and m-chlorobenzoic acid)10
in dichloromethane. These conditions furnished the 1,2-
diketone derivative 5a bearing a 3-chlorobenzoic ester unit,
but the yield was only 20% (Table 1, entry 1). We noticed
that a pre-treatment removing the m-chlorobenzoic acid
O
mCPBA
CH2Cl2, 0 °C
Cl
OMe
O
O
•
R
R
HO
a: R = Me: 35%
b: R = CF3: 47%
O
6
7
Scheme 5 Oxidation of ketone-derived α-hydroxyallenes 6
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

C
Synthesis
R. Klemme et al.
Paper
The observed reactions of α-hydroxy-substituted meth-
oxyallene derivatives 4 and 6 not only involve an oxidation,
but also an unprecedented incorporation of m-chloroben-
zoic acid into the product. A plausible mechanism of this
transformation of A is shown in Scheme 6. The oxidation of
A with mCPBA at the electron-rich double bond regioselec-
yield as a mixture of two diastereomers (57:43). Due to the
protected hydroxyl group of precursor 8 the mechanism as
depicted in Scheme 6 is interrupted after formation of the
O-silylated intermediate D. Due to the bulky silyl group the
cyclization to intermediates analogous to E (and subse-
quently formation of F) is not possible, but O-silylated D di-
rectly reacts with the carboxylate to provide the isolated
product 9. The very low diastereoselectivity of this step is
not surprising since no significant stereocontrol can be ex-
pected for the addition of the nucleophile to the corre-
sponding oxocarbenium ion.13
5c
tively forms the epoxide B that is ring-opened under the
acidic reaction conditions to the enol C. Subsequent ring
closing of its keto tautomer D leads to the protonated epox-
ide E. The nucleophilic attack of the carboxylate ArCOO–
opens this highly reactive intermediate to deliver after
elimination of methanol product 5. Alternatively, the over-
all process may also be explained by ring opening of E to
give carbenium ion F followed by its trapping by the car-
boxylate and release of methanol. A result presented below
indicates that the pathway via carbenium ion F may be the
preferred one. We cannot rigorously exclude an alternative
mCPBA
CH2Cl2, 0 °C
OMe
O
OTBS
•
Ph
OTBS
Ph
OMe
5
5%
ArCOO
(dr = 57:43)
8
9
1
route to 5 via compound 9 (R = H) that may undergo an
[
Ar = 3-ClC6H4]
acyl transfer; however, this mechanism seems to be less
likely under the acidic reaction conditions.
Scheme 7 Oxidation of O-silylated methoxyallene derivative 8 leading
to product 9
OMe
R2
O
OMe
R2
HO
OMe
R2
•
mCPBA
+
H
We attempted the oxidation of α-hydroxy-substituted
methoxyallene derivative 4b using other oxidation reagents
instead of mCPBA. However, no clear reaction outcome was
observed using MMPP (magnesium monoperoxyphthalate),
RuCl /NaIO , or DMDO (dimethyldioxirane), only decompo-
1
1
R O
R O
1
R O
A
B
C
3
4
sition of the starting material occurred or hydrolysis of the
enol ether unit of 4b leading to the corresponding α,β-un-
saturated ketone was observed. When the oxidation of 4b
was performed with peracetic acid (employed as a 35%
aqueous solution) at –78 °C the 3-acetoxy-substituted 1,2-
diketone 10 was obtained in 38% yield (Scheme 8). This ex-
ample demonstrated that other peracids can also be applied
furnishing the 1,2-diketones with the corresponding acid
unit as substituent.
OMe
O
OMe
OH
O
OMe
R2
O
O
R2
R2
R1 = H
1
H
R O
F
E
D
+
ArCO2
MeOH
MeCO3H
CH2Cl2, –78 °C
OMe
O
OAc
–
R1 = TBS
+ ArCO2
OR1
•
1
0
O
O
38%
10
HO
4b
O
O
Ar
O
10
R2
R2
OMe
Scheme 8 Oxidation of 4b using peracetic acid leading to 1,2-diketone
derivative 10
O
ArCOO
5
[Ar = 3-ClC6H4]
9
Having attained access to functionalized 1,2-diketones
of type 5, we turned our attention to their conversion into
subsequent products by taking advantage of the 1,2-dicar-
bonyl unit. An obvious and useful application is the con-
densation of these compounds with aromatic 1,2-diamines
leading to quinoxalines that are well known as biologically
active heterocycles.14 1,2-Diketones 5a–c and 7b smoothly
underwent the condensation reaction with o-phenylenedi-
amine (11) in the presence of cerium ammonium nitrate
Scheme 6 Proposed mechanism for the formation of 1,2-diketones 5
or of compounds 9
A control experiment was performed in order to con-
firm the mechanism proposed above. For this purpose, the
O-silylated allene derivative 8 was subjected to the stan-
dard oxidation protocol with mCPBA (Scheme 7). Com-
1
pound 9 (R = TBS) bearing a ketal unit was formed in 55%
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

D
Synthesis
R. Klemme et al.
Paper
(
CAN) in water at ambient temperature15 affording the cor-
responding quinoxaline derivatives 12a–d in 60–72% yield
O
OTBS
OMe
•
OTBS
mCPBA, CH2Cl2, 0 °C
3%
(Scheme 9, Table 2).
O
O
Ar
O
4
HO
O
CAN
H2O, r.t.
O
H2N
Ar
+
N
N
4e (dr = 83:17)
5e (dr = 90:10)
O
O
Ar
R2
O
1
1, CAN
H O, r.t.
R1
or 7b
Ar = 3-ClC6H4]
H2N
71%
R1 R2
O
2
5
11
12
N
N
OTBS
OOCAr
[
TBAF, THF, r.t.
1%
N
Scheme 9 Condensation reaction of functionalized 1,2-diketones 5a–
c and 7b with o-phenylenediamine (11) leading to quinoxaline deriva-
tives 12a–d
N
5
OOCAr
OH
1
2e (dr = 88:12)
13 (dr = 93:7)
Table 2 Preparation of Quinoxaline Derivatives 12a–d
4-O2NC6H4COCl
4
7%
DMAP, Et3N, CH2Cl2, r.t.
Entry
5 or 7
R1
R2
12
12a
Yield of 12
1
2
3
5a
5b
5c
7b
cyclohexyl
(CH
H
71%
72%a
68%
60%
N
N
OOCAr
2
)
10Me
H
12b
12c
12d
Ph
H
4
Me
CF
3
O
O
a
Quinoxaline derivative 12b was also obtained using an alternative protocol
NH Cl (50 mol%), MeOH, rt, 50 min] in 84% yield.
4
[Ar = 3-ClC6H4]
16
[
In order to gain additional insight into the mechanism
NO2
14 (dr = 95:5)
of the oxidation reaction discussed in Scheme 6, we were
interested to get an X-ray crystal structure analysis of one
of the suitably functionalized 1,2-diketones or their deriva-
tives. We therefore investigated the methoxyallene deriva-
tive 4e obtained as an isomeric mixture (anti/syn = 83:17)17
from enantiopure O-silylated (S)-lactaldehyde. As shown in
Scheme 10, the oxidation of the α-hydroxy-substituted me-
thoxyallene derivative 4e afforded product 5e in 43% yield
with a similar ratio of diastereomers (anti/syn = 90:10). The
conversion of 5e into the corresponding quinoxaline deriva-
tive was achieved according to the procedure described
above, leading to 12e in reasonable yield with an anti/syn
ratio of 88:12. To obtain a suitable crystalline compound,
we tried to converted 12e into the corresponding com-
pound bearing a p-nitrobenzoic ester at C-1 of the side-
chain. However, after desilylation of 12e with TBAF by a
standard procedure, esterification of the desilylated inter-
mediate with p-nitrobenzoic chloride afforded the unex-
pected product 14 as a diastereomeric mixture (dr = 95:5).
Apparently, during the first deprotection step an acyl group
migration occurred, shifting the 3-ClC H CO substituent to
Scheme 10 Preparation of quinoxaline derivative 14 starting from
methoxyallene derivative 4e
aration of both diastereomers, we were able to obtain suit-
able crystals of the major isomer of 14 for an X-ray crystal
structure analysis (Figure 2). The crystal structure proves
the constitution of the compound (and the unexpected acyl
group migration) and the configurations at C-1 and C-2 as
1R and 2S revealing an anti-configuration of compound 14.
It is very likely that the acyl migration during the conver-
sion of 12e to 13 occurs under retention of configuration
and therefore compound 12e should also have 1R and 2S
configurations at its stereogenic centers.
6
4
the free hydroxyl group at C-2. The driving force for this
reversible) migration may be the lower repulsion of the
(
bulky quinoxaline moiety and the arylcarbonyloxy group.
The esterification in the next step then occurred at the re-
maining hydroxyl group at C-1. After chromatographic sep-
Figure 2 Molecular structure of the major diastereomer of compound
1
4 (thermal ellipsoid of 50% probability)
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

E
Synthesis
R. Klemme et al.
Paper
A nucleophilic attack of the m-chlorobenzoate anion to
intermediate E (Scheme 6) requires an inversion of configu-
ration of the attacked epoxide carbon atom and hence this
center should have (S)-configuration for the major diaste-
reomers of 12e and 14, respectively. However, this stereo-
genic center of quinoxaline 14 has (R)-configuration and
hence a diastereoselective addition of the carboxylate to
the acyclic intermediate F is more likely. Due to the neigh-
boring stereogenic center the observed anti-configuration
is induced with preference resulting mainly in overall re-
tention of configuration at this carbon. The high diastereo-
2-amino-substituted thiophene derivative 17 although only
in 16% yield. This sobering result shows that highly func-
tionalized carbonyl compounds such as 5a are not ideal
precursors for the Gewald multicomponent reaction and
probably give many (unidentified) side products.
Since 4-oxoalk-2-enoates are interesting starting mate-
rials for the synthesis of complex molecular scaffolds we
also examined their formation by Wittig olefination of 1,2-
diketones 5.20 However it was not clear whether there will
be any preference for one of the two ketone moieties pres-
ent in these precursors. The Wittig reactions of 1,2-dike-
tones 5a or 5b with one equiv of the stabilized phos-
phorane 18 took place under typical conditions20 smoothly
furnishing the two regioisomeric α,β-unsaturated carbox-
ylic esters 19a,b and 20a,b in decent combined yields and
exclusively as E-isomers. In both cases, the products could
be separated by column chromatography or HPLC. The pre-
ferred olefinations of 5a and 5b at the sterically less hin-
dered methyl ketone moiety was confirmed by the NMR da-
13
selectivity of this step is nevertheless surprising.
After the successful preparation of quinoxalines 12 we
also checked the feasibility of converting 1,2-diketones 5
into functionalized imidazole and thiophene derivatives
(
Scheme 11). For example, according to a protocol de-
18
scribed by Breslin et al. the synthesis of the trisubstituted
imidazole 15 was carried out by the condensation of 1,2-
diketone 5b with 1.5 equiv of benzaldehyde and 8.5 equiv
of ammonium acetate in acetic acid at 100 °C. The forma-
tion of the additional C–C double bond is due to the elimi-
nation of m-chlorobenzoic acid under the relatively harsh
conditions applied. No intermediate compound still bearing
1
ta. In the H NMR spectra of compounds 19 two sets of sig-
nals attributable to methyl group (δ = ~2.3) and the newly
generated olefinic proton (δ = ~6.5) showing a small allylic
coupling constant of ~1–1.5 Hz prove the proposed assign-
ment for the major regioisomers.
the ArCO group was observed. A modified Gewald proto-
2
19
col was applied to 1,2-diketone derivative 5a with sulfur
In this report we demonstrate that a series of α-hy-
droxy-substituted methoxyallenes 4 and 6 can be easily ox-
idized with mCPBA to provide 3-acyloxy-substituted 1,2-
diketone derivatives 5 and 7 in reasonable yields. These
compounds are valuable starting materials for a quick ac-
cess to synthetically important target molecules21 as shown
by the synthesis of numerous heterocycles, for instance qui-
noxalines 12, imidazole 15, and thiophene 17, as well as by
the regioselective preparation of 4-oxoalk-2-enoates 19
and 20. The herein reported results again emphasize the
versatility of alkoxyallenes as synthetically highly useful
and flexible key compounds.
in the presence of KF-Al O as base leading to the expected
2
3
O
PhCHO (1.5 equiv)
NH4OAc (8.4 equiv)
AcOH, 100 °C, 20 min
Ph
O
O
Ar
HN
N
10
O
57%
9
5
b
15
NC
CO2Me
O
O
1
6
O
O
MeO2C
S8, KF-Al2O3
EtOH, 85 °C
O
O
Ar
Ar
Reactions were generally performed under argon in flame-dried
flasks. Solvents and reagents were added by syringe. Solvents were
dried using standard procedures. Reagents were purchased and were
used as received without further purification unless stated. The start-
H2N
1
6%
S
O
5
a
17
ing materials 4c, 4e, 6a, and 8 were prepared according to liter-
ature procedures. Pre-treatment of mCPBA was performed according
22
17
12
23
11
to ref. Reactions were monitored by TLC. Products were purified by
column chromatography on silica gel (32–63 μm). Unless otherwise
stated, yields refer to chromatographically homogeneous and spec-
CO2Me
8
MeO2C
CH2Cl2, r.t.
6–19 h
O
R
O
R
Ph3P
O
R
1
O
Ar
O
O
Ar
1
O
O
Ar
troscopically pure materials ( H NMR spectroscopy). NMR spectra
1
+
were recorded with JEOL (ECX 400, Eclipse 500) instruments. Chemi-
1
13
cal shifts are reported relative to TMS ( H: δ = 0.00) and CDCl
( C:
3
O
O
CO2Me
20a,b
13
δ = 77.0). Integrals are in accordance with assignments. C NMR
spectra are H-decoupled; signals marked with * correspond to 2 C at-
1
5
a,b
19a,b
oms. MS and HRMS analyses were performed with a Varian Ionspec
QFT-7 instrument (ESI-FT ICRMS). IR spectra were measured with a
spectrophotometer 5 SXC Nicolet or a Nicolet Smart DuraSamplIR
ATR spectrophotometer. Elemental analyses were carried out with a
Vario EL Elemental Analyzer. Melting points were measured with a
a (R = cyclohexyl): 67%
b (R = (CH2)10Me): 65%
(19a:20a = 75:25)
(19b:20b = 65:35)
[
Ar = 3-ClC6H4]
Scheme 11 Synthesis of imidazole derivative 15, thiophene derivative
7, and 4-oxoalk-2-enoates 19 and 20 from 1,2-diketones 5a,b
1
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

F
Synthesis
R. Klemme et al.
Paper
1
Reichert apparatus (Thermovar) and are uncorrected. Optical rota-
H NMR (CDCl , 400 MHz): δ = 0.88 (t, J = 6.4 Hz, 3 H, Me), 1.15–1.60
3
tions ([α] ) were determined with Perkin–Elmer 141 or Perkin–Elmer
(m, 18 H, 9 CH ), 1.79–1.93 (m, 2 H, CH ), 2.41 (s, 3 H, Me), 5.70 (dd,
D
2
2
241 polarimeter at the temperatures given.
J = 5, 7.5 Hz, 1 H, CH), 7.49 (dd, J = 7.3, 8.2 Hz, 1 H, Ar), 7.57 (d, J = 8.2
Hz, 1 H, Ar), 7.94 (d, J = 7.3 Hz, 1 H, Ar), 8.02 (s, 1 H, Ar).
13
1,2-Diketone Derivatives 5 and 7; General Procedure 1 (GP1)
C NMR (CDCl , 125.8 MHz): δ = 14.1 (q, Me), 22.7 (t, CH ), 24.3 (q,
3 2
The α-hydroxy-substituted methoxyallene 4 (or 6) was dissolved in
CH Cl and cooled to 0 °C. After addition of mCPBA (1–1.5 equiv, used
Me), 25.5, 29.3, 29.35, 29.43, 29.48, 29.57*, 30.1, 31.9 (9 t, 10 CH
75.5 (d, CH), 128.0, 129.8, 129.85 (3 d, Ar), 130.5 (s, Ar), 133.5 (d, Ar),
134.7 (s, Ar), 165.1 (s, CO Ar), 193.9, 196.6 (2 s, C=O).
2
),
2
2
after pre-treatment, see above) the suspension was stirred for the re-
quired time (2–5 h). The mixture was quenched by addition of H O (1
2
2
Anal. Calcd for C22H31ClO (394.9): C, 66.91; H, 7.91. Found: C, 67.43;
4
mL/mmol of substrate) and extracted with CH Cl (3 × 5 mL/mmol of
2
2
H, 8.45.
substrate). The combined organic extracts were dried (Na SO ) and
2
4
concentrated. The residue was purified by column chromatography
silica gel, hexanes/EtOAc) to afford 5 (or 7).
2
,3-Dioxo-1-phenylbutyl 3-Chlorobenzoate (5c)
According to GP1, a solution of methoxyallene derivative 4c (1.95 g,
1.0 mmol) and mCPBA (4.07 g, 16.5 mmol) dissolved in CH Cl2 (30
(
1
2
1-Methoxy-2-oxopropyl 3-Chlorobenzoate (2)
mL) was stirred for 3 h at 0 °C. Work-up and column chromatography
hexanes/EtOAc 6:1) afforded 5c (1.63 g, 47%) as a yellow oil.
According to GP1, a solution of methoxyallene (1, 3.50 g, 50.0 mmol)
and mCPBA (18.5 g, 75.0 mmol; commercially available mCPBA) dis-
solved in CH Cl (100 mL) was stirred for 3 h at 0 °C. Work-up and col-
(
IR (neat): 3070–2875 (=C–H, C–H), 1715 (C=O), 1245 cm–1 (C–Cl).
2
2
1
H NMR (CDCl , 250 MHz): δ = 2.33 (s, 3 H, Me), 6.89 (s, 1 H, CH),
umn chromatography (hexanes/EtOAc 4:1) afforded 2 (5.60 g, 46%) as
a colorless oil.
IR (neat): 3075–2845 (=C–H, C–H), 1735 (C=O), 1260 cm–1 (C–Cl).
3
7.37–7.46, 7.52–7.62 (2 m, 3 H, 2 H, Ph, Ar), 7.56 (m , 2 H, Ar), 7.97
c
(m , 1 H, Ar), 8.05 (s, 1 H, Ar).
c
13
C NMR (CDCl , 125.8 MHz): δ = 24.1 (q, Me), 77.3 (d, CH), 128.3,
1
3
H NMR (CDCl , 500 MHz): δ = 2.30 (s, 3 H, Me), 3.60 (s, 3 H, OMe),
3
128.9, 129.4, 130.06, 130.1, 130.15 (6 d, Ph, Ar), 130.8, 131.3 (2 s, Ph,
5.97 (s, 1 H, CH), 7.38–7.43, 7.55–7.58, 7.92–7.97, 8.02–8.08 (4 m, 1 H
Ar), 133.8 (d, Ar), 134.8 (s, Ar), 165.1 (s, CO Ar), 190.4, 196.0 (2 s,
C=O).
HRMS (80 eV): m/z [M + H]+ calcd for C17H14ClO : 317.0581; found:
2
each, Ar).
13
C NMR (CDCl , 125.8 MHz): δ = 25.2 (q, Me), 57.7 (q, OMe), 98.2 (d,
3
4
CH), 128.0, 129.8*, 129.86, 129.89, 134.7 (2 d, 2 s, d, Ar), 164.5 (s,
317.0588.
CO Ar), 199.6 (s, C=O).
2
Anal. Calcd for C11H11ClO4 (242.7): C, 54.45, H 4.57. Found: C, 54.24;
H, 4.12.
1
-(Benzyloxy)-3,4-dioxopentan-2-yl 3-Chlorobenzoate (5d)
According to GP1, a solution of methoxyallene derivative 4d (0.706 g,
.21 mmol) and mCPBA (0.790 g, 3.21 mmol) dissolved in CH Cl (30
3
2
2
1
-Cyclohexyl-2,3-dioxobutyl 3-Chlorobenzoate (5a)
According to GP1, a solution of methoxyallene derivative 4a (0.710 g,
.90 mmol) and mCPBA (1.44 g, 5.85 mmol) dissolved in CH Cl (20
mL) was stirred for 3 h at 0 °C. Work-up and column chromatography
hexanes/EtOAc 4:1) afforded 5d (0.370 g, 32%) as a yellow oil.
(
3
2
2
IR (neat): 3070–2870 (=C–H, C–H), 1720, 1700 (C=O), 1260 cm–1 (C–Cl).
mL) was stirred for 3 h at 0 °C. Work-up and column chromatography
hexanes/EtOAc 4:1) afforded 5a (0.638 g, 51%) as a yellow solid; mp
7–60 °C.
1
H NMR (CDCl , 250 MHz): δ = 2.35 (s, 3 H, Me), 3.91 (dd, J = 3.5, 11.2
(
5
3
Hz, 1 H, CH O), 4.20 (dd, J = 5.2, 11.2 Hz, 1 H, CH O), 4.52, 4.59 (AB
system, JAB = 12.0 Hz, 1 H each, CH O), 6.07 (dd, J = 3.5, 5.2 Hz, 1 H,
CHO), 7.22–7.43, 7.52–7.58 (2 m, 6 H, 1 H, Ar, Ph), 7.95 (br d, J ~ 6 Hz,
1 H, Ar), 8.05 (t, J = 1.7 Hz, 1 H, Ar).
2
2
IR (KBr): 3070–2850 (=C–H, C–H), 1715, 1700 (C=O), 1250 cm–1 (C–Cl).
2
1
H NMR (CDCl , 250 MHz): δ = 1.10–2.10 (m, 11 H, CH, 5 CH ), 2.40 (s,
3
2
3
H, Me), 5.57 (d, J = 5.9 Hz, 1 H, CH), 7.37–7.45, 7.54–7.60, 7.90–8.12
13
C NMR (CDCl , 100.8 MHz): δ = 23.9 (q, Me), 68.4, 73.5 (2 t, 2 CH ),
3
2
(3 m, 1 H, 1 H, 2 H, Ar).
75.4 (d, CH), 127.8, 128.1, 128.2, 128.6, 129.9, 130.1, 130.6, 133.5,
13
C NMR (CDCl , 125.8 MHz): δ = 23.8 (q, Me), 25.7, 25.8, 25.9, 28.1,
3
134.6, 136.9 (7 d, 3 s, Ar, Ph), 164.9 (s, CO Ar), 191.3, 196.3 (2 s, C=O).
HRMS (ESI): m/z [M + H]+ calcd for C19H18ClO : 361.0843; found:
2
2
1
8.2 (5 t, 5 CH ), 39.0 (d, CH), 77.9 (d, CH), 127.9, 129.7, 129.8, 133.5,
2
5
34.6 (2 d, s, d, s, Ar), 165.2 (s, CO Ar), 194.2, 196.4 (2 s, C=O).
2
361.0851.
HRMS (80 eV): m/z [M + Na]+ calcd for C17H19ClNaO : 345.0864;
4
found: 345.0871.
(2S)-2-(tert-Butyldimethylsiloxy)-4,5-dioxohexan-3-yl 3-Chloro-
UV-Vis (CHCl ): λ (log ε) = 285 (3.2), 428 nm (1.7).
benzoate (5e)
3
Anal. Calcd for C17H19ClO (322.8): C, 63.26; H, 5.93. Found: C, 63.20;
H, 5.95.
According to GP1, a solution of methoxyallene derivative 4e (0.491 g,
1.90 mmol; anti/syn 83:17) and mCPBA (0.703 g, 2.85 mmol) dis-
solved in CH Cl (20 mL) was stirred for 3 h at 0 °C. Work-up and col-
4
2
2
umn chromatography (hexanes/EtOAc 6:1) afforded 5e (0.318 g, 43%,
two diastereomers = 90:10) as a yellow solid; mp 159 °C.
IR (neat): 3060–2855 (=C–H, C–H), 1725, 1710 cm–1 (C=O).
2
,3-Dioxopentadecan-4-yl 3-Chlorobenzoate (5b)
According to GP1, a solution of methoxyallene derivative 4b (1.21 g,
.75 mmol) and mCPBA (1.75 g, 7.12 mmol) dissolved in CH Cl (20
4
2
2
mL) was stirred for 3 h at 0 °C. Work-up and column chromatography
hexanes/EtOAc 4:1) afforded 5b (1.99 g, 57%) as a yellow oil.
IR (neat): 3070–2880 (=C–H, C–H), 1710 (C=O), 1245 cm–1 (C–Cl).
1
H NMR (CDCl , 400 MHz): δ = 0.03, 0.09 (2 s, 3 H each, OSiMe ), 0.83
3
2
(
(s, 9 H, SitBu), 1.38 (d, J = 6.4 Hz, 3 H, Me), 2.38 (s, 3 H, Me), 4.37 (m , 1
c
H, 2-H), 5.72 (d, J = 6.1 Hz, 1 H, 3-H), 7.40 (dd, J = 7.6, 8.3 Hz, 1 H, Ar),
.52–7.58, 7.88–7.94 (2 m, 1 H each, Ar), 7.99 (t, J = 1.9 Hz, 1 H, Ar).
7
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

G
Synthesis
R. Klemme et al.
Paper
13
13
C NMR (CDCl , 100.8 MHz): δ = –5.1, –4.5 (2 q, SiMe ), 17.9 (s, C–Si),
C NMR (CDCl , 125.8 MHz): δ = –7.2, –6.8, –6.3 (3 q, SiMe ), 16.4,
3
2
3
2
2
1
1
1.2, 23.7 (2 q, 2 Me), 25.7 (q, SitBu), 69.1, 77.1 (2 d, C-2, C-3), 128.0,
25.2 (s, q, SitBu), 26.0, 26.6 (2 q, Me), 51.4, 51.5 (2 q, OMe), 75.3, 77.8
(2 d, CH), 100.7, 101.0 (2 s, COO), 126.1, 126.3, 126.34, 126.8, 126.9,
128.2 (6 d, Ph, Ar), 130.7, 131.0 (2 s, Ph, Ar), 133.6, 133.9 (2 d, Ar),
29.8, 129.9, 130.5, 133.5, 134.5 (3 d, s, d, s, Ar), 164.8 (s, CO Ar),
2
93.7, 195.4 (2 s, C=O).
1
35.3, 135.9 (2 s, Ar), 161.5, 161.53 (2 s, CO Ar), 203.5, 204.1 (2 s,
The following NMR signals could be assigned to the minor diastereo-
mer:
2
C=O).
HRMS (80 eV): m/z [M + Na]+ calcd for C24
found: 485.1525.
H31ClNaO Si: 485.1527;
1
5
H NMR (CDCl , 400 MHz): δ = 0.05, 0.11 (2 s, 3 H each, OSiMe ), 0.85
3
2
(
(
1
s, 9 H, SitBu), 1.28 (d, J = 6.4 Hz, 3 H, Me), 2.37 (s, 3 H, Me), 4.49–4.60
m, 1 H, 2-H), 5.90 (d, J = 4.8 Hz, 1 H, 3-H), 8.02 (m , 1 H, Ar).
Anal. Calcd for C24H31ClO Si (463.0): C, 62.25; H, 6.75. Found: C, 62.91;
H, 7.02.
c
5
3
C NMR (CDCl , 100.8 MHz): δ = 68.0, 77.4 (2 d, C-2, C-3).
3
HRMS (ESI): m/z [M + H]+ calcd for C19H28ClO Si: 399.1394; found:
5
2
,3-Dioxopentadecan-4-yl Acetate (10)
399.1393.
A solution of methoxyallene derivative 4b (1.14 g, 4.48 mmol) in
CH Cl (25 mL) was cooled to –78 °C. After the addition of 35% aq per-
2
2
2
-Methyl-3,4-dioxopentan-2-yl 3-Chlorobenzoate (7a)
acetic acid solution (1.50 mL, 6.72 mmol), the mixture was stirred for
h at this temperature. Water (5 mL) was added, the aqueous phase
was extracted with CH Cl (2 × 10 mL), and the combined organic
According to GP1, a solution of methoxyallene derivative 6a (1.20 g,
0.7 mmol) and mCPBA (3.05 g, 12.4 mmol) dissolved in CH Cl (25
3
1
2
2
2
2
mL) was stirred for 3 h at 0 °C. Work-up and column chromatography
hexanes/EtOAc 6:1) afforded 7a (1.00 g, 35%) as a yellow oil.
phases were dried (Na SO ). After removal of the solvent, the residue
2
4
(
was purified by column chromatography (hexanes/EtOAc 6:1) to yield
10 (0.508 g, 38%) as a yellow oil.
IR (neat): 3075–2945 (=C–H, C–H), 1715, 1700 (C=O), 1265 cm–1 (C–Cl).
1
IR (ATR): 2930–2855 (=C–H, C–H), 1745, 1725, 1715 (C=O), 1235 cm–1
H NMR (CDCl , 500 MHz): δ = 1.72 (s, 6 H, 2 Me), 2.36 (s, 3 H, Me),
3
7.36–7.43, 7.54–7.60, 7.87–7.94, 7.98–8.03 (4 m, 1 H each, Ar).
(C–Cl).
13
1
C NMR (CDCl , 125.8 MHz): δ = 24.2, 24.3 (2 q, Me), 30.7 (q, Me),
H NMR (CDCl , 250 MHz): δ = 0.88 (t, J = 7.0 Hz, 3 H, Me), 1.09–1.44,
3
3
83.0 (s, CO), 127.8, 129.7*, 130.1, 133.8, 134.4 (2 d, 2 s, d, Ar), 166.0 (s,
1.56–1.85 (2 m, 18 H, 2 H, 10 CH ), 2.11, 2.36 (2 s, 3 H each, Me), 5.43
2
CO Ar), 196.7, 197.0 (2 s, C=O).
(dd, J = 4.5, 8.3 Hz, 1 H, CH).
2
13
Anal. Calcd for C13H13ClO (268.7): C, 58.11; H, 4.88. Found: C, 57.75;
C NMR (CDCl , 100.8 MHz): δ = 14.1 (q, Me), 20.3 (t, CH ), 22.6, 24.0
3 2
4
H, 4.74.
(2 q, 2 Me), 25.3, 29.1, 29.3, 29.5, 29.6*, 30.1, 31.9* (7 t, CH ), 74.3 (d,
2
CH), 170.9 (s, CO Ar), 194.4, 196.7 (2 s, C=O).
2
1
(
,1,1-Trifluoro-2-methyl-3,4-dioxopentan-2-yl 3-Chlorobenzoate
7b)
According to GP1, a solution of methoxyallene derivative 6b (1.00 g,
.50 mmol) and mCPBA (2.03 g, 8.25 mmol) dissolved in CH Cl (25
HRMS (80 eV): m/z [M + K]+ calcd for C17H30KO : 337.1784; found:
4
337.1806.
UV-Vis (CHCl ): λ (log ε) = 281 (0.7), 427 nm (1.9).
3
5
2
2
mL) was stirred for 3 h at 0 °C. Work-up and column chromatography
hexanes/EtOAc 4:1) afforded 7b (0.673 g, 47%) as a yellow wax.
IR (ATR): 3075–2885 (=C–H, C–H), 1720, 1700 (C=O), 1260 cm–1 (C–Cl).
Quinoxaline Derivatives 12; General Procedure 2 (GP2)
(
A mixture of 1,2-diketone 5 (or 7) (1 equiv), o-phenylenediamine (11,
1.25–2 equiv), and CAN (0.05–0.15 equiv) in water (3–10 mL/mmol of
1
H NMR (CDCl , 400 MHz): δ = 1.93 (s, 3 H, Me), 2.38 (s, 3 H, Me), 7.41
substrate) was vigorously stirred at room temperature for the time
indicated. The mixture was then diluted with EtOAc (10–30 mL/mmol
of substrate) and washed with water (3 × 10 mL/mmol of substrate).
3
(dd, J = 9.6, 6.3 Hz, 1 H, Ar), 7.60 (ddd, J = 8.0, 2.0, 1.0 Hz, 1 H, Ar), 7.88
–
7.92 (m, 1 H, Ar), 7.96 – 8.00 (m, 1 H, Ar).
1
3
The organic layer was dried (Na SO ) and filtered, and the filtrate was
evaporated under reduced pressure. The residue was purified by flash
chromatography (hexanes/EtOAc).
C NMR (CDCl , 100.8 MHz): δ = 17.7, 24.3 (2 q, 2 Me), 82.3 (q,
2 4
3
2J = 29.1 Hz, C–O), 122.2 (q, JCF = 285 Hz, CF ), 128.3, 129.3, 130.0,
1
1
CF
3
30.1, 134.5, 134.9 (d, s, 3 d, s, Ar), 165.1 (s, CO Ar), 188.4, 193.9 (2 s,
2
C=O).
Cyclohexyl(3-methylquinoxalin-2-yl)methyl 3-Chlorobenzoate
Anal. Calcd for C13H10ClF O (322.7): C, 48.39; H, 3.12. Found: C,
3
4
(12a)
48.45; H, 2.98.
According to GP2, a mixture of 1,2-diketone derivative 5a (0.118 g,
0
.365 mmol), diamine 11 (0.050 g, 0.460 mmol), and CAN (0.010 g,
1
-(tert-Butyldimethylsiloxy)-2-methoxy-3-oxo-1-phenylbutan-2-
0.018 mmol) dissolved in water (1 mL) was stirred for 30 min at room
yl 3-Chlorobenzoate (9)
temperature. Work-up and column chromatography (hexanes/EtOAc
:1) afforded 12a (0.103 g, 71%) as a viscous orange oil.
According to GP1, a solution of methoxyallene derivative 8 (3.20 g,
4
11.0 mmol) and mCPBA (4.06 g, 16.5 mmol) dissolved in CH Cl (30
2 2
IR (neat): 3065–2850 (=C–H, C–H), 1720 cm–1 (C=O).
mL) was stirred for 3 h at 0 °C. Work-up and column chromatography
1
(
hexanes/EtOAc
diastereomers = 57:43) as a colorless oil.
IR (neat): 3070–2845 (=C–H, C–H), 1720, 1700 cm–1 (C=O).
6:1)
afforded
9
(2.79
g,
55%;
two
H NMR (CDCl , 250 MHz): δ = 1.15–1.35, 1.65–1.90 (2 m, 11 H, CH,
3
CH ), 2.97 (s, 3 H, Me), 5.96 (d, J = 8.9 Hz, 1 H, CH), 7.34–7.40, 7.50–
7.55, 7.65–7.70, 7.93–8.08 (4 m, 1 H, 1 H, 3 H, 3 H, Ar).
2
13
1
C NMR (CDCl , 100.8 MHz): δ = 22.8 (q, Me), 25.6, 25.8, 26.2, 28.8,
3
H NMR (CDCl , 250 MHz): δ = –0.24 (s, 1.7 H, SiMe ), –0.17 (s, 1.3 H,
3
2
2
1
1
9.4 (5 t, 5 CH ), 41.9 (d, CH), 78.3 (d, CH), 127.9, 128.4, 129.0, 129.1,
SiMe ), –0.01 (s, 1.7 H, SiMe ), 0.19 (s, 1.3 H, SiMe ), 0.88 (s, 5.1 H, SitBu),
2
2
2
2
29.7, 129.8, 129.9 (7 d, Ar), 131.6 (s, Ar), 133.1 (d, Ar), 134.5 (s, Ar),
0.94 (s, 3.9 H, SitBu), 1.92 (s, 1.3 H, Me), 2.48 (s, 1.7 H, Me), 2.97 (s, 1.7
41.0, 141.3 (2 s, Ar), 152.8, 153.5 (2 s, C=N), 165.2 (s, CO Ar).
H, OMe), 3.76 (s, 1.3 H, OMe), 5.166 (s, 0.45 H, CH), 5.174 (s, 0.55 H,
2
CH), 7.30–7.44, 7.52–7.64, 7.84–7.94, 7.97, 8.05 (3 m, 2 m , 9 H, Ph).
c
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

H
Synthesis
R. Klemme et al.
Paper
HRMS (80 eV): m/z [M + Na]+ calcd for C23H23ClN NaO : 417.1340;
found: 417.1351.
13
C NMR (CDCl , 125.8 MHz): δ = 20.0 (q, C-9), 24.2 (qq, J = 3.0 Hz,
3 CF
3
2
2
2
1
C-11), 85.1 (q, JCF = 29.2 Hz, C-10), 124.6 (q, JCF = 284.9 Hz, C-12),
1
1
5
28.2, 128.3, 129.5, 130.1, 130.3, 130.7, 130.9 (7 d, C-1–C-4, C-15–C-
7), 134.0 (d, C-19), 134.2, 135.1 (2 s, C-14, C-18), 139.8, 141.3 (2 s, C-
, C-6), 148.3, 151.9 (2 s, C-7, C-8), 162.9 (s, C-13).
+
1
-(3-Methylquinoxalin-2-yl)dodecyl 3-Chlorobenzoate (12b)
According to GP2, a mixture of 1,2-diketone derivative 5b (0.464 g,
.17 mmol), diamine 11 (0.136 g, 1.26 mmol), and CAN (0.053 g, 0.10
1
HRMS (ESI): m/z [M + H] calcd for C19H15ClF N O : 395.0696; found:
3 2 2
mmol) dissolved in water (10 mL) was stirred for 30 min at room tem-
perature. Work-up and column chromatography (hexanes/EtOAc 8:1)
afforded 12b (0.391 g, 72%) as a colorless oil.
395.0771.
(2S)-2-(tert-Butyldimethylsiloxy)-1-(3-methylquinoxalin-2-yl)pro-
IR (neat): 3090–2850 (=C–H, C–H), 1720 cm–1 (C=O).
pyl 3-Chlorobenzoate (12e)
1
According to GP2, a mixture of 1,2-diketone derivative 5e (0.087 g,
H NMR (CDCl , 250 MHz): δ = 0.86 (t, J = 7.1 Hz, 3 H, Me), 1.15–1.65
3
0.220 mmol), diamine 11 (0.030 g, 0.280 mmol), and CAN (0.008 g,
(
m, 18 H, CH ), 2.09–2.18, 2.22–2.30 (2 m, 1 H each, CH ), 2.90 (s, 3 H,
2
2
0.015 mmol) dissolved in water (1 mL) was stirred for 30 min at room
Me), 6.26 (dd, J = 5.5, 8.3 Hz, 1 H, CH), 7.37 (t, J = 7.9 Hz, 1 H, Ar), 7.51–
.53, 7.63–7.71, 7.96–8.04 (3 m, 1 H, 2 H, 3 H, Ar), 7.68 (t, J = 1.9 Hz, 1
H, Ar).
temperature. Work-up and column chromatography (hexanes/EtOAc
:1) afforded 12e (0.073 g, 71%; two diastereomers = 88:12) as a vis-
7
4
cous orange oil.
13
C NMR (CDCl , 125.8 MHz): δ = 14.1 (q, Me), 22.5 (q, Me), 22.6 (t,
3
CH ), 25.7, 29.3, 29.32, 29.36, 29.47, 29.54, 29.55, 29.56, 31.8, 33.5 (10
2
Major diastereomer
t, 10 CH ), 74.6 (d, CH), 127.9, 128.3, 129.0, 129.1, 129.7, 129.72, 129.8
2
[
α
]
2
2
+
1
0
4
.
2
(
c
0
.
5
,
C
H
C
l
)
.
(6 d, Ar), 131.6 (s, Ar), 133.1 (d, Ar), 134.5 (s, Ar), 140.9, 141.5 (2 s, Ar),
D
3
IR (ATR): 3065–2855 (=C–H, C–H), 1725 cm–1 (C=O).
1
52.0, 153.3 (2 s, C=N), 165.1 (s, CO Ar).
2
HRMS (80 eV): m/z [M + Na]+ calcd for C28H35ClN NaO : 489.2279;
1
2
2
H NMR (CDCl , 400 MHz): δ = –0.72, –0.09 (2 s, 3 H each, OSiMe ),
3
2
found: 489.2290.
0.61 (s, 9 H, SitBu), 1.51 (d, J = 6.4 Hz, 3 H, Me), 3.02 (s, 3 H, Me), 4.65
m , 1 H, 2-H), 5.92 (d, J = 9.5 Hz, 1 H, 1-H), 7.40 (dd, J = 7.6, 8.3 Hz, 1
H, Ar), 7.51 (td, J = 1.3, 8.3 Hz, 1 H, Ar), 7.60–7.74 (m, 2 H, Ar), 7.93 (d,
J = 7.6 Hz, 1 H, Ar), 7.96–8.10 (m, 3 H, Ar).
(
Anal. Calcd for C28H35ClN O (467.0): C, 72.01; H, 7.55; N, 6.00. Found:
C, 72.39; H, 7.86; N, 5.95.
c
2
2
13C NMR (CDCl
2
1
, 100.8 MHz): δ = –5.7, –4.9 (2 q, SiMe
1.7, 22.9 (2 q, 2 Me), 25.7 (q, SitBu), 71.0, 76.6 (2 d, C-1, C-2), 127.9,
28.4, 128.8, 129.0, 129.7, 129.8, 129.9 (7 d, Ar), 131.3 (s, Ar), 133.2
), 17.5 (s, C–Si),
(
3-Methylquinoxalin-2-yl)(phenyl)methyl 3-Chlorobenzoate (12c)
3
2
According to GP2, a mixture of 1,2-diketone derivative 5c (0.160 g,
0
0
.505 mmol), diamine 11 (0.068 g, 0.628 mmol), and CAN (0.014 g,
.027 mmol) dissolved in water (3 mL) was stirred for 30 min at room
(d, Ar), 134.6 (s, Ar), 141.0, 141.3 (2 s, Ar), 153.9, 154.1 (2 s, C=N),
1
64.8 (s, CO Ar).
temperature. Work-up and column chromatography (hexanes/EtOAc
:1) afforded 12c (0.134 g, 68%) as a colorless oil.
2
4
HRMS (80 eV): m/z [M + H]+ calcd for C25H32ClN O Si: 471.1865;
2 3
IR (neat): 3090–2850 (=C–H, C–H), 1725 cm–1 (C=O).
found: 471.1878.
1
H NMR (CDCl , 400 MHz): δ = 2.77 (s, 3 H, Me), 7.30 (s, 1 H, CH),
3
Minor diastereomer
7
.35–7.45, 7.49–7.58, 7.63–7.76, 7.95–8.11 (4 m, 4 H, 3 H, 2 H, 3 H, Ph,
[
α
]
2
2
+
4
2
.
8
(
c
0
.
2
2
,
C
H
C
l
)
.
Ar), 8.14 (dd, J = 1.3, 1.9 Hz, 1 H, Ar).
D
3
1
13
H NMR (CDCl , 400 MHz): δ = 0.01, 0.12 (2 s, 3 H each, OSiMe ), 0.83
3 2
C NMR (CDCl , 100.8 MHz): δ = 22.7 (q, Me), 77.3 (d, CH), 128.0,
3
(s, 9 H, SitBu), 1.11 (d, J = 6.3 Hz, 3 H, Me), 2.97 (s, 3 H, Me), 4.72 (qd,
128.2, 128.3, 128.8, 128.9, 129.2, 129.4, 129.7, 129.9, 129.94 (10 d, Ph,
J = 6.3, 7.6 Hz, 1 H, 2-H), 6.19 (d, J = 7.6 Hz, 1 H, 1-H), 7.36 (t, J = 7.9
Hz, 1 H, Ar), 7.51 (ddd, J = 8.0, 2.1, 1.1 Hz, 1 H, Ar), 7.64–7.73 (m, 2 H,
Ar), 7.94–8.00 (m, 2 H, Ar), 8.03–8.08 (m, 2 H, Ar).
Ar), 131.5 (s, Ph), 133.0 (d, Ar), 135.0, 136.5, 141.0, 141.5 (4 s, Ar),
1
51.9, 152.1 (2 s, C=N), 164.8 (s, CO Ar).
2
+
HRMS (80 eV): m/z [M + H] calcd for C23H17ClN O : 389.1051; found:
2
2
The following 13C NMR signals could be assigned (CDCl , 100.8 MHz):
389.1057.
3
δ = –4.7, –4.5 (2 q, SiMe ), 25.78 (q, SitBu), 70.0, 78.2 (2 d, C-1, C-2).
2
Anal. Calcd for C23H16ClN O (387.9): C, 71.04; H, 4.41; N, 7.20. Found:
2
2
HRMS (80 eV): m/z [M + H]+ calcd for C25H32ClN O Si: 471.1865;
C, 70.65; H, 4.69; N, 7.08.
2
3
found: 471.1876.
1
,1,1-Trifluoro-2-(3-methylquinoxalin-2-yl)propan-2-yl 3-Chloro-
(
2S)-1-Hydroxy-(3-methylquinoxalin-2-yl)propan-2-yl 3-Chloro-
benzoate (12d)
benzoate (13)
According to GP2, a mixture of 1,2-diketone derivative 7b (0.226 g,
To a solution of 12e (0.68 g, 0.145 mmol; two diastereomers = 88:12)
in THF (1 mL) was added 1 M TBAF in THF (0.29 mL, 0.29 mmol). The
mixture was stirred for 1 h at room temperature. Then, the mixture
was filtered through a pad of silica gel (hexanes/EtOAc 1:1) and con-
centrated under reduced pressure. The crude product was purified by
column chromatography (hexanes/EtOAc 2:1) to yield 13 (0.026 g,
51%, two diastereomers = 93:7) as a yellow oil.
0
.570 mmol), diamine 11 (0.123 g, 1.18 mmol), and CAN (0.021 g,
0.052 mmol) dissolved in water (3 mL) was stirred for 30 min at room
temperature. Work-up and column chromatography (hexanes/EtOAc
:1) afforded 12d (0.134 g, 60%) as a colorless oil.
4
IR (ATR): 3070–2890 (=C–H, C–H), 1735 (C=O), 1195 cm–1 (C–F).
1
H NMR (CDCl , 500 MHz,): δ = 2.39 (d, J = 0.9 Hz, 3 H, Me), 2.73 (s, 3
3
H, Me), 7.44 (t, J = 7.9 Hz, 1 H, Ar), 7.61 (ddd, J = 1.1, 2.1, 8.0 Hz, 1 H,
Ar), 7.70–7.78 (m, 2 H, Ar), 7.97–8.02 (m, 2 H, Ar), 8.06 (t, J = 1.9 Hz, 1
H, Ar), 8.08–8.11 (m, 1 H, Ar).
1
H NMR (CDCl , 400 MHz): δ = 1.28 (d, J = 6.4 Hz, 3 H, Me), 2.94 (s, 3
3
H, Me), 4.74 (s, 1 H, OH), 5.39–5.42 (m, 1 H, 1-H), 5.46 (dq, J = 3.2, 6.4
Hz, 1 H, 2-H), 7.39 (t, J = 7.9 Hz, 1 H, Ar), 7.54 (ddd, J = 0.9, 2.0, 8.0 Hz,
1
H, Ar), 7.71–7.79, 7.95–7.98, 8.02–8.09 (3 m, 2 H, 1 H, 3 H, Ar).
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

I
Synthesis
R. Klemme et al.
Paper
1
The following H NMR signals could be assigned to the minor diaste-
min. After cooling to room temperature, ice water (20 g) and concd
reomer (CDCl , 400 MHz): δ = 1.62 (d, J = 6.4 Hz, 3 H, Me), 2.82 (s, 3 H,
NH (reaching pH ~ 8–9) were added and the mixture was extracted
3
3
Me), 5.14 (d, J = 2.5 Hz, 1 H, 1-H).
with Et O (2 × 8 mL). The combined organic layers were dried
2
(
Na SO ) and filtered, and the filtrate was evaporated under reduced
2 4
pressure. The residue was purified by flash chromatography
hexanes/EtOAc 6:1) to afford imidazole derivative 15 (0.183 g, 57%)
as a colorless oil.
IR (ATR): 3070–2950 (=C–H, C–H), 1600 cm–1 (C=C).
(
1R,2S)-1-(3-Methylquinoxalin-2-yl)-1-(4-nitrobenzoyloxy)pro-
(
pan-2-yl 3-Chlorobenzoate (14)
Quinoxaline derivative 13 (0.026 g, 0.073 mmol, two
diastereomers = 93:7), p-nitrobenzoyl chloride (0.015 g, 0.078 mmol),
and DMAP (0.007 g, 0.055 mmol) were dissolved in CH Cl (1 mL). Af-
1
2
2
H NMR (CDCl , 500 MHz,): δ = 0.86 (t, J = 7.1 Hz, 3 H, Me), 1.05–1.50,
3
ter addition of Et N (0.008 g, 0.080 mmol) the mixture was stirred
3
2.10–2.20 (2 m, 18 H, 2 H, 10 CH ), 2.25 (s, 3 H, Me), 5.85–6.08 (m, 1
H, =CH), 6.25 (d, J = 16.0 Hz, 1 H, =CH), 7.23–7.37, 7.74–7.82 (2 m, 3 H,
2 H, Ph).
13
2
under an argon atmosphere at room temperature for 16 h. Then, wa-
ter (2 mL) and CH Cl (3 mL) were added to the mixture and the aque-
2
2
ous phase was extracted with CH Cl (3 × 5 mL). The combined organ-
2
2
C NMR (CDCl , 125.8 MHz): δ = 11.5 (q, Me), 14.1, 16.5, 22.7, 24.7,
3
ic layers were dried (Na SO ) and filtered, and the filtrate was evapo-
2
4
2
1
C).
9.2, 29.3, 29.5, 29.6, 33.2 (9 t, 9 CH ), 31.9 (q, Me), 118.1 (d, =CH),
2
rated under reduced pressure. The residue was purified by column
chromatography (neutral alumina, hexanes/EtOAc 1:1) to give diester
25.1, 128.2, 128.6, 128.7, 130.2, 145.2 (4 d, 2 s, =CH, Ph, imidazole-
14 (0.017 g, 47%, two diastereomers = 95:5) as a pale yellow solid.
HRMS (ESI): m/z [M + H]+ calcd for C22H33N : 325.2638; found:
3
2
Another reaction starting from configurationally pure major isomer
of precursor 12e (0.072 g, 0.153 mmol) gave after desilylation and es-
terification as described above the pure major diastereomer of 14
25.2657.
Methyl 2-Amino-4-[2-(3-chlorobenzoyloxy)-2-cyclohexylacetyl]thio-
phene-3-carboxylate (17)
(
0.008 g, 12% yield after two steps) as a pale yellow solid; mp 141 °C;
22
[α]D +5.0 (c 0.01, CHCl3).
IR (ATR): 3075–2845 (=C–H, C–H), 1720 cm–1 (C=O).
A mixture of 1,2-diketone derivative 5a (0.200 g, 0.820 mmol), methyl
cyanoacetate (16, 0.062 g, 0.620 mmol), sulfur (0.020 g, 0.620 mmol),
and KF-Al O (0.124 g) in EtOH (2 mL) was heated to 85 °C in a sealed
1
H NMR (CDCl , 700 MHz): δ = 1.71 (d, J = 6.5 Hz, 3 H, Me), 3.05 (s, 3
3
2
3
H, Me), 5.92 (dq, J = 5.2, 6.5 Hz, 1 H, 2-H), 6.61 (d, J = 5.1 Hz, 1 H, 1-H),
tube for 2.5 h. The mixture was allowed to cool to room temperature
and diluted with CH Cl (10 mL). The resulting precipitate was re-
7
(
.37 (t, J = 7.8 Hz, 1 H, Ar), 7.54 (ddd, J = 1.1, 2.2, 8.0 Hz, 1 H, Ar), 7.70
ddd, J = 1.4, 6.9, 8.2 Hz, 1 H, Ar), 7.75 (ddd, J = 1.4, 6.9, 8.4 Hz, 1 H,
Ar), 7.85 (ddd, J = 1.1, 1.5, 7.8 Hz, 1 H, Ar), 7.95–7.96 (m, 1 H, Ar),
2
2
moved by filtration and the solution was concentrated under reduced
pressure. The residue was purified by column chromatography (hex-
anes/EtOAc 4:1) to give 17 (0.044 g, 16%) as a pale yellow oil.
IR (ATR): 3440–3250 (N–H), 3070–2850 (=C–H, C–H), 1740, 1710 cm–1
8.02–8.04 (m, 2 H, Ar), 8.31–8.36 (m, 4 H, Ar).
13
C NMR (CDCl , 176.0 MHz): δ = 15.6, 22.5 (2 q, 2 Me), 71.8, 75.1 (2 d,
3
C-1, C-2), 123.7, 127.7, 128.5, 129.29, 129.32, 129.75, 129.79, 130.5,
(C=O).
131.1, 131.5 (10 d, Ar), 133.3, 134.7, 134.9 (3 s, Ar), 140.8, 141.7,
1
H NMR (CDCl , 250 MHz): δ = 0.80–1.40, 1.55–1.89, 1.95–2.15 (3 m,
3
149.9 (3 s, Ar), 150.9, 152.4 (2 s, C=N), 164.1, 164.4 (2 s, CO Ar).
2
5
H, 5 H, 1 H, CH, 5 CH ), 3.78 (s, 3 H, OMe), 5.51 (d, J = 6.1 Hz, 1 H,
2
1
The following H NMR signals could be assigned to the minor diaste-
CH), 6.10 (br s, 2 H, NH ), 6.80 (s, 1 H, =CH), 7.37–7.44, 7.53–7.58,
2
reomer (CDCl , 700 MHz): δ = 1.43 (d, J = 6.5 Hz, 3 H, Me), 3.03 (s, 3 H,
3
7.92–7.96 (3 m, 1 H, 1 H, 2 H, Ar).
Me), 6.30 (m , 1 H, 2-H), 7.52 (ddd, J = 1.1, 2.2, 8.0 Hz, 1 H, Ar), 7.77–
c
13
C NMR (CDCl , 100.8 MHz): δ = 26.0, 26.1, 26.2, 27.1, 30.1 (5 t, 5
3
7.80 (m, 1 H, Ar), 7.99–8.00 (m, 1 H, Ar), 8.18–8.24 (m, 2 H, Ar), 8.21–
CH ), 39.6 (d, CH), 51.2 (q, OMe), 82.2 (d, CH), 104.5, 112.1, 122.7 (s, d,
2
8.24 (m, 2 H, Ar).
s, thienyl), 127.9, 129.74, 129.77, 131.5, 133.2, 134.6, 139.8 (3 d, s, d, 2
+
HRMS (ESI): m/z [M + H] calcd for C26H21ClN O : 506.1113; found:
3
6
s, Ar, thienyl), 164.6, 164.9 (2 s, CO Ar, CO Me), 194.9 (s, C=O).
2
2
+
5
06.1146; m/z [M + Na] calcd for C26H20ClN NaO : 528.0933; found:
3 6
HRMS (80 eV): m/z [M + Na]+ calcd for C21H22ClNNaO S: 458.0804;
5
528.0962.
found: 458.0776.
Crystal Data
C26H20ClN O , M = 505.90, triclinic, P1, a = 8.6386(13), b = 9.2367(14),
(
3
4
E)-1-Cyclohexyl-5-methoxy-3-methyl-2,5-dioxopent-3-enyl
-Chlorobenzoate (19a) and (E)-2-Acetyl-1-cyclohexyl-4-methoxy-
-oxobut-2-enyl 3-Chlorobenzoate (20a)
3
6
r
c = 15.275(2) Å, α = 85.791(3)°, β = 74.646(4)°, γ = 85.096(3)°,
V = 1169.4(3) Å , Z = 2, ρ = 1.437 g cm–3, μ = 0.213 mm–1 MoKα
3
,
c
Phosphorane 18 (0.598 g, 1.70 mmol) was added to a solution of 1,2-
diketone 5a (0.550 g, 1.70 mmol) in CH Cl (10 mL) and the mixture
λ = 0.71073 Å, T = 123 K, 15878 measured reflections, 9728 unique
reflections, and 9033 observed reflections with I > 2σ(I), Rint = 0.0211,
2
2
2
was stirred at room temperature for 16 h. After removal of the sol-
vent, the residue was purified by column chromatography (hex-
anes/EtOAc 15:1 to 9:1) to yield 19a and 20a (0.250 g of 19a; 0.177 g
as a mixture of both products; combined yield 67%) as colorless oils. A
sample (0.090 g) of 19a and 20a could be separated by HPLC (hex-
anes/i-PrOH 98:2) to afford pure 20a.
The structure was solved by direct methods, a final refinement on F
2
with 653 parameters converged at wR(F ) = 0.0960, R(F) = 0.0363,
24
Flack parameter 0.05(3). CCDC 1445384 (14) contains the supple-
mentary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data Cen-
tre via www.ccdc.cam.ac.uk/data_request/cif.
Compound 19a
(E)-4-(Dodec-1-enyl)-5-methyl-2-phenyl-1H-imidazole (15)
IR (ATR): 3070–2855 (=C–H, C–H), 1715, 1695 (C=O), 1575 (C=C),
1
,2-Diketone 5b (0.395 g, 1.00 mmol) and NH OAc (0.648 g, 8.40
4
–1
1250 cm (C–Cl).
mmol) were added to a solution of benzaldehyde (0.158 g, 1.50
mmol) in AcOH (1.2 mL) and the mixture was heated at 100 °C for 20
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

J
Synthesis
R. Klemme et al.
Paper
1
13
H NMR (CDCl , 500 MHz): δ = 1.10–1.40, 1.55–2.10 (2 m, 6 H, 5 H,
C NMR (CDCl , 125.8 MHz): δ = 14.2 (q, Me), 22.7, 23.5, 29.2*, 29.4*,
3
3
CH, 5 CH ), 2.31 (d, J = 1.6 Hz, 3 H, Me), 3.80 (s, 3 H, CO Me), 5.57 (d,
29.5*, 29.6 (6 t, 9 CH ), 29.7 (q, Me), 32.0 (t, CH ), 52.1 (q, OMe), 74.3
2
2
2
2
J = 5.2 Hz, 1 H, CH), 6.65 (q, J = 1.6 Hz, 1 H, =CH), 7.35–7.45, 7.52–7.60,
(d, CH), 116.9 (d, =CH), 127.9, 129.8, 130.1, 131.3, 132.5, 133.7 (3 d, s,
7.90–8.05 (3 m, 1 H, 1 H, 2 H, Ar).
d, s, Ar), 158.3 (s, =C), 164.3, 164.9 (2 s, CO Ar, CO Me), 203.5 (s, C=O).
2
2
13
HRMS (ESI): m/z [M + H]+ calcd for C25H36ClO : 450.2173; found:
C NMR (CDCl , 125.8 MHz): δ = 13.9 (q, Me), 25.80, 25.84, 26.0, 28.0,
3
5
2
1
1
9.6 (5 t, 5 CH ), 39.8 (d, CH), 51.8 (q, OMe), 79.5 (d, CH), 125.3, 127.9,
29.75, 129.77, 131.1, 133.4, 134.6, 149.9 (4 d, s, d, 2 s, Ar, C=CH),
450.2179.
2
65.0, 166.2 (2 s, CO Ar, CO Me), 198.9 (s, C=O).
2
2
Anal. Calcd for C20H23ClO (378.9): C, 63.41; H, 6.12. Found: C, 62.99;
H, 5.46.
Acknowledgment
5
Generous support by the Deutsche Forschungsgemeinschaft and Bay-
er HealthCare is most gratefully acknowledged. We also thank An-
dreas Mavroskoufis, Johannes Hannemann, Alex Bottke, and Lee
Garrett for their experimental assistance.
Compound 20a
IR (ATR): 3070–2880 (=C–H, C–H), 1715, 1690 (C=O), 1575 (C=C),
–1
1
250 cm (C–Cl).
1
H NMR (CDCl , 500 MHz): δ = 1.02–1.40, 1.63–1.95 (2 m, 6 H, 5 H,
3
CH, 5 CH ), 2.41 (s, 3 H, Me), 3.72 (s, 3 H, CO Me), 5.37 (d, J = 6.6 Hz, 1
H, CH), 5.85 (s, 1 H, =CH), 7.39–7.46, 7.56–7.61, 7.93–8.04 (3 m, 1 H, 1
H, 2 H, Ar).
Supporting Information
2
2
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561751.
S
u
p
p
ortioIgnfmr oaitn
S
u
p
p
o
nrtogI
i
f
rm oaitn
13
C NMR (CDCl , 100.5 MHz): δ = 25.6, 25.7, 26.0, 27.6, 29.6 (5 t, 5
3
CH ), 30.7 (q, Me), 39.6 (d, CH), 52.0 (q, OMe), 78.4 (d, CH), 118.1,
2
1
27.8, 129.6, 130.0, 131.1, 133.6, 134.8, 156.9 (4 d, s, d, 2 s, Ar, C=CH),
References
164.3, 165.1 (2 s, CO Ar, CO Me), 203.3 (s, C=O).
2
2
+
HRMS (ESI): m/z [M + Na] calcd for C20H23ClNaO : 401.1126; found:
(1) (a) Modern Allene Chemistry; Vol. 1 and 2; Krause, N.; Hashmi,
A. S. K., Eds.; Wiley-VCH: Weinheim, 2004. (b) Science of Synthe-
sis; Vol. 44; Krause, N., Ed.; Thieme: Stuttgart, 2007.
5
401.1122.
(
2) For selected reviews dealing with the chemistry of alkoxyal-
lenes, see: (a) Zimmer, R.; Reissig, H.-U. In Modern Allene Chem-
istry; Vol. 1; Krause, N.; Hashmi, A. S. K., Eds.; Wiley-VCH:
Weinheim, 2004, 425. (b) Brasholz, M.; Reissig, H.-U.; Zimmer,
R. Acc. Chem. Res. 2009, 42, 45. (c) Pfrengle, F.; Reissig, H.-U.
Chem. Soc. Rev. 2010, 39, 549. (d) Lechel, T.; Reissig, H.-U. Pure
Appl. Chem. 2010, 82, 1835. (e) Nedolya, N. A.; Tarasova, O.;
Volostnykh, O. G.; Albanov, A. L.; Klyba, L. V.; Trofimov, B. A.
Synthesis 2011, 2192. (f) Bouché, L.; Reissig, H.-U. Pure Appl.
Chem. 2012, 84, 23. (g) Zimmer, R.; Pfrengle, F.; Lechel, T.;
Reissig, H.-U. ChemCatChem 2013, 5, 2100. (h) Zimmer, R.;
Reissig, H.-U. Chem. Soc. Rev. 2014, 43, 2888. (i) Le Bras, J.;
Muzart, J. Chem. Soc. Rev. 2014, 43, 3003. (j) Reissig, H.-U.;
Zimmer, R. In Multicomponent Reactions in Organic Synthesis;
Zhu, J.; Wang, Q.; Wang, M.-X., Eds.; Wiley-VCH: Weinheim,
2015, 301.
(
E)-1-Methoxy-3-methyl-1,4-dioxohexadeca-2-en-5-yl 3-Chloro-
benzoate (19b) and (E)-3-Acetyl-1-methoxy-1-oxopentadeca-2-
en-4-yl 3-Chlorobenzoate (20b)
Phosphorane 18 (0.267 g, 0.79 mmol) was added to a solution of 1,2-
diketone 5b (0.310 g, 0.79 mmol) in CH Cl (10 mL) and the mixture
was stirred at room temperature for 19 h. After removal of the sol-
vent, the residue was purified by column chromatography (hex-
anes/EtOAc 9:1 to 4:1) to yield 19b and 20b (0.145 g 19b, 0.051 g of
2
2
2
0b, 0.034 g mixture of both products; combined yield 65%) as color-
less oils.
Compound 19b
IR (ATR): 3070–2860 (=C–H, C–H), 1715, 1700 (C=O), 1570 (C=C),
1
–1
250 cm (C–Cl).
1
H NMR (CDCl , 500 MHz): δ = 0.88 (t, J = 7.1 Hz, 3 H, Me), 1.18–1.40,
3
(
3) (a) Horvath, A.; Bäckvall, J.-E. Oxidation of Allenes, In Modern
Allene Chemistry; Krause, N.; Hashmi, A. S. K., Eds.; Wiley-VCH:
Weinheim, 2004, 973. (b) Adams, C. S.; Weatherly, C. D.; Burke,
E. G.; Schomaker, J. M. Chem. Soc. Rev. 2014, 43, 3136.
1
.45–1.55, 1.86–1.93 (3 m, 16 H, 2 H, 2 H, 10 CH ), 2.30 (d, J = 1.0 Hz, 3
2
H, Me), 3.80 (s, 3 H, OMe), 5.71 (t, J = 6.4 Hz, 1 H, OCH), 6.62 (q, J = 1.0
Hz, 1 H, =CH), 7.40 (t, J = 8.0 Hz, 1 H, Ar), 7.52–7.59, 7.94–7.97, 8.04 (2
m, m , 1 H each, Ar).
c
(
4) For the ozonolysis of alkoxyallenes, see: (a) Hormuth, S.;
Reissig, H.-U.; Dorsch, D. Liebigs Ann. Chem. 1994, 121. (b) Okala
Amombo, G. M.; Hausherr, A.; Reissig, H.-U. Synlett 1999, 1871.
1
3
C NMR (CDCl , 125.8 MHz): δ = 13.9, 14.1 (2 q, 2 Me), 22.7, 25.5,
3
2
9.4, 29.42*, 29.6, 29.7*, 31.3, 32.0 (8 t, 10 CH ), 51.8 (q, OMe), 76.0 (d,
2
CH), 125.3, 128.0, 129.8, 129.84, 129.87, 130.5, 133.4, 134.6, 149.1 (4
d, s, d, 2 s, Ar, C=CH), 165.0, 166.1 (2 s, CO Ar, CO Me), 198.6 (s, C=O).
HRMS (ESI): m/z [M + H]+ calcd for C25H36ClO : 450.2173; found:
4
(c) Langler, R. F.; Raheja, R. K.; Schank, K.; Beck, H. Helv. Chim.
2
2
Acta 2001, 84, 1943. (d) Zimmer, R.; Taszarek, M.; Schefzig, L.;
Reissig, H.-U. Synlett 2008, 2046. (e) Prisyazhnyuk, V.; Jachan,
M.; Brüdgam, I.; Zimmer, R.; Reissig, H.-U. Collect. Czech. Chem.
Commun. 2009, 74, 1069.
5
50.2186.
Compound 20b
(5) Epoxidation of methoxyallenes using DMDO: (a) Crandell, J. K.;
Batal, D. J.; Lin, F.; Reix, T.; Nadol, G. S.; Ng, R. A. Tetrahedron
1992, 48, 1427. (b) Spencer, W. T. III; Levin, M. D.; Frontier, A. J.
Org. Lett. 2011, 13, 414. Epoxidation of alkoxyallenes using
mCPBA: (c) Hayakawa, R.; Shimizu, M. Org. Lett. 2000, 2, 4079.
IR (ATR): 3075–2865 (=C–H, C–H), 1715, 1695 (C=O), 1570 (C=C),
–1
1
250 cm (C–Cl).
1
H NMR (CDCl , 500 MHz): δ = 0.87 (t, J = 6.9 Hz, 3 H, Me), 1.20–1.50,
3
1
.81–1.93 (2 m, 18 H, 2 H, 10 CH ), 2.43 (s, 3 H, Me), 3.73 (s, 3 H,
2
(d) Hayakawa, R.; Makino, H.; Shimizu, M. Chem. Lett. 2001, 756.
OMe), 5.52 (dd, J = 5.2, 7.7 Hz, 1 H, OCH), 5.89 (br s, 1 H, =CH), 7.43 (t,
J = 8.0 Hz, 1 H, Ar), 7.57–7.59, 7.93–7.95, 8.01 (2 m, m , 1 H each, Ar).
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(
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2
(
2
2
(
Other prominent 1,2-diketone representatives are the immuno-
suppressive FK506 and its derivatives (review): (g) Stütz, A.;
Grassberger, M. A.; Baumann, K.; Edmunds, A. J. F.; Hiestand, P.;
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(21) An alternative formation of 1,2-diketones starting from alkoxy-
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1
993, Chap. 27, 427.
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(
8
(
(
(
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(
(
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procedure described in ref. 22.
(24) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K