Acid-catalyzed synthesis of α,β-disubstituted conjugated enones by a Meyer-Schuster-type rearrangement in allenols

Article abstract of DOI:10.1002/adsc.201400928

A novel, direct and simple methodology to gain access to α,β-disubstituted conjugated enones from α-allenols in a sustainable metal catalysis context, considering the inexpensiveness and environmentally friendliness of iron(III) species and protons, has b

Full text of DOI:10.1002/adsc.201400928

UPDATES
DOI: 10.1002/adsc.201400928
Acid-Catalyzed Synthesis of a,b-Disubstituted Conjugated
Enones by a Meyer–Schuster-Type Rearrangement in Allenols
Benito Alcaide,a,* Pedro Almendros,b,* Sara Cembellꢀn,a
and Teresa Martꢀnez del Campoa
a
Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Quꢀmica Orgꢁnica I, Unidad Asociada al CSIC, Facultad
de Quꢀmica, Universidad Complutense de Madrid, 28040 Madrid, Spain
Fax : (+34)-91-394-4103; e-mail: alcaideb@quim.ucm.es
Instituto de Quꢀmica Orgꢁnica General, Consejo Superior de Investigaciones Cientꢀficas, IQOG-CSIC, Juan de la Cierva
b
3, 28006 Madrid, Spain
Fax : (+34)-91-564-4853; e-mail: Palmendros@iqog.csic.es
Received: September 22, 2014; Revised: November 18, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400928.
Abstract: A novel, direct and simple methodology
to gain access to a,b-disubstituted conjugated
enones from a-allenols in a sustainable metal catal-
ysis context, considering the inexpensiveness and
environmentally friendliness of iron(III) species
and protons, has been developed.
Keywords: alcohols; allenes; Brønsted acids; homo-
geneous catalysis; Lewis acids
Scheme 1. Alkynol versus allenol isomerization.
The use of a,b-unsaturated ketones as starting materi- complished.[3] Besides, the allenol rearrangement
als to prepare a variety of compounds, as well as the could provide competitive advantages, because in con-
presence of this structural unit in a large number of trast with the alkynol rearrangement, the allenic ver-
biologically active natural products have led to in- sion could afford internally substituted conjugated
creased recent interest in methods for preparing such enones. On the other hand, iron-catalyzed processes
compounds.[1] Classical methods such as aldol conden- have attracted recent attention because iron is one of
sation and olefination strategies present serious draw- the most inexpensive and environmentally benign
backs. Thus, harsh conditions and modest yields are metals on earth.[4] Following up on our combined in-
usually encountered in the aldol condensation, while terest in the area of allenes and metals,[5] and consid-
the generation of noxius waste by-products coupled ering the economic attractiveness and the environ-
with low atom economy are disadvantages of Wittig- mentally friendliness of iron species, we chose to
type reactions. Besides, these traditional protocols study the iron-catalyzed reaction of a-allenols as a sus-
usually require strong basic conditions, which may be tainable metal-catalyzed route to access a,b-disubsti-
incompatible with selectivity control as well as sensi- tuted conjugated enones [Scheme 1, Eq. (2)].
tive functional groups. An alternative method for the
Starting allenols 1 were readily prepared in good
synthesis of a,b-unsaturated ketones is the Meyer– overall yield from the appropriate carbaldehyde
Schuster rearrangement [Scheme 1, Eq. (1)], which through a regioselective indium-mediated Barbier-
starts from propargylic alcohols and consists in type carbonyl-allenylation reaction in aqueous media
a formal 1,3-hydroxy shift followed by tautomeriza- using our methodology.[6] Initially, we were attempting
tion.[2] In this regard, the rearrangement of allenic al- the iron-catalyzed cycloisomerization reaction of alle-
cohols may be a possible solution to produce a,b-un- nol 1a. Unexpectedly, the alkenone 2a was obtained
saturated ketones with high reaction efficiency; al- using either iron(III) chloride hexahydrate or
though this achievement has not yet been fully ac- iron(III) triflate. Considering the abundance and non-
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gold complexes are good catalysts for this rearrange-
ment, a reaction of allenol 1a in the presence of
[(Ph3P)AuNTf2] was also carried out.[7] The reaction
does take a different course, with a separable mixture
of oxycyclization and carbocyclization adducts 3 and 4
being obtained [Scheme 2, Eq. (6)].[8] It was interest-
ing at this point to test the reactivity of a protected al-
lenol moiety under gold-catalyzed conditions. When
the hydroxy functionality in 1a was protected in the
form of a methyl ether as in 5a, the gold-catalyzed
Meyer–Schuster type rearrangement occurred,[9] but
in low yield [Scheme 2, Eq. (7)].
Scheme 2. Divergent metal-catalyzed rearrangement of alle-
nol derivatives 1a and 5a.
toxicity of iron(III) species, we became interested in
developing an allenol-based Meyer–Schuster rear-
rangement methodology for the preparation of func-
tionalized a,b-unsaturated ketones. The reaction was
next optimized by screening solvent and temperature.
A 52% yield of a,b-unsaturated ketone 2a was ob-
tained through the use of FeCl3·6H2O (10 mol%) and
dichloromethane as the solvent at 408C [Scheme 2,
Eq. (3)]. A similar result was encountered through
the use of catalytic amounts of Fe(OTf)3 [Scheme 2,
Eq. (4)]. This reaction could also be catalyzed by
Bi(OTf)3 and In(OTf)3, but with diminished effective-
ness. Different Lewis acid catalysts such as InCl3,
ZnCl2, and AgOTf were found to be completely inef-
fective in carrying out any reorganization of the alle-
nol. A Brønsted acid such as the super acid TfOH
was shown to efficiently transform 1a into 2a at low
Scheme 3. Acid-catalyzed rearrangement of allenols 1. Re-
agents and conditions: i) 10 mol% TfOH, CH2Cl2, À208C,
temperature [Scheme 2, Eq. (5)]. To check whether 14 h; ii) 10 mol% Fe(OTf)3, CH2Cl2, reflux, 14 h.
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Acid-Catalyzed Synthesis of a,b-Disubstituted Conjugated Enones
vided the 3-alkenyloxindole rearranged adduct 8b as
sole product (Scheme 4), it was thus apparent that
substitution at the nitrogen atom of the heterocycle
should have little effect upon the reactivity of the al-
lenol moiety. Allenic 5-chloroindolinone 7c smoothly
provided the rearranged adduct 8c in reasonable yield
(Scheme 4). The major product for the methyl-substi-
tuted allenol 7d was assigned to be the E form, a,b-
unsaturated ketone 8d, the unexpected Z isomer 9d
being the minor component (Scheme 4).[12] The iron-
catalyzed rearrangement reaction of (indol-3-yl)-a-al-
lenols 10a and 10b afforded N-Boc deprotected a,b-
unsaturated ketones 11a and 11b in modest yields
(Scheme 4).[13]
Unfortunately, enantiopure allenols 12–14 derived
from aliphatic aldehydes were not as rewarding as
their aromatic counterparts. Neither Fe(OTf)3 nor
TfOH reacted well, because decomposition adducts
were detected. Interestingly, the use of FeCl3·6H2O
afforded identifiable products. However, this variation
led to less efficiency in terms of chemical yields of the
ketone derivatives 15 and 17 (Scheme 5). Chloro-
Scheme 4. Fe(OTf)3-catalyzed rearrangement of indole-
linked allenols 7 and 10.
With the optimized conditions in hand, we then ex-
amined the generality of this acid-catalyzed rear-
rangement protocol in a-allenols 1. When allenols 1c–
1e, 1g, and 1i were tested as precursors using triflic
acid catalysis, they furnished the corresponding reor-
ganization products 2c–2e, 2g, and 2i (Scheme 3).
Complete conversion was observed for phenyl-substi-
tuted allenes 1b, 1f, 1h, 1j, and 1k but complicated re-
action mixtures were obtained. Competing reactions
lead to the exclusion of the above allenols as efficient
substrates for the TfOH-promoted reaction. Fortu-
nately, Fe(OTf)3 did afford the corresponding a,b-un-
saturated ketones 2b, 2f, 2h, 2j, and 2k in fair yields
(Scheme 3). The reactions were selective and only
Meyer–Schuster adducts were formed, with no trace
of isomeric oxycyclization products. Electron-with-
drawing and electron-donating substituents on the
aryl ring were tolerated with only little influence on
the reactivity (Scheme 3). Chlorodienes 6 were often
obtained as important components during the
FeCl3·6H2O-catalyzed
reaction
of
a-allenols
1 (Scheme 3).
3-Methyleneindolin-2-ones are not only recognized
as versatile intermediates in organic synthesis,[10] but
also exhibit interesting biological activities.[11] Conse-
quently, the iron-catalyzed stereoselective synthesis of
3-alkenyloxindole 8a from 2-indolinone-tethered alle-
nol 7a under similar conditions is noteworthy
(Scheme 4). Allenic NH-indolinone 7b smoothly pro- Scheme 5. FeCl3-catalyzed rearrangement of allenols 12–14.
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Scheme 6. Labelling experiment.
Scheme 8. Mechanistic explanation for the iron-catalyzed re-
arrangement of allenols through addition–elimination.
cohol group in the allenol moiety. Initial s-coordina-
tion of the metal to the hydroxy group of allenols 1,
7, and 10, leads to complexes 20. Separation of the al-
cohol group by Fe(OTf)3 generates allenic cation 21,
which would facilitate the nucleophilic addition of
water to the carbenium ion, thus leading to a metallat-
ed intermediate 22-Fe. Next, demetallation yields
neutral dienol species 22 and regenerates the iron cat-
alyst. Finally, isomerization could generate a,b-unsa-
Scheme 7. Mechanistic explanation for the iron-catalyzed re-
arrangement of allenols through elimination–addition.
dienes 16a, 16b, and 18 were obtained in appreciable turated ketones 2, 8, and 11 (Scheme 7). However,
amounts. Surprisingly, tricycle 19 was obtained as taking all the experiments into account, an alternative
major component from allene sugar derivative 14 addition–elimination mechanism scenario as sketched
(Scheme 5). Importantly, no erosion of the stereo- in Scheme 8 cannot be completely ruled out.
chemical integrity was observed in enantiopure prod-
ucts 15–19.
In conclusion, a novel, direct and simple methodol-
ogy to gain access to a,b-disubstituted conjugated
In order to interpret the rearrangement reaction enones from a-allenols in a sustainable metal catalysis
outcome in a more useful manner, an 18O-labelling context, considering the inexpensiveness and environ-
experiment was planned. 18O-incorporation was moni- mentally friendliness of iron(III) species and protons,
tored as an indicator of a mechanistic scenario that in- has been developed.
volves an indirect intermolecular 1,3-shift of the OH
group. Mass spectrometric analysis of the product of
reaction of allenol 1e under Fe(OTf)3 catalysis in
Experimental Section
presence of 100 mol% H218O showed that the a,b-un-
saturated ketone 2e was partially 18O-labelled
(Scheme 6), revealing that the carbonylic oxygen
atom may arise from external H2O.
General Methods
1H NMR and 13C NMR spectra were recorded on a Bruker
Avance-300 or Bruker AMX-500. NMR spectra were re-
corded in CDCl3 solutions unless otherwise stated. Chemical
shifts are given in ppm relative to TMS (1H, 0.0 ppm), or
CDCl3 (13C, 77.0 ppm). Coupling constants J are expressed
in Hertz (multiplicity: s=singulet, d=doublet, dd=double
doublet, t=triplet, dt=double triplet, q=quadruplet,
quint=quintuplet, sext=sextuplet, sept=septuplet, m=
multiplet). Low and high resolution mass spectra were taken
on an AGILENT 6520 Accurate-Mass QTOF LC/MS spec-
The high stereoselectivity of the rearrangement
which occurs by (E)-alkene formation, is independent
of the stereochemistry of the starting a-allenol (race-
mic or enantiopure). This fact and the labelling ex-
periment may indicate a stepwise path with the partic-
ipation of carbocationic species. A possible reaction
pathway leading to a,b-unsaturated ketones from a-
allenols was proposed as shown in Scheme 7.
Fe(OTf)3 acts as a Lewis acid interacting with the al- trometer using the electrospray mode (ES) unless otherwise
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Acid-Catalyzed Synthesis of a,b-Disubstituted Conjugated Enones
stated. IR spectra were recorded on a Bruker Tensor 27
spectrometer. Specific rotations [a]D are given in 10À1 deg
cm2 gÀ1 at 208C, and the concentration (c) is expressed in g
per 100 mL. All commercially available compounds were
used without further purification.
CH), 122.5 (Ar, CH), 119.7 (Ar, CH), 117,3 (=CH), 25.7
(Me), 12.9 (Me); IR (CHCl3): n=3061, 1666 (CO), 1476,
1223, 745, 695 cmÀ1; HR-MS (ES): m/z=328.1473, calcd. for
C23H20O2 [M]+: 328.1463.
a,b-Unsaturated ketone 2e: From 340 mg (1.75 mmol) of
allenol 1e, chromatography of the residue using hexanes/
ethyl acetate (8:1) as eluent gave compound 2e as a colorless
oil; yield: 239 mg (70%); 1H NMR (300 MHz, CDCl3,
258C): d=7.38 (d, 1H, J=0.9 Hz), 7.32 (d, 2H, J=8.9 Hz),
7.28 (d, 2H, J=8.8 Hz), 2.39 (s, 3H), 1.96 (d, 3H, J=
1.3 Hz); 13C NMR (75 MHz, CDCl3, 258C): d=200.0, 138.1,
134.4, 130.9 (2C), 129.5, 128.8 (2C), 128.7, 25.9, 13.0; IR
(CHCl3): n=3070, 1668 (CO), 751, 696 cmÀ1; HR-MS (ES):
m/z=194.0497, calcd. for C11H11ClO [M]+: 194.0498.
Typical Procedure for the TfOH-Catalyzed
Rearrangement Reaction of a-Allenols 1
To a cooled solution of the appropriate allenol 1 (1.0 mmol)
in dichloromethane (10 mL) at À208C, TfOH (0.10 mmol)
was added. The reaction mixture was stirred at À208C until
the starting material disappeared as indicated by TLC.
Water (1 mL) was added, and the mixture was allowed to
warm to room temperature before being partitioned be-
tween dichloromethane and water. The organic extract was
concentrated under vacuum, and purified by flash column
chromatography eluting with ethyl acetate/hexanes mixtures.
Spectroscopic and analytical data for pure forms of com-
pounds 2 are given below.[14]
a,b-Unsaturated ketone 2g: From 40 mg (0.21 mmol) of
a-allenol 1g, chromatography of the residue using hexanes/
ethyl acetate (6:1) as eluent gave compound 2g as a colorless
1
oil; yield: 26 mg (65%); H NMR (300 MHz, CDCl3, 258C):
d=7.40 (s, 1H), 7.34 (d, 2H, J=8.8 Hz), 6.88 (d, 2H, J=
8.9 Hz), 3.78 (s, 3H), 2.38 (s, 3H), 2.00 (d, 3H, J=1.2 Hz);
13C NMR (75 MHz, CDCl3, 258C): d=200.3, 139.6, 135.9,
131.6 (2C), 129.8, 128.5, 113.9 (2C), 55.4, 28.5, 12.9; IR
a,b-Unsaturated ketone 2a: From 134 mg (0.53 mmol) of
a-allenol 1a, chromatography of the residue using hexanes/
ethyl acetate (5:1) as eluent gave compound 2a as a colorless
(CHCl3): n=3069, 1670 (CO), 1481, 1236, 751, 696 cmÀ1
;
HR-MS (ES): m/z=190.0998, calcd. for C12H14O2 [M]+:
190.0994.
1
oil; yield: 88 mg (65%); H NMR (300 MHz, CDCl3, 258C):
d=7.66 (s, 1H, =CH), 7.45 (dd, 1H, J=7.7, 1.3 Hz, Ar),
7.34 (t, 2H, J=7.6 Hz, Ar), 7.31 (td, 1H, J=7.4, 1.6 Hz,
Ar), 7.18 (t, 1H, J=7.9 Hz, Ar), 7.11 (t, 1H, J=7.4 Hz, Ar),
6.97 (m, 3H, Ar), 2.36 (s, 3H, COMe), 2.01 (t, 3H, J=
1.2 Hz, Me); 13C NMR (75 MHz, CDCl3, 258C): d=202.2
(CO), 157.2, 155.0, 138.6, 134.9 (=CH), 130.6 (Ar, CH),
130.0 (Ar, CH), 129.8 (Ar, 2CH), 127.7, 123.3 (Ar, CH),
123.3 (Ar, CH), 119.1 (Ar, CH), 118.1 (Ar, 2CH), 25.7
(Me), 12.3 (Me); IR (CHCl3): n=3066, 1668 (CO), 1484,
1238, 753 cmÀ1; HR-MS (ES): m/z=252.1142, calcd. for
C17H16O2 [M]+: 252.1150.
a,b-Unsaturated ketone 2i: From 100 mg (0.57 mmol) of
a-allenol 1i, chromatography of the residue using hexanes/
ethyl acetate (9:1) as eluent gave compound 2i as a colorless
1
oil; yield: 61 mg (61%); H NMR (300 MHz, CDCl3, 258C):
d=7.42 (s, 1H), 7.27 (d, 2H, J=8.0 Hz), 7.15 (d, 2H, J=
8.0 Hz), 2.38 (s, 3H), 2.32 (s, 3H), 1.99 (d, 3H, J=1.3 Hz);
13C NMR (75 MHz, CDCl3, 258C): d=200.0, 140.3, 139.1,
137.2, 133.2, 130.2 (2C), 129.6 (2C), 26.3, 22.0, 13.4; IR
(CHCl3): n=3074, 1672 (CO), 1482, 1233, 752, 697 cmÀ1
;
HR-MS (ES): m/z=174.1047, calcd. for C12H14O [M]+:
174.1045.
a,b-Unsaturated ketone 2c: From 108 mg (0.33 mmol) of
a-allenol 1c, chromatography of the residue using hexanes/
ethyl acetate (10:1) as eluent gave compound 2c as a color-
less oil; yield: 67 mg (61%); 1H NMR (300 MHz, CDCl3,
258C): d=7.60 (s, 1H, =CH), 7.44 (m, 1H, Ar), 7.43 (d, 2H,
J=9.0 Hz, Ar), 7.34 (td, 1H, J=7.7, 1.7 Hz, Ar), 7.20 (td,
1H, J=7.9, 1.0 Hz, Ar), 6.96 (dd, 1H, J=8.1, 1.1 Hz, Ar),
6.84 (d, 2H, J=9.0 Hz, Ar), 2.37 (s, 3H, COMe), 1.99 (t,
3H, J=1.4 Hz, Me); 13C NMR (75 MHz, CDCl3, 258C): d=
198.6 (CO), 159.1, 157.8, 138.9, 134.4 (=CH), 132.8 (Ar,
2CH), 130.8 (Ar, CH), 130.2 (Ar, CH), 128.7, 123.9 (Ar,
CH), 119.8 (Ar, 2CH), 119.2 (Ar, CH), 116.4, 25.8 (Me),
13.0 (Me); IR (CHCl3): n=3066, 1667 (CO), 1477, 1234,
Typical Procedure for the Fe(OTf)3-Catalyzed
Rearrangement Reaction of a-Allenols 1, 7, and 10
To a solution of the appropriate allenol 1 (1.0 mmol) in di-
chloromethane (10 mL), Fe(OTf)3 (0.10 mmol) was added.
The reaction mixture was stirred at reflux temperature until
the starting material disappeared as indicated by TLC. After
filtration through a pad of Celite, the mixture was concen-
trated under vacuum, and purified by flash column chroma-
tography eluting with ethyl acetate/hexanes mixtures. Spec-
troscopic and analytical data for pure forms of compounds
2, 8, 9, and 11 are given below.
756 cmÀ1
;
HR-MS (ES): m/z=330.0245, calcd. for
C17H15BrO2 [M]+: 330.0255.
a,b-Unsaturated ketone 2d: From 238 mg (0.73 mmol) of
allenol 1d, chromatography of the residue using hexanes/
ethyl acetate (20:1) as eluent gave compound 2d as a color-
a,b-Unsaturated ketone 2b: From 68 mg (0.22 mmol) of
a-allenol 1b, chromatography of the residue using hexanes/
ethyl acetate (7:1) as eluent gave compound 2b as a colorless
1
1
less oil; yield: 147 mg (62%); H NMR (300 MHz, CDCl3,
oil; yield: 36 mg (51%); H NMR (300 MHz, CDCl3, 258C):
258C): d=7.60 (s, 1H, =CH), 7.49 (m, 3H, Ar), 7.32 (m,
4H, Ar), 7.24 (t, 3H, J=7.6 Hz, Ar), 7.07 (t, 1H, J=7.5 Hz,
Ar), 6.90 (dd, 1H, J=8.0, 1.2 Hz, Ar), 6.85 (d, 1H, J=
7.3 Hz, Ar), 2.36 (s, 3H, COMe), 1.94 (d, 3H, J=1.3 Hz,
Me); 13C NMR (75 MHz, CDCl3, 258C): d=200.4 (CO),
155.4, 153.4, 153.2, 137.6, 136.8, 135.2 (Ar, CH), 133.4, 131.4
(Ar, CH), 130.4 (Ar, CH), 129.8 (Ar, CH), 129.1 (Ar, 2CH),
128.7 (Ar, CH), 128.0 (Ar, 2CH), 127.3 (Ar, CH), 124.3 (Ar,
d=7.94 (s, 1H, =CH), 7.37 (m, 6H, Ar), 7.15 (m, 3H, Ar),
7.01 (d, 2H, J=8.6 Hz, Ar), 6.87 (d, 1H, J=8.1 Hz, Ar),
6.76 (d, J=4.1 Hz, Ar), 2.33 (s, 3H, COMe); 13C NMR
(75 MHz, CDCl3, 258C): d=199.4 (CO), 157.4, 156.1, 156.0,
142.0, 133.6 (=CH), 130.9 (Ar, CH), 130.3 (Ar, CH), 129.9
(Ar, 2CH), 129.8 (Ar, 2CH), 128.7 (Ar, 2CH), 127.8 (Ar,
CH), 126.6, 123.4 (Ar, CH), 123.0 (Ar, CH), 118.9 (Ar, CH),
118.6 (Ar, 2CH), 27.4(Me); IR (CHCl3): n=3061, 1675
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(CO), 1482, 1233, 752, 695 cmÀ1; HR-MS (ES): m/z=
314.1306, calcd. for C22H18O2 [M]+: 314.1307.
a,b-Unsaturated ketone 8b: From 60 mg (0.23 mmol) of
a-allenol 7b, chromatography of the residue using hexanes/
ethyl acetate (2:1) as eluent gave compound 8b as a colorless
a,b-Unsaturated ketone 2f: From 200 mg (0.78 mmol) of
a-allenol 1f, chromatography of the residue using hexanes/
ethyl acetate (8:1) as eluent gave compound 2f as a colorless
oil; yield: 110 mg (55%); 1H NMR (300 MHz, CDCl3,
258C): d=7.59 (s, 1H, =CH), 7.42 (m, 3H, Ar), 7.16 (m,
2H, Ar), 7.14 (d, 2H, J=8.6 Hz, Ar), 6.96 (d, 2H, J=
8.5 Hz, Ar), 2.30 (s, 3H, Me); 13C NMR (75 MHz, CDCl3,
258C): d=199.1 (CO), 141.3, 137.2 (=CH), 136.6, 135.1,
133.1, 132.0 (Ar, 2CH), 129.4 (Ar, 2CH), 129.2 (Ar, 2CH),
128.5 (Ar, 2CH), 128.1 (Ar, CH), 28.0 (Me); IR (CHCl3):
n=2930, 1662 (CO), 1457, 1090, 810 cmÀ1; HR-MS (ES):
m/z=256.0659, calcd. for C16H13OCl [M]+: 256.0655.
1
oil; yield: 38 mg (62%); H NMR (300 MHz, CDCl3, 258C):
d=7.44 (m, 5H), 7.10 (m, 1H), 6.75 (d, 1H, J=7.7 Hz), 6.66
(m, 2H), 2.40 (s, 3H); 13C NMR (75 MHz, CDCl3, 258C):
d=167.7, 150.4, 147.9, 141.7, 132.9, 131.1, 130.2, 129.9, 129.4
(2C), 127.8 (2C), 123.7, 122.0, 121.5, 109.9, 29.0; IR
(CHCl3): n=2936, 1706 (CO), 1606 (CO), 1482, 755,
695 cmÀ1
;
HR-MS (ES): m/z=263.0956, calcd. for
C17H13NO2 [M]+: 263.0946.
a,b-Unsaturated ketone 8c: From 125 mg (0.38 mmol) of
allenol 7c, chromatography of the residue using hexanes/
ethyl acetate (4:1) as eluent gave compound 8c as a colorless
1
oil; yield: 63 mg (49%); H NMR (500 MHz, CDCl3, 258C):
a,b-Unsaturated ketone 2h: From 95 mg (0.38 mmol) of
allenol 1h, chromatography of the residue using hexanes/
ethyl acetate (5:1) as eluent gave compound 2h as a colorless
d=7.50 (m, 4H, Ar), 7.20 (m, 2H, Ar), 6.73 (d, 1H, J=
8.3 Hz, Ar), 6.70 (d, 1H, J=2.1 Hz, Ar), 3.24 (s, 3H, NMe),
2.48 (s, 3H, COMe); 13C NMR (125 MHz, CDCl3, 258C):
d=203.4 (CO), 166.4 (CO), 153.0, 143.0, 132.4, 130.3 (Ar,
CH), 129.7 (Ar, CH), 129.5 (Ar, 2CH), 128.3 (Ar, CH),
127.7 (Ar, 2CH), 127.4, 123.3 (Ar, CH), 123.0, 122.0, 109.1
(Ar, CH), 28.9 (Me), 26.1 (NMe); IR (CHCl3): n=2924,
1707 (CO), 1608 (CO), 1485, 755, 698 cmÀ1; HR-MS (ES):
m/z=311.0724, calcd. for C18H14ClNO2 [M]+: 311.0713.
1
oil; yield: 49 mg (52%); H NMR (300 MHz, CDCl3, 258C):
d=7.55 (s, 1H), 7.34 (m, 3H), 7.11 (dd, 2H, J=8.0, 1.9 Hz),
6.90 (d, 2H, J=8.9 Hz), 6.61 (d, 2H, J=8.9 Hz), 3.68 (s,
3H), 2.22 (s, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=
199.2, 160.5, 138.8, 138.7, 137.5, 132.7 (2C), 129.6 (2C),
129.2 (2C), 128.5, 127.2, 113.8 (2C), 55.2, 27.9; IR (CHCl3):
n=3075, 1670 (CO), 1471, 1225, 742, 692 cmÀ1; HR-MS
(ES): m/z=252.1157, calcd. for C17H16O2 [M]+: 252.1150.
a,b-Unsaturated ketone 2j: From 220 mg (0.93 mmol) of
a-allenol 1j, chromatography of the residue using hexanes/
ethyl acetate (20:1) as eluent gave compound 2j as a color-
a,b-Unsaturated ketones 8d and 9d: From 111 mg
(0.45 mmol) of a-allenol 7d, chromatography of the residue
using hexanes/ethyl acetate (4:1) as eluent gave the less
polar compound 8d (yield: 32 mg, 35%) and the more polar
compound 9d ꢃ(yield: 11 mg, 12%). a,b-Unsaturated ketone
8d: Colorless oil; 1H NMR (300 MHz, CDCl3, 258C): d=
7.26 (dd, 1H, J=8.3, 1.9 Hz, Ar), 7.14 (d, 1H, J=2.0 Hz,
Ar), 6.74 (d, 1H, J=8.3 Hz, Ar), 3.23 (s, 3H, NMe), 2.62 (s,
3H, Me), 2.50 (s, 3H, Me); 13C NMR (75 MHz, CDCl3,
258C): d=205.2 (CO), 167.3 (CO), 151.6, 141.1, 129.2 (Ar,
CH), 127.6, 122.6 (Ar, CH), 121.5, 120.8, 108.9 (Ar, CH),
28.4 (NMe), 25.9 (Me), 15.7 (Me); IR (CHCl3): n=2925,
1715 (CO), 1604 (CO), 1475, 756 cmÀ1; HR-MS (ES): m/z=
249.0567, calcd. for C13H12ClNO2 [M]+: 249.0557. a,b-Unsa-
1
less oil; yield. 112 mg (51%); H NMR (300 MHz, CDCl3,
258C): d=7.64 (s, 1H, =CH), 7.40 (m, 3H, Ar), 7.19 (dd,
2H, J=7.8, 2.0 Hz, Ar), 6.99 (d, 2H, J=8.3 Hz, Ar), 6.93 (d,
2H, J=8.3 Hz, Ar), 2.32 (s, 3H, Me), 2.28 (s, 3H, Me);
13C NMR (75 MHz, CDCl3, 258C): d=199.3 (CO), 140.0,
139.6, 139.0 (=CH), 137.2, 131.7, 130.9 (Ar, 2CH), 129.5
(Ar, 2CH), 129.0 (Ar, 4CH), 127.8 (Ar, CH), 27.9 (Me),
21.3 (Me); IR (CHCl3): n=2900, 1653 (CO), 1434, 815 cmÀ1
;
HR-MS (ES): m/z=236.1199, calcd. for C17H16O [M]+:
236.1201.
1
turated ketone 9d: Colorless oil; H NMR (300 MHz, CDCl3,
a,b-Unsaturated ketone 2k: From 161 mg (0.72 mmol) of
a-allenol 1k, chromatography of the residue using hexanes/
ethyl acetate (30:1) as eluent gave compound 2k as a color-
less oil; yield: 80 mg (50%); 1H NMR (300 MHz, CDCl3,
258C): d=7.66 (s, 1H, =CH), 7.42 (m, 3H, Ar), 7.18 (m,
5H, Ar), 7.05 (d, 2H, J=7.7 Hz, Ar), 2.33 (s, 3H, Me);
13C NMR (75 MHz, CDCl3, 258C): d=199.3 (CO), 140.9,
138.8 (=CH), 136.9, 134.6, 130.8 (Ar, 2CH), 129.5 (Ar,
2CH), 129.2 (Ar, CH), 129.0 (Ar, 2CH), 128.2 (Ar, 2CH),
127.9 (Ar, CH), 27.9 (Me); IR (CHCl3): n=2915, 1660
(CO), 1426, 1024 cmÀ1; HR-MS (ES): m/z=222.1041, calcd.
for C16H14O [M]+: 222.1045.
258C): d=7.50 (d, 1H, J=2.0 Hz, Ar), 7.30 (dd, 1H, J=8.3,
1.9 Hz, Ar), 6.77 (d, 1H, J=8.3 Hz, Ar), 3.20 (s, 3H, NMe),
2.49 (s, 3H, Me), 2.36 (s, 3H, Me); 13C NMR (75 MHz,
CDCl3, 258C): d=206.3 (CO), 170.3 (CO), 165.9, 142.7,
129.1 (Ar, CH), 127.6, 123.9 (Ar, CH), 123.0, 109.1 (Ar,
CH), 28.6 (NMe), 25.9 (Me), 17.4 (Me); IR (CHCl3): n=
2920, 1706 (CO), 1600 (CO), 1461, 736 cmÀ1; HR-MS (ES):
m/z=249.0564, calcd. for C13H12ClNO2 [M]+: 249.0557.
a,b-Unsaturated Ketone 11a: From 94 mg (0.26 mmol) of
a-allenol 10a, chromatography of the residue using hexanes/
ethyl acetate (6:1) as eluent gave compound 11a as a color-
less oil; yield: 18 mg (20%); 1H NMR (300 MHz, CDCl3,
258C): d=8.30 (s, 1H, NH), 8.12 (m, 2H, Ar), 7.97 (s, 1H,
Ar), 7.72 (m, 3H, Ar), 7.49 (m, 3H, Ar + =CH), 7.35 (m,
2H, Ar), 2.36 (s, 3H, COMe); 13C NMR (75 MHz, CDCl3,
258C): d=172.8 (CO), 171.3, 129.5 (=CH), 129.1, 128.9 (Ar,
2CH), 128.7 (Ar, CH), 128.1 (Ar, CH), 127.4 (2C), 127.3
(Ar, CH), 125.1 (Ar, CH), 123.2 (Ar, CH), 118.4 (Ar, CH),
115.2 (Ar, CH), 110.7 (Ar, CH), 28.0 (Me); IR (CHCl3): n=
3370 (NH), 3057, 1734 (CO) 1457, 1152, 754 cmÀ1; HR-MS
(ES): m/z=261.1166, calcd. for C18H15NO [M]+: 261.1154.
a,b-Unsaturated Ketone 11b: From 82 mg (0.27 mmol) of
a-allenol 10b, chromatography of the residue using hexanes/
a,b-Unsaturated ketone 8a: From 140 mg (0.50 mmol) of
a-allenol 7a, chromatography of the residue using hexanes/
ethyl acetate (2:1) as eluent gave compound 8a as a colorless
1
oil; yield: 79 mg (57%); H NMR (300 MHz, CDCl3, 258C):
d=7.43 (m, 5H), 7.16 (m, 1H), 6.72 (d, 1H, J=7.7 Hz), 6.68
(m, 2H), 3.17 (s, 3H), 2.41 (s, 3H); 13C NMR (75 MHz,
CDCl3, 258C): d=204.4, 167.1, 151.8, 145.0, 133.4, 130.5,
130.2, 129.7 (2C), 128.7, 128.3 (2C), 123.6, 122.4, 121.1,
108.7, 29.5, 26.4; IR (CHCl3): n=2932, 1705 (CO), 1610
(CO), 1482, 754, 696 cmÀ1; HR-MS (ES): m/z=277.1093,
calcd. for C18H15NO2 [M]+: 277.1103.
6
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ÝÝ
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UPDATES
Acid-Catalyzed Synthesis of a,b-Disubstituted Conjugated Enones
ethyl acetate (6:1) as eluent gave compound 11b as a color-
less oil; yield: 19 mg (26%); 1H NMR (300 MHz, CDCl3,
258C): d=8.64 (s, 1H, NH), 7.91 (s, 1H, =CH), 7.82 (d, 1H,
J=7.1 Hz, Ar), 7.59 (d, 1H, J=2.8 Hz, Ar), 7.46 (d, 1H, J=
7.1 Hz, Ar), 7.29 (m, 2H, Ar), 2.55 (s, 3H, COMe);
13C NMR (75 MHz, CDCl3, 258C): d=172.6 (CO), 135.4,
132.8, 131.1 (Ar, CH), 129.4, 126.1 (Ar, CH), 124.5, 123.3
(Ar, CH), 120.9 (Ar, CH), 118.5 (Ar, CH), 111.4 (Ar, CH),
25.5 (Me), 19.6 (Me); IR (CHCl3): n=3314 (NH), 1708
(CO) 1460, 1245, 748 cmÀ1; HR-MS (ES): m/z=199.1005,
calcd. for C13H13NO [M]+: 199.0997.
ketone 15a: colorless oil; [a]D: +32.0 (c 1.0, CHCl3);
1H NMR (300 MHz, CDCl3, 258C): d=7.27 (t, 2H, J=
7.3 Hz, Ar), 7.00 (t, 1H, J=7.4 Hz, Ar), 6.92 (d, 2H, J=
7.9 Hz, Ar), 6.55 (dd, 1H, J=9.4, 1.3 Hz, =CH), 5.45 (d, 1H,
J=4.4 Hz, H3), 4.79 (dd, 1H, J=9.4, 4.4 Hz, H4), 3.23 (dd,
1H, J=14.0, 7.7 Hz, NCHH), 2.88 (dd, 1H, J=14.0, 6.7 Hz,
NCHH), 2.23 (s, 3H, COMe), 1.86 (m, 1H, CH isobut), 1.85
(d, 3H, J=1.3 Hz, Me), 0.98 (d, 3H, J=7.4 Hz, Me), 0.95
(d, 3H, J=6.8 Hz, Me); 13C NMR (75 MHz, CDCl3, 258C):
d=198.5 (CO), 165.4 (CO), 156.5, 142.8, 134.6 (=CH), 130.7
(Ar, 2CH), 122.5 (Ar, CH) 115.2 (Ar, 2CH), 81.1 (CH), 56.8
(CH), 48.7 (NCH2), 26.5 (CH isobut), 24.6 (Me), 19.3 (Me),
19.3 (Me); IR (CHCl3): n=1757 (CO), 1673 (CO), 1232,
754 cmÀ1
;
HR-MS (ES): m/z= 301.1682, calcd. for
Typical Procedure for the Iron-Catalyzed
C18H23NO3 [M]+: 301.1678. Chlorodiene 16a: colorless oil;
[a]D: +7.8 (c 0.2, CHCl3); 1H NMR (300 MHz, CDCl3,
258C): d=7.28 (t, 2H, J=7.3 Hz, Ar), 7.01 (t, 1H, J=
7.3 Hz, Ar), 6.98 (dd, 2H, J=8.8, 1.1 Hz, Ar), 5.47 (dd, 1H,
J=9.8, 1.5 Hz, =CH), 5.45 (d, 1H, J=1.3 Hz, =CHH), 5.29
(d, 1H, J=4.4 Hz, H3), 5.14 (d, 1H, J=1.2 Hz, =CHH),
4.76 (dd, 1H, J=9.9, 4.5 Hz, H4), 3.16 (dd, 1H, J=14.0,
7.9 Hz, NCHH), 2.88 (dd, 1H, J=14.0, 6.7 Hz, NCHH), 1.92
(d, 3H, J=1.5 Hz, Me),.1.88 (m, 1H, CH isobut), 0.95 (d,
3H, J=6.9 Hz, Me), 0.92 (d, 3H, J=6.7 Hz, Me); 13C NMR
(75 MHz, CDCl3, 258C): d=165.8 (CO), 157.3, 142.5, 138.1,
129.5 (Ar, 2CH), 123.8 (Ar, CH), 122.2 (=CH), 115.7 (Ar,
2CH), 115.3 (=CH2), 81.7 (CH), 57.3 (CH), 48.2 (NCH2),
27.5 (CH isobut), 22. 6 (Me), 20.3 (Me), 20.3 (Me); IR
(CHCl3): n=3342 (OH), 1758 (CO), 1236, 756 cmÀ1; HR-MS
(ES): m/z=319.1324, calcd. for C18H22ClNO2 [M]+: 319.1339.
Chlorodiene (E)-16b and chlorodiene (Z)-16b: From
140 mg (0.38 mmol) of allenol 12b, chromatography of the
residue using hexanes/ethyl acetate (3:1) as eluent gave the
less polar compound (E)-16b (yield: 41 mg, 27%) and the
more polar compound (Z)-16b (yield: 15 mg, 10%). Enol
Rearrangement Reaction of a-Allenols 1 and 12–14
To
a solution of the appropriate allenol 1 or 12–14
(1.0 mmol) in dichloromethane (10 mL), FeCl3·6H2O
(0.10 mmol or 0.20 mmol) was added. The reaction mixture
was stirred at reflux temperature until the starting material
disappeared as indicated by TLC. After filtration through
a pad of Celite, the mixture was concentrated under
vacuum, and purified by flash column chromatography elut-
ing with ethyl acetate/hexanes mixtures. Spectroscopic and
analytical data for pure forms of compounds 2, 6, and 15–19
are given below.
a,b-Unsaturated ketone 2d and chlorodiene 6d: From
238 mg (0.73 mmol) of allenol 1d, chromatography of the
residue using hexanes/ethyl acetate (20:1) as eluent gave the
less polar compound 6d (yield: 114 mg, 46%) and the more
polar compound 2d (yield: 52 mg (22%). Chlorodiene 6d:
colorless oil; 1H NMR (300 MHz, CDCl3, 258C): d=7.48
(dd, 2H, J=7.0, 1.5 Hz, Ar), 7.36 (td, 2H, J=7.6, 1.6 Hz,
Ar), 7.28 (t, 1H, J=7.0 Hz, Ar), 7.15 (m, 3H, Ar), 7.02 (td,
1H, J=7.8, 1.6 Hz, Ar), 6.88 (td, 1H, J=7.6, 1.0 Hz, Ar),
6.81 (dd, 1H, J=8.0, 1.2 Hz, Ar), 6.67 (dd, 1H, J=8.2,
1.0 Hz, Ar), 6.34 (s, 1H, =CH), 5.08 (d, 1H, J=1.1 Hz, =
CHH), 4.91 (d, 1H, J=1.1 Hz, =CHH), 1.92 (d, 3H, J=
1.4 Hz, Me); 13C NMR (75 MHz, CDCl3, 258C): d=154.9,
153.8, 139.8, 137.8, 136.2, 133.2, 131.2 (Ar, CH), 130.3 (Ar,
CH), 129.7, 129.3 (Ar, 2CH), 128.6 (Ar, CH), 128.3 (Ar,
CH), 128.1 (Ar, 2CH), 127.2 (Ar, CH), 124.7 (Ar, CH),
123.7 (Ar, CH), 122.7 (Ar, CH), 119.3 (Ar, CH), 117.7 (=
CH), 115.3 (=CH2), 23.3 (Me); IR (CHCl3): n=3060, 1477,
1430, 1228, 744, 694 cmÀ1; HR-MS (ES): m/z=346.1138,
calcd. for C23H19ClO [M]+: 346.1124.
1
(E)-16b: colorless oil; [a]D: +23.3 (c 0.3, CHCl3); H NMR
(300 MHz, CDCl3, 258C): d=7.22 (m, 4H, Ar), 7.18 (m,
3H, Ar), 6.91 (d, 2H, J=7.7 Hz, Ar), 6.90 (m, 1H, Ar), 5.96
(d, 1H, J=10.1 Hz, =CH), 5.69 (d, 1H, J=1.0 Hz, =CHH),
5.33 (d, 1H, J=4.4 Hz, H-3), 5.29 (d, 1H, J=1.2 Hz, =
CHH), 4.85 (dd, 1H, J=9.9, 4.4 Hz, H-4), 3.12 (dd, 1H, J=
13.9, 7.6 Hz, NCHH), 2.89 (dd, 1H, J=13.9, 6.9 Hz,
NCHH), 1.86 (sept, 1H, J=6.7 Hz, CH isobut), 0.89 (d, 3H,
J=6.7 Hz, Me), 0.86 (d, 3H, J=6.6 Hz, Me); 13C NMR
(75 MHz, CDCl3, 258C): d=165.6 (CO), 157.1, 145.9, 136.6,
135.9, 129.5 (Ar, 2CH), 128.8 (Ar, CH), 128.6 (Ar, 2CH),
126.7 (Ar, 2CH), 124.5 (=CH), 122.3 (Ar, CH), 118.6 (=
CH2), 115.5 (Ar, 2CH), 81.8 (CH), 58.0 (CH), 48.6 (NCH2),
27.6 (CH isobut), 20.3 (Me), 20.3 (Me); IR (CHCl3): n=
3405 (OH), 3061, 1761 (CO), 1235, 757, 694 cmÀ1; HR-MS
(ES): m/z=381.1508, calcd. for C23H24ClNO2 [M]+: 381.1496.
Enol (Z)-16b: colorless oil; [a]D: +15.4 (c 0.2, CHCl3);
1H NMR (300 MHz, CDCl3, 258C): d=7.42 (m, 4H, Ar),
7.26 (m, 3H, Ar), 7.14 (d, 2H, J=7.4 Hz, Ar), 7.00 (m, 1H,
Ar), 6.30 (d, 1H, J=2.8 Hz, =CH), 5.69 (d, 1H, J=1.6 Hz, =
CHH), 5.26 (d, 1H, J=1.6 Hz, =CHH), 5.08 (d, 1H, J=
4.2 Hz, H-3), 4.78 (dd, 1H, J=4.1, 2.8 Hz, H-4), 3.33 (dd,
1H, J=13.9, 8.0 Hz, NCHH), 3.12 (dd, 1H, J=14.0, 6.6 Hz,
NCHH), 2.00 (m, 1H, CH isobut), 1.04 (d, 3H, J=6.7 Hz,
Me), 0.99 (d, 3H, J=6.7 Hz, Me); 13C NMR (75 MHz,
CDCl3, 258C): d=165.1 (CO), 156.2, 145.3, 137.1, 132.2,
130.7 (Ar, CH), 129.5 (Ar, CH), 128.8 (Ar, CH), 128.5 (Ar,
a,b-Unsaturated ketone 2e and chlorodiene 6e: From
340 mg (1.75 mmol) of allenol 1e, chromatography of the
residue using hexanes/ethyl acetate (8:1) as eluent gave the
less polar compound 6e (yield: 112 mg, 30%) and the more
polar compound 2e (yield: 65 mg, 19%). Chlorodiene 6e:
1
colorless oil; H NMR (300 MHz, CDCl3, 258C): d=7.22 (d,
2H, J=8.6 Hz), 7.17 (d, 2H, J=8.8 Hz), 6.21 (d, 1H, J=
1.2 Hz), 5.21 (d, 1H, J=1.3 Hz), 5.05 (d, 1H, J=1.3 Hz),
1.97 (s, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=139.6,
136.3, 135.0, 132.8, 130.0 (2C), 128.3 (2C), 128.1, 115.5, 23.7;
IR (CHCl3): n=3060, 1478, 745, 692 cmÀ1; HR-MS (ES):
m/z=212.0143, calcd for C11H10Cl2 [M]+: 212.0160.
a,b-Unsaturated ketone 15a and chlorodiene 16a: From
101 mg (0.33 mmol) of allenol 12a, chromatography of the
residue using hexanes/ethyl acetate (3:1) as eluent gave the
less polar compound 16a (yield: 10 mg, 9%) and the more
polar compound 15a (yield: 8 mg 8%). a,b-Unsaturated
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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ÞÞ
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UPDATES
Benito Alcaide et al.
2CH), 128.0 (Ar, CH), 127.4 (Ar, CH), 125.6 (Ar, 2CH),
124.9 (=CH), 121.7 (Ar, CH), 120.4 (=CH2), 88.1 (CH), 60.7
(CH), 48.6 (NCH2), 27.4 (CH isobut), 20.5 (Me), 20.5 (Me);
IR (CHCl3): n=3396 (OH), 3062, 1758 (CO), 1231, 760,
CHH), 5.41 (d, 1H, J=1.5 Hz, =CHH), 5.14 (dd, 1H, J=
8.0, 3.1 Hz, H4), 4.71 (d, 1H, J=4.0 Hz, H2), 4.64 (d, 1H,
J=3.2 Hz, H3), 1.98 (d, 3H, J=1.0 Hz, Me), 1.60 (s, 3H,
Me), 1.35 (s, 3H, Me); 13C NMR (75 MHz, CDCl3, 258C):
d=157.1, 141.4, 135.8, 129.7 (Ar, 2CH), 124.8 (=CH), 121.7
(Ar, CH), 115.3 (Ar, 2CH), 113.6 (=CH2), 111.8, 104.8
(CH), 82.7 (CH), 81.5 (CH), 75.9 (CH), 26.8 (Me), 26.2
(Me), 15.0 (Me); IR (CHCl3): n=3475 (OH), 1726, 1492,
1231, 1076, 1020, 756 cmÀ1; HR-MS (ES): m/z=336.1141,
calcd. for C18H21ClO4 [M]+: 336.1128. Tricycle 19: colorless
699 cmÀ1
;
HR-MS (ES): m/z=381.1481, calcd. for
C23H24ClNO2 [M]+: 381.1496.
a,b-Unsaturated ketone 15c: From 28 mg (0.08 mmol) of
a-allenol 12c, chromatography of the residue using hexanes/
ethyl acetate (4:1) as eluent gave compound 15c as a color-
less oil; yield: 5 mg (20%); [a]D =: +25.3 (c 0.6, CHCl3);
1H NMR (300 MHz, CDCl3, 258C): d=7.30 (m, 6H, Ar),
7.03 (m, 2H, Ar), 6.90 (d, 2H, J=7.9 Hz, Ar), 6.34 (dd, 1H,
J=9.5, 1.3 Hz, =CH), 5.41 (d, 1H, J=4.5 Hz, H3), 4.65 (dd,
1H, J=9.5, 4.5 Hz, H4), 4.57 (d, 1H, J=14.8 Hz, NCHH),
4.29 (d, 1H, J=14.9 Hz, NCHH), 2.06 (s, 3H, COMe), 1.64
(d, 3H, J=1.3 Hz, Me); 13C NMR (75 MHz, CDCl3, 258C):
d=198.9 (CO), 164.7 (CO), 156.9, 142.4, 134.8, 134.5 (=CH),
129.6 (Ar, 2CH), 129.0 (Ar, 2CH), 128.7 (Ar, 2CH), 128.3
(Ar, CH), 122.5 (Ar, CH), 115.2 (Ar, 2CH), 81.8 (CH), 55.9
(CH), 45.2 (NCH2), 25.5 (Me), 11.4 (Me); IR (CHCl3): n=
3063, 1760 (CO), 1682 (CO), 1234, 754, 699 cmÀ1; HR-MS
(ES): m/z=335.1526, calcd. for C21H21NO3 [M]+: 335.1521.
a,b-Unsaturated ketone 15d: From 12 mg (0.03 mmol) of
a-allenol 12d, and after chromatography of the residue
using hexanes/ethyl acetate (3:1) as eluent gave compound
15d as a colorless oil; yield: 4 mg (31%); [a]D: +18.3 (c 0.5,
1
oil; [a]D: +38.5 (c 0.2, CHCl3); H NMR (300 MHz, CDCl3,
258C): d=7.22 (dt, 1H, J=7.6, 1.5 Hz, Ar), 7.14 (t, 1H, J=
8.0 Hz, Ar), 6.93 (td, 1H, J=7.5, 1.1 Hz, Ar), 6.80 (dd, 1H,
J=8.2, 1.2 Hz, Ar), 5.93 (d, 1H, J=3.6 Hz, H1), 4.72 (m,
1H, H2), 4.71 (m, 2H, =CH2), 4.65 (dd, 1H, J=3.9, 2.0 Hz,
H4), 4.51 (d, 1H, J=1.6 Hz, H3), 3.85 (d, 1H, J=3.8 Hz,
CH), 1.79 (t, 3H, J=3.1 Hz, Me), 1.57 (s, 3H, Me), 1.36 (s,
3H, Me); 13C NMR (75 MHz, CDCl3, 258C): d=209.0 (CO),
152.9, 128.9 (Ar, CH), 127.9 (Ar, CH), 121.1 (Ar, CH),
119.8, 116.3 (Ar, CH), 111.9, 105.2 (CH), 97.0, 83.3 (CH),
78.8 (CH), 75.7 (CH), 74.1 (=CH2), 40.3 (CH), 26.6 (Me),
26.2 (Me), 16.5 (Me); IR (CHCl3): n=2927, 1738 (CO),
1216, 1078, 1015, 757 cmÀ1; HR-MS (ES): m/z=316.1298,
calcd. for C18H20O5 [M]+: 316.1311.
1
CHCl3); H NMR (300 MHz, CDCl3, 258C): d=7.31 (d, 2H,
Acknowledgements
J=9.1 Hz, Ar), 6.92 (d, 2H, J=9.2 Hz, Ar), 6.89 (d, 2H, J=
9.1 Hz, Ar), 6.82 (d, 2H, J=9.1 Hz, Ar), 6.65 (dd, 1H, J=
9.2, 1,3 Hz, =CH), 5.47 (d, 1H, J=4.8 Hz, H3), 5.17 (dd,
1H, J=9.2, 4.8 Hz, H4), 3.81 (s, 3H, OMe), 3.77 (s, 3H,
OMe), 2.26 (s, 3H, Me), 1.97 (d, 3H, J=1.5 Hz, Me);
13C NMR (75 MHz, CDCl3, 258C): d=197.2 (CO), 161.9
(CO), 156.8, 155.1, 151.1, 142.7, 135.3 (=CH), 130.4, 118.3
(Ar, 2CH), 116.5 (Ar, 2CH), 114.7 (Ar, 2CH), 114.6 (Ar,
2CH), 82.0 (CH), 56.4 (CH), 55.6 (OMe), 55. 5. (OMe),
25.7 (Me), 11.9 (Me); IR (CHCl3): n=2924, 1755 (CO),
1675 (CO), 1508, 1247, 628 cmÀ1; HR-MS (ES): m/z=
381.1578, calcd for C22H23NO5 [M]+: 381.1576.
Support for this work by MINECO (Projects CTQ2012-
33664-C02-01 and CTQ2012-33664-C02-02) is gratefully ac-
knowledged. S. C. thanks MEC for a predoctoral grant
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UPDATES
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[14] Experimental procedures as well as full spectroscopic
and analytical data for compounds not included in this
Experimental Section are described in the Supporting
Information. It contains as well copies of NMR spectra
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Adv. Synth. Catal. 0000, 000, 0 – 0
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!

UPDATES
10 Acid-Catalyzed Synthesis of a,b-Disubstituted Conjugated
Enones by a Meyer–Schuster-Type Rearrangement in
Allenols
Adv. Synth. Catal. 2015, 357, 1 – 10
Benito Alcaide,* Pedro Almendros,* Sara Cembellꢀn,
Teresa Martꢀnez del Campo
10
asc.wiley-vch.de
ꢂ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!