Direct allenol-based stereocontrolled access to substituted (E)-1,3-enynes

Article abstract of DOI:10.1039/c2ob26085a

A stereoselective synthesis of 1-substituted (E)-2-aryl-but-1-en-3-ynes, including tetrasubstituted alkenes, has been developed from aryl-substituted α-allenols by treatment with the AcCl-NaOH (aqueous) system. This transformation might be explained throu

Full text of DOI:10.1039/c2ob26085a

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PAPER
Direct allenol-based stereocontrolled access to substituted (E)-1,3-enynes†
Benito Alcaide,*a Pedro Almendros*b and Teresa Martínez del Campoa
Received 5th June 2012, Accepted 3rd August 2012
DOI: 10.1039/c2ob26085a
A stereoselective synthesis of 1-substituted (E)-2-aryl-but-1-en-3-ynes, including tetrasubstituted alkenes,
has been developed from aryl-substituted α-allenols by treatment with the AcCl–NaOH (aqueous) system.
This transformation might be explained through the elimination of acetic acid, made up of a δ-hydrogen
and the acetate group in the initially formed α-allenic acetate.
protocol in such reactions, and many water soluble compounds
do not need to be converted into their derivatives and can be
Introduction
The important medicinal properties of compounds containing the
1,3-enyne moiety, in addition to the use of functionalized 1,3-
enynes as building blocks for the preparation of bioactive mole-
cules or organic electronic material, are now well established.1,2
On the other hand, during the past decades the allene group has
developed from almost a rarity to an established member of the
weaponry utilized in modern organic synthetic chemistry.3 In
particular, transformations involving allenols have been pursued
with renewed interest.4 However, surprisingly, the direct prep-
aration of 1,3-enynes from allenolic moieties has not been men-
tioned in the literature; only Lee and Ma have independently
reported two-step procedures starting from very activated alle-
nols, namely, 2-(methoxycarbonyl)-2,3-allenols.5 We now report
direct stereocontrolled access to the (E)-1,3-enyne moiety from
aryl-substituted α-allenols.
reacted directly), as well as unique reactivity and selectivity that
are not often attained under dry conditions.7 In this context,
efforts were directed towards a direct approach for the stereo-
selective synthesis of functionalized 1,3-enynes 2 by reaction of
aryl-substituted α-allenols 1 in an aqueous medium. Initial
experiments were carried out using as a model substrate allenol
1a just by the addition of acetyl chloride and aqueous NaOH.
We observed that the reaction did not proceed “on water”, prob-
ably because substrate 1a is completely insoluble in aqueous
media. After some experimentation, it was found that the use of
a biphasic water–dichloromethane mixture was necessary for the
reaction to occur. When phenyl-substituted allenol 1a was
treated with acetyl chloride and aqueous NaOH–dichloro-
methane (1 : 1) at room temperature, the 1,2-diphenyl (E)-1,3-
enyne 2a was directly formed in 76% yield after 24 h (Scheme 1).
Thus, allenol 1a undergoes elimination of water, made up of a
δ-hydrogen and the hydroxyl group.8 Having established the
optimal reaction conditions, we explored the scope of the
Results and discussion
Starting materials for enyne formation, aryl-substituted α-alle-
nols 1, were readily prepared in good yields from the corre-
sponding aldehyde via the regiocontrolled indium-mediated
Barbier-type carbonyl-allenylation reaction using our previously
described methodology.6 Water-based organic reactions have
been gaining in popularity because of their synthetic advantages
(many reactive functional groups, such as hydroxy, amine, and
carboxylic functions, do not require the protection–deprotection
aGrupo de Lactamas y Heterociclos Bioactivos, Departamento de
Química Orgánica I, Unidad Asociada al CSIC, Facultad de Química,
Universidad Complutense de Madrid, 28040-Madrid, Spain.
E-mail: alcaideb@quim.ucm.es; Fax: +34-91-3944103
bInstituto de Química Orgánica General, IQOG, Consejo Superior de
Investigaciones Científicas (CSIC), Juan de la Cierva 3, 28006-Madrid,
Spain. E-mail: Palmendros@iqog.csic.es; Fax: +34-91-5644853
†Electronic supplementary information (ESI) available: Compound
characterization data for all compounds and experimental procedures not
included in the Experimental section as well as copies of NMR spectra.
See DOI: 10.1039/c2ob26085a
Scheme 1 Direct synthesis of arene-tethered (E)-1,3-enynes 2a–g from
allenols 1a–g.
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Scheme 2 Direct synthesis of enantiopure (E)-1,3-enynes 2h–l from
allenols 1h–l.
methodology by subjecting a range of aryl-substituted α-allenols
1b–g to dehydration/rearrangement and the results are shown in
Scheme 1. In each case, the crude reaction mixtures are extre-
mely clean and (E)-1,3-enynes 2b–g are the only products
detected (Scheme 1).9 Besides, as revealed in Scheme 1, various
aryl-substituted allenols were suitable for such a reaction. For
example, phenyl, p-methoxyphenyl, and p-bromophenyl substi-
tuents at the allene side were tolerated. Next, we decided to use
heteroaromatic α-allenol derivatives as the reactants. Tolerance
toward this type of substituent at the alkene end was demon-
strated by the obtention of the corresponding indole derivative
2g in fair yield.
Satisfied with the above results, we set out to evaluate the
reaction for substrates that contain stereocenters. Thus, a series
of aliphatic enantiopure α-allenol derivatives were tested
(Scheme 2). Allenols 1h and 1i were smoothly converted into
the desired 1,3-enynes 2h and 2i. To assess scope, the even more
challenging enantiopure 2-azetidinone-tethered allenols 1j–l
were tested as precursors. Similarly, the aliphatic chain bearing a
β-lactam moiety also afforded the expected (E)-1,3-enynes 2j–l
as single isomers. These results indicate that the stereochemical
integrity at the heterocyclic stereocenters was retained in the
course of the reaction.
Despite Lee’s and Ma’s statement that tetrasubstituted alkenes
bearing ethynyl groups could not be prepared because acylation
of the corresponding tertiary allenolic moiety did not work,5 we
decided to test our method with highly hindered allenols 1m–r.
To our delight, when the allene substituent was moved in the
2-azetidinone ring from position C4 to C3, as in (3R,4S)-
3-hydroxy-3-(1-phenylpropa-1,2-dienyl)azetidin-2-ones 1m–q, it
furnished the corresponding enyne β-lactams 2m–q in fair yields
in its reaction with the AcCl–NaOH (aqueous) system. Whereas
the reaction of allenols 1m, 1n, 1p, and 1q did take place with
complete stereoselectivity, thus forming adducts (E)-2m, (E)-2n,
(E)-2p, and (E)-2q, the dehydration/rearrangement of its
dimethoxyaryl homologue 1o gave 1,3-enynes 2o with the
absence of total stereoselectivity [(E)-2o/(Z)-2o = 78 : 22]. Fortu-
nately, the isomeric 1,3-enynes (E)-2o and (Z)-2o were easily
separated by column chromatography. Remarkably, Scheme 3
shows how the mild conditions of the process allow the
Scheme 3 Direct synthesis of tetrasubstituted 1,3-enynes 2m–q from
tertiary allenols 1m–q.
Scheme 4 Proposed mechanism for the direct formation of 1,3-enynes
2 from allenols 1.
stereoselective formation of tetrasubstituted enyne β-lactams
without harming the sensitive four-membered ring. However,
when the tether for the tetrasubstituted enyne formation is an
NH-oxindole ring, e.g. 1r, the reaction did not give the expected
product 2r, instead, an unidentified mixture was formed
(Scheme 3).
A possible reaction course for the dehydration/rearrangement
process is shown in Scheme 4. Initially, the reaction of allenols 1
with acetyl chloride affords the non-isolable allenic acetates 3.
Next, sodium hydroxide abstracts the distal allenic proton of
intermediates 3, which evolve to (E)-1,3-enynes 2 through sub-
sequent triple bond generation with concomitant acetate
elimination.
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1
as a colorless oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 7.40
(d, 2H, J = 8.6 Hz), 7.35 (d, 2H, J = 8.1 Hz), 7.26 (d, 2H, J =
8.6 Hz), 7.17 (d, 2H, J = 8.0 Hz), 5.64 (t, 1H, J = 2.2 Hz), 5.32
(dd, 1H, JAB = 12.3, 2.5 Hz), 5.26 (dd, 1H, JAB = 12.3, 2.5 Hz),
2.57 (s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ = 207.6,
138.6, 137.6, 132.9, 131.4 (2C), 129.1 (2C), 128.5 (2C), 126.7
(2C), 120.8, 109.0, 81.5, 72.1, 21.1; IR (CHCl3): ν = 3360,
2992, 1941 cm−1; HRMS (ES): calcd for C17H1579BrO [M]+:
314.0306; found: 314.0303.
Conclusions
In conclusion, we have successfully accomplished a very attrac-
tive strategy for the direct stereoselective synthesis of the chemi-
cally and biologically relevant 1,3-enyne moiety from readily
available aryl-substituted α-allenols.
Experimental section
1H NMR and 13C NMR spectra were recorded on a Bruker
Avance AVIII-700 with a cryoprobe, a Bruker Avance-300, a
Varian VRX-300S or a Bruker AC-200. NMR spectra were
recorded in CDCl3 solutions, unless otherwise stated. Chemical
shifts are given in ppm relative to TMS (1H, 0.0 ppm) or CDCl3
(13C, 76.9 ppm). Low and high resolution mass spectra were
taken on an AGILENT 6520 Accurate-Mass QTOF LC/MS
spectrometer using the electronic impact (EI) or electrospray
modes (ES) unless otherwise stated. Specific rotation [α]D is
given in 10−1 deg cm2 g−1 at 20 °C, and the concentration (c) is
expressed in g per 100 mL. All commercially available com-
pounds were used without further purification.
α-Allenic alcohol (−)-1i
From 397 mg (3.05 mmol) of (R)-2,3-O-isopropylideneglyceral-
dehyde and after chromatography of the residue using hexanes–
ethyl acetate (6 : 1) as the eluent, we obtained compound (−)-1i
(505 mg, 60%) as a colorless oil; [α]D = −10.0 (c 0.2, CHCl3);
1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.39 (d, 2H, J =
8.9 Hz), 6.91 (d, 2H, J = 8.9 Hz), 5.30–5.28 (m, 2H), 4.90 (dd,
1H, J = 6.3, 2.6 Hz), 4.36 (td, 1H, J = 6.6, 3.8 Hz), 4.13 (dd,
1H, J = 13.7, 7.2 Hz), 4.06 (dd, 1H, J = 12.4, 6.6 Hz),
3.94–3.92 (m, 1H), 3.84 (s, 3H), 1.51 (s, 3H), 1.39 (s, 3H); 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 207.5, 158.9. 133.0, 127.8
(2C), 126.0, 114.1 (2C), 109.2, 80.9, 77.2, 69.4, 64.5, 55.3,
26.4, 24.9; IR (CHCl3): ν = 3362, 2994, 1942 cm−1; HRMS
(ES): calcd for C16H20O4 [M]+: 276.1362; found: 276.1362.
Indium-promoted reaction between 3-substituted prop-2-ynyl
bromides and aldehydes; general procedure for the synthesis of
α-allenic alcohols 1a–o
1-Bromo-3-phenyl-2-propyne, 1-bromo-3-(p-methoxyphenyl)-2-
propyne, or 1-bromo-3-(p-bromophenyl)-2-propyne (3.0 mmol)
was added to a well stirred suspension of the corresponding alde-
hyde (1.0 mmol) and indium powder (6.0 mmol) in THF–
NH4Cl (aq. sat.) (1 : 5, 5 mL) at 0 °C. After disappearance of the
starting material (TLC) the mixture was extracted with ethyl
acetate (3 × 5 mL). The organic extract was washed with brine,
dried (MgSO4) and concentrated under reduced pressure. Chrom-
atography of the residue using ethyl acetate–hexanes mixtures
gave analytically pure compounds. Spectroscopic and analytical
data for previously unreported α-allenic alcohols 1 follow.
α-Allenic alcohol (+)-1j
From 500 mg (2.01 mmol) of the corresponding β-lactam carb-
aldehyde and after chromatography of the residue using
hexanes–ethyl acetate (4 : 1) as the eluent, we obtained com-
pound (+)-1i (431 mg, 59%) as a colorless oil; [α]D = +43.3
(c 0.4, CHCl3); 1H NMR (300 MHz, CDCl3, 25 °C): δ =
7.46–7.40 (m, 2H), 7.40–7.35 (m, 2H), 7.33–7.31 (m, 1H),
7.29–7.22 (m, 2H), 7.02–6.95 (m, 3H), 5.22 (d, 1H, J = 5.0 Hz),
5.23–5.18 (m, 1H), 5.12–5.08 (m, 1H), 5.06 (br s, 1H), 4.18 (dd,
1H, J = 6.6, 5.0 Hz), 3.36 (dd, 1H, J = 13.7, 8.5 Hz), 3.19 (dd,
1H, J = 13.7, 6.6 Hz), 2.22 (br s, 1H), 2.07–1.98 (m, 1H), 0.96
(d, 3H, J = 6.7 Hz), 0.92 (d, 3H, J = 6.6 Hz); 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 207.8, 166.6, 157.7, 134.0, 129.4
(2C), 128.8 (2C), 127.5, 126.8 (2C), 122.4, 116.0 (2C), 107.2,
80.6, 80.3, 69.8, 60.5, 49.6, 27.0, 20.4, 20.2; IR (CHCl3): ν =
α-Allenic alcohol 1e
From 250 mg (2.08 mmol) of p-anisaldehyde and after chrom-
atography of the residue using hexanes–ethyl acetate (6 : 1) as
the eluent, we obtained compound 1e (374 mg, 68%) as a color-
3364, 2991, 1943, 1744 cm−1
; HRMS (ES): calcd for
C23H25NO3 [M]+: 363.1834; found: 363.1839.
1
less oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 7.35 (d, 2H,
J = 8.0 Hz), 7.29 (d, 2H, J = 9.0 Hz), 7.15 (d, 2H, J = 7.9 Hz),
6.81 (d, 2H, J = 8.9 Hz), 5.64 (br s, 1H), 5.34 (dd, 1H, JAB
=
α-Allenic alcohol (+)-1l
11.9, 2.6 Hz), 5.29 (dd, 1H, JAB = 11.9, 2.6 Hz), 3.77 (s, 3H),
2.34 (s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ = 207.2,
158.7, 139.1, 137.5, 133.0, 129.1 (2C), 128.1 (2C), 126.9 (2C),
113.9 (2C), 109.5, 81.3, 72.3, 55.2, 21.1; IR (CHCl3): ν = 3365,
2990, 1944 cm−1; HRMS (ES): calcd for C18H18O2 [M]+:
266.1307; found: 266.1304.
From 463 mg (1.64 mmol) of the corresponding β-lactam carb-
aldehyde and after chromatography of the residue using
hexanes–ethyl acetate (4 : 1) as the eluent, we obtained com-
pound (+)-1l (283 mg, 44%) as a colorless oil; [α]D = +14.5
(c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3, 25 °C): δ =
7.28–7.22 (m, 9H), 7.18–7.13 (m, 3H), 6.94–6.85 (m, 3H), 5.11
(d, 1H, J = 5.0 Hz), 5.00–4.92 (m, 4H), 4.79 (d, 1H, J = 14.8
Hz), 4.37 (d, 1H, J = 14.8 Hz); 13C NMR (75 MHz, CDCl3,
25 °C): δ = 207.8, 166.5, 157.7, 135.9, 133.9, 129.4 (2C), 128.8
(2C), 128.7 (2C), 128.4 (2C), 127.8, 127.5, 126.7 (2C), 122.3,
116.0 (2C), 106.8, 80.6, 80.4, 70.2. 59.8, 45.8; IR (CHCl3):
α-Allenic alcohol 1f
From 290 mg (0.92 mmol) of p-bromobenzaldehyde and after
chromatography of the residue using hexanes–ethyl acetate
(10 : 1) as the eluent, we obtained compound 1f (191 mg, 69%)
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ν = 3361, 2988, 1940, 1741 cm−1; HRMS (ES): calcd for
α-allenol 1 (0.20 mmol) in dichloromethane (4 mL). The reac-
tion was stirred for 24 h before being partitioned between
dichloromethane and water. The aqueous phase was extracted
with dichloromethane (3 × 10 mL). The organic extract was
washed with water and brine, dried (MgSO4) and concentrated
under reduced pressure. Chromatography of the residue using
ethyl acetate–hexanes mixtures gave analytically pure com-
pounds. Spectroscopic and analytical data for compounds 2
follow.
C26H23NO3 [M]+: 397.1678; found: 397.1675.
α-Allenic alcohol 1n
From 110 mg (0.29 mmol) of the corresponding azetidine-2,3-
dione and after chromatography of the residue using hexanes–
ethyl acetate (2 : 1) as the eluent, we obtained compound 1n
1
(67 mg, 63%) as a colorless oil; H NMR (300 MHz, CDCl3,
25 °C): δ = 7.50 (d, 2H, J = 7.1 Hz), 7.36–7.17 (m, 10H), 6.70
(d, 2H, J = 9.1 Hz), 5.30 (d, 2H, J = 5.3 Hz), 5.24 (s, 1H), 3.66
(s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ = 208.0, 164.9,
156.4, 133.5, 132.6, 130.4, 129.1, 129.0 (2C), 128.6 (2C), 128.2
(2C), 128.1 (2C), 127.7, 119.0 (2C), 114.3 (2C), 105.6, 86.0,
(E)-1,3-Enyne 2a
From 200 mg (0.90 mmol) of α-allenol 1a and after chromato-
graphy of the residue using hexanes–ethyl acetate (10 : 1) as the
eluent, we obtained compound 2a (139 mg, 76%) as a colorless
81.2, 67.9, 55.5; IR (CHCl3): ν = 3371, 2998, 1946, 1749 cm−1
;
HRMS (ES): calcd for C25H21NO3 [M]+: 383.1521; found:
383.1530.
oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 8.03 (d, 2H, J =
1
7.3 Hz), 7.79 (d, 2H, J = 7.0 Hz), 7.48–7.43 (m, 4H), 7.37 (d,
2H, J = 7.3 Hz), 7.29 (s, 1H), 3.59 (d, 1H, J = 0.6 Hz); 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 139.2, 136.4, 136.2, 129.1
(2C), 128.6, 128.5 (2C), 128.3 (2C), 128.0, 126.4 (2C), 121.0,
85.3, 82.4; IR (CHCl3): ν = 3285, 3020, 1600 cm−1; HRMS
(ES): calcd for C16H12 [M]+: 204.0939; found: 204.0937.
α-Allenic alcohol 1o
From 215 mg (1.70 mmol) of the corresponding azetidine-2,3-
dione and after chromatography of the residue using hexanes–
ethyl acetate (2 : 1) as the eluent, we obtained compound 1o
1
(198 mg, 68%) as a colorless oil; H NMR (300 MHz, CDCl3,
(E)-1,3-Enyne 2b
25 °C): δ = 7.41 (d, 2H, J = 7.0 Hz), 7.24–7.15 (m, 6H),
7.03–6.99 (m, 2H), 6.40 (br s, 1H), 6.35 (s, 1H), 6.34 (s, 1H),
5.20 (d, 1H, JAB = 12.6 Hz), 5.15 (d, 1H, JAB = 12.6 Hz), 4.84
(d, 1H, J = 15.0 Hz), 4.57 (s, 1H), 3.81 (d, 1H, J = 15.0 Hz),
3.70 (s, 6H); 13C NMR (75 MHz, CDCl3, 25 °C): δ = 207.5,
168.3, 161.2, 136.0, 134.9, 132.5, 128.7 (2C), 128.4 (2C), 128.3
(2C), 128.1 (2C), 127.7, 127.5, 106.3 (2C), 105.3, 100.9, 87.2,
81.0, 77.1, 67.8, 55.4 (2Me), 44.0; IR (CHCl3): ν = 3373, 3000,
1947, 1750 cm−1; HRMS (ES): calcd for C27H25NO4 [M]+:
427.1784; found: 427.1792.
From 200 mg (0.79 mmol) of α-allenol 1b and after chromato-
graphy of the residue using hexanes–ethyl acetate (8 : 1) as the
eluent, we obtained compound 2b (125 mg, 67%) as a colorless
1
oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 7.88 (d, 2H, J =
8.8 Hz), 7.63 (d, 2H, J = 7.1 Hz), 7.33–7.17 (m, 3H), 7.10 (s,
1H), 6.85 (d, 2H, J = 8.8 Hz), 3.76 (s, 3H), 3.46 (s, 1H); 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 159.8, 139.4, 135.9, 130.6
(2C), 129.1, 128.6 (2C), 127.6, 126.2 (2C), 118.2, 113.7 (2C),
84.9, 82.8, 55.3; IR (CHCl3): ν = 3286, 3021, 1599 cm−1
;
HRMS (ES): calcd for C17H14O [M]+: 234.1045; found:
234.1037.
α-Allenic alcohol (+)-1q
From 150 mg (0.52 mmol) of the corresponding azetidine-2,3-
dione and after chromatography of the residue using hexanes–
ethyl acetate (3 : 1) as the eluent, we obtained compound (+)-1q
(153 mg, 60%) as a colorless oil; [α]D = +2.3 (c 0.2, CHCl3); 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 7.57–7.55 (m, 4H), 7.46
(d, 2H, J = 9.0 Hz), 6.85 (d, 2H, J = 9.0 Hz), 5.31 (s, 2H), 4.63
(s, 1H), 4.55 (dd, 1H, J = 13.7, 6.7 Hz), 4.40 (d, 1H, J = 6.7
Hz), 4.30 (d, 1H, J = 8.9, 6.7 Hz), 3.80 (m, 4H), 1.47 (s, 3H),
1.38 (s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ = 207.9,
166.2. 156.8, 131.7 (2C), 130.5, 130.0 (2C), 128.3, 121.9, 120.2
(2C), 114.1 (2C), 109.9, 105.3, 84.2, 81.3, 76.4, 66.8, 66.5,
(E)-1,3-Enyne 2c
From 200 mg (0.85 mmol) of α-allenol 1c and after chromato-
graphy of the residue using hexanes–ethyl acetate (5 : 1) as the
eluent, we obtained compound 2c (133 mg, 71%) as a colorless
1
oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 7.96 (d, 2H, J =
8.0 Hz), 7.80 (dd, 2H, J = 8.0, 1.3 Hz), 7.48–7.38 (m, 3H),
7.29–7.27 (m, 2H), 7.27 (s, 1H), 3.60 (d, 1H, J = 0.7 Hz), 2.46
(s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ = 139.3, 138.7,
136.4, 133.4, 129.1 (2C), 129.0 (2C), 128.4 (2C), 127.8, 126.3
(2C), 119.6, 85.1, 82.6, 21.4; IR (CHCl3): ν = 3288, 3016,
1601 cm−1; HRMS (ES): calcd for C17H14 [M]+: 218.1096;
found: 234. 218.1087.
55.5, 26.5, 25.2; IR (CHCl3): ν = 3381, 3003, 1945, 1752 cm−1
;
HRMS (ES): calcd for C24H2479BrNO5 [M]+: 485.0838; found:
485.0829.
(E)-1,3-Enyne 2d
General procedure for the synthesis of (E)-1,3-enynes 2a–o in
aqueous media
From 200 mg (0.78 mmol) of α-allenol 1d and after chromato-
graphy of the residue using hexanes–ethyl acetate (6 : 1) as the
eluent, we obtained compound 2d (166 mg, 89%) as a colorless
oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 7.81 (d, 2H, J =
8.5 Hz), 7.62 (dd, 2H, J = 8.5, 1.0 Hz), 7.32–7.24 (m, 5H), 7.08
Tetrabutyl ammonium iodide (cat), 50% aqueous sodium
hydroxide (5 mL) and acetyl chloride (0.22 mmol) were sequen-
tially added at room temperature to a solution of the appropriate
1
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(s, 1H), 3.47 (d, 1H, J = 0.6 Hz); 13C NMR (75 MHz, CDCl3,
25 °C): δ = 138.8, 134.9, 134.6, 134.1, 130.3 (2C), 128.5 (4C),
128.2, 126.4 (2C), 121.3, 85.9, 82.1; IR (CHCl3): ν = 3283,
3019, 1606 cm−1; HRMS (ES): calcd for C16H11Cl [M]+:
238.0549; found: 238.0554.
(75 MHz, CDCl3, 25 °C): δ = 136.5, 136.4, 128.4 (3C), 126.1
(2C), 125.3, 109.6, 84.8, 19.6, 75.1, 68.9, 26.7, 25.8; IR
(CHCl3): ν = 3298, 3080, 1610 cm−1; HRMS (ES): calcd for
C15H16O2 [M]+: 228.1150; found: 228.1143.
(E)-1,3-Enyne (+)-2i
(E)-1,3-Enyne 2e
From 120 mg (0.43 mmol) of α-allenol (−)-1i and after chrom-
atography of the residue using hexanes–ethyl acetate (4 : 1) as
the eluent, we obtained compound (+)-2i (82 mg, 73%) as a col-
From 315 mg (1.18 mmol) of α-allenol 1e and after chromato-
graphy of the residue using hexanes–ethyl acetate (6 : 1) as the
eluent, we obtained compound 2e (187 mg, 63%) as a colorless
1
orless oil; [α]D = +18.3 (c 0.6, CHCl3); H NMR (300 MHz,
1
oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 7.93 (d, 2H, J =
CDCl3, 25 °C): δ = 7.57 (d, 2H, J = 9.1 Hz), 6.89 (d, 2H, J =
9.1 Hz), 6.35 (dd, 1H, J = 8.3, 0.6 Hz), 5.31–5.22 (m, 1H), 4.28
(dd, 1H, J = 8.3, 6.2 Hz), 3.83 (s, 3H), 3.69 (dd, 1H, J = 8.3, 7.3
Hz), 3.40 (d, 1H, J = 0.6 Hz), 1.49 (s, 3H), 1.45 (s, 3H); 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 159.9, 134.2, 129.0, 127.4
(2C), 124.8, 113.8 (2C), 109.5, 84.6, 79.8, 75.2, 68.9, 55.3,
26.7, 25.8; IR (CHCl3): ν = 3296, 3084, 1611 cm−1; HRMS
(ES): calcd for C16H18O3 [M]+: 258.1256; found: 258.1251.
8.3 Hz), 7.73 (d, 2H, J = 8.9 Hz), 7.26 (d, 2H, J = 8.3 Hz), 7.20
(s, 1H), 6.98 (d, 2H, J = 8.9 Hz), 3.89 (s, 3H), 3.58 (d, 1H, J =
0.7 Hz), 2.44 (s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ =
159.4, 138.3, 134.7, 133.6, 131.8, 128.9 (2C), 128.8 (2C), 127.4
(2C), 119.1, 113.8 (2C), 84.9, 82.7, 55.3, 21.4; IR (CHCl3): ν =
3284, 3010, 1606 cm−1; HRMS (ES): calcd for C18H16O [M]+:
248.1201; found: 248.1191.
(E)-1,3-Enyne 2f
(E)-1,3-Enyne (+)-2j
From 290 mg (0.92 mmol) of α-allenol 1f and after chromato-
graphy of the residue using hexanes–ethyl acetate (10 : 1) as the
eluent, we obtained compound 2f (191 mg, 69%) as a colorless
From 155 mg (0.43 mmol) of α-allenol (+)-1j and after chrom-
atography of the residue using hexanes–ethyl acetate (3 : 1) as
the eluent, we obtained compound (+)-2j (131 mg, 88%) as a
1
1
oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 7.76 (d, 2H, J =
colorless oil; [α]D = +72.7 (c 1.5, CHCl3); H NMR (300 MHz,
8.0 Hz), 7.47 (d, 2H, J = 8.8 Hz), 7.38 (d, 2H, J = 8.8 Hz), 7.09
(d, 2H, J = 8.0 Hz), 7.07 (s, 1H), 3.42 (d, 1H, J = 0.6 Hz), 2.27
(s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ = 139.0, 138.2,
136.6, 133.1, 131.4 (2C), 129.1 (2C), 129.0 (2C), 127.8 (2C),
121.7, 118.4, 85.5, 82.1, 21.4; IR (CHCl3): ν = 3290, 3027,
1598 cm−1; HRMS (ES): calcd for C17H1379Br [M]+: 296.0201;
found: 296.0205.
CDCl3, 25 °C): δ = 7.43–7.39 (m, 2H), 7.25–7.22 (m, 3H),
7.18–7.14 (m, 2H), 6.93–6.88 (m, 3H), 6.41 (dd, 1H, J = 9.6,
0.6 Hz), 5.34 (d, 1H, J = 4.4 Hz), 5.09 (dd, 1H, J = 9.6, 4.4 Hz),
3.40 (d, 1H, J = 0.6 Hz), 3.14 (dd, 1H, J = 13.9, 7.7 Hz), 2.85
(dd, 1H, J = 13.9, 6.7 Hz), 1.97–1.85 (m, 1H), 0.89 (t, 6H, J =
6.7 Hz); 13C NMR (75 MHz, CDCl3, 25 °C): δ = 165.7, 157.3,
136.4, 131.3, 129.5 (2C), 129.4, 128.9, 128.5 (2C), 126.3 (2C),
122.3, 115.5 (2C), 85.0, 81.9, 79.8, 59.2, 48.7, 27.5. 20.4 (2C);
IR (CHCl3): ν = 3290, 3033, 1734, 1606 cm−1; HRMS (ES):
calcd for C23H23NO2 [M]+: 345.1729; found: 345.1735.
(E)-1,3-Enyne 2g
From 50 mg (0.14 mmol) of α-allenol 1g and after chromato-
graphy of the residue using hexanes–ethyl acetate (4 : 1) as the
eluent, we obtained compound 2g (33 mg, 68%) as a colorless
(E)-1,3-Enyne (+)-2k
1
oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 8.09 (d, 1H, J =
From 91 mg (0.26 mmol) of α-allenol (+)-1k and after chrom-
atography of the residue using hexanes–ethyl acetate (3 : 1) as
the eluent, we obtained compound (+)-2k (55 mg, 63%) as a col-
8.0 Hz), 7.65–7.62 (m, 1H), 7.28–7.25 (m, 7H), 7.21 (s, 1H),
6.24 (t, 1H, J = 6.7 Hz), 3.13–2.97 (m, 1H), 1.59 (s, 9H); 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 170.2, 138.1, 131.6 (2C),
128.2 (2C), 127.9 (2C), 127.8, 126.1, 124.7, 124.1, 123.1,
122.8, 119.8, 118.7, 115.5, 85.1, 83.0, 28.1, 28.2 (3C); IR
(CHCl3): ν = 3281, 3007, 1707, 1602 cm−1; HRMS (ES): calcd
for C23H21NO2 [M]+: 343.1572; found: 343.1580.
1
orless oil; [α]D = +23.3 (c 1.5, CHCl3); H NMR (300 MHz,
CDCl3, 25 °C): δ = 7.59 (dd, 2H, J = 8.0, 1.9 Hz), 7.34 (d, 2H,
J = 9.0 Hz), 7.30–7.26 (m, 3H), 6.78 (d, 2H, J = 9.0 Hz), 6.54
(d, 1H, J = 9.6 Hz), 5.31 (dd, 1H, J = 9.6, 4.8 Hz), 4.74 (d, 1H,
J = 4.8 Hz), 3.69 (s, 3H), 3.54 (s, 1H), 3.45 (s, 3H); 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 163.3, 156.5, 147.0, 136.1, 132.3,
131.0, 128.9, 128.8 (2C), 126.3 (2C), 118.5 (2C), 114.5 (2C),
86.0, 85.0, 75.9, 59.0, 58.5, 55.5; IR (CHCl3): ν = 3292, 3030,
1731, 1603 cm−1; HRMS (ES): calcd for C21H19NO3 [M]+:
333.1365; found: 333.1371.
(E)-1,3-Enyne (+)-2h
From 135 mg (0.55 mmol) of α-allenol (+)-1h and after chrom-
atography of the residue using hexanes–ethyl acetate (7 : 1) as
the eluent, we obtained compound (+)-2h (88 mg, 69%) as a col-
1
orless oil; [α]D = +30.0 (c 0.5, CHCl3); H NMR (300 MHz,
(E)-1,3-Enyne (+)-2l
CDCl3, 25 °C): δ = 7.55 (dd, 2H, J = 8.2, 1.6 Hz), 7.28–7.23
(m, 3H), 6.39 (d, 1H, J = 8.2 Hz), 5.18 (dd, 1H, J = 14.5, 7.2
Hz), 4.21 (dd, 1H, J = 8.2, 6.3 Hz), 3.62 (dd, 1H, J = 8.2, 7.2
Hz), 3.34 (s, 1H), 1.41 (s, 3H), 1.37 (s, 3H); 13C NMR
From 75 mg (0.19 mmol) of α-allenol (+)-1l and after chromato-
graphy of the residue using hexanes–ethyl acetate (3 : 1) as the
eluent, we obtained compound (+)-2l (61 mg, 84%) as a
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1
colorless oil; [α]D = +50.0 (c 1.9, CHCl3); H NMR (300 MHz,
106.3 (2C), 100.6, 85.1, 79.2, 77.1, 62.3, 55.4 (2C), 44.5; IR
(CHCl3): ν = 3282, 3066, 1726, 1595 cm−1; HRMS (ES): calcd
for C27H23NO3 [M]+: 409.1678; found: 365.409.1697.
CDCl3, 25 °C): δ = 7.26–7.13 (m, 12H), 6.89–6.86 (m, 3H),
6.26 (dd, 1H, J = 9.8, 0.6 Hz), 5.30 (d, 1H, J = 4.4 Hz), 5.00
(dd, 1H, J = 9.8, 4.4 Hz), 4.53 (d, 1H, J = 14.7 Hz), 4.16 (d, 1H,
J = 14.7 Hz), 3.26 (d, 1H, J = 0.6 Hz); 13C NMR (75 MHz,
CDCl3, 25 °C): δ = 164.9, 157.2, 136.3, 135.3, 131.0 (2C),
129.5 (2C), 129.2, 128.8 (4C), 128.4 (2C), 127.9 (2C), 126.2,
122.2, 115.4 (2C), 85.1, 82.1, 79.6, 58.3, 45.0; IR (CHCl3): ν =
(Z)-1,3-Enyne 2o
Colorless oil; 1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.31 (dd,
2H, J = 7.4, 1.9 Hz), 7.25–7.19 (m, 4H), 7.15–7.11 (m, 4H),
6.27–6.24 (m, 3H), 4.97 (s, 1H), 4.86 (d, 1H, J = 15.1 Hz), 3.78
(d, 1H, J = 15.1 Hz), 3.62 (s, 6H), 3.51 (s, 1H); 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 162.8, 161.1, 147.3, 137.5, 135.4,
133.8, 129.3, 128.8 (2C), 128.6 (2C), 128.2 (2C), 128.1 (2C),
127.9, 127.8, 118.9, 105.8 (2C), 101.1, 85.2, 79.2, 63.7, 55.4
3288, 303q, 1735, 1605 cm−1
; HRMS (ES): calcd for
C26H21NO2 [M]+: 379.1572; found: 379.1578.
(E)-1,3-Enyne (−)-2m
(2C), 44.4; IR (CHCl3): ν = 3283, 3060, 1726, 1597 cm−1
;
From 105 mg (0.26 mmol) of α-allenol (+)-1m and after chrom-
atography of the residue using hexanes–ethyl acetate (2 : 1) as
the eluent, we obtained compound (−)-2m (85 mg, 84%) as a
colorless oil; [α]D = −126.9 (c 2.6, CHCl3); 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 8.08 (dd, 2H, J = 8.0, 1.9 Hz),
7.57 (d, 2H, J = 9.1 Hz), 7.44–7.41 (m, 3H), 6.90 (d, 2H, J =
9.1 Hz), 4.82 (d, 1H, J = 5.6 Hz), 4.60 (dd, 1H, J = 12.6, 6.7
Hz), 4.21 (d, 2H, J = 6.7 Hz), 3.81 (s, 3H), 3.51 (s, 1H), 1.44 (s,
3H), 1.35 (s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ =
158.5, 156.6, 142.1, 133.3, 131.2, 129.9, 129.2 (2C), 128.2
(2C), 123.1, 120.0 (2C), 114.1 (2C), 109.7, 85.5, 80.8, 77.2,
67.0, 61.8, 55.4, 26.4, 25.5; IR (CHCl3): ν = 3285, 3044, 1726,
1598 cm−1; HRMS (ES): calcd for C24H23NO4 [M]+: 389.1627;
found: 389.1629.
HRMS (ES): calcd for C27H23NO3 [M]+: 409.1678; found:
409.1683.
(E)-1,3-Enyne (−)-2p
From 390 mg (1.03 mmol) of α-allenol (+)-1p and after chrom-
atography of the residue using hexanes–ethyl acetate (2 : 1) as
the eluent, we obtained compound (−)-2p (252 mg, 65%) as a
1
colorless oil; [α]D = −16.0 (c 0.3, CHCl3); H NMR (300 MHz,
CDCl3, 25 °C): δ = 8.15 (d, 1H, J = 8.2 Hz), 8.14 (d, 1H, J =
7.8 Hz), 7.46–7.34 (m, 8H), 5.10 (d, 1H, J = 14.9 Hz), 4.54 (dd,
1H, J = 12.5, 6.0 Hz), 4.40 (d, 1H, J = 14.9 Hz), 4.23 (dd, 1H, J
= 8.9, 6.6 Hz), 4.10 (d, 1H, J = 6.0 Hz), 4.00 (dd, 1H, J = 8.9,
6.0 Hz), 3.39 (s, 1H), 1.50 (s, 3H), 1.41 (s, 3H); 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 161.4, 143.8, 135.9, 133.3, 129.8,
129.1 (2C), 128.8 (2C), 128.6 (2C), 128.4, 128.3 (2C), 127.8,
122.2, 109.7, 84.5, 80.5, 67.3, 61.0, 45.7, 26.5, 25.3; IR
(CHCl3): ν = 3280, 3039, 1723, 1595 cm−1; HRMS (ES): calcd
for C24H23NO3 [M]+: 373.1678; found: 373.1677.
(E)-1,3-Enyne 2n
From 110 mg (0.29 mmol) of α-allenol 1n and after chromato-
graphy of the residue using hexanes–ethyl acetate (2 : 1) as the
eluent, we obtained compound 2n (67 mg, 63%) as a colorless
1
oil; H NMR (300 MHz, CDCl3, 25 °C): δ = 8.09 (dd, 2H, J =
8.4, 1.6 Hz), 7.43–7.40 (m, 2H), 7.33–7.23 (m, 8H), 6.71 (d,
2H, J = 9.1 Hz), 5.38 (s, 1H), 3.64 (s, 3H), 3.13 (s, 1H); 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 158.8, 156.8, 147.0, 136.2,
133.8, 131.4, 130.3, 129.3 (2C), 129.2, 129.1 (2C), 128.8 (2C),
128.5 (2C), 123.5, 118.9 (2C), 114.9 (2C), 86.3, 79.7, 63.7,
55.8; IR (CHCl3): ν = 3284, 3064, 1728, 1596 cm−1; HRMS
(ES): calcd for C25H19NO2 [M]+: 365.1416; found: 365.1412.
(E)-1,3-Enyne (−)-2q
From 145 mg (0.30 mmol) of α-allenol (+)-1q and after chrom-
atography of the residue using hexanes–ethyl acetate (2 : 1) as
the eluent, we obtained compound (−)-2q (77 mg, 55%) as a
1
colorless oil; [α]D = −2.4 (c 0.1, CHCl3); H NMR (300 MHz,
CDCl3, 25 °C): δ = 8.00 (d, 2H, J = 8.8 Hz), 7.58 (d, 2H, J =
8.8 Hz), 7.57 (d, 2H, J = 9.0 Hz), 6.93 (d, 2H, J = 9.0 Hz), 4.83
(d, 1H, J = 5.3 Hz), 4.66–4.59 (m, 1H), 4.22 (d, 1H, J = 6.3
Hz), 4.21 (d, 1H, J = 7.1 Hz), 3.84 (s, 3H), 3.55 (s, 1H), 1.45 (s,
3H), 1.37 (s, 3H); 13C NMR (75 MHz, CDCl3, 25 °C): δ =
158.4, 156.8, 142.6, 132.3, 131.4 (2C), 131.1, 130.8 (2C),
124.5, 121.9, 119.8 (2C), 114.2 (2C), 109.8, 85.9, 80.3, 76.9,
66.9, 61.9, 55.5, 26.4, 25.5; IR (CHCl3): ν = 3280, 3046, 1726,
1597 cm−1; HRMS (ES): calcd for C24H2279BrNO4 [M]+:
467.0732; found: 467.0751.
Reaction of allenol 1o. Preparation of (E)-1,3-enyne 2o and
(Z)-1,3-enyne 2o
From 65 mg (0.15 mmol) of α-allenol 1o and after chromato-
graphy of the residue using hexanes–ethyl acetate (5 : 1) as the
eluent, 38 mg (62%) of the less polar compound (E)-2o and
11 mg (18%) of the more polar compound (Z)-2o were obtained.
(E)-1,3-Enyne 2o
Colorless oil; 1H NMR (300 MHz, CDCl3, 25 °C): δ = 8.09 (dd,
2H, J = 8.2, 1.6 Hz), 7.33–7.11 (m, 8H), 6.40–6.36 (m, 3H),
4.83 (d, 1H, J = 15.1 Hz), 4.79 (s, 1H), 3.88 (d, 1H, J = 15.1
Hz), 3.69 (s, 6H), 3.04 (s, 1H); 13C NMR (75 MHz, CDCl3,
25 °C): δ = 161.5, 160.9, 147.4, 138.0, 135.3, 133.3, 129.7,
128.8 (2C), 128.7 (2C), 128.6 (2C), 128.3 (2C), 127.8, 122.5,
Acknowledgements
Support for this work by the DGI-MICINN (Project CTQ2009-
09318), Comunidad Autónoma de Madrid (Project S2009/
PPQ-1752) and UCM-Santander (Grant GR35/10-A) is grate-
fully acknowledged.
7608 | Org. Biomol. Chem., 2012, 10, 7603–7609
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This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 7603–7609 | 7609