Stereoselective synthesis of 1,2,3-trisubstituted 1,3-dienes through novel [3,3]-sigmatropic rearrangements in α-allenic methanesulfonates: Application to the preparation of fused tricyclic systems by tandem rearrangement/Diels-Alder reaction

Article abstract of DOI:10.1002/ejoc.200400527

An unprecedented stereoselective and general synthesis of 1,2,3-trisubstituted 1,3-dienes from α-allenols just by treatment with a methanesulfonyl chloride/tertiary amine system has been developed. This transformation might be tentatively explained in terms of a migration of the methanesulfonyl group in the initially formed α-allenic methanesulfonate to give the corresponding mesyloxy-diene through a [3,3]-sigmatropic rearrangement. This reactivity pattern was incorporated into a domino process, allowing the development of a novel one-pot synthetic strategy for the preparation of fused tricycles from monocyclic allenols, masked functionalized dienes, when subjected to a domino allenol transposition/intramolecular Diels-Alder reaction process. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Full text of DOI:10.1002/ejoc.200400527

FULL PAPER
Stereoselective Synthesis of 1,2,3-Trisubstituted 1,3-Dienes through Novel
[3,3]-Sigmatropic Rearrangements in α-Allenic Methanesulfonates:
Application to the Preparation of Fused Tricyclic Systems by Tandem
Rearrangement/Diels؊Alder Reaction
[a]
[b]
[a]
[a]
´
Benito Alcaide,* Pedro Almendros,* Cristina Aragoncillo, and Marıa C. Redondo
Dedicated to the memory of Dr. Juan C. del Amo[‡]
Keywords: Allenes / Cycloaddition / Dienes / Domino reactions / Sigmatropic rearrangement
An unprecedented stereoselective and general synthesis of
1,2,3-trisubstituted 1,3-dienes from α-allenols just by treat-
ment with a methanesulfonyl chloride/tertiary amine system
incorporated into a domino process, allowing the develop-
ment of a novel one-pot synthetic strategy for the preparation
of fused tricycles from monocyclic allenols, masked func-
has been developed. This transformation might be tentat- tionalized dienes, when subjected to a domino allenol trans-
ively explained in terms of a migration of the methanesul-
fonyl group in the initially formed α-allenic methanesulfon-
ate to give the corresponding mesyloxy-diene through a
[3,3]-sigmatropic rearrangement. This reactivity pattern was
position/intramolecular Diels−Alder reaction process.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
Introduction
asymmetric synthesis of natural products and derivatives of
biological interest[4] we initiated a study into the use of al-
lene substrates in organic synthesis. Here we present full
details of a novel, simple, stereoselective, and general syn-
thesis of 1,2,3-trisubstituted 1,3-dienes from α-allenols,[5]
together with its incorporation into a domino transposition/
intramolecular DielsϪAlder reaction scheme for the prep-
aration of tricyclic compounds.[6]
Heteroatom-substituted 1,3-dienes are versatile reagents
in chemical synthesis, playing a very important role in
cycloadditions. Danishefsky and co-workers, for example,
developed
1-methoxy-3-trimethylsiloxybuta-1,3-diene,
which has had many creative applications in complex or-
ganic synthesis.[1] Trost and colleagues prepared another
kind of heteroatomic 1,3-dienes, 2-alkoxy-3-alkyl(aryl)-
thiobuta-1,3-dienes, which have been used as regiochemical
control elements in cycloadditions.[2]
Results and Discussion
Allylic and propargylic alcohols react with metal com-
plexes to form 1,3-transposition products. Surprisingly, the
corresponding rearrangement of allenyl alcohols has been
virtually ignored, only Trost, en route to aldol- or Mannich-
type products, having recently postulated the formation of
an intermediate involving the 1,3-transposition of α-allenic
alcohols.[3] In our ongoing project directed toward the
The starting substrates, the α-allenic alcohols 2, were pre-
pared in aqueous media in a totally regioselective fashion[7]
from propargyl bromides, through metal-mediated Barbier-
type carbonyl allenylation of the appropriate aldehyde 1
(Scheme 1, Table 1).
[a]
´
´
´
Departamento de Quımica Organica I, Facultad de Quımica,
Universidad Complutense de Madrid,
28040 Madrid, Spain
Fax: (internat.) ϩ 34-91-3944103
E-mail: alcaideb@quim.ucm.es
[b]
´
´
Instituto de Quımica Organica General, Consejo Superior de
Scheme 1. Regioselective preparation of α-allenic alcohols 2 in
aqueous media
´
Investigaciones Cientıficas,
Juan de la Cierva 3, 28006 Madrid, Spain
Fax: (internat.) ϩ 34-91-5644853
E-mail: iqoa392@iqog.csic.es
In an initial experiment, the α-allenol syn-(ϩ)-2a
(1.0 mmol) and methanesulfonyl chloride (1.1 mmol) were
mixed in dichloromethane at room temperature. Next, tri-
[‡]
A victim of the terrorist attack in Madrid on March 11, 2004.
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
98
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400527
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Stereoselective Synthesis of 1,2,3-Trisubstituted 1,3-Dienes from α-Allenols
Table 1. Indium-mediated Barbier-type carbonyl allenylation of aldehydes 1[a]
FULL PAPER
[a]
All reactions were carried out on 1 mmol scale. PMP ϭ 4-MeOC6H4.[b] Yield of pure, isolated product with correct analytical and
spectroscopic data.
ethylamine (1.2 mmol) was slowly added to the reaction Gratifyingly, the enantiopure diene (ϩ)-3a was obtained in
mixture at 0 °C, and the reaction was then allowed to pro- similar yield and with similar selectivity.
ceed for 30 minutes at room temperature. To our delight,
We also performed a solvent screen for the one-pot al-
this gave the 2,3-difunctionalized diene (ϩ)-3a as the only lenol-diene transformation. The reaction worked well in po-
product, in reasonable yield and with total stereoselectivity. lar aprotic solvents such as DMF, providing similar yields
The susceptibility of the reaction to stereochemically differ- of the 1,3-diene (ϩ)-3a. There was no significant solvent
ent β-lactam allenic alcohols was examined next, by explor- effect in the observed yield or stereoselectivity when a few
ing the potential for the use of the α-allenol anti-(ϩ)-2a.[8] other solvents (tetrahydrofuran or toluene) were also scre-
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B. Alcaide, P. Almendros, C. Aragoncillo, M. C. Redondo
Tandem, cascade, or domino reactions are being increas-
FULL PAPER
ened. We next investigated the range of potential allenol
components. We found that β-lactam α-allenols bearing ingly widely applied to the construction of natural and de-
substituents of different natures at the N1 or C3 positions signed molecules.[10] Such processes, in which (ideally) a
of the 2-azetidinone ring were excellent substrates for the single event triggers the conversion of a starting material
conversion of the allene moiety into 1,3-dienes. Up to this into a product that then becomes a substrate for the next
point, we had established that reactions with β-lactam al- reaction until termination affords a stable final product, are
lenols provided excellent results. We were not certain, how- highly desirable not only due to their elegance, but also be-
ever, whether α-allenols with aromatic or heteroaromatic cause of their efficiency and economy in terms of reagent
substituents might serve as precursors for the allene-conju- consumption and purification. Often, these multi-step, one-
gated diene conversion, so we treated different α-allenols pot procedures are accompanied by dramatic increases in
derived from (hetero)aromatic aldehydes with methanesul- molecular complexity and impressive selectivity.
fonyl chloride in the presence of triethylamine in dichloro-
In view of the importance of ring structures in essentially
methane. Interestingly, the sulfonyl chloride/tertiary amine all classes of natural products,[11] the constructions of rings
system was able to induce the preparation of 1-aryl-2,3-tri- represents a central theme in organic synthesis. Many syn-
substituted 1,3-dienes in good yields and with full stereo- thetic routes devise a ring-closure reaction at some stage,
control (Scheme 2, Table 2).[9]
since many synthetic targets possess at least one cycle in
their core structure. The discovery of new molecular diver-
sity from nature and the demand for more efficient and en-
vironmentally benign chemical processes dictates and in-
vites the further development of sustainable methodologies.
Domino reactions based on DielsϪAlder chemistry are im-
portant examples of such synthetic strategies,[12] but the in-
tricacy of routes to the appropriate functionalized 1,3-di-
enes is often a major drawback to practical use of these
reactions. Because tandem reactions offer many advantages
over stepwise processes, we decided to attempt a novel
method for the straightforward synthesis of functionalized
polycyclic compounds from monocyclic aldehydes. Our ap-
proach was based on regioselective condensation between
aldehydes and propargyl bromides to give α-allenols,
masked functionalized dienes, which then underwent a
domino allenol transposition/intramolecular DielsϪAlder
reaction process upon treatment with methanesulfonyl chlo-
ride. Thus, we first thought that α-allenol-tethered alkenes
2 might be appropriate precursors for the construction of
the tricyclic cores of some bioactive products. Treatment of
α-allenyl alcohols 2 bearing alkenyl tethers with meth-
anesulfonyl chloride/triethylamine in toluene at 190 °C in
sealed tubes afforded the expected products, the fused tri-
cycles 6, in moderate yields (35Ϫ54%) and in most cases
with good stereoselectivities (drs up to 100:0) (Scheme 4).
The applicability of the tandem transposition/cycload-
dition reaction approach for the synthesis of tricycles was
still restricted to α-allenol-tethered alkenes (enallenes). We
next turned our attention to the applicability of the domino
reaction to α-allenyl alcohols 2 bearing alkynyl tethers (al-
lenynes). The extra alkynyl moiety was indeed tolerated in
this process, and the usefulness of this approach for the
stereoselective synthesis of polycyclic β-lactams and chro-
menes is shown in Scheme 5. The hydroxybenzochromene
7d, the result of further mesylate cleavage with concomitant
aromatization, was the only product resulting from the ther-
mally induced reaction of α-allenol 2k. Tricycles 6dϪ6f, as
well as 7e, were prepared as racemic mixtures.
Scheme 2. Stereoselective preparation of 1,2,3-trisubstituted 1,3-
dienes 3 from α-allenols 2
Total E stereoselectivity was observed for every single α-
allenyl alcohol used as starting material. The stereochem-
istry at the double bond for dienes 3 was assigned by quali-
tative homonuclear NOE difference spectra. In most cases
these 2,3-difunctionalized 1,3-dienes are reasonably stable,
although they decompose after prolonged storage at 20 °C.
The mechanism of the one-pot allenol-diene transform-
ation is depicted in Scheme 3. The extremely high selectivity
observed in the formation of dienes 3 may indicate a peri-
cyclic reaction pathway, the allenol component reacting
with methanesulfonyl chloride, resulting in a methanesul-
fonate intermediate. Next, the α-allenic methanesulfonate 4
generated in situ undergoes a [3,3]-sigmatropic rearrange-
ment, involving the chair-like six-membered cyclic tran-
sition structure 5, to give the corresponding mesyloxy-diene
counterpart 3.
Although this multibond formation reaction for the syn-
thesis of tricycles appears complex, it is in fact simple: the
methanesulfonyl chloride/triethylamine system promotes
the formation of the corresponding 2-mesyloxy 1,3-diene
Scheme 3. Feasible reaction pathway for the transformation of α-
allenic alcohols 2 into 1,3-dienes 3
100
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Stereoselective Synthesis of 1,2,3-Trisubstituted 1,3-Dienes from α-Allenols
FULL PAPER
Table 2. Methanesulfonyl chloride/triethylamine-promoted synthesis of (E)-1,2,3-trifunctionalized 1,3-dienes 3 from α-allenols 2[a]
[a]
All reactions were carried out on 1 mmol scale. PMP ϭ 4-MeOC6H4. In all cases, compounds 2 refer to the syn isomers, except for
Entry 2.[b] Yield of pure, isolated product with correct analytical and spectroscopic data.
from the appropriate α-allenol, and is followed by a sub- sition states similar to those depicted in Scheme 6. In the 2-
sequent intramolecular [4ϩ2] cycloaddition reaction.
azetidinone series the sense of diastereoselectivity seems to
The stereochemical outcomes of the IMDA reactions be controlled by the C4 stereogenic center in the β-lactam
producing tricycles 7 may be explained in terms of tran- ring.
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B. Alcaide, P. Almendros, C. Aragoncillo, M. C. Redondo
FULL PAPER
Scheme 5. Stereoselective synthesis of tricycles 7 from monocyclic
allenynes; reagents and conditions: a) CH3SO2Cl, Et3N, toluene,
sealed tube, 190 °C
Scheme 4. Stereoselective synthesis of tricycles 6 from monocyclic
enallenes; reagents and conditions: a) CH3SO2Cl, Et3N, toluene,
sealed tube, 190 °C
Conclusions
In conclusion, we have successfully developed a strategy
for the one-step stereoselective synthesis of tricycles Ϫ
found in many biologically active natural products, such as
β-lactams, chromenes, and pyrrolizidines Ϫ from mono-
cyclic α-allenic alcohols. These products contain mesylate
functional groups, which might also be useful substrates for
further functionalization through transition metal-catalyzed
processes. The ready availability of allenols Ϫ through the
Barbier-type reaction between aldehydes and propargyl
bromides in aqueous media, for example Ϫ makes such a
strategy very attractive. This unprecedented domino se-
quence represents a practical opportunity to connect the
rapidly expanding fields of environmentally benign chemis-
try and multiple bond-forming processes.
Scheme 6
102
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Stereoselective Synthesis of 1,2,3-Trisubstituted 1,3-Dienes from α-Allenols
FULL PAPER
9.0, 2.7 Hz, 1 H), 2.73 (dq, J ϭ 17.6, 2.7 Hz, 1 H), 2.07 (t, J ϭ
2.7 Hz, 1 H), 2.02 (br. s, 1 H), 1.85 (t, J ϭ 3.0 Hz, 3 H) ppm. 13C
NMR (75 MHz, CDCl3, 25 °C): δ ϭ 205.0, 166.2, 156.4, 130.9,
120.6, 113.9, 100.1, 81.3, 78.8, 70.2, 56.8, 55.5, 49.9, 15.6, 14.5 ppm.
IR (CHCl3): ν˜ ϭ 3420, 2990, 2121, 1941, 1745 cmϪ1. MS (CI):
m/z (%) ϭ 298 (100) [M ϩ H]ϩ, 297 (32) [M]ϩ. C18H19NO3 (297.3):
calcd. C 72.71, H 6.44, N 4.71; found C 72.77, H 6.43, N 4.73.
Experimental Section
1
General Methods: H NMR and 13C NMR spectra were recorded
with Bruker Avance 300, Varian VRX 300S, or Bruker AC 200
instruments. NMR spectra were recorded in CDCl3 solutions, ex-
cept if stated otherwise. 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 a HP5989A spectrometer in
the chemical ionization (CI) modes unless otherwise stated. Specific
rotations: measured at 20 °C, concentration (c) is expressed in g per
100 mL. All commercially available compounds were used without
further purification. The starting substrates, the 4-oxoazetidine-2-
carbaldehydes 1aϪh, were prepared both in racemic and in op-
tically pure forms by our previously described methodologies. En-
antiopure 2-azetidinones (ϩ)-1a and 1dϪh were obtained as single
cis enantiomers from imines of (R)-2,3-O-(isopropylidene)glyceral-
dehyde, through Staudinger reactions with the corresponding acid
chlorides in the presence of Et3N, followed by sequential acidic
acetonide hydrolysis and oxidative cleavage.[13] Racemic com-
pounds (Ϯ)-1b and (Ϯ)-1c were obtained from N,N-bis(p-methoxy-
phenyl)glyoxal diimine in one-pot fashion as single cis diastereoiso-
mers.[14] The aromatic aldehydes 1i and 1j were prepared from sal-
icylaldehyde as described in the literature.[15] Heteroaromatic alde-
hyde 1k was prepared from pyrrole-2-carboxaldehyde,[16] while
aldehydes 1l and 1m were obtained from indole-2-carboxylic acid
as previously reported.[16]
(3R,4S)-1-Benzyl-4-[(R)-1-hydroxy-2-methyl-2,3-butadienyl]-3-(2-
propenyloxy)-2-azetidinone [(؉)-2d]: This compound was obtained
from aldehyde (ϩ)-1d (70 mg, 0.280 mmol); chromatography of the
residue with hexanes/ethyl acetate (1:1) as eluent gave compound
(ϩ)-2d (68 mg, 80%) as a colorless oil. [α]2D5 ϭ ϩ24.6 (c ϭ 0.8 in
1
CHCl3). H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.26 (m, 5 H),
5.89 (m, 1 H), 5.25 (m, 2 H), 4.71 (m, 4 H), 4.28 (m, 4 H), 3.79 (d,
J ϭ 12.0 Hz, 1 H), 2.65 (d, J ϭ 4.4 Hz, 1 H), 1.63 (t, J ϭ 2.9 Hz,
3 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 205.3, 167.7,
135.9, 133.2, 128.6, 128.1, 127.5, 118.1, 99.5, 81.4, 77.2, 72.4, 70.4,
58.7, 45.1, 15.8 ppm. IR (CHCl3): ν˜ ϭ 3428, 2994, 1939, 1741
cmϪ1. MS (CI): m/z (%) ϭ 300 (100) [M ϩ H]ϩ, 299 (20) [M]ϩ.
C18H21NO3 (299.36): calcd. C 72.22, H 7.07, N 4.68; found C
72.12, H 7.10, N 4.66.
(3R,4S)-1-(3-Butenyl)-4-[(R)-1-hydroxy-2-methyl-2,3-butadienyl]-3-
methoxy-2-azetidinone [(؉)-2f]: This compound was obtained from
aldehyde (ϩ)-1f (95 mg, 0.52 mmol); chromatography of the residue
with hexanes/ethyl acetate (1:1) as eluent gave compound (ϩ)-2f
(95 mg, 77%) as a colorless oil. [α]2D5 ϭ ϩ46.1 (c ϭ 0.7 in CHCl3).
1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 5.73 (m, 1 H), 5.06 (m,
2 H), 4.81 (q, J ϭ 3.0 Hz, 1 H), 4.42 (d, J ϭ 4.8 Hz, 1 H), 4.23 (m,
1 H), 3.94 (t, J ϭ 4.6 Hz, 1 H), 3.55 (s, 3 H), 3.50 (m, 1 H), 3.20
(ddd, J ϭ 13.6, 7.0, 6.0 Hz, 1 H), 2.67 (br. s, 1 H), 2.31 (m, 2 H),
1.79 (t, J ϭ 3.0 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C):
δ ϭ 205.4, 167.7, 135.0, 116.8, 99.8, 83.3, 77.2, 70.3, 59.5, 59.3,
40.7, 31.9, 16.0 ppm. IR (CHCl3): ν˜ ϭ 3421, 2992, 1942, 1747
cmϪ1. MS (CI): m/z (%) ϭ 238 (100) [M ϩ H]ϩ, 237 (19) [M]ϩ.
C13H19NO3 (237.3): calcd. C 65.80, H 8.07, N 5.90; found C 65.87,
H 8.09, N 5.88.
Indium-Promoted Reactions between 3-Substituted Prop-2-ynyl Bro-
mides and Carbaldehydes 1. General Procedure for the Synthesis of
α-Allenic Alcohols 2: 1-Bromo-2-butyne or 1-bromo-3-phenyl-2-
propyne (3.0 mmol) was added at 0 °C to a well stirred suspension
of the corresponding carbaldehyde 1 (1.0 mmol) and indium pow-
der (6.0 mmol) in THF/NH4Cl (aq. satd.) (1:5, 5 mL). After disap-
pearance of the starting material (TLC), the mixture was extracted
with ethyl acetate (3 ϫ 5 mL). The organic extract was washed with
brine, dried (MgSO4), and concentrated under reduced pressure.
Chromatography of the residue with ethyl acetate/hexanes or di-
chloromethane/ethyl acetate mixtures gave analytically pure com-
pounds. Spectroscopic and analytical data for some representative
pure forms of 2 follow.[17]
(3R,4S)-1-(3-Butynyl)-4-[(R)-1-hydroxy-2-methyl-2,3-butadienyl]-3-
methoxy-2-azetidinone [(؉)-2h]: This compound was obtained from
aldehyde (ϩ)-1h (137 mg, 0.756 mmol); chromatography of the resi-
due with hexanes/ethyl acetate (1:1) as eluent gave compound (ϩ)-
2h (123 mg, 69%) as a colorless oil. [α]2D5 ϭ ϩ40.2 (c ϭ 1.0 in
CHCl3). 1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 4.84 (td, J ϭ
3.2, 1.0 Hz, 1 H), 4.48 (d, J ϭ 4.8 Hz, 1 H), 4.25 (m, 1 H), 4.03 (t,
J ϭ 4.8 Hz, 1 H), 3.59 (m, 1 H), 3.58 (s, 3 H), 3.36 (dt, J ϭ 13.7,
6.8 Hz, 1 H), 2.59 (d, J ϭ 4.6 Hz, 1 H), 2.50 (td, J ϭ 7.3, 2.7 Hz,
1 H), 1.99 (t, J ϭ 2.7 Hz, 1 H), 1.81 (t, J ϭ 3.2 Hz, 3 H) ppm. 13C
NMR (75 MHz, CDCl3, 25 °C): δ ϭ 205.4, 167.6, 99.7, 83.5, 81.2,
77.3, 70.4, 70.0, 59.9, 59.6, 40.2, 17.9, 16.1 ppm. IR (CHCl3): ν˜ ϭ
3424, 2989, 2118, 1940, 1745 cmϪ1. MS (CI): m/z (%) ϭ 236 (100)
[M ϩ H]ϩ, 235 (17) [M]ϩ. C13H17NO3 (235.3): calcd. C 66.36, H
7.28, N 5.95; found C 66.43, H 7.26, N 5.94.
Preparation of α-Allenic Alcohols (؎)-2c and anti-(؎)-2c: The less
polar anti-(Ϯ)-2c (17 mg, 9%) and the more polar (Ϯ)-2c (157 mg,
81%) were obtained from aldehyde (Ϯ)-1c (159 mg, 0.654 mmol)
after chromatography of the residue with dichloromethane/ethyl
acetate (9:1) as eluent.
(3RS,4SR)-4-[(RS)-1-Hydroxy-2-methyl-2,3-butadienyl]-1-(p-meth-
oxyphenyl)-3-(2-propynyl)-2-azetidinone [(؎)-2c]: Colorless oil. 1H
NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.28 and 6.86 (dd, J ϭ 6.6,
2.2 Hz, each 2 H), 4.70 (m, 3 H), 4.35 (dd, J ϭ 5.4, 4.6 Hz, 1 H),
3.78 (s, 3 H), 3.58 (m, 1 H), 2.87 (td, J ϭ 6.3, 2.7 Hz, 1 H), 2.40
(br. s, 1 H), 2.09 (t, J ϭ 2.7 Hz, 1 H), 1.75 (t, J ϭ 3.0 Hz, 3 H)
ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 205.8, 166.2, 156.5,
130.2, 119.9, 114.3, 98.7, 81.9, 77.6, 69.7, 68.9, 57.1, 55.4, 50.7,
15.2, 14.8 ppm. IR (CHCl3): ν˜ ϭ 3422, 2990, 2120, 1940, 1749
cmϪ1. MS (CI): m/z (%) ϭ 298 (100) [M ϩ H]ϩ, 297 (25) [M]ϩ.
C18H19NO3 (297.3): calcd. C 72.71, H 6.44, N 4.71; found C 72.78,
H 6.46, N 4.70.
1-(2-Allyloxyphenyl)-2-methylbuta-2,3-dien-1-ol (2i): This com-
pound was obtained from aldehyde 1i (207 mg, 1.27 mmol); chro-
matography of the residue with hexanes/ethyl acetate (4:1) as eluent
gave compound 2i (167 mg, 60%) as a colorless oil. 1H NMR
(300 MHz, CDCl3, 25 °C): δ ϭ 7.26 (m, 2 H), 6.93 (m, 2 H), 6.05
(3RS,4SR)-4-[(SR)-1-Hydroxy-2-methyl-2,3-butadienyl]-1-(p-meth- (m, 1 H), 5.36 (m, 3 H), 4.81 (td, J ϭ 2.9, 0.9 Hz, 2 H), 5.47 (dt,
oxyphenyl)-3-(2-propynyl)-2-azetidinone [anti-(؎)-2c]: Colorless oil.
J ϭ 5.1, 1.5 Hz, 2 H), 2.93 (d, J ϭ 6.8 Hz, 1 H), 1.64 (t, J ϭ 3.2 Hz,
1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.39 and 6.85 (dd, J ϭ
3 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 205.0, 156.1,
6.6, 2.2 Hz, each 2 H), 4.81 (m, 1 H), 4.53 (m, 1 H), 4.47 (m, 2 H), 133.0, 130.1, 128.6, 128.0, 120.8, 117.5, 111.9, 102.2, 77.3, 70.9,
3.79 (s, 3 H), 3.54 (dt, J ϭ 9.0, 5.4 Hz, 1 H), 2.91 (ddd, J ϭ 17.6,
68.9, 15.3 ppm. IR (CHCl3): ν˜ ϭ 3416, 1223, 761 cmϪ1. MS (CI):
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FULL PAPER
m/z (%) ϭ 217 (100) [M ϩ H]ϩ, 216 (15) [M]ϩ. C14H16O2 (216.3):
calcd. C 77.75, H 7.46; found C 77.86, H 7.43.
H), 4.74 (d, J ϭ 4.9 Hz, 1 H), 3.78 (s, 3 H), 3.48 (s, 3 H), 3.06 (s,
3 H), 2.07 (d, J ϭ 1.2 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3,
25 °C): δ ϭ 163.2, 156.5, 152.1, 133.7, 130.7, 124.8, 118.5, 114.5,
105.4, 84.9, 58.9, 56.2, 55.5, 38.0, 13.9 ppm. IR (CHCl3): ν˜ ϭ 1742,
1365, 1170 cmϪ1. MS (CI): m/z (%) ϭ 368 (100) [M ϩ H]ϩ, 367
(12) [M]ϩ. C17H21NO6S (367.4): calcd. C 55.57, H 5.76, N 3.81;
found C 55.66, H 5.73, N 3.79.
1-(2-Propargyloxyphenyl)-2-methylbuta-2,3-dien-1-ol (2k): This
compound was obtained from aldehyde 1j (104 mg, 0.65 mmol);
chromatography of the residue with hexanes/ethyl acetate (4:1) as
eluent gave compound 2k (126 mg, 91%) as a colorless oil. 1H
NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.29 (m, 3 H), 7.01 (m, 2 H),
5.35 (m, 1 H), 4.84 (m, 2 H), 4.37 (d, J ϭ 2.2 Hz, 2 H), 2.72 (d,
J ϭ 6.6 Hz, 1 H), 2.51 (t, J ϭ 2.4 Hz, 1 H), 1.64 (t, J ϭ 3.2 Hz, 3
H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 204.9, 155.1,
130.7, 128.6, 128.1, 121.6, 112.3, 102.2, 78.4, 77.5, 75.6, 70.3, 56.1,
15.3 ppm. IR (CHCl3): ν˜ ϭ 3381, 3314, 2124, 1245, 752 cmϪ1. MS
(CI): m/z (%) ϭ 215 (100) [M ϩ H]ϩ, 214 (11) [M]ϩ. C14H14O2
(214.3): calcd. C 78.48, H 6.59; found C 78.37, H 6.62.
(3RS,4SR)-1-(p-Methoxyphenyl)-4-[(2-methyl-3-methylsulfonyloxy-
1,3-butadienyl]-3-(2-propynyl)-2-azetidinone [(؎)-3c]: This com-
pound was obtained from allenol (Ϯ)-2c (47 mg, 0.16 mmol); chro-
matography of the residue with dichloromethane/ethyl acetate (9:1)
as eluent gave compound (Ϯ)-3c (52 mg, 96%) as a colorless oil.
1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.26 and 6.83 (d, J ϭ
9.0 Hz, 2 H), 6.11 (d, J ϭ 8.8 Hz, 1 H), 5.28 (dd, J ϭ 11.2, 2.9 Hz,
1 H), 4.70 (m, 3 H), 4.93 (dd, J ϭ 9.0, 5.8 Hz, 1 H), 3.76 (s, 3 H),
1-(1-Acryloyl-1H-pyrrol-2-yl)-2-methylbuta-2,3-dien-1-ol (2m): This
compound was obtained from aldehyde 1k (34 mg, 0.22 mmol);
chromatography of the residue with hexanes/ethyl acetate (4:1) as
eluent gave compound 2m (28 mg, 62%) as a colorless oil. 1H NMR
(300 MHz, CDCl3, 25 °C): δ ϭ 7.14 (dd, J ϭ 3.4, 1.5 Hz, 1 H),
6.88 (dd, J ϭ 16.8, 10.0 Hz, 1 H), 6.65 (dd, J ϭ 16.6, 1.6 Hz, 1 H),
6.34 (m, 1 H), 6.24 (t, J ϭ 3.4 Hz, 1 H), 6.08 (dd, J ϭ 10.0, 1.5 Hz,
1 H), 5.26 (dt, J ϭ 8.3, 2.3 Hz, 1 H), 4.67 (m, 3 H), 1.76 (t, J ϭ
3.2 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 205.6,
165.1, 136.6, 133.6, 127.8, 121.6, 115.4, 111.9, 100.6, 76.4, 68.5,
16.2 ppm. IR (CHCl3): ν˜ ϭ 3392, 1679 cmϪ1. MS (CI): m/z (%) ϭ
204 (100) [M ϩ H]ϩ, 203 (16) [M]ϩ. C12H13NO2 (203.2): calcd. C
70.92, H 6.45, N 6.89; found C 71.00, H 6.42, N 6.91.
3.68 (m, 1 H), 3.04 (s, 3 H), 2.58 (m, 2 H), 2.01 (m, 4 H) ppm. 13
C
NMR (75 MHz, CDCl3, 25 °C): δ ϭ 164.2, 156.2, 152.2, 134.2,
131.0, 125.3, 118.0, 114.3, 104.8, 80.7, 70.2, 55.4, 52.9, 37.8, 31.5,
15.2, 14.1 ppm. IR (CHCl3): ν˜ ϭ 2120, 1740, 1362, 1172 cmϪ1. MS
(CI): m/z (%) ϭ 376 (100) [M ϩ H]ϩ, 375 (15) [M]ϩ. C19H21NO5S
(375.4): calcd. C 60.78, H 5.64, N 3.73; found C 60.89, H 5.61,
N 3.71.
(3R,4S)-1-Benzyl-4-[(2-methyl-3-methylsulfonyloxy-1,3-butadienyl]-
3-(2-propenyloxy)-2-azetidinone [(؉)-3d]: This compound was ob-
tained from allenol (ϩ)-2d (69 mg, 0.23 mmol); chromatography of
the residue with dichloromethane/ethyl acetate (9:1) as eluent gave
compound (ϩ)-3d (37 mg, 46%) as a colorless oil. [α]2D5 ϭ ϩ64.6
1
(c ϭ 0.4 in CHCl3). H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.31
1-(N-Propargylindol-2-yl)-2-methylbuta-2,3-dien-1-ol (2o): This
compound was obtained from aldehyde 1m (100 mg, 0.54 mmol);
chromatography of the residue with hexanes/ethyl acetate (8:1) as
eluent gave compound 2o (94 mg, 73%) as a colorless oil. 1H NMR
(300 MHz, CDCl3, 25 °C): δ ϭ 7.61 (dm, J ϭ 7.8 Hz, 1 H), 7.45
(dm, J ϭ 8.3 Hz, 1 H), 7.28 (tm, J ϭ 7.1 Hz, 1 H), 7.15 (m, 1 H),
6.41 (s, 1 H), 5.36 (br. s, 1 H), 5.28 (m, 4 H), 2.40 (br. s, 1 H), 2.27
(t, J ϭ 2.4 Hz, 1 H), 1.71 (t, J ϭ 3.2 Hz, 3 H) ppm. 13C NMR
(75 MHz, CDCl3, 25 °C): δ ϭ 204.7, 138.0, 137.6, 127.4, 122.3,
120.9, 120.1, 109.5, 102.5, 101.2,78.8, 78.5, 72.1, 68.4, 33.2, 15.4
ppm. IR (CHCl3): ν˜ ϭ 3396, 2126 cmϪ1. MS (CI): m/z (%) ϭ 238
(100) [M ϩ H]ϩ, 237 (14) [M]ϩ. C16H15NO (237.3): calcd. C 80.98,
H 6.37, N 5.90; found C 80.84, H 6.39, N 5.91.
(m, 2 H), 7.23 (m, 3 H), 5.95 (dd, J ϭ 9.8, 0.5 Hz, 1 H), 5.82 (m,
1 H), 5.22 (m, 4 H), 4.73 (d, J ϭ 4.6 Hz, 1 H), 4.66 (d, J ϭ 14.9 Hz,
1 H), 4.33 (dd, J ϭ 9.5, 4.6 Hz, 1 H), 4.07 (m, 2 H), 3.97 (d, J ϭ
14.9 Hz, 1 H), 3.07 (s, 3 H), 1.68 (d, J ϭ 1.2 Hz, 3 H) ppm. 13C
NMR (75 MHz, CDCl3, 25 °C): δ ϭ 166.5, 152.3, 135.1, 133.9,
134.4, 128.8, 128.4, 127.9, 124.0, 118.2, 104.9, 83.5, 71.9, 55.0, 44.3,
38.1, 13.4 ppm. IR (CHCl3): ν˜ ϭ 1742, 1370, 1170 cmϪ1. MS (CI):
m/z (%) ϭ 378 (100) [M ϩ H]ϩ, 377 (23) [M]ϩ. C19H23NO5S
(377.5): calcd. C 60.46, H 6.14, N 3.71; found C 60.57, H 6.10,
N 3.73.
(3R,4S)-1-(3-Butenyl)-3-methoxy-4-[(2-methyl-3-methylsulfonyloxy-
1,3-butadienyl]-2-azetidinone [(؉)-3f]: This compound was obtained
from allenol (ϩ)-2f (70 mg, 0.29 mmol); chromatography of the
residue with dichloromethane/ethyl acetate (9:1) as eluent gave
compound (ϩ)-3f (75 mg, 90%) as a colorless oil. [α]2D5 ϭ ϩ80.0
Methanesulfonyl Chloride/Tertiary Amine System: Induced Reac-
tions of α-Allenic Alcohols 2. General Procedure for the Synthesis of
2,3-Difunctionalized 1,3-Dienes 3: Methanesulfonyl chloride
(1.10 mmol) and triethylamine (1.20 mmol) were added sequen-
tially and dropwise at 0 °C to a solution of the corresponding α-
allenol 2 (1.0 mmol) in dichloromethane (10 mL). The resulting
stirred mixture was warmed to room temperature until disappear-
ance of the starting allenol. The reaction mixture was diluted with
water (2 mL). The organic phase washed with brine (2 mL), dried
(MgSO4), and concentrated under reduced pressure. Chromatogra-
phy of the residue, with elution with dichloromethane/ethyl acetate
or hexanes/ethyl acetate mixtures, gave analytically pure func-
tionalized 1,3-dienes 3.
1
(c ϭ 0.7 in CHCl3). H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 5.96
(d, J ϭ 9.0 Hz, 1 H), 5.71 (m, 1 H), 5.25 (dd, J ϭ 15.4, 2.9 Hz, 2
H), 5.07 (m, 2 H), 4.53 (m, 2 H), 3.37 (s, 3 H), 3.38 (m, 1 H), 3.12
(s, 3 H), 3.04 (m, 1 H), 2.26 (m, 2 H), 1.92 (d, J ϭ 1.2 Hz, 3 H)
ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 166.5, 152.2, 134.7,
133.6, 124.5, 117.1, 105.1, 85.4, 58.6, 55.8, 39.5, 37.9, 32.0, 13.6
ppm. IR (CHCl3): ν˜ ϭ 1734, 1368, 1174 cmϪ1. MS (CI): m/z (%) ϭ
316 (100) [M ϩ H]ϩ, 315 (16) [M]ϩ. C14H21NO5S (315.4): calcd. C
53.32, H 6.71, N 4.44; found C 53.42, H 6.68, N 4.46.
(3R,4S)-1-(3-Butynyl)-3-methoxy-4-[(2-methyl-3-methylsulfonyloxy-
1,3-butadienyl]-2-azetidinone [(؉)-3h]: This compound was ob-
tained from allenol (ϩ)-2h (56 mg, 0.24 mmol); chromatography of
the residue with dichloromethane/ethyl acetate (9:1) as eluent gave
compound (ϩ)-3h (49 mg, 73%) as a colorless oil. [α]2D5 ϭ ϩ54.3
(3R,4S)-3-Methoxy-1-(p-methoxyphenyl)-4-[(2-methyl-3-methyl-
sulfonyloxy-1,3-butadienyl]-2-azetidinone [(؉)-3a]: This compound
was obtained from allenol (ϩ)-2a (44 mg, 0.41 mmol); chromatog-
raphy of the residue with hexanes/ethyl acetate (1:1) as eluent gave
compound (ϩ)-2a (35 mg, 59%) as a colorless oil. [α]2D5 ϭ ϩ103.7
(c ϭ 0.7 in CHCl3). H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 5.32
1
1
(c ϭ 0.6 in CHCl3). H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.28 and 5.24 (d, J ϭ 2.9 Hz, each 1 H), 4.71 and 4.65 (t, J ϭ 4.9 Hz,
and 6.85 (d, J ϭ 9.0 Hz, each 2 H), 6.08 (dd, J ϭ 9.3, 0.5 Hz, 1 each 1 H), 3.49 (m, 1 H), 3.41 (s, 3 H), 3.16 (m, 1 H), 3.15 (s, 3
H), 5.31 (dd, J ϭ 14.1, 2.9 Hz, 2 H), 4.94 (dd, J ϭ 9.3, 4.9 Hz, 1
H), 2.42 (ddd, J ϭ 13.6, 7.3, 2.7 Hz, 1 H), 2.03 (t, J ϭ 2.7 Hz, 1
104
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 98Ϫ106

Stereoselective Synthesis of 1,2,3-Trisubstituted 1,3-Dienes from α-Allenols
FULL PAPER
H), 1.96 (d, J ϭ 1.2 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3,
25 °C): δ ϭ 166.6, 152.2, 133.9, 124.3, 105.2, 85.7, 81.0, 70.4, 58.7, 1 H), 2.89 (dd, J ϭ 6.9, 5.1 Hz, 1 H), 2.36 (s, 3 H), 2.23 (m, 1 H),
56.4, 39.1, 38.1, 18.3, 13.7 ppm. IR (CHCl3): ν˜ ϭ 2119, 1735, 1372, 2.12 (m, 1 H), 1.93 (m, 1 H), 1.52 (s, 3 H), 1.09 (m, 2 H), 0.79 (m,
3.0 Hz, 1 H), 3.50 (dd, J ϭ 10.5, 4.0 Hz, 1 H), 3.22 (t, J ϭ 10.5 Hz,
1175 cmϪ1. MS (CI): m/z (%) ϭ 314 (100) [M ϩ H]ϩ, 313 (12) 1 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 168.5, 142.9,
[M]ϩ. C14H19NO5S(313.4): calcd. C 53.66, H 6.11, N 4.47; found
C 53.76, H 6.08, N 4.44.
136.9, 128.9, 124.4, 116.5, 78.9, 69.2, 55.1, 45.9, 44.0, 38.5, 34.4,
28.0, 24.7, 14.4 ppm. IR (CHCl3): ν˜ ϭ 1740, 1370, 1171 cmϪ1. MS
(CI): m/z (%) ϭ 378 (100) [M ϩ H]ϩ, 377 (23) [M]ϩ. C19H23NO5S
(377.5): calcd. C 60.46, H 6.14, N 3.71; found C 60.34, H 6.16,
N 3.73.
3-[2-(Allyloxy)phenyl]-2-methyl-1-methyleneprop-2-enyl 4-Methane-
sulfonate (3i): This compound was obtained from allenol 2i (29 mg,
0.13 mmol); chromatography of the residue with hexanes/ethyl
acetate (4:1) as eluent gave compound 3i (24 mg, 62%) as a color-
less oil. H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.25 (m, 2 H), allenol (ϩ)-2f (69 mg, 0.29 mmol); chromatography of the residue
6.90 (m, 2 H), 6.61 (s, 1 H), 6.05 (m, 1 H), 5.27 (m, 4 H), 4.55 (tt, with hexanes/ethyl acetate (1:1) as eluent gave compound (ϩ)-6c
Tricyclic β-Lactam (؉)-6c: This compound was obtained from
1
J ϭ 7.1, 1.5 Hz, 2 H), 3.17 (s, 3 H), 2.01 (d, J ϭ 0.7 Hz, 3 H) ppm.
(44 mg, 47%) as a colorless oil. [α]2D5 ϭ ϩ119.5 (c ϭ 0.9 in CHCl3).
13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 156.5, 153.9, 133.0, 130.4, 1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 4.05 (dd, J ϭ 4.4, 1.2 Hz,
128.9, 128.6, 127.3, 120.3, 117.9, 111.7, 104.4, 69.0, 38.0, 14.8 ppm. 1 H), 3.69 (dd, J ϭ 12.9, 4.6 Hz, 1 H), 3.49 (s, 3 H), 2.76 (dd, J ϭ
IR (CHCl3): ν˜ ϭ 1360, 1175, 765 cmϪ1. MS (EI): m/z (%) ϭ 295
(7) [M ϩ H]ϩ, 294 (100) [M]ϩ. C15H18O4S (294.4): calcd. C 61.20,
H 6.16; found C 61.31, H 6.12.
10.3, 4.4 Hz, 1 H), 2.38 (s, 3 H), 2.21 (m, 3 H), 1.78 (s, 3 H), 1.46
(m, 1 H), 1.21 (dd, J ϭ 12.5, 7.0 Hz, 1 H), 1.02 (m, 1 H), 0.79 (m,
3 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 166.8, 143.3,
124.8, 84.7, 58.7, 56.9, 41.1, 39.1, 37.9, 35.8, 31.0, 29.4, 28.3, 13.3
ppm. IR (CHCl3): ν˜ ϭ 1741, 1372, 1168 cmϪ1. MS (CI): m/z (%) ϭ
316 (100) [M ϩ H]ϩ, 315 (14) [M]ϩ. C14H21NO5S (315.4): calcd. C
53.32, H 6.71, N 4.44; found C 53.41, H 6.69, N 4.46.
1-Acryloyl-2-[2-methyl-3-(methylsulfonyloxy)buta-1,3-dienyl]-1H-
pyrrole (3l): This compound was obtained from allenol 2m (24 mg,
0.12 mmol); chromatography of the residue with hexanes/ethyl
acetate (4:1) as eluent gave compound 3l (16 mg, 48%) as a color-
less oil. 1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.43 (dd, J ϭ Tricyclic Chromene 6d: This compound was obtained from allenol
4.0, 1.8 Hz, 1 H), 7.23 (dd, J ϭ 3.8, 1.7 Hz, 1 H), 6.87 (dd, J ϭ
2i (58 mg, 0.26 mmol); chromatography of the residue with hex-
16.8, 10.2 Hz, 1 H), 6.58 (dd, J ϭ 16.8, 1.7 Hz, 1 H), 6.38 (m, 2 anes/ethyl acetate (4:1) as eluent gave compound 6d (37 mg, 47%),
1
H), 6.03 (dd, J ϭ 10.2, 1.7 Hz, 1 H), 5.31 (m, 2 H), 3.19 (s, 3 H),
containing ca. 15% of its anti epimer, as a colorless oil. H NMR
2.02 (d, J ϭ 1.2 Hz, 3 H) ppm. IR (CHCl3): ν˜ ϭ 1679, 1364, 1173 (300 MHz, CDCl3, 25 °C): δ ϭ 6.97 (m, 3 H), 6.76 (m, 1 H), 3.87
cmϪ1. MS (CI): m/z (%) ϭ 282 (100) [M ϩ H]ϩ, 281 (11) [M]ϩ. (dd, J ϭ 10.7, 8.1 Hz, 1 H), 3.72 (dd, J ϭ 10.7, 3.7 Hz, 1 H), 2.94
C13H15NO4S (281.3): calcd. C 55.50, H 5.37, N 4.98; found C
55.40, H 5.33, N 5.00.
(br. s, 1 H), 2.17 (s, 3 H), 2.11 (m, 2 H), 1.72 (td, J ϭ 1.9, 0.7 Hz,
3 H), 1.61 (m, 1 H), 1.31 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ ϭ 153.9, 142.2, 130.7, 128.2, 125.9, 124.5, 119.8,
116.9, 67.2, 40.1, 39.1, 30.7, 25.8, 23.0, 16.9 ppm. IR (CHCl3): ν˜ ϭ
1366, 1170, 758 cmϪ1. MS (EI): m/z (%) ϭ 295 (21) [M ϩ H]ϩ, 294
(100) [M]ϩ. C15H18O4S (294.4): calcd. C 61.20, H 6.16; found C
61.32, H 6.12.
3-(1-Ethynyl-1H-indol-2-yl)-1-methyleneprop-2-enyl 4-Methanesul-
fonate (3n): This compound was obtained from allenol 2o (51 mg,
0.21 mmol); chromatography of the residue with hexanes/ethyl
acetate (5:1) as eluent gave compound 3n (32 mg, 50%) as a color-
less oil. 1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.62 (d, J ϭ
7.6 Hz, 1 H), 7.27 (m, 4 H), 6.56 (s, 1 H), 5.36 (m, 2 H), 4.89 (d, Tricyclic Pyrrolizidine 6f: This compound was obtained from
J ϭ 2.4 Hz, 2 H), 3.15 (s, 3 H), 2.23 (t, J ϭ 2.4 Hz, 1 H), 2.13 (d,
allenol 2m (48 mg, 0.23 mmol); chromatography of the residue with
J ϭ 1.2 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ hexanes/ethyl acetate (3:1) as eluent gave compound 6f (28 mg,
1
137.1, 135.1, 132.0, 128.5, 123.3, 121.4, 120.8, 119.9, 118.0, 109.6,
35%) as a colorless oil. H NMR (300 MHz, CDCl3, 25 °C): δ ϭ
105.6, 105.5, 78.7, 73.1, 38.6, 33.2, 15.8 ppm. IR (CHCl3): ν˜ ϭ 7.04 (d, J ϭ 3.0 Hz, 1 H), 6.45 (t, J ϭ 3.0 Hz, 1 H), 6.11 (m, 1 H),
2121, 1370, 1168 cmϪ1. MS (CI): m/z (%) ϭ 316 (100) [M ϩ H]ϩ, 3.92 (d, J ϭ 7.6 Hz, 1 H), 3.41 (m, 1 H), 3.06 (s, 3 H), 2.39 (m, 2
315 (14) [M]ϩ. C17H17NO3S (315.4): calcd. C 64.74, H 5.43, N 4.44;
found C 64.84, H 5.40, N 4.42.
H), 2.05 (m, 2 H), 1.97 (s, 3 H) ppm. IR (CHCl3): ν˜ ϭ 1734, 1370,
1166 cmϪ1. MS (CI): m/z (%) ϭ 282 (100) [M ϩ H]ϩ, 281 (12)
[M]ϩ. C13H15NO4S (281.3): calcd. C 55.50, H 5.37, N 4.98; found
C 55.62, H 5.40, N 4.96.
Domino Transposition/Intramolecular Diels؊Alder Reaction in α-
Allenol-tethered Alkenes/Alkynes. 2. General Procedure for the Syn-
thesis of Tricycles 6 and 7: Methanesulfonyl chloride (1.10 mmol)
Tricyclic β-Lactam (؎)-7a: This compound was obtained from
and triethylamine (1.20 mmol) were sequentially added dropwise to allenol (Ϯ)-2c (62 mg, 0.21 mmol); chromatography of the residue
a solution of the corresponding α-allenyl alcohol 2 (1.0 mmol) and with hexanes/ethyl acetate (1:1) as eluent gave compound (Ϯ)-6a
hydroquinone (cat.) in toluene (10 mL). The resulting solution was (35 mg, 45%) as a colorless oil. 1H NMR (300 MHz, CDCl3, 25
heated in a sealed tube at 190 °C until disappearance of the starting
material (TLC). The reaction mixture was allowed to cool to room
temperature, and the solvent was removed under reduced pressure.
Chromatography of the residue, with elution with dichloromethane/
°C): δ ϭ 7.38 and 6.82 ppm (dd, J ϭ 6.0, 2.0 Hz, each 2 H), 4.99
(br. s, 1 H), 3.71 (t, J ϭ 3.4 Hz, 1 H), 3.38 (m, 1 H), 2.86 (m, 2 H),
2.57 (m, 2 H), 2.34 (s, 3 H), 2.13 (m, 1 H), 1.84 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3, 25 °C): δ ϭ 168.0, 157.3, 147.5, 141.6,
ethyl acetate or hexanes/ethyl acetate mixtures, gave analytically 141.3, 129.6, 123.7, 122.1, 121.8, 116.1, 114.4, 61.5, 55.5, 52.7, 48.8,
pure fused tricycles 6 and 7.
39.1, 37.6, 29.9, 29.6, 16.1 ppm. IR (CHCl3): ν˜ ϭ 2120, 1743, 1366,
1170 cmϪ1. MS (CI): m/z (%) ϭ 376 (100) [M ϩ H]ϩ, 375 (16)
[M]ϩ; elemental analysis calcd (%) for C19H21NO5S (377.5): calcd.
C 60.78, H 5.64, N 3.73; found C 60.89, H 5.61, N 3.75.
Tricyclic β-Lactam (؉)-6b: This compound was obtained from
allenol (ϩ)-2d (73 mg, 0.24 mmol); chromatography of the residue
with hexanes/ethyl acetate (1:2) as eluent gave compound (ϩ)-6b
(50 mg, 54%) as a colorless oil. [α]2D5 ϭ ϩ10.0 (c ϭ 1.0 in CHCl3).
Tricyclic β-Lactam (؉)-7c: This compound was obtained from
1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.27 (m, 5 H), 4.76 (d, allenol (ϩ)-2h (59 mg, 0.25 mmol); chromatography of the residue
J ϭ 16.1 Hz, 1 H), 4.65 (d, J ϭ 5.9 Hz, 1 H), 3.76 (dd, J ϭ 16.1, with hexanes/ethyl acetate (1:2) as eluent gave compound (ϩ)-7c
Eur. J. Org. Chem. 2005, 98Ϫ106
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
105

B. Alcaide, P. Almendros, C. Aragoncillo, M. C. Redondo
B. Alcaide, P. Almendros, C. Aragoncillo, M. C. Redondo,
FULL PAPER
[6a]
(41 mg, 52%) as a colorless oil. [α]2D5 ϭ ϩ77.0 (c ϭ 0.5 in CHCl3).
1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 5.60 (br. s, 1 H), 4.51
(dd, J ϭ 4.1, 1.2 Hz, 1 H), 3.92 (m, 1 H), 3.64 (s, 3 H), 3.45 (m, 1
H), 3.41 (d, J ϭ 4.4 Hz, 1 H), 3.14 (m, 3 H), 3.13 (s, 3 H), 2.69 (m,
1 H), 1.73 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ
166.8, 141.1, 131.8, 122.8, 120.4, 81.1, 59.5, 58.8, 40.9, 39.7, 39.0,
Chem. Commun. 2002, 1472. It has been reported that allenic
N-tosyl-2-oxazolidinones can undergo 1,3-sulfonyl migration
[6b]
to afford unisolated azadiene intermediates.
H. Horino, M.
Kimura, S. Tanaka, T. Okajima, Y. Tamaru, Chem. Eur. J.
2003, 9, 2419. There is literature precedence for the 1,3-shift
[6c]
of sulfonyl groups in γ,γ-difluorinated allylic sulfonates:
T.
33.9, 29.8, 14.2 ppm. IR (CHCl3): ν˜ ϭ 1745, 1375, 1170 cmϪ1
MS(CI): m/z (%) ϭ314 (100) [M
H]ϩ, 313 (20) [M]ϩ.
C14H19NO5S (313.4): calcd. C 53.66, H 6.11, N 4.47; found C
53.78, H 6.08, N 4.49.
.
Yamazaki, S. Hiraoka, J. Sakamoto, T. Kitazume, Org. Lett.
2001, 3, 743.
ϩ
[7]
It has been proposed that reactions between propargyl bro-
mides and metals generate equilibria between allenyl and pro-
pargyl organometallics. This metallotropic rearrangement
often results in poor regioselection in the final organic product,
because both organometallic species can react with the car-
bonyl compound.
Tricyclic Chromene 7d: This compound was obtained from allenol
2k (48 mg, 0.22 mmol); chromatography of the residue with hex-
anes/ethyl acetate (4:1) as eluent gave compound 7d (25 mg, 52%)
as a colorless oil. 1H NMR (300 MHz, CDCl3, 25 °C): δ ϭ 7.74
(m, 1 H), 7.27 (m, 1 H), 7.09 (m, 2 H), 6.96 and 6.75 (d, J ϭ
8.0 Hz, each 1 H), 5.01 (br. s, 1 H), 4.90 (s, 2 H), 2.53 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3, 25 °C): δ ϭ 156.6, 154.4, 130.8, 128.6,
128.2, 127.2, 124.4, 122.6, 121.2, 120.4, 117.3, 113.5, 69.6, 14.3
ppm. IR (CHCl3): ν˜ ϭ 1372, 1166, 762 cmϪ1. MS (EI): m/z (%) ϭ
213 (6) [M ϩ H]ϩ, 212 (100) [M]ϩ. C14H12O2 (212.2): calcd. C
79.22, H 5.70; found C 79.36, H 5.75.
[8]
[9]
α-Allenol anti-(ϩ)-2a was obtained as a very minor component
from indium-mediated BarbierϪtype coupling between 1-
bromo-2-butyne and 4-oxoazetidine-2-carbaldehyde (ϩ)-1a.
For the preparation of 3-aryl-1,3-dienes through Suzuki reac-
[9a]
tion of α-allenols, see:
M. Yoshida, T. Gotou, M. Ihara,
Chem. Commun. 2004, 1124. For the synthesis of 1-aryl-3-
bromo-1,3-dienes through SN2Ј-type additionϪelimination re-
[9b]
actions of 1-aryl-2,3-allenols, see:
S. Ma, G. Wang, Tetra-
hedron Lett. 2002, 43, 5723. For the palladium-catalyzed prep-
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[9c]
A. Horvath, J.-E. Bäckvall, J. Org. Chem. 2001, 66, 8120.
Supporting Information (see also footnote on the first page of this
article): Compound characterization data and experimental pro-
cedures for compounds (ϩ)-2a, (؎)-2b, (ϩ)-2e, (ϩ)-2g, 2j, 2l, 2n,
(؎)-3b, (ϩ)-3e, (ϩ)-3g, 3j, 3k, 3m, (؎)-6a, 6e, (Ϫ)-7b, and 7e.
[10]
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L. F. Tietze, U. Beifuss, Angew.
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Acknowledgments
[10e]
K. C. Nicolau, T. Montagnon, S. A. Snyder, Chem. Com-
Support for this work by the DGI-MCYT (Project
BQU2003Ϫ07793-C02Ϫ01) is gratefully acknowledged. C. A. and
M. C. R. thank the CAM and MEC, respectively, for predoctoral
grants.
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Full spectroscopic and analytical data for compounds not in-
cluded in this Exp. Sect. are described in the Supporting Infor-
mation.
[5]
[6]
Trisubstituted carbonϪcarbon double bonds are present in a
diverse set of organic molecules and the development of new
methods for their synthesis remains an ongoing challenge in
synthetic organic chemistry.
For a preliminary communication of a part of this work, see:
Received July 27, 2004
106
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