Wittig rearrangements of (heteroaryl)alkyl propargyl ethers - Synthesis of allenic and propargylic alcohols

Article abstract of DOI:10.1002/1099-0690(200210)2002:20<3465::AID-EJOC3465>3.0.CO;2-T

(Heteroaryl)alkyl propargyl ethers have been synthesized and treated with nBuLi in THF at -78°C. The resulting α- or α′-lithio derivatives could be trapped with iodomethane, affording the corresponding α- or α′-methylated products. Treatment in the absence of an external electrophile resulted either in allenic alcohols or in propargylic alcohols, or in mixtures of both compounds, probably arising from competing [1,2]- and [2,3]-Wittig rearrangements, in varying ratios. A high anti diastereoselectivity was observed in the propargylic alcohols produced. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200210)2002:20<3465::AID-EJOC3465>3.0.CO;2-T

FULL PAPER
Wittig Rearrangements of (Heteroaryl)alkyl Propargyl Ethers ؊
Synthesis of Allenic and Propargylic Alcohols
Saverio Florio,[b] Catia Granito,[a] Giovanni Ingrosso,[a] and Luigino Troisi*[a]
Keywords: Allenic and propargylic alcohols / (Heteroaryl)alkyl propargyl ethers / Heterocycles / Sigmatropic
rearrangements
(Heteroaryl)alkyl propargyl ethers have been synthesized
and treated with nBuLi in THF at −78 °C. The resulting α-
or αЈ-lithio derivatives could be trapped with iodomethane,
affording the corresponding α- or αЈ-methylated products.
Treatment in the absence of an external electrophile resulted
either in allenic alcohols or in propargylic alcohols, or in mix-
tures of both compounds, probably arising from competing
[1,2]- and [2,3]-Wittig rearrangements, in varying ratios. A
high anti diastereoselectivity was observed in the propar-
gylic alcohols produced.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
tereoselectivity and good enantiomeric enrichment.[14] En-
couraged by these findings, we next turned our attention
to the behaviour of (heteroaryl)alkyl propargyl ethers with
strong bases. In this paper we report a stereoselective pre-
paration of propargylic and allenic alcohols, based on [1,2]-
and [2,3]-Wittig rearrangements of (heteroaryl)alkyl pro-
pargyl ethers.
Sigmatropic rearrangements are a powerful tool for new
CϪC bond formation, already widely exploited in the syn-
thesis of several organic compounds of considerable biolo-
gical and pharmacological interest.
While Claisen rearrangements of phenyl propargyl
ethers,[1] thioethers[2] and amines[3] have been extensively
studied, only a few examples of related [1,2]- and [2,3]-Wit-
tig sigmatropic rearrangements have been reported. Enanti-
oselective [1,2]-Wittig rearrangements of benzyl propargyl
ethers in the presence of external chiral ligands[4] have been
investigated by Nakai et al., as has the rearrangement of O-
glycosides to afford potential precursors of interesting bio-
logical compounds.[5] Examples of [2,3]-Wittig rearrange-
ments, proceeding with high diastereo- and enantioselectivi-
ties, have been reported for crotyl,[6] allyl[7] and cinnamyl[8]
ethers. Competing [1,2]- and [2,3]-Wittig rearrangements
have been described for allyl and propargyl furfuryl ethers[9]
and for macrocyclic allyl propargyl ethers.[10] Such Wittig
rearrangements provide allenic and propargylic alcohols,
which can alternatively be prepared through the coupling
reactions of carbanions with electrophiles.[11Ϫ13]
Results and Discussion
A number of (heteroaryl)alkyl propargyl ethers for sub-
jection to sigmatropic rearrangements were prepared by
three alternative synthetic routes (Scheme 1).
Compounds 1a, 2a and 5aϪ7a were prepared by stirring
a solution of the corresponding (heteroaryl)alkyl carbinol
and the corresponding propargyl bromide in a two-phase
system, with tetrabutylammonium bromide (TBAB) as
phase-transfer catalyst. Compounds 3a and 10aϪ14a were
prepared by treatment of the appropriate (heteroaryl)alkyl
chloride with the propargyl alcohols in a two-phase system,
again with TBAB as phase-transfer catalyst. Compounds
4a, 8a and 9a were prepared from the corresponding (het-
eroaryl)alkyl carbinol and the propargyl chloride, with so-
dium hydroxide in acetone. A more detailed description is
given in the Exp. Sect. During the above preparations, we
found that compound 1a is prone to desilylation, affording
2-(prop-2-ynyloxymethyl)benzothiazole in high yield (94%).
The substrate 1a could therefore not be used for our investi-
gation. Compound 12a could be isolated only by purifica-
tion of the crude compound by flash column chromato-
graphy; attempted purification by column chromatography
caused ring-cleavage to give (quantitative conversion) N-(2-
hydroxy-1,1-dimethylethyl)-2-(3-phenylprop-2-ynyloxy)-
We have recently shown that deprotonated (nBuLi in
THF at Ϫ78 °C) allyl (heteroaryl)alkyl ethers give rise to
allylic and homoallylic alcohols as a result of competing
[1,2]- and [2,3]-Wittig rearrangements, with interesting dias-
[a]
Dipartimento di Scienze
Ambientali, University of Lecce,
e
Tecnologie Biologiche ed
Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy
Fax: (internat.) ϩ 39-0832/320701
E-mail: luigino.troisi@unile.it
[b]
CNR, Istituto di Chimica dei Composti Organometallici-
ICCOM, Sezione di Bari, Dipartimento Farmaco-Chimico,
University of Bari,
Via E. Orabona 4, 70125 Bari, Italy
Eur. J. Org. Chem. 2002, 3465Ϫ3472  2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/02/1020Ϫ3465 $ 20.00ϩ.50/0
3465

S. Florio, C. Granito, G. Ingrosso, L. Troisi
FULL PAPER
Scheme 2. Synthesis of propargylic and allenic alcohols by compet-
itive [1,2]- and [2,3]-Wittig rearrangements of (heteroaryl)alkyl pro-
pargyl ethers
Scheme 1. Synthesis of (heteroaryl)alkyl propargyl ethers: [a]isol-
ated yields
Table 1. Summary of the [1,2]- and [2,3]-Wittig rearrangements of
(heteroaryl)alkyl propargyl ethers
acetamide, the structure of which was established by IR,
1H/13C NMR and GC-MS analysis. Similar behaviour has
been reported for analogous substrates.[15]
Substrate
Type of rearrangement
Products (% yield)[a]
2a
[2,3]
[1,2]
[2,3]
[2,3]
[1,2]
[2,3]
[1,2]
[2,3]
[2,3]
[2,3]
[1,2]
[1,2]
[2,3]
[2,3]
[1,2]
[1,2]
2c (66)
(Heteroaryl)alkyl propargyl ethers 2aϪ14a were treated
with nBuLi in THF at Ϫ78 °C. After the reaction mixture
had been allowed to warm slowly to room temperature
(1Ϫ2 h), we isolated propargylic alcohols, allenic alcohols
or both compounds in varying ratios, probably arising from
competing [1,2]- and [2,3]-Wittig rearrangements, in good
yields (Scheme 2, Table 1).
In more detail, substrates 2a, 4a, 7a, 8a, 11a and 12a
exclusively underwent the [2,3]-Wittig rearrangement to af-
ford the allenic alcohols as the sole products. An analogous
rearrangement for allyl (heteroaryl)alkyl ethers has recently
been described[14] and extensively investigated for various
substrates.[16] In contrast, substrates 9a, 10a, 13a and 14a
underwent the [1,2]-Wittig rearrangement to give the pro-
pargylic alcohols as the sole products. Such a rearrange-
ment is likely to proceed by a radical dissociation/recomb-
3a
3b (25)
3a
3c (45)
4c (54)
5b (9) (anti)
5c (78)
6b (75) (anti)
6c (20)
7c (79)
8c (70)
9b (90) (anti/syn ϭ 75:25)
10b (90)
11c (80)
12c (55)
13b (50) (anti)
14b (65) (anti/syn ϭ 70:30)
4a
5a
5a
6a
6a
7a
8a
9a
10a
11a
12a
13a
14a
[a]
Isolated yields.
ination mechanism, according to the literature.[17] (Het- propargylic alcohol through the [2,3]- and/or the [1,2]-Wit-
eroaryl)alkyl propargyl ethers 3a, 5a and 6a, underwent tig rearrangement. Contrary to what might have been ex-
both the [1,2]- and [2,3]-Wittig rearrangements to generate pected from the influence of the R and RЈ substituents, we
the propargylic and the allenic alcohols in variable ratios noticed that the substrate 4a produced only compound 4c,
(Table 1). The Het, R and RЈ substituents seem to play a by the [2,3]-Wittig rearrangement. Probably, the combined
key role in stabilizing the α- and/or the αЈ-carbon atom de- influence of Het, R and RЈ substituents together with the
protonated structure, which evolve to the allenic and/or the aggregation and solvation of the intermediate lithium com-
3466
Eur. J. Org. Chem. 2002, 3465Ϫ3472

Synthesis of Allenic and Propargylic Alcohols
FULL PAPER
pound give this unexpected result. An interestingly high were deprotonated with nBuLi in the presence of iodome-
anti diastereoselectivity was observed in the propargylic al- thane. Compound 2a exclusively afforded the methylation
cohols obtained; for the substrates 5a, 6a and 13a the pro- product 5a (95% yield), while 10a gave the coupling product
pargylic alcohol isolated was only of the anti type, as shown 10d (30% yield) together with the [1,2]-rearranged product
in Table 1. Deprotonation of substrates 9a and 14a resulted 10b, thus confirming that the occurrence of the [2,3]- or the
in reasonable anti/syn ratios (anti/syn ϭ 75:25 and 70:30, [1,2]-Wittig rearrangement is governed by the generation of
respectively). The stereochemistry was assigned to the syn the carbanion at the α- or at the αЈ-carbon atom, respect-
and anti isomers on the basis of coupling constant values ively[14] (Scheme 3).
(3J) measured between the two vicinal protons HA and HB
(Figure 1).
Scheme 3. Deprotonation of (heteroaryl)alkyl propargyl ethers in
the presence of iodomethane as the electrophile
No [1,2]-Wittig rearrangement product was isolated when
the deprotonation took place at the α-carbon atom, and
no [2,3]-Wittig rearrangement product was obtained when
deprotonation occurred at the αЈ-carbon atom. Treatment
of the above substrates with a stronger base such as tert-
butyllithium (tBuLi) did not produce any change, contrarily
to what has been reported by Tsubuki et al., for propargyl
furfuryl ethers.[9]
In conclusion, we have shown that (benzothiazolyl-, thia-
zolyl-, pyridinyl- and oxazolinyl)alkyl propargyl ethers,
when deprotonated with strong bases in THF and in the
absence of an external electrophile, undergo competing
[1,2]- and [2,3]-Wittig rearrangements. Either propargylic or
allenic alcohols, or variable ratios of both, were isolated in
good yields. The competition between the [2,3]- and [1,2]-
rearrangements might be explained in terms of different
proton acidities at the α- or the αЈ-carbon atom, due to
the different electron-withdrawing ability of the heterocyclic
group involved, while the high anti diastereoselectivity ob-
served for the [1,2]-Wittig rearrangement might be ex-
plained in terms of transition state energy.
Figure 1. syn and anti isomers of a propargylic alcohol; the stereo-
chemistry was assigned on the basis of coupling constant of the
vicinal protons HA and HB
Since the substituents Het and the propargyl group
linked to the stereogenic centre were bulkier than the others
(CH3 and OH), it is reasonable that the most stable con-
formations of both the syn and the anti isomer should be
those in which there is an antiperiplanar orientation of Het
and the propargyl group, with no gauche interaction be-
tween them.[18] This explains why HA and HB are coupled
more strongly in the anti isomer (3JAB anti
than in the syn isomer (3J
AB syn ϭ 3.9 Ϫ 4.0 Hz). The intra-
,
ϭ 6.6 Ϫ 7.0 Hz)
,
molecular hydrogen bonding occurring in each of the two
rotamers (between OH and Het) supports the most prob-
able conformation predicted for each diastereomer.
The observed anti diastereoselectivity might be explained
in terms of transition state energy as illustrated in Figure 2.
The lithiated starting propargylic ether, in a first step, radic-
alizes and then isomerizes, evolving into a six-membered
chair-like transition state that places both the R and the
RЈ groups in equatorial situations. The final result is the
propargylic alcohol of anti configuration.
The various functionalities Ϫ such as the triple bond, the
cumulated double bond, the alcohol and the heterocyclic
function Ϫ confer remarkable synthetic interest on the
above compounds. With benzothiazole, thiazole, and ox-
azoline as the heterocycle, the option of freeing the masked
acyl groups makes them potential intermediates for more
complicated organic syntheses.
Experimental Section
Figure 2. Supposed mechanism explaining the high anti diastereo-
General Remarks: nBuLi was a commercial solution in hexanes (Al-
drich) and was titrated with N-pivaloyl-o-toluidine prior to use.[19]
THF, TBAB, benzothiazole, 4-methylthiazole, propargyl bromides
selectivity of propargylic alcohols
In order to prove that the Wittig rearrangement occurs
through the carbanionic intermediate, substrates 2a and 10a [(3-bromoprop-1-ynyl)trimethylsilane, 1-bromobut-2-yne], but-2-
Eur. J. Org. Chem. 2002, 3465Ϫ3472 3467

S. Florio, C. Granito, G. Ingrosso, L. Troisi
FULL PAPER
yn-1-ol, acetaldehyde and benzaldehyde were of commercial grade
(Aldrich), as were 3-phenylprop-2-yn-1-ol, 2,4,4-trimethyl-2-oxazo-
line and 2-ethyl-4,4-dimethyl-2-oxazoline (Lancaster), and were
used without further purification. 2-(Chloromethyl)pyridine is
available (Aldrich) as the hydrochloride, from which it can be ob-
tained by treatment with 5% NaOH solution. (3-Chloroprop-1-yn-
yl)benzene was prepared by chlorination of 3-phenylprop-2-yn-1-
ol, as previously reported.[20] ‘‘Petroleum ether’’ refers to the 40Ϫ60
°C boiling fraction. The 1H and the 13C NMR spectra were re-
corded with a Bruker AC 200 apparatus (200 MHz and 50.3 MHz,
7.88 (dd, J ϭ 0.8, 7.7 Hz, 1 H), 7.99 (dd, J ϭ 0.8, 8.0 Hz, 1 H)
ppm. 13C NMR (50.3 MHz): δ ϭ 3.6, 22.2, 57.5, 74.3, 74.7, 83.3,
122.1, 123.2, 125.1, 126.0, 135.0, 153.2, 175.3 ppm. GC-MS
(70 eV): m/z (%) ϭ 231 (8) [Mϩ], 216 (45), 201 (15), 186 (28), 163
(100), 162 (82), 136 (17). IR (film): ν˜ ϭ 3060 cmϪ1, 2990, 2920,
2850, 2220, 1520, 1440, 1320, 1090, 760, 730.
2-(1-But-2-ynyloxyethyl)-4-methylthiazole (6a): Yield: 466 mg
(80%), oil. 1H NMR (200 MHz): δ ϭ 1.56 (d, J ϭ 6.5 Hz, 3 H),
1.82 (t, J ϭ 2.4 Hz, 3 H), 2.41 (d, J ϭ 0.8 Hz, 3 H), 4.10 (dq, J ϭ
2.4, 12.0 Hz, 1 H), 4.19 (dq, J ϭ 2.4, 12.0 Hz, 1 H), 4.95 (q, J ϭ
6.5 Hz, 1 H), 6.85 (q, J ϭ 0.8 Hz, 1 H) ppm. 13C NMR (50.3 MHz):
δ ϭ 2.8, 16.1, 21.7, 56.3, 73.0, 74.0, 82.0, 112.2, 151.1, 172.1 ppm.
GC-MS (70 eV): m/z (%) ϭ 194 (3) [Mϩ], 180 (71), 150 (14), 127
(100), 126 (65). IR (film): ν˜ ϭ 3100 cmϪ1, 2990, 2915, 2860, 2230,
1530, 1450, 1370, 1315, 1200, 1090, 1040, 980, 740.
1
for H and 13C, respectively), with CDCl3 as solvent and TMS as
1
internal standard (δH ϭ 7.26 ppm for H spectra; δH ϭ 77.0 ppm
for 13C spectra). The IR spectra were recorded with
a
PerkinϪElmer Model 283 spectrometer. GC-MS analyses were per-
formed with a HewlettϪPackard HP-5890 series II gas chromato-
graph (5% phenylmethylsiloxane capillary column, 30 m, 0.25 mm
i.d.), equipped with an HP 5971 mass-selective detector operating
at 70 eV (EI). Melting points are uncorrected. A Jasco P-1020 po-
larimeter was used for polarimetric measurements. TLC was per-
formed on Merck silica gel plates with F-254 indicator; viewing
was under UV light (254 nm). Column chromatography was per-
formed on silica gel (63Ϫ200 µm), flash column chromatography
was performed on silica gel (40Ϫ63 µm) with petroleum ether/di-
ethyl ether (Et2O) mixtures as eluents. All reactions involving air-
sensitive reagents were performed under nitrogen in oven-dried
glassware by syringe/septum cap techniques.
2-(But-2-ynyloxyphenylmethyl)-4-methylthiazole (7a): Yield: 648 mg
(84%), oil. 1H NMR (200 MHz): δ ϭ 1.83 (t, J ϭ 2.3 Hz, 3 H),
2.38 (d, J ϭ 0.8 Hz, 3 H), 4.13 (dq, J ϭ 2.3, 15.4 Hz, 1 H), 4.26
(dq, J ϭ 2.3, 15.4 Hz, 1 H), 5.94 (s, 1 H), 6.81 (q, J ϭ 0.8 Hz, 1
H), 7.27Ϫ7.55 (m, 5 H) ppm. 13C NMR (50.3 MHz): δ ϭ 3.5, 16.9,
56.7, 74.1, 79.1, 83.3, 113.9, 127.2, 128.2, 128.5, 139.1, 152.0, 171.2
ppm. GC-MS (70 eV): m/z (%) ϭ 257 (1) [Mϩ], 242 (24), 189 (100),
152 (16), 105 (38). IR (film): ν˜ ϭ 3100 cmϪ1, 3060, 3030, 2920,
2850, 2220, 1530, 1500, 1450, 1300, 1140, 1080, 1060, 700.
Compounds 3a and 10aϪ14a: These compounds were prepared by
stirring a solution of the corresponding (heteroaryl)alkyl chloride
(3 mmol) and the propargylic alcohol (3 mmol) in a two-phase sys-
tem (50 mL of THF/50 mL of 10% aqueous NaOH solution) with
TBAB (0.2 mmol) under phase-transfer conditions for 1Ϫ3 h at 40
°C (monitoring the reaction by TLC). The resulting mixtures were
quenched with 40Ϫ100 mL of a saturated aqueous NH4Cl solution
and extracted with Et2O (3 ϫ 20 mL). The combined organic layers
were dried (Na2SO4) and concentrated in vacuo. The crude prod-
ucts 3a, 10a and 11a were purified by column chromatography (sil-
ica gel 63Ϫ200 µm; petroleum ether/Et2O, 8:2 for 3a and 1:1 for
10a and 11a) to afford the pure (heteroaryl)alkyl propargyl ethers
(oils), yields: 85Ϫ95%. The crude products 12aϪ14a were purified
by flash column chromatography (silica gel 40Ϫ63 µm; petroleum
ether/Et2O, 1:1) to afford the pure (heteroaryl)alkyl propargyl
ethers (oils), yields: 60Ϫ75%. On attempted purification by column
chromatography (silica gel 63Ϫ200 µm), compound 12a underwent
ring-cleavage to afford (quantitative conversion) N-(2-hydroxy-1,1-
dimethylethyl)-2-(3-phenylprop-2-ynyloxy)acetamide; yield 209 mg
General Procedure for the Preparation of (Heteroaryl)alkyl Propar-
gyl Ethers: Compounds 1a, 2a and 5aϪ7a were prepared by stirring
a solution of the appropriate (heteroaryl)alkyl carbinol (3 mmol)
and the corresponding propargyl bromide (4 mmol) at room tem-
perature in a two-phase system (50 mL of THF/50 mL of 10%
aqueous NaOH solution) with TBAB (0.2 mmol) under phase-
transfer conditions for 1 h. The resulting mixtures were quenched
with 40Ϫ100 mL of a saturated aqueous NH4Cl solution and ex-
tracted with Et2O (3 ϫ 20 mL). The combined organic layers were
dried (Na2SO4) and concentrated in vacuo. The crude products
were purified by column chromatography (silica gel 63Ϫ200 µm;
petroleum ether/Et2O, 1:1) to afford the pure (heteroaryl)alkyl pro-
pargyl ethers (oils); yields: 60Ϫ94%. The propargylic ether 5a was
alternatively prepared by means of the coupling reaction with iodo-
methane according to the procedure reported for compound 10d.
2-(Prop-2-ynyloxymethyl)benzothiazole (1a): Yield: 572 mg (94%),
1
oil. H NMR (200 MHz): δ ϭ 2.54 (t, J ϭ 2.4 Hz, 1 H), 4.36 (d,
J ϭ 2.4 Hz, 2 H), 5.02 (s, 2 H), 7.35Ϫ7.52 (m, 2 H), 7.87 (d, J ϭ
7.5 Hz, 1 H), 8.00 (d, J ϭ 8.0 Hz, 1 H) ppm. 13C NMR (50.3 MHz):
δ ϭ 58.3, 68.7, 75.7, 78.4, 121.7, 123.2, 125.1, 126.0, 135.2, 152.9,
168.8 ppm. GC-MS (70 eV): m/z (%) ϭ 203 (8) [Mϩ], 202 (13), 174
(27), 149 (100). IR (film): ν˜ ϭ 3300 cmϪ1, 3060, 2920, 2850, 2120,
1520, 1440, 1350, 1310, 1100, 760.
1
(80%), oil. H NMR (200 MHz): δ ϭ 1.26 (s, 3 H), 1.28 (s, 3 H),
3.55 (s, 2 H), 4.02 (s, 2 H), 4.41 (s, 2 H), 6.55 (br. s, 1 H, exchanges
with D2O), 6.65 (br. s, 1 H exchanges with D2O), 7.26Ϫ7.42 (m, 5
H) ppm. 13C NMR (50.3 MHz): δ ϭ 24.0, 24.5, 42.8, 56.0, 59.1,
68.9, 83.2, 87.1, 121.0, 128.2, 128.9, 130.8, 170.1 ppm. GC-MS
(70 eV): m/z (%) ϭ 261 (0) [Mϩ], 130 (17), 115 (55), 113 (100), 98
(48). IR (film): ν˜ ϭ 3480 (br.) cmϪ1, 3070, 3030, 2990, 1710, 1580,
1500, 1430, 1310, 1150, 1100, 810, 740.
2-(But-2-ynyloxymethyl)benzothiazole (2a): Yield: 391 mg (60%),
1
oil. H NMR (200 MHz): δ ϭ 1.85 (t, J ϭ 2.2 Hz, 3 H), 4.31 (q,
J ϭ 2.2 Hz, 2 H), 4.99 (s, 2 H), 7.32Ϫ7.50 (m, 2 H), 7.88 (d, J ϭ
7.5 Hz, 1 H), 7.99 (d, J ϭ 8.0 Hz, 1 H) ppm. 13C NMR (50.3 MHz):
δ ϭ 3.5, 59.2, 68.5, 74.3, 83.8, 121.7, 123.0, 125.1, 126.4, 131.1,
153.2, 169.5 ppm. GC-MS (70 eV): m/z (%) ϭ 217 (10) [Mϩ], 216
(12), 202 (28), 187 (16), 149 (100). IR (film): ν˜ ϭ 3060 cmϪ1, 2920,
2860, 2220, 1520, 1440, 1350, 1100, 760, 730.
2-(3-Phenylprop-2-ynyloxymethyl)benzothiazole (3a): Yield: 711 mg
(85%), oil. H NMR (200 MHz): δ ϭ 4.58 (s, 2 H), 5.08 (s, 2 H),
1
7.27Ϫ7.50 (m, 7 H), 7.86 (dd, J ϭ 0.8, 7.5 Hz, 1 H), 8.0 (dd, J ϭ
0.8, 7.5 Hz, 1 H) ppm. 13C NMR (50.3 MHz): δ ϭ 59.3, 68.9, 84.1,
87.3, 121.8, 122.0, 123.2, 125.3, 126.1, 128.3, 128.7, 131.8, 135.0,
153.2, 169.3 ppm. GC-MS (70 eV): m/z (%) ϭ 279 (7) [Mϩ], 249
(6), 149 (100), 115 (26). IR (film): ν˜ ϭ 3035 cmϪ1, 2925, 2860, 2220,
1520, 1440, 1350, 1090.
2-(1-But-2-ynyloxyethyl)benzothiazole (5a): Yield: 554 mg (80%),
1
oil. H NMR (200 MHz): δ ϭ 1.66 (d, J ϭ 6.5 Hz, 3 H), 1.83 (t,
J ϭ 2.3 Hz, 3 H), 4.18 (dq, J ϭ 2.3, 15.0 Hz, 1 H), 4.27 (dq, J ϭ
2-(3-Phenylprop-2-ynyloxymethyl)pyridine (10a): Yield: 636 mg
2.3, 15.0 Hz, 1 H), 5.10 (q, J ϭ 6.5 Hz, 1 H), 7.32Ϫ7.50 (m, 2 H), (95%), oil. 1H NMR (200 MHz): δ ϭ 4.4 (s, 2 H), 4.7 (s, 2 H),
3468
Eur. J. Org. Chem. 2002, 3465Ϫ3472

Synthesis of Allenic and Propargylic Alcohols
FULL PAPER
7.03Ϫ7.38 (m, 7 H), 7.57 (td, J ϭ 1.7, 6.0 Hz, 1 H), 8.46 (d, J ϭ 122.0, 123.3, 125.2, 126.0, 128.2, 128.5, 131.8, 135.1, 153.2, 175.0
3.0 Hz, 1 H) ppm. 13C NMR (50.3 MHz): δ ϭ 59.1, 72.6, 84.8, ppm. GC-MS (70 eV): m/z (%) ϭ 293 (12) [Mϩ], 263 (11), 163
87.3, 121.6, 122.5, 128.2, 128.5, 131.7, 131.8, 136.6, 149.2, 158.0 (100), 115 (42). IR (CHCl3): ν˜ ϭ 3060 cmϪ1, 2980, 2805, 2240,
ppm. GC-MS (70 eV): m/z (%) ϭ 223 (3) [Mϩ], 115 (20), 93 (100). 1600, 1520, 1490, 1440, 1310, 1190, 1090, 760, 730, 690.
IR (film): ν˜ ϭ 3060 cmϪ1, 3020, 2860, 2240, 1600, 1490, 1440, 1360,
4-Methyl-2-[(3-phenylprop-2-ynyloxy)methylphenyl]thiazole
(8a):
1260, 1110, 1090, 760, 690.
Yield: 159 mg (50%), oil. 1H NMR (200 MHz): δ ϭ 2.4 (d, J ϭ
0.8 Hz, 3 H), 4.4 (d, J ϭ 16.0 Hz, 1 H), 4.55 (d, J ϭ 16.0 Hz, 1 H),
6.03 (s, 1 H), 6.84 (q, J ϭ 0.8 Hz, 1 H), 7.24Ϫ7.52 (m, 10 H) ppm.
13C NMR (50.3 MHz): δ ϭ 17.1, 57.3, 76.3, 79.6, 84.2, 113.9, 122.0,
127.2, 128.1, 128.4, 128.5, 128.6, 131.8, 139.0, 152.7, 171.2 ppm.
GC-MS (70 eV): m/z (%) ϭ 319 (13) [Mϩ], 290 (7), 242 (15), 189
(100), 115 (87). IR (film): ν˜ ϭ 3060 cmϪ1, 3020, 2215, 1910, 1840,
1600, 1480, 1440, 1170, 1080, 1060, 750, 680.
2-(But-2-ynyloxymethyl)pyridine (11a): Yield: 430 mg (89%), oil. 1H
NMR (200 MHz): δ ϭ 1.85 (t, J ϭ 2.3 Hz, 3 H), 4.24 (q, J ϭ
2.3 Hz, 2 H), 4.7 (s, 2 H), 7.24 (t, J ϭ 4.5 Hz, 1 H), 7.46 (d, J ϭ
8.0 Hz, 1 H), 7.69 (td, J ϭ 1.7, 8.0 Hz, 1 H), 8.55 (d, J ϭ 4.5 Hz,
1 H) ppm. 13C NMR (50.3 MHz): δ ϭ 3.5, 58.5, 71.9, 74.6, 83.0,
121.5, 122.4, 136.8, 148.6, 157.7 ppm. GC-MS (70 eV): m/z (%) ϭ
161 (1) [Mϩ], 160 (8), 146 (5), 130 (5), 118 (7), 93 (100), 78 (10).
IR (film): ν˜ ϭ 3060 cmϪ1, 3020, 2920, 2850, 2220, 1590, 1440, 1350,
1140, 1100, 1080, 740.
4-Methyl-2-[1-(3-phenylprop-2-ynyloxy)ethyl]thiazole (9a): Yield:
1
103 mg (40%), oil. H NMR (200 MHz): δ ϭ 1.63 (d, J ϭ 6.7 Hz,
3 H), 2.44 (d, J ϭ 0.8 Hz, 3 H), 4.39 (d, J ϭ 16.0 Hz, 1 H), 4.48
(d, J ϭ 16.0 Hz, 1 H), 5.05 (q, J ϭ 6.7 Hz, 1 H), 6.85 (q, J ϭ
0.8 Hz, 1 H), 7.26Ϫ7.45 (m, 5 H) ppm. 13C NMR (50.3 MHz): δ ϭ
17.0, 22.6, 57.4, 74.5, 77.1, 86.5, 113.6, 128.2, 128.5, 131.5, 131.8,
152.4, 171.1 ppm. GC-MS (70 eV): m/z (%) ϭ 257 (11) [Mϩ], 242
(33), 180 (20), 127 (100), 115 (85). IR (film): ν˜ ϭ 3060 cmϪ1, 2910,
2840, 1650, 1490, 1440, 1360, 1300, 1200, 1080, 750, 680.
4,4-Dimethyl-2-(3-phenylprop-2-ynyloxymethyl)-4,5-dihydro-1,3-
oxazole (12a): Yield: 440 mg (60%), oil. H NMR (200 MHz): δ ϭ
1
1.26 (s, 3 H), 1.27 (s, 3 H), 3.96 (s, 2 H), 4.27 (s, 2 H), 4.48 (s, 2
H), 7.25Ϫ7.30 (m, 3 H), 7.39Ϫ7.43 (m, 2 H) ppm. 13C NMR (50.3
MHz): δ ϭ 28.1, 59.0, 63.6, 67.1, 79.1, 83.8, 87.0, 122.2, 128.1,
128.4, 131.6, 161.8 ppm. GC-MS (70 eV): m/z (%) ϭ 243 (2) [Mϩ],
242 (9), 228 (23), 170 (27), 130 (58), 115 (81), 113 (100), 98 (83).
IR (film): ν˜ ϭ 3040 cmϪ1, 2950, 2870, 2220, 1660, 1590, 1430, 1100,
750, 680.
General Procedure for the Preparation of (Heteroaryl)alkyl Carbin-
ols and Chlorides: (Benzothiazol-2-yl)methanol[21] used for the pre-
paration of ethers 1a and 2a, (1-benzothiazol-2-yl)ethanol[21] used
for ethers 4a and 5a, 1-(4-methylthiazol-2-yl)ethanol[14] used for 6a
and 9a, and (2-chloromethyl)benzothiazole[21] used for ether 3a
were prepared as reported. (4-Methylthiazol-2-yl)phenylmethanol,
needed for the preparation of the substrates 7a and 8a, was pre-
pared by direct deprotonation of 4-methylthiazole (5 mmol) in 50
mL of THF at Ϫ78 °C, by dropwise addition, under N2, first of a
solution of nBuLi in hexanes (2.5 , 2.4 mL, 6.0 mmol) and then
of a solution of benzaldehyde (6 mmol) in THF (3 mL). The mix-
ture was allowed to warm slowly to room temperature (over ca.
1 h), then quenched with 50 mL of a saturated aqueous NH4Cl
solution and extracted with Et2O (3 ϫ 20 mL). The combined or-
ganic layers were dried (Na2SO4) and concentrated in vacuo. The
crude product was purified by column chromatography (silica gel
63Ϫ200 µm; petroleum ether/Et2O, 1:1) to afford pure (4-methyl-
thiazol-2-yl)phenylmethanol (solid); yield 95%. 2-(Chloromethyl)-
pyridine, needed for the preparation of the ethers 10a and 11a, was
obtained by treatment of the commercially available hydrochloride
(Aldrich) with 5% NaOH solution. The (chloroalkyl)oxazolines
needed for the ethers 12aϪ14a were prepared by chlorination of
the corresponding commercially available 2-methyl and 2-ethyl de-
rivatives as reported.[22]
2-(1-But-2-ynyloxyethy)-4,4-dimethyl-4,5-dihydro-1,3-oxazole (13a):
1
Yield: 405 mg (70%), oil. H NMR (200 MHz): δ ϭ 1.19 (s, 3 H),
1.21 (s, 3 H), 1.35 (dt, J ϭ 0.7, 6.7 Hz, 3 H), 1.74Ϫ1.77 (m, 3 H),
3.88 (s, 2 H), 4.07Ϫ4.13 (m, 2 H), 4.25 (q, J ϭ 6.7 Hz, 1 H) ppm.
13C NMR (50.3 MHz): δ ϭ 3.4, 18.4, 28.06, 28.12, 56.9, 66.9, 69.4,
74.4, 79.0, 82.5, 164.7 ppm. GC-MS (70 eV): m/z (%) ϭ 195 (0)
[Mϩ], 194 (1), 180 (5), 140 (13), 127 (100), 126 (40), 112 (26), 108
(22), 53 (68). IR (film): ν˜ ϭ 3045 cmϪ1, 2960, 2885, 2215, 1660,
1590, 1440, 1360, 1100.
4,4-Dimethyl-2-[1-(3-phenylprop-2-ynyloxy)ethyl]-4,5-dihydro-1,3-
1
oxazole (14a): Yield: 580 mg (75%), oil. H NMR (200 MHz): δ ϭ
1.29 (s, 3 H), 1.30 (s, 3 H), 1.47 (d, J ϭ 6.7 Hz, 3 H), 3.98 (s, 2 H),
4.43 (q, J ϭ 6.7 Hz, 1 H), 4.47 (d, J ϭ 4.8 Hz, 2 H), 7.28Ϫ7.33 (m,
3 H), 7.41Ϫ7.46 (m, 2 H) ppm. 13C NMR (50.3 MHz): δ ϭ 18.7,
28.2, 57.4, 67.1, 69.9, 79.2, 84.7, 86.3, 122.5, 128.2, 128.4, 131.8,
164.9 ppm. GC-MS (70 eV): m/z (%) ϭ 257 (1) [Mϩ], 256 (1), 242
(2), 170 (5), 158 (7), 127 (100), 126 (38), 115 (57). IR (film): ν˜ ϭ
3040 cmϪ1, 2950, 2880, 2220, 1660, 1590, 1440, 1360, 1100, 750,
685.
Compounds 4a, 8a and 9a: These compounds were prepared by stir-
ring a solution of the corresponding (heteroaryl)alkyl carbinol
(1 mmol) and (3-chloroprop-2-ynyl)benzene (2 mmol) in acetone
(50 mL)/NaOH (2 g, 50 mmol) for 24 h at 60 °C. The resulting
mixtures were quenched with 40Ϫ100 mL of a saturated aqueous
NH4Cl solution and extracted with Et2O (3 ϫ 20 mL). The com-
bined organic layers were dried (Na2SO4) and concentrated in va-
cuo. The crude products were purified by column chromatography
(silica gel 63Ϫ200 µm; petroleum ether/Et2O, 1:1) to afford the pure
(heteroaryl)alkyl propargyl ethers (4a solid; 8a and 9a oils);
yields: 40Ϫ80%.
(4-Methylthiazol-2-yl)phenylmethanol: Yield: 974 mg (95%), m.p.
90Ϫ92 °C (petroleum ether). 1H NMR (200 MHz): δ ϭ 2.33 (d,
J ϭ 0.7 Hz, 3 H), 4.2 (br. s, 1 H, exchanges with D2O), 6.0 (s, 1
H), 6.77 (q, J ϭ 0.7 Hz, 1 H), 7.26Ϫ7.56 (m, 5 H) ppm. 13C NMR
(50.3 MHz): δ ϭ 16.8, 73.4, 113.9, 126.5, 128.2, 128.5, 141.5, 152.2,
174.1 ppm. GC-MS (70 eV): m/z (%) ϭ 205 (88) [Mϩ], 176 (20),
128 (18), 105 (15), 100 (100), 79 (25), 77 (33). IR (CHCl3): ν˜ ϭ
3600 cmϪ1, 3350 br., 3060, 2990, 1530, 1450, 1380, 1300, 1160,
1130, 1030.
2-[1-(3-Phenylprop-2-ynyloxy)ethyl]benzothiazole
(4a):
Yield:
General Procedure for the [1,2]- and [2,3]-Wittig Rearrangements of
(Heteroaryl)alkyl Propargyl Ethers: The [1,2]- and [2,3]-Wittig re-
arrangements were performed by stirring a solution of the propar-
234 mg (80%), m.p. 72Ϫ73 °C (n-hexane). 1H NMR (200 MHz):
δ ϭ 1.71 (d, J ϭ 6.5 Hz, 3 H), 4.45 (d, J ϭ 16.0 Hz, 1 H), 4.56 (d,
J ϭ 16.0 Hz, 1 H), 5.20 (q, J ϭ 6.5 Hz, 1 H), 7.24Ϫ7.52 (m, 7 H), gylic ether (1 mmol) in 10 mL of THF under N2 at Ϫ 78 °C with
7.90 (dd, J ϭ 1.4, 7.8 Hz, 1 H), 7.99 (dd, J ϭ 1.4, 8.0 Hz, 1 H) dropwise addition of a solution of nBuLi in hexanes (2.5 , 0.44
ppm. 13C NMR (50.3 MHz): δ ϭ 22.2, 58.3, 75.0, 84.1, 86.7, 121.8, mL, 1.1 mmol). The mixture was allowed to warm slowly to room
Eur. J. Org. Chem. 2002, 3465Ϫ3472
3469

S. Florio, C. Granito, G. Ingrosso, L. Troisi
FULL PAPER
temperature (over ca. 1 h), and was then quenched with 30 mL of
a saturated aqueous NH4Cl solution and extracted with Et2O (3 ϫ
10 mL). The combined organic layers were dried (Na2SO4) and
concentrated in vacuo. The crude products 2c, 3cϪ8c, 11c, 3b, 5b,
6b, 9b and 10b were purified by column chromatography (silica gel
63Ϫ200 µm; petroleum ether/Et2O, 1:1) to afford the pure propar-
gylic and allenic alcohols; yields: 54Ϫ95%. The crude products 12c,
13b and 14b were purified by flash column chromatography (silica
gel 40Ϫ63 µm; petroleum ether/Et2O, 1:1) to afford the pure pro-
pargylic and allenic alcohols (oils), yields: 50Ϫ65%.
(dd, J ϭ 1.2, 7.5 Hz, 1 H) ppm. 13C NMR (50.3 MHz): δ ϭ 14.3,
28.6, 75.2, 78.4, 105.0, 121.7, 123.0, 125.0, 126.0, 135.7, 152.6,
178.0, 208.0 ppm. GC-MS (70 eV): m/z (%) ϭ 231 (1) [Mϩ], 214
(100), 178 (27), 136 (66), 109 (13). IR (film): ν˜ ϭ 3400 (br.) cmϪ1
,
3060, 2995, 2930, 2850, 1960, 1510, 1440, 1370, 1315, 1120, 855,
760, 730.
2-(4-Methylthiazol-2-yl)-hex-4-yn-3-ol (6b): anti, yield: 146 mg
(75%), oil. 1H NMR (200 MHz): δ ϭ 1.47 (d, J ϭ 7.0 Hz, 3 H),
1.81 (d, J ϭ 2.0 Hz, 3 H), 2.40 (d, J ϭ 0.9 Hz, 3 H), 3.30 (quintet,
J ϭ 7.0 Hz, 1 H), 3.80 (br. s, 1 H, exchanges with D2O), 4.53 (dq,
J ϭ 2.0, 7.0 Hz, 1 H), 6.75 (q, J ϭ 0.9 Hz, 1 H) ppm. 13C NMR
(50.3 MHz): δ ϭ 3.5, 16.8, 17.5, 44.2, 66.1, 78.0, 82.3, 112.2, 152.2,
172.3 ppm. GC-MS (70 eV): m/z (%) ϭ 195 (6) [Mϩ], 180 (10), 127
(96), 126 (100). IR (film): ν˜ ϭ 3300 (br.) cmϪ1, 2990, 2920, 2850,
2240, 1530, 1450, 1310, 1220, 1140, 1020.
1-(Benzothiazol-2-yl)-2-methylbuta-2,3-dien-1-ol (2c): Yield: 143 mg
(66%), oil. 1H NMR (200 MHz): δ ϭ 1.68 (t, J ϭ 3.0 Hz, 3 H),
3.55 (br. s, 1 H, exchanges with D2O), 4.82Ϫ4.86 (m, 2 H), 5.48 (t,
J ϭ 1.7 Hz, 1 H), 7.30Ϫ7.44 (m, 2 H), 7.80 (dd, J ϭ 0.9, 7.1 Hz, 1
H), 7.93 (dd, J ϭ 7.9 Hz, 1 H) ppm. 13C NMR (50.3 MHz): δ ϭ
13.8, 73.3, 78.2, 100.1, 121.8, 123.2, 125.0, 126.2, 136.2, 153.1,
169.5, 206.3 ppm. GC-MS (70 eV): m/z (%) ϭ 217 (3) [Mϩ], 216
3-Methyl-2-(4-methylthiazol-2-yl)penta-3,4-dien-2-ol (6c): Yield:
1
39 mg (20%), oil. H NMR (200 MHz): δ ϭ 1.69 (t, J ϭ 3.0, Hz,
(6), 200 (100), 164 (26), 136 (27). IR (film): ν˜ ϭ 3300 (br.) cmϪ1
,
3 H), 1.75 (s, 3 H), 2.42 (d, J ϭ 0.9 Hz, 3 H), 3.50 (br. s, 1H
exchanges with D2O), 4.87 (q, J ϭ 3.0 Hz, 2 H), 6.81 (q, J ϭ
0.9 Hz, 1 H) ppm. 13C NMR (50.3 MHz): δ ϭ 14.1, 17.3, 28.7,
74.6, 78.0, 105.1, 114.2, 151.3, 172.1, 205.2 ppm. GC-MS (70 eV):
m/z (%) ϭ 195 (1) [Mϩ], 194 (3), 180 (16), 178 (100), 142 (64), 100
(85). IR (film): ν˜ ϭ 3300 (br.) cmϪ1, 2990, 2920, 2850, 1920, 1530,
1440, 1370, 1300, 1100.
3065, 3000, 2940, 2860, 1940, 1520, 1440, 1330, 1150, 1050, 860,
760, 730.
1-(Benzothiazol-2-yl)-4-phenylbut-3-yn-2-ol (3b): Yield: 70 mg
1
(25%), oil. H NMR (200 MHz): δ ϭ 3.56Ϫ3.63 (m, 2 H), 4.6 (br.
s, 1 H, exchanges with D2O), 5.17 (dd, J ϭ 6.2, 5.1 Hz, 1 H),
7.24Ϫ7.50 (m, 7 H), 7.83 (dd, J ϭ 1.4, 7.7 Hz, 1 H), 8.0 (dd, J ϭ
0.8, 7.6 Hz, 1 H) ppm. 13C NMR (50.3 MHz): δ ϭ 41.4, 61.5, 84.5,
90.1, 121.5, 122.7, 125.2, 126.0, 128.2, 128.5, 128.7, 131.7, 136.2,
152.1, 171.3 ppm. GC-MS (70 eV): m/z (%) ϭ 279 (14) [Mϩ], 260
(100), 149 (46). IR (film): ν˜ ϭ 3400 (br.) cmϪ1, 3060, 3040, 2935,
2860, 2250, 1600, 1495, 1440, 1320.
2-Methyl-1-(4-methylthiazol-2-yl)-1-phenylbuta-2,3-dien-1-ol (7c):
Yield: 203 mg (79%), oil. 1H NMR (200 MHz): δ ϭ 1.77 (t, J ϭ
3.0 Hz, 3 H), 2.41 (d, J ϭ 0.9 Hz, 3 H), 4.49 (br. s, 1 H, exchanges
with D2O), 4.63 (q, J ϭ 3.0 Hz, 2 H), 6.78 (q, J ϭ 0.9 Hz, 1 H),
7.30Ϫ7.40 (m, 3 H), 7.62 (dd, J ϭ 2.0, 8.3 Hz, 2 H) ppm. 13C NMR
(50.3 MHz): δ ϭ 14.8, 16.6, 77.2, 79.5, 105.0, 114.2, 126.1, 127.6,
127.8, 142.1, 151.3, 174.0, 205.1 ppm. GC-MS (70 eV): m/z (%) ϭ
257 (4) [Mϩ], 240 (100), 204 (50), 126 (30), 105 (40), 77 (25). IR
(film): ν˜ ϭ 3420 (br.) cmϪ1, 3100, 3060, 3020, 2920, 2850, 1960,
1530, 1450, 1170, 1040, 850, 760, 700.
1-(Benzothiazol-2-yl)-2-phenylbuta-2,3-dien-1-ol (3c): Yield: 125 mg
(45%), oil. 1H NMR (200 MHz): δ ϭ 3.2 (br. s, 1 H, exchanges
with D2O), 5.25 (s, 2 H), 6.09 (t, J ϭ 1.7 Hz, 1 H), 7.15Ϫ7.51 (m,
7 H), 7.84 (dd, J ϭ 1.2, 7.9 Hz, 1 H), 7.99 (dd, J ϭ 1.1, 7.5 Hz, 1
H) ppm. 13C NMR (50.3 MHz): δ ϭ 71.5, 81.5, 110.2, 121.8, 123.0,
125.3, 126.2, 126.9, 127.4, 128.6, 133.0, 136.1, 153.1, 173.2, 208.1
ppm. GC-MS (70 eV): m/z (%) ϭ 279 (28) [Mϩ], 278 (11), 264 (38),
149 (100), 115 (31). IR (film): ν˜ ϭ 3400 (br.) cmϪ1, 3065, 2960,
2920, 2865, 1945, 1600, 1500, 1440, 1320, 1090.
1-(4-Methylthiazol-2-yl)-1,2-diphenylbuta-2,3-dien-1-ol (8c): Yield:
1
223 mg (70%), oil. H NMR (200 MHz): δ ϭ 2.41 (d, J ϭ 0.9 Hz,
3 H), 4.8 (br. s, 1 H, exchanges with D2O), 4.89 (s, 2 H), 6.78 (q,
J ϭ 0.9 Hz, 1 H), 7.20Ϫ7.40 (m, 8 H), 7.68 (dd, J ϭ 1.5, 8.0 Hz, 2
H) ppm. 13C NMR (50.3 MHz): δ ϭ 16.9, 79.5, 80.0, 112.1, 115.3,
126.6, 126.7, 127.9, 128.0, 128.2, 128.5, 143.1, 151.3, 175.2, 209.1
ppm. GC-MS (70 eV): m/z (%) ϭ 319 (10) [Mϩ], 204 (100), 126
(30), 105 (40), 77 (15). IR (film): ν˜ ϭ 3350 (br.) cmϪ1, 3060, 2905,
2840, 1935, 1600, 1490, 1430, 1160, 1040, 1025, 850, 750, 690.
2-(Benzothiazol-2-yl)-3-phenylpenta-3,4-dien-2-ol
(4c):
Yield:
158 mg (54%), oil. 1H NMR (200 MHz): δ ϭ 1.54 (s, 3 H), 3.6 (br.
s, 1 H, exchanges with D2O), 4.46 (d, J ϭ 2.5 Hz, 2 H), 7.10Ϫ8.2
(m, 9 H) ppm. 13C NMR (50.3 MHz): δ ϭ 27.2, 74.0, 74.2, 100.2,
121.2, 123.2, 125.1, 125.5, 126.2, 128.0, 128.2, 129.6, 138.1, 152.3,
168.2, 205.1 ppm. GC-MS (70 eV): m/z (%) ϭ 293 (0) [Mϩ], 177
4-(4-Methylthiazol-2-yl)-1-phenylpent-1-yn-3-ol (9b): Total yield:
231 mg (90%), oil. anti, yield: 173 mg (75%), oil. 1H NMR
(200 MHz): δ ϭ 1.57 (d, J ϭ 6.6 Hz, 3 H), 2.44 (s, 3 H), 3.48
(quintet, J ϭ 6.6 Hz, 1 H), 3.65 (br. s, 1 H, exchanges with D2O),
4.78 (d, J ϭ 6.6 Hz, 1 H), 6.8 (s, 1 H) 7.27Ϫ7.7 (m, 5 H) ppm. 13C
NMR (50.3 MHz): δ ϭ 16.9, 17.5, 44.2, 66.5, 66.9, 88.0, 112.6,
128.1, 128.3, 131.7, 135.7, 152.2, 172.3 ppm. GC-MS (70 eV): m/z
(%) ϭ 257 (20) [Mϩ], 242 (5), 228 (7), 131 (28), 127 (100), 126 (70).
IR (film): ν˜ ϭ 3300 (br.) cmϪ1, 3060, 3020, 2990, 2920, 2850, 2240,
1600, 1530, 1450, 1310, 1220, 1140, 1020. syn, yield: 58 mg (25%),
(81), 162 (12), 149 (40), 135 (100). IR (film): ν˜ ϭ 3200 (br.) cmϪ1
,
2960, 2830, 1900, 1640, 1450, 1400, 1200, 1080, 710, 680, 650.
2-(Benzothiazol-2-yl)hex-4-yn-3-ol (5b): anti, yield: 21 mg (9%) oil.
1H NMR (200 MHz): δ ϭ 1.62 (d, J ϭ 7.0 Hz, 3 H), 1.81 (d, J ϭ
2.2 Hz, 3 H), 3.35 (quint, J ϭ 7.0 Hz, 1 H), 3.8 (br. s, 1 H, ex-
changes with D2O), 4.60 (dq, J ϭ 7.0, 2.2 Hz, 1 H), 7.32Ϫ7.50 (m,
2 H), 7.83 (dd, J ϭ 1.4, 7.7 Hz, 1 H), 8.0 (dd, J ϭ 0.8, 7.6 Hz, 1
H) ppm. 13C NMR (50.3 MHz): δ ϭ 3.6, 17.4, 45.2, 66.1, 79.2,
82.1, 121.2, 123.2, 125.1, 126.0, 138.1, 151.5, 178.0 ppm. GC-MS
(70 eV): m/z (%) ϭ 231 (10) [Mϩ], 214 (10), 178 (100), 136 (95),
109 (12). IR (film): ν˜ ϭ 3300 (br.) cmϪ1, 2995, 2920, 2855, 2240,
1510, 1440, 1370, 1315, 1220, 1140, 1020, 850, 760, 730.
1
oil. H NMR (200 MHz): δ ϭ 1.55 (d, J ϭ 6.6 Hz, 3 H), 2.44 (s, 3
H), 3.60 (m, 1 H), 3.60 (br. s, 1 H, exchanges with D2O), 4.88 (d,
J ϭ 4.0 Hz, 1 H), 6.8 (s, 1 H) 7.27Ϫ7.7 (m, 5 H) ppm. 13C NMR
(50.3 MHz): δ ϭ 16.9, 17.4, 45.0, 67.1, 67.5, 88.3, 113.2, 128.1,
128.5, 132.2, 135.7, 152.2, 172.1 ppm. GC-MS (70 eV): m/z (%) ϭ
2-(Benzothiazol-2-yl)-3-methylpenta-3,4-dien-2-ol
(5c):
Yield:
180 mg (78%) oil. H NMR (200 MHz): δ ϭ 1.75 (t, J ϭ 3.0 Hz, 3 257 (20) [Mϩ], 242 (4), 228 (6), 131 (30), 127 (100), 126 (75). IR
1
H), 1.85 (s, 3 H), 4.15 (br. s, 1 H, exchanges with D2O), 4.88Ϫ4.98
(m, 2 H), 7.30Ϫ7.5 (m, 2 H), 7.83 (dd, J ϭ 1.4, 7.8 Hz, 1 H), 8.01 1600, 1530, 1450, 1310, 1220, 1140, 1020.
(film): ν˜ ϭ 3300 (br.) cmϪ1, 3060, 3020, 2990, 2920, 2850, 2240,
3470
Eur. J. Org. Chem. 2002, 3465Ϫ3472

Synthesis of Allenic and Propargylic Alcohols
FULL PAPER
4-Phenyl-1-(pyridin-2-yl)but-3-yn-2-ol (10b): Yield: 201 mg (90%),
a saturated aqueous NH4Cl solution and extracted with Et2O (3 ϫ
oil. 1H NMR (200 MHz): δ ϭ 3.23Ϫ3.32 (m, 2 H), 4.65 (br. s, 1 20 mL). The combined organic layers were dried (Na2SO4) and
H, exchanges with D2O), 5.07 (dd, J ϭ 4.7, 6.5 Hz, 1 H), 7.13Ϫ7.35
(m, 7 H), 7.63 (td, J ϭ 1.8, 8.4 Hz, 1 H), 8.50 (dd, J ϭ 0.8, 5.0 Hz,
1 H) ppm. 13C NMR (50.3 MHz): δ ϭ 44.2, 62.1, 84.6, 89.7, 121.9,
concentrated in vacuo. The crude product was purified by column
chromatography (silica gel 63Ϫ200 µm; petroleum ether/Et2O, 6:4)
to afford the pure (heteroaryl)alkyl propargyl ether 10d (oil, 30%
122.8, 124.1, 128.0, 128.2, 131.1, 136.8, 148.6, 158.7 ppm. GC-MS yield) and the [1,2]-rearranged product 10b (oil, 40% yield).
(70 eV): m/z (%) ϭ 223 (15) [Mϩ], 207 (25), 204 (41), 130 (35), 93
2-[(1-Methyl-3-phenylprop-2-ynyloxy)methyl]pyridine (10d): Yield:
71 mg (30%), oil. H NMR (200 MHz): δ ϭ 1.61 (d, J ϭ 5.5 Hz, 3
(100). IR (film): ν˜ ϭ 3350 (br.) cmϪ1, 3060, 2960, 2920, 2840, 2230,
1
1600, 1570, 1470, 1440, 1050, 755, 690.
H), 4.57 (q, J ϭ 5.5 Hz, 1 H), 4.73 (d, J ϭ 16.0 Hz, 1 H), 4.98 (d,
J ϭ 16.0 Hz, 1 H), 7.16Ϫ7.52 (m, 7 H), 7.69 (t, J ϭ 7.6 Hz, 1 H),
8.56 (d, J ϭ 4.4 Hz, 1 H) ppm. 13C NMR (50.3 MHz): δ ϭ 22.2,
66.2, 71.3, 85.2, 88.6, 121.6, 122.3, 128.1, 128.3, 128.4, 131.7, 136.7,
148.9, 158.0 ppm. GC-MS (70 eV): m/z (%) ϭ 237 (4) [Mϩ], 208
2-Methyl-1-(pyridin-2-yl)buta-2,3-dien-1-ol (11c): Yield: 129 mg
(80%), oil. 1H NMR (200 MHz): δ ϭ 1.52 (t, J ϭ 3.3 Hz, 3 H),
4.7Ϫ4.8 (m, 3 H, one of which is attributable to OH, after exchange
with D2O), 5.25 (s, 1 H), 7.25Ϫ7.40 (m, 2 H), 7.69 (td, J ϭ 1.7,
7.6 Hz, 1 H), 8.53 (d, J ϭ 4.0 Hz, 1 H) ppm. 13C NMR (50.3 MHz):
δ ϭ 13.0, 74.1, 75.6, 100.9, 121.2, 122.5, 136.7, 147.3, 159.0, 208.2
ppm. GC-MS (70 eV): m/z (%) ϭ 161 (3) [Mϩ], 160 (10), 144 (20),
93 (100), 78 (20). IR (film): ν˜ ϭ 3400 (br.) cmϪ1, 3060, 3020, 2920,
2850, 1960, 1450, 1050, 900, 760, 700.
(10), 194 (7), 128 (17), 107 (48), 93 (100). IR (film): ν˜ ϭ 3060 cmϪ1
,
3010, 2920, 2860, 2240, 1600, 1490, 1440, 1370, 1260, 1110, 1090,
760, 690.
Acknowledgments
This work was carried out in the framework of the National Project
‘‘Stereoselezione in sintesi Organica: Metodologie ed Applicazioni’’
supported by the Ministero dell’Universita e della Ricerca Scientif-
ica e Tecnologica, Rome. We also thank the Italian Consiglio Na-
zionale delle Ricerche (CNR), Rome and the University of Lecce
for financial support.
1-(4,4-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-2-phenylbuta-2,3-dien-
1-ol (12c): Yield: 135 mg (55%), oil. 1H NMR (200 MHz): δ ϭ 1.28
(s, 6 H), 3.83 (br. s, 3 H, one of which is attributable to OH, after
exchange with D2O) 5.05 (s, 2 H), 5.87 (s, 1 H), 7.30Ϫ7.50 (m, 5
H) ppm. 13C NMR (50.3 MHz δ ϭ 28.1, 68.2, 71.5, 80.5, 110.2,
122.2, 123.0, 126.1, 126.9, 127.0, 164.9, 206.2 ppm. GC-MS
(70 eV): m/z (%) ϭ 243 (9) [Mϩ], 226 (40), 128 (100), 116 (52), 115
(67). IR (film): ν˜ ϭ 3400 (br.) cmϪ1, 3060, 2960, 2865, 1600, 1500,
1440, 1320, 1095, 750, 695.
`
[1] [1a]
[1b]
I. Iwai, J. Ide, Chem. Pharm. Bull. Jpn. 1962, 10, 926.
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Iwai, J. Ide, Chem. Pharm. Bull. Jpn. 1963, 11, 1042. [1c] I. Iwai,
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[1d]
1
J. Ide, Quart. Rev. 1968, 22, 411.
J. Zsindely, H. Schmid,
anti, yield: 100 mg (50%), oil. H NMR (200 MHz): δ ϭ 1.23 (s, 3
H), 1.25 (s, 3 H), 1.32 (d, J ϭ 7.0 Hz, 3 H), 1.42 (d, J ϭ 0.7 Hz, 3
H), 2.6 (m, 1 H), 2.8 (br. s, 1 H, exchanges with D2O), 3.95 (s, 2
H), 4.80 (d, J ϭ 7.0 Hz, 1 H) ppm. 13C NMR (50.3 MHz): δ ϭ
3.5, 13.8, 18.5, 18.8, 28.2, 57.0, 62.4, 66.9, 69.5, 79.1, 165.0 ppm.
GC-MS (70 eV): m/z (%) ϭ 195 (1) [Mϩ], 194 (3), 178 (85), 142
(42), 124 (30), 43 (100). IR (film): ν˜ ϭ 3400 (br.) cmϪ1, 3050, 2990,
2850, 2230, 1660, 1510, 1440, 1375, 1305, 1100.
Helv. Chim. Acta 1968, 51, 1510.[1e] H.J. Hansen, H. Schmid,
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[2d]
[2e]
4-(4,4-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-phenylpent-1-yn-3-ol
(14b): Total yield: 167 mg (65%), oil. anti, yield: 120 mg (70%), oil.
1H NMR (200 MHz): δ ϭ 1.28 (s, 6 H), 1.35 (d, J ϭ 7.0 Hz, 3 H),
2.80 (quint, J ϭ 7.0 Hz, 1 H), 3.00 (br. s, 1 H, exchanges with
D2O), 3.93 (s, 2 H), 4.62 (d, J ϭ 7.0 Hz, 1 H), 7.2Ϫ7.9 (m, 5 H)
ppm. 13C NMR (50.3 MHz): δ ϭ 14.6, 28.2, 28.3, 29.6, 40.1, 65.0,
66.9, 78.7, 126.1, 128.1, 128.3, 131.7, 170.0 ppm. GC-MS (70 eV):
m/z (%) ϭ 257 (1) [Mϩ], 241 (5), 142 (100), 116 (40). IR (film): ν˜ ϭ
3400 (br.) cmϪ1, 3060, 2995, 2940, 2850, 2230, 1660, 1510, 1450,
1370, 1315, 1120, 855, 760, 730. syn, yield: 45 mg (30%), oil. 1H
NMR (200 MHz): δ ϭ 1.28 (s, 6 H), 1.35 (d, J ϭ 7.0 Hz, 3 H),
2.80 (m, 1 H), 3.0 (br. s, 1 H, exchanges with D2O), 3.93 (s, 2 H),
4.77 (d, J ϭ 3.9 Hz, 1 H), 7.20Ϫ7.90 (m, 5 H) ppm. 13C NMR
(50.3 MHz): δ ϭ 14.6, 28.2, 28.3, 29.6, 40.1, 65.0, 66.9, 78.7, 126.1,
128.1, 128.3, 131.7, 170.0 ppm. GC-MS (70 eV): m/z (%) ϭ 257 (1)
George, J. Chem. Soc., Chem. Commun. 1970, 433.
B. W.
Bycroft, W. Landon, J. Chem. Soc., Chem. Commun. 1970, 168.
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[8]
[Mϩ], 241 (5), 142 (100), 116 (40). IR (film): ν˜ ϭ 3400 (br.) cmϪ1
,
3060, 2995, 2940, 2850, 2230, 1660, 1510, 1450, 1370, 1315, 1120,
855, 760, 730.
[9]
General Procedure for the Preparation of (Heteroaryl)alkyl Propar-
gyl Ethers by Coupling Reactions: Compound 10d was prepared by
dropwise addition, at Ϫ78 °C under N2, first of a solution of nBuLi
in hexanes (2.5 , 0.5 mL, 1.25 mmol) and then of the iodomethane
(4 mmol) to a stirring solution of compound 10a (1 mmol) in 15
mL of THF. The mixture was allowed to warm slowly to room
temperature (over ca. 1 h), and was then quenched with 40 mL of
[10]
[11]
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3471

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Received March 11, 2002
[O02133]
3472
Eur. J. Org. Chem. 2002, 3465Ϫ3472