Propylene glycol cyclic sulfate as a substitute for propylene oxide in reactions with acetylides

Article abstract of DOI:10.1081/SCC-120015819

Lithium acetylides react cleanly with propylene glycol cyclic sulfate to give, after acidic hydrolysis, homopropargylic alcohols in good yield. The benzyl and TBDPS protecting groups are stable to these conditions, but the THP, TBS, acetal and orthoester groups are not. The readily available (S)-cyclic sulfate gives the (S)-alcohol without loss of stereochemical integrity.

Full text of DOI:10.1081/SCC-120015819

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Propylene Glycol Cyclic Sulfate as a Substitute for
Propylene Oxide in Reactions with Acetylides
Roderick W. Bates & Tushar B. Maiti
To cite this article: Roderick W. Bates & Tushar B. Maiti (2003) Propylene Glycol Cyclic Sulfate
as a Substitute for Propylene Oxide in Reactions with Acetylides, Synthetic Communications,
33:4, 633-640, DOI: 10.1081/SCC-120015819
To link to this article: http://dx.doi.org/10.1081/SCC-120015819
Published online: 16 Aug 2006.
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 4, pp. 633–640, 2003
Propylene Glycol Cyclic Sulfate as a Substitute
for Propylene Oxide in Reactions with Acetylides
2
Roderick W. Bates1, and Tushar B. Maiti
*
1ChulabhornResearch Institute, Laksi,
Bangkok, Thailand
2Department of Chemistry, University of North Texas,
Denton, Texas, USA
ABSTRACT
Lithium acetylides react cleanly with propylene glycol cyclic sulfate
to give, after acidic hydrolysis, homopropargylic alcohols ingood
yield. The benzyl and TBDPS protecting groups are stable to these
conditions, but the THP, TBS, acetal and orthoester groups are not.
The readily available (S)-cyclic sulfate gives the (S)-alcohol without
loss of stereochemical integrity.
*Correspondence: Roderick W. Bates, Chulabhorn Research Institute,
Vibahavadi-Rangsit Road, Laksi, Bangkok, Thailand 10210; Fax:
þ66 2 574 2027; E-mail: roderick@tubtim.cri.or.th.
633
DOI: 10.1081/SCC-120015819
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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634
Bates and Maiti
INTRODUCTION
Epoxides are widely used as electrophiles in synthetic organic
chemistry.[1] Whilst they react with a wide range of nucleophiles, their
reactions with many important carbon nucleophiles, in particular
alkynyl lithium reagents,[1b] are complicated by the need to use a highly
polar co-solvent[2] or a Lewis acid[3] such as BF3ꢀOEt2, or by prior
conversion of the nucleophile to an aluminium derivative.[4]
Propylene oxide (methyl oxirane) 1 has found considerable use in
organic synthesis to introduce a suitably functionalized methyl group.[5]
Various syntheses of both the (R) an d S() enantiomers have been
reported.[6] These materials are also commercially available. The
particular disadvantage of this epoxide is its boiling point, 35ꢁC, which
makes its isolation, storage and use somewhat tricky.
Recently, interest has grown in the use of cyclic sulfates.[7] They have
[8]
beendescribed as ‘‘like epoxides only more reactive.’’
Although there
are numerous examples of ring opening of cyclic sulfates by heteroatom
nucleophiles, the number of examples of carbon nucleophiles is small.
It was surprising to find only a few examples of the reaction of a cyclic
sulfate with an acetylide anion,[9] although the corresponding reaction of
epoxides is a frequently used procedure. The cyclic sulfate of propylene
glycol 2[10] could be a useful and easily handled substitute for propylene
oxide inthis reaction, especially because the ( S) enantiomer can be easily
prepared from inexpensive (S)-methyl lactate (Sch. 1).
RESULTS AND DISCUSSION
The reactionbetweencyclic sulfate 2 and lithium acetylides is quite
general (Sch. 2, Table 1) and, in all cases, only products arising from
attack at the less substituted carbonof the cyclic sulfate were observed.
Various lithium acetylides, generated by treatment of the acetylenes 3
inTHF with n-butyl lithium at ꢂ78ꢁC under N2, reacted smoothly and
rapidly with cyclic sulfate 2 to give the hemisulfate 4 which was then

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Propylene Glycol Cyclic Sulfate
635
Scheme 1.
Scheme 2.
Table 1. Yields of homopropargylic alcohols.
Entry
Alkyne
R
Product:yield
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
Ph
SiMe3
CH(OEt)2
C(OEt)3
CH2OBn
CH2OTHP
CH2OTBS
CH2OTBDPS
5a:71%
5b:74%a
5c:69%b
5i:81%
5e:79%
6:19% þ 5j: 31%
5g:10% þ 5j: 48%
5h:90%
3g
3h
aFor hydrolysis, the sulfuric acid must be added before the water, otherwise the
lithium hydroxide generated can cause partial desilylation resulting in a yield of
5b of 55% or less.
bAfter reprotection with ethanol, triethyl orthoformate and PPTS.
hydrolyzed with a small amount of water (1 equiv.) and conc. sulfuric
acid (0.3 equiv.)[11] to give the homopropargyl alcohols 5.
Phenyl acetylene 3a and trimethylsilylacetylene 3b reacted smoothly
(Entries 1 and 2). With 3,3-diethoxypropyne 3c,[12] not surprisingly,
acetal hydrolysis occurred concurrently with sulfate hydrolysis, and
reprotectionwas required to give the desired product 5c (Entry 3). Use of
3,3,3-triethoxypropyne 3d[13] resulted inhydrolysis of the ortho ester to

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636
Bates and Maiti
give the known ethyl ester 5i cleanly, and in good yield (Entry 4).[14] The
anion of 3d is a convenient and stable alternative to the unstable anion of
ethyl propiolate.
We also examined four different propargylic ethers to test the stabil-
ity of some common protecting groups. The benzyl group was highly
stable; the benzyl protected product 5e was obtained in good yield and
merely a trace of deprotected material 5j was observed by TLC (Entry 5).
The THP group was found to be too labile (Entry 6); both hydrolytic
deprotection and scrambling were observed to give a complex mixture
from which the known diol 5j[15] and the bis-ether 6, amongst others,
[5c]
could be isolated. Inthis case the epoxide method
is clearly superior.
The TBS group was also found to be labile (Entry 7). A low yield of
the desired compound 5g was obtained, accompanied by a larger amount
of diol 5j. In contrast, the TBDPS group was found to be entirely stable
to the hydrolysis conditions and compound 5h was obtained in good
yield (Entry 8).
Whenthe ( S)-enantiomer of cyclic sulfate 2 was used inthe reaction
with alkyne 3e, subsequent analysis of the Mosher’s ester of the product
showed that the stereochemical integrity had been conserved and (S)-5e
was obtained with an e.e. of >95%.[16] Hydrolysis of the hemisulfate has
been shown to occur by cleavage of the O–S bond and therefore with
retention of configuration.[17] Surprisingly, the methylene groups flanking
the ether oxygenof the Mosher’s esters were clearly resolved adn
were therefore used for the determination. The methine protons of the
diastereomers, a to the ester group, were not well resolved.
CONCLUSION
Cyclic sulfate 2 is a useful and easily handled substitute for propylene
oxide, provided that the associated protecting groups are, like the benzyl
and TBDPS groups, sufficiently stable, or when acid catalyzed
deprotectionis a useful procedure, such as inthe case of the ortho ester

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Propylene Glycol Cyclic Sulfate
637
group. Addition of Lewis acids or polar co-solvents is unnecessary. The
reactionis also useful for the sytnhesis of optically pure alcohols.
Extension of this work to other cyclic sulfates and acetylenes, as well
as its applicationintotal synthesis, is inhand.
EXPERIMENTAL SECTION
Flash chromatography was carried out onsilica gel (230–400 mesh,
Merck). Melting points were determined on a Buchi 535. NMR spectra
were recorded ona VarianGemini 2000 at 200 MHz ( 1H) with CDCl3
as the solvent and residual CHCl3 or Me4Si as the internal reference.
Coupling constants are in Hz. IR spectra were recorded, neat, on a PE
1760X instrument. MS were recorded on a Finigan GCQ insturment and
HRMS on a Finigan Mat 90 instrument. Optical rotation data were
recorded ona Jasco P-1020 polarimeter. Propargyl alcohol derivatives
were prepared by standard methods. 3,3-Diethoxypropyne and 3,3,3-
triethoxypropyne were prepared by literature methods.[12,13] THF was
distilled from Na/benzophenone and dichloromethane was distilled
from CaH2. All other materials were commercial and used as supplied.
Cyclic Sulfate 2[10]: Thionyl chloride (820 mL, 11.2 mmol) was added
dropwise to (S)-propylene glycol (712 mg, 9.35 mmol) in carbon
tetrachloride (10 mL) and dichloromethane (5 mL). The mixture was
heated at reflux for 30 minand cooled to 0 ꢁC. Acetonitrile (10 mL),
water (15 mL), ruthenium trichloride trihydrate (1.6 mg, 0.1 mol%) and
sodium periodate (3.0 g, 14 mmol) were added sequentially. The reaction
was stirred for 30 minat room temperature, thenextracted with ether.
The organic layer was washed with NaHCO3 and brine, dried (Na2SO4)
and evaporated. The residue was purified by distillation (Kugelruhr, 50ꢁC
(oven) at 1 mmHg) to give the cyclic sulfate 2 as anoil. 1H NMR ꢀ 5.15
(1H, m, CH3CH), 4.75 (1H, dd, J ¼ 5.3, 9.6 Hz), 4.32 (1H, dd, J ¼ 8.5,
9.6 Hz), 1.60 (3H, d, J ¼ 6.5 Hz); 13C NMR: ꢀ 79.8, 74.0, 17.9;
31
½ꢁꢃD ¼ þ16.5 (c ¼ 0.16, CH2Cl2).
Typical Procedure for the Synthesis of
Homopropargyl Alcohols
n-BuLi inhexanes (0.97 mL of a 1.6 M solution) was added dropwise
to a solutionof benzyl propargyl ether 3e (229 mg, 1.56 mmol) inTHF
(2 mL) at ꢂ78ꢁC under nitrogen. The clear solution was stirred

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638
Bates and Maiti
for 30 min, then a solution of the cyclic sulfate (S)-2 (180 mg, 1.3 mmol) in
THF (2 mL) was added via cannula. The mixture was stirred at ꢂ78ꢁC
for 1 h, thenallowed to warm to room temperature and stirred for a
further 30 min. Water (24 mL) and concentrated sulfuric acid (21 mL)
were added and the now opaque, cloudy mixture[18] was stirred for
15 minat room temperature. The acid was neutralized with saturated
sodium bicarbonate solution. The mixture was extracted twice with
ether. The combined organic layers were washed with saturated aqueous
sodium chloride solution, dried (MgSO4) and evaporated. The residue
was purified by flash chromatography onsilica gel (6 g) eluting with 20%
ether/hexane, to give 1-(phenylmethoxy)-2-hexyn-5-ol 5e (187 mg, 71%)
as anoil. 1H NMR ꢀ 7.3 (5H, m), 4.48 (2H, s), 4.18 (2H, t, J ¼ 2 Hz), 3.96
(1H, m), 2.4 (2H, m), 2.0 (1H, brs), 1.27 (3H, d, J ¼ 7 Hz); 13C NMR ꢀ
137.2, 128.3, 128.0, 127.8, 83.5, 78.2, 71.5, 66.3, 57.5, 29.1, 22.2; ꢂ/cmꢂ1
:
3397, 2998, 2240, 1455; m/z (EI): 205 (5) (Mþ þ H), 187 (58) (Mþ ꢂ OH),
31
159 (34) (BnOC4H4þ), 91(100) (C7H7þ); HRMS calcd. for C13H16O2:
204.1150; found 204.1150; ½ꢁꢃD ¼ þ4.6 (c ¼ 0.065, CH2Cl2).
Other homopropargyl alcohols were prepared similarly.
1
1-Phenyl-1-pentyn-4-ol 5a: H NMR ꢀ 7.3 (5H, m,), 4.05 (1H, m),
2.63 (1H, dd, J ¼ 17, 5), 2.51 (1H, dd, J ¼ 17, 7), 2.3 (1H, brs), 1.30
13
(3H, d, J ¼ 6); C NMR ꢀ 131.5, 128.1, 127.7, 123.3, 86.2, 82.7, 66.4,
29.7, 22.2; ꢂ/cmꢂ1: 3372, 2978, 2928, 2233, 1600, 1489, 1122; m/z (EI):
161 (2) (Mþ þ H), 143 (5) (Mþ ꢂ OH), 115 (100) (PhC3Hþ2 ), HRMS
calcd. for C11H12O 160.0888, found 160.0891.
1
1-Trimethylsilyl-1-pentyn-4-ol 5b: H NMR ꢀ 3.92 (1H, sextet, J ¼ 6),
2.42 (1H, dd, J ¼ 17,5), 2.31 (1H, dd, J ¼ 17, 6), 2.0 (1H, brs), 1.22 (3H, d,
J ¼ 6), 0.10 (9H, s); 13C NMR ꢀ 103.4, 86.9, 66.1, 30.1, 22.0, ꢂ3.1;
ꢂ/cmꢂ1: 3361, 2961, 2178, 1256.
1
1,1-Diethoxy-2-hexyn-5-ol 5c: H NMR ꢀ 5.25 (1H, m), 3.94 (1H,
sextet, J ¼ 6), 3.6 (4H, m), 2.39 (2H, m), 2.20 (1H, brs), 1.23 (3H, d,
J ¼ 6), 1.19 (6H, t, J ¼ 7); 13C NMR ꢀ 91.1, 82.8, 77.4, 65.8, 60.4, 28.8,
22.1, 14.8; ꢂ/cmꢂ1: 3428, 2978, 2239, 1361, 1056; m/z (EI): 185 (3)
(Mþ þ H), 141 (100) (Mþ ꢂ OEt); HRMS calcd. for C8H13O2
(Mþ ꢂ OEt): 141.0916, found 141.0918.
1-(t-Butyldimethylsiloxy)-2-hexyn-5-ol 5g: 1H NMR ꢀ 4.28 (2H, t,
J ¼ 2), 3.91 (1H, sextet, J ¼ 5), 2.33 (2H, m), 2.0 (1H, brs), 1.22 (3H, d,
J ¼ 6), 0.86 (9H, s), 0.09 (6H, s); 13C NMR ꢀ 82.6, 80.9, 66.3, 51.0, 29.1,
25.6, 22.3, 17.6, ꢂ3.6.
1
1-(t-Butyldiphenylsiloxy)-2-hexyn-5-ol 5h: H NMR ꢀ 7.72 (4H, m),
7.40 (6H, m), 4.33 (2H, d, J ¼ 2), 3.82 (1H, sextet, J ¼ 6), 2.28 (2H, m),
2.20 (1H, brs), 1.20 (3H, d, J ¼ 6), 1.05 (9H, s); 13C NMR ꢀ 135.5, 134.7,
129.7, 127.6, 81.8, 80.9, 66.3, 52.8, 29.2, 26.6, 22.3, 19.1; ꢂ/cmꢂ1: 3394,

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Propylene Glycol Cyclic Sulfate
639
2928, 2856, 2239, 1433, 1122; m/z (EI) 295 (54), 217 (100), 199 (71);
HRMS calcd. for C22H28O2Si 352.1859, found 352.1860.
Ethyl 5-hydroxy-2-hexynoate 5i[14]: 1H NMR ꢀ 4.19 (2H, q, J ¼ 7 Hz),
4.02 (1H, sept, J ¼ 5), 2.47 (2H, m), 2.32 (1H, brd, J ¼ 4 Hz), 1.27 (3H, t,
J ¼ 7 Hz), 1.26 (3H, t, J ¼ 6 Hz); 13C NMR ꢀ; ꢂ/cmꢂ1: 3394, 2978, 2239,
1717, 1261.
2-Hexyn-1,5-diol 5j[15]
dquin, J ¼ 5, 6.5), 3.0 (2H, brs), 2.46 (1H, ddt, J ¼ 17, 4, 2), 2.32 (1H,
ddt, J ¼ 17, 7, 2), 1.22 (3H, d, J ¼ 6).
:
1H NMR ꢀ 4.26 (2H, t, J ¼ 2), 3.98 (1H,
ACKNOWLEDGMENTS
Generous financial support from the Thailand Research Fund is
gratefully acknowledged. Preliminary experiments were supported by
the Robert A. Welch Foundation.
REFERENCES
1. (a) Gorzynski Smith, J. Synthesis 1984, 629; (b) Garratt, P.J.
Comprehensive Organic Synthesis; Trost, B.M., Ed.; Pergamon:
Oxford, 1991; Vol. 3, 277.
2. Brandsma, L. Preparative Acetylenic Chemistry; Elsevier:
Amsterdam, 1988; 40.
3. Yamaguchi, M.; Hirao, I. TetrahedronLett. 1983, 24, 391; see also:
Eis, M.J.; Wrobel, J.E.; Ganem, B. J. Am. Chem. Soc. 1984, 106,
3693; Cink, R.D.; Forsyth, C.J. J. Org. Chem. 1995, 60, 8122; Ooi, T.;
Kagashima, N.; Ichikawa, I.; Maruoka, K. J. Am. Chem. Soc. 1999,
121, 3328.
4. Fried, J.; Lin, C.H.; Ford, S.H. Tetrahedron Lett. 1969, 1379.
5. For examples of reactions of propylene oxide with acetylides, see:
(a) Seebach, D.; Seidel, W. TetrahedronLett. 1982, 23, 159;
(b) Hillis, L.R.; Ronald, R.C. J. Org. Chem. 1985, 50, 470;
(c) Nokamai, J.; Taniguchi, T.; Ogawa, Y. Chem. Lett. 1995, 43.
6. Ellis, M.K.; Golding, B.T. Org. Syn. Coll. 1990, 7, 356; Mori, K.;
Senda, S. Tetrahedron 1985, 41, 541.
7. For reviews, see Lohray, B.B. Synthesis 1992, 1035; Lohray, B.B.;
Bhusan, V. Adv. Het. Chem. 1997, 68, 90; Byun, H.-S.; He, L.;
Bittman, R. Tetrahedron 2000, 56, 7051. For recent examples of C–C
bond formation, see Hoye, T.R.; Crawford, K.B. J. Org. Chem.
1994, 59, 520; Baldwin, J.E.; Adlington, R.M.; Gollins, D.W.;

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640
Bates and Maiti
Godfrey, C.R.A. Tetrahedron 1995, 51, 5169; Stiasny, H.C. Synthesis
1996, 259.
8. Gao, Y.; Sharpless, K.B. J. Am. Chem. Soc. 1988, 110, 7538.
9. Tomalia, D.A.; Falk, J.C. J. Heterocycl. Chem. 1972, 9, 891; Bates,
R.W.; Fernandez-Moro, R.; Ley, S.V. Tetrahedron 1991, 47, 9929;
Pais, G.C.G.; Byun, H.-S.; Sadlofsky, J.A.; Bittman, R. J.
Org.Chem. 1998, 63, 2560; Fernandes, R.A.; Kumar, P.
Tetrahedron 1999, 55, 13445; Gourlain, T.; Wadouachi, A.;
Beauere, D. Synthesis 1999, 2, 290. A Payne rearrangement of a
´
hydroxymethyl cyclic sulfate, followed by acetylide attack onthe
resulting epoxide has been reported: Ko, S.Y. Tetrahedron Lett.
1994, 35, 3601.
10. Berridge, M.S.; Franceschini, M.P.; Rosenfield, E.; Tewson, T.J.
J. Org. Chem. 1990, 55, 1211. Preparationby the method of Gao
and Sharpless[8] is higher yielding and more convenient. Propylene
glycol is appreciably hygroscopic, but it may be conveniently dried
by azeotropic removal of water with toluene.
11. Kim, B.M.; Sharpless, K.B. TetrahedronLett. 1989, 30, 655.
12. Le Coq, A.; Gorgues, A. Org. Syn. Coll. 1988, 6, 954.
13. Prepared by bromination of triethyl orthopropionate (Beyerstedt,
F.; McElvain, S.M. J. Am. Chem. Soc. 1937, 59, 1273; Walters,
P.M.; McElvain, S.M. J. Am. Chem. Soc. 1940, 62, 1482), then
elimination, bromination and elimination again (Stetter, H.;
Uerdingen, W.; Synthesis 1973, 207; Gassman, P.G.; Chavan, S.P.
TetrahedronLett. 1988, 29, 3407). For both elimination reactions,
powdered KOH inDMSO was used inplace of KO t-Bu. An
alternative method has been described.[14]
14. For the corresponding epoxide reaction, see Boche, G.; Bigalke, J.
TetrahedronLett. 1984, 25, 955.
15. Trost, B.M.; Krause, L.; Portnoy, M. J. Am. Chem. Soc. 1997, 119,
11319.
16. Dale, D.E.; Rhee, C.K. TetrahedronLett. 1991, 32, 7165.
17. For numerous examples, see Ref.[7]
18. The rapid formation of a cloudy precipitate indicates that sufficient
acid has beenadded. If the mixture is not opaque, hydrolysis of the
hemisulfate does not occur and more acid is required.
Received inthe UK December 3, 2001