Heterocycles via intramolecular platinum-catalyzed propargylic substitution

Article abstract of DOI:10.1016/j.tet.2011.03.115

We report a Pt(II)-catalyzed cyclization of nucleophile-tethered propargylic acetates yielding substituted heterocycles containing multiple heteroatoms including morpholines, dioxanes, and sulfamates with high cis-selectivity.

Full text of DOI:10.1016/j.tet.2011.03.115

Tetrahedron 67 (2011) 5046e5053
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Heterocycles via intramolecular platinum-catalyzed propargylic substitution
*
Qiren Liang, Jef K. De Brabander
Department of Biochemistry and Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9038, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
We report a Pt(II)-catalyzed cyclization of nucleophile-tethered propargylic acetates yielding substituted
heterocycles containing multiple heteroatoms including morpholines, dioxanes, and sulfamates with
high cis-selectivity.
Received 24 February 2011
Received in revised form 22 March 2011
Accepted 29 March 2011
Available online 8 April 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Propargylic substitution
Tetrahydropyrans
Morpholines
Dioxanes
Sulfamates
Platinum catalysis
1. Introduction
Heterocyclic compounds continue to dominate the curiosity of
biologists and chemist alike.1 With a seemingly limitless range of
structures and substitution patterns, all of which possess inherent
value in medicinal chemistry and as synthetic building blocks, the
need for improved and increasingly creative methods for their
preparation persists. Tetrahydropyrans in particular are important
substructures found in many polyketide-derived natural products,
which bear the 1,3-dioxygenation pattern. Recently, we reported
a novel platinum-catalyzed propargylic substitution of
u-hydroxy
propargylic esters.2 This cyclization yielded 2,6-cis-disubstituted
tetrahydropyrans and tetrahydrofurans by way of a Pt(II)-templated
activation of the ester and subsequent intramolecular SN20 sub-
stitution (Fig. 1). Given the importance of heterocyclic compounds
in chemistry and biology, we wondered if it would be feasible to
access heterocycles with multiple heteroatoms using this meth-
odology. In the context of biologically important tetrahydropyran-
containing natural products, this strategy would allow access to
heterocyclic analogs with potential improved potency.3 Herein, we
describe that this can be achieved by incorporation of heteroatoms
within the tether linking the propargylic acetate and the cyclizing
nucleophile (see box in Fig.1). We also demonstrate that in addition
to alcohols, sulfonamides, and sulfamates are equally competent
nucleophiles in this chemistry.
Fig. 1 Pt(II)-catalyzed propargylic substitution.
2. Results and discussion
First, we explored the possibility of implementing the intra-
molecular propargylic substitution for the construction of non-
symmetrical 2,6-disubstituted morpholines. The 1,4-morpholine
unit is prevalent in nature and is featured in compounds with
a range of functions including antidepressant,4 antiparasitic,5 anti-
tumor,6 antioxidant,7 and anti-inflammatory8 activities.9 Over 100
compounds listed in the world drug index contain a morpholine
subunit. Additionally, morpholines have enjoyed use as tools in
chemical synthesis.10 Given the ubiquity of morpholines it is un-
surprising that many preparatory methods have been de-
veloped.11,12 Despite these notable advances, to the best of our
* Corresponding author. Tel.: þ1 214 648 7808; fax: þ1 214 648 0320; e-mail
address: jef.debrabander@utsouthwestern.edu (J.K. De Brabander).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.115

Q. Liang, J.K. De Brabander / Tetrahedron 67 (2011) 5046e5053
5047
Table 2
knowledge there are few examples of selective formation of non-
Formation of 3-substituted morpholines 4a
C2-symmetrical cis-2,6-disubstituted morpholines.11e,f,l,o
As alluded to earlier, our approach toward 2,6-disubstituted
morpholines hinges on the cyclization of
u-hydroxy propargylic
acetates containing a Boc-protected nitrogen atom in the tether,
materials that were readily prepared on scale and in high yield.13 As
shown in Table 1, treatment of propargylic acetates 1aei with
a catalytic amount of Zeise’s dimer ([(CH2CH2)Cl2Pt]2, 2.5 mol %) in
tetrahydrofuran at rt provided morpholines 2aei in excellent
yields. When diastereomeric mixtures of secondary alcohols 1bed,
1f, or 1h were used as starting materials, only cis-products were
obtained in high diastereomeric excess (>10:1 ratio). This dynamic
kinetic resolution, via epimerization at the propargylic position,14
was also observed in our previous study for the synthesis of
alkyne-substituted tetrahydropyrans.2a,15 As shown in Eq. 1, we had
previously postulated that the propargylic substitution occurs from
a metal-templated allenyl acetate (B) via SN20 substitution.
Entry
Substrate
R1
Yieldb
1
2
3
4
3a
3b
3c
3d
Ph
65
76
74
71
PhCH2CH2
CH3(CH2)5
CH3(CH2)3
a
Reaction conditions: propargylic acetate (0.1
[Cl2Pt(CH2H2)]2, rt.
M
in THF), 2.5 mol %
b
Isolated yield (%).
investigated, for example, in use as photoreceptors,22 in per-
fumes,23 and as anti-tumoral24 and anti-viral agents,25 there re-
mains a pressing need for additional methods for their preparation.
A simple derivation of the original substrates by inclusion of an
oxygen atom in the tether was envisaged to allow access to 1,4-
dioxanes of varying substitution patterns. Satisfyingly, stirring
oxygen-tethered
u-hydroxy propargylic acetates 5aeh, materials
which were readily prepared on gram scale,13 with a catalytic
amount of Zeise’s dimer in THF at rt, afforded the cis-2,6-di-
substituted-1,4-dioxanes 6aeh in excellent yields (85e90%) and
diastereoselectivity (6eeh, 14:1 to 19:1) as illustrated in Table 3.
There are few preparations in the literature for cis-2,6-disubstited-
1,4-dioxanes where the substituents are non-identical.26 Therefore,
this methodology represents a valuable route to these synthetically
useful synthons without the need for desymmetrization before
further elaboration.
(1)
Table 1
Formation of 2,6-disubstituted morpholines 2a
Table 3
Formation of 2,6-disubstituted-1,4-dioxanes 6a
Entry
Substrate
R1
R2
Yieldb
cis/transc
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
Ph
H
85
82
86
88
88
85
84
98
87
d
Et
i-Pr
Ph
H
Ph
H
13:1
10:1
14:1
d
Ph
20:1
d
Entry
Substrate
R1
R2
Yieldb
cis/transc
CH3(CH2)5
CH3(CH2)5
CH3(CH2)3
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
PhCH2CH2
Ph
CH3(CH2)5
CH3(CH2)3
Ph
CH3(CH2)5
CH3(CH2)5
CH3(CH2)3
H
H
H
H
Ph
Ph
Et
Et
86
88
85
87
89
90
85
85
d
Et
H
10:1
d
d
d
a
d
Reaction conditions: propargylic acetate (0.1
[Cl2Pt(CH2H2)]2, rt.
M in THF), 2.5 mol %
14:1
19:1
14:1
14:1
b
Isolated yield (%).
c
Determined by 1H NMR spectroscopy.
5g
5h
a
Reaction conditions: propargylic acetate (0.1
[Cl2Pt(CH2H2)]2, rt.
M in THF), 2.5 mol %
The allenylester arises from a 1,3-acetate or double 1,2-acetate
shift of propargylic acetate A.16 Both the stepwise rearrangement
and a hapto-2 to hapto-1 isomerization (B to C) would permit
epimerization at the propargylic carbon.
With these results in hand, it was of interest to assess whether
the nucleophilic residue could be switched to nitrogen and the
tether residue to oxygen as an entry to alternatively substituted
morpholines. As shown in Table 2, cyclization of oxygen-tethered
sulfonamides 3aed, readily prepared from simple starting mate-
rials,13 under the standard conditions provided 3-substituted
morpholines 4aed in good yield (65e76%).17
We next pursued 2,6-disubstituted-1,4-dioxanes, which have
previously been prepared by a number of methods including ep-
oxide opening,18 cyclodimerization of epoxides,19 selenylation20
and by use of iron-promoted intramolecular cyclizations of allylic
ethers.21 As their utility in a number of applications continues to be
b
Isolated yield (%).
c
Determined by 1H NMR spectroscopy.
Cyclic sulfamates, while only rarely occurring in nature,27 have
enjoyed use as building blocks in synthetic chemistry. Du Bois and
Wehn elegantly demonstrated their use in cross-coupling re-
actions28 and subsequently as intermediates in the synthesis of the
bis-guanidinium toxin (þ)-saxitoxin.29 Despite a promising future
for their continued use as intermediates toward amino alcohols and
polyamines, preparations of cyclic sulfamates have been relatively
limited; including, for example, rhodium-catalyzed CeH in-
sertions28 and reduction of the corresponding sulfamidates.30
We envisaged a route toward these increasingly important
heterocycles by incorporation of a terminal, unsubstituted sulfa-
mate as the nucleophilic residue for propargylic substitution. The

5048
Q. Liang, J.K. De Brabander / Tetrahedron 67 (2011) 5046e5053
substrates 7aeg were prepared from commercially available ma-
terials in good yield.13 Armed with the knowledge from the mor-
pholine preparation that sulfonamides were effective nucleophiles
in these propargylic substitutions (Table 2), we were pleased to
confirm that unsubstituted sulfamates were equally competent in
this chemistry, as illustrated in Table 4. Gratifyingly, the trans-
formations to cyclic sulfamates proceeded in high yields (81e88%),
and syn/anti mixtures of starting materials 7ceg (1:1) converged to
q¼quartet, m¼multiplet, br¼broad, app.¼apparent), and coupling
constants (H/Hz). 1He1H coupling constants were taken from the
spectra. Infrared spectra were recorded on a PerkineElmerI 1000
series FTIR, with wavenumbers expressed in cmꢀ1, using samples
prepared as thin films between NaCl plates. Electrospray ionization
mass spectra (ESI-MS) were recorded on a Shimadzu 2010-LCMS.
Procedures for the preparation of all substrate materials 1aei,
3aed, 5aeh, and 7aeg can be found in the Supplementary data.
single cis-disubstituted products
8 with excellent diaster-
eoselectivity (20:1 to 25:1).15
4.2. Propargylic acetates 1aei
4.2.1. 1-((tert-Butoxycarbonyl)(2-hydroxyethyl)-amino)-6-phenyl-
hex-3-yn-2-yl acetate (1a). dH (400 MHz, CDCl3) 7.28e7.24 (2H, m),
7.20e7.15 (3H, m), 5.53 (1H, m), 3.67 (2H, m), 3.58e3.14 (4H, m),
2.78 (2H, t, J¼7.6 Hz), 2.46 (2H, t, J¼7.6 Hz), 2.04 (3H, s), 1.44 (9H, s);
dC (75 MHz, CDCl3) 169.6, 156.6, 140.1, 128.3, 128.2, 126.3, 86.6, 80.8,
76.2, 62.7, 62.0, 52.4, 51.5, 34.5, 28.2, 20.9, 20.8; nmax (liquid film)
3436, 2959, 1728, 1638, 1463, 1274, 1123, 1072, 742 cmꢀ1; MS (ESI):
MNaþ, found 398.1. C21H29NO5 requires 398.1.
Table 4
Formation of cyclic sulfamates 8a
Entry
R1
R2
Yieldb
cis/transc
4.2.2. 1-((tert-Butoxycarbonyl)(2-hydroxybutyl)amino)-6-phenyl-
hex-3-yn-2-yl acetate (1b). dH (300 MHz, CDCl3) 7.31e7.26 (2H, m),
7.23e7.17 (3H, m), 5.57 (1H, m), 3.68 (1H, m), 3.55e3.18 (4H, m),
2.81 (2H, app. t, J¼7.5 Hz), 2.48 (2H, app. t, J¼6.6 Hz), 2.05 (3H, s),
1.46 (11H, s), 0.96 (3H, t, J¼7.8 Hz); dC (75 MHz, CDCl3) 169.8, 157.2,
140.5, 128.6, 128.5, 126.6, 86.9, 81.2, 76.5, 73.1, 62.9, 55.3, 53.2, 52.7,
34.8, 28.3, 21.2, 21.1, 10.0; nmax (liquid film) 3474, 2974, 1746, 1694,
1455, 1411, 1368, 1230, 1157, 1025, 749, 700 cmꢀ1; MS (ESI): MNaþ,
found 426.2. C23H33NO5 requires 426.2.
1
2
3
4
5
6
7
7a
7b
7c
7d
7e
7f
PhCH2CH2
Ph
PhCH2CH2
Ph
CH3(CH2)5
CH3(CH2)5
Ph
H
H
88
85
81
82
82
84
84
d
d
CH3
CH3
CH3
CH2OTBDPS
CH2OTBDPS
22:1
25:1
20:1
25:1
20:1
7g
a
Reaction conditions: propargylic acetate (0.1
[Cl2Pt(CH2H2)]2, rt.
M in THF), 2.5 mol %
b
Isolated yield (%).
c
Determined by 1H NMR spectroscopy.
4.2.3. 1-((tert-Butoxycarbonyl)(2-hydroxy-3-methyl-butyl)amino)-
6-phenylhex-3-yn-2-yl acetate (1c). dH (500 MHz, CDCl3) 7.31e7.27
(2H, m), 7.23e7.19 (3H, m), 5.64 (1H, m), 3.55 (2H, m), 3.50 (1H, m),
3.32 (2H, m), 2.83 (2H, t, J¼7.0 Hz), 2.51 (2H, app. td, J¼8.0, 2.0 Hz),
2.07 (3H, s), 1.61e1.69 (1H, m), 1.48 (9H, s), 0.96 (3H, m), 0.95 (3H,
m); dC (75 MHz, CDCl3) 169.9, 157.3, 140.5, 128.6, 128.5, 126.6, 86.9,
81.2, 76.6, 76.1, 62.7, 53.6, 52.9, 34.9, 32.5, 28.5, 21.2, 21.1, 18.9, 17.4;
nmax (liquid film) 3477, 2962, 1745, 1692, 1454, 1411, 1367, 1229,
1166, 1022, 889, 748, 699 cmꢀ1; MS (ESI): MNaþ, found 440.2.
C24H35NO5 requires 440.2.
3. Conclusion
In conclusion, we have demonstrated the usefulness of the
intramolecular propargylic substitution of nucleophile-tethered
propargylic acetates. Particularly noteworthy is the incorporation
of a range of functionality to produce a range of mono- and di-
substituted heterocycles containing multiple heteroatoms, such as
morpholines, dioxanes, and cyclic sulfamates. The methodology
described herein provides these heterocycles from readily available
starting materials under operationally mild conditions and with
high diastereoselectivity. Further extension of this work to gain
entry to other classes of heterocycles is currently underway.
4.2.4. 1-((tert-Butoxycarbonyl)(2-hydroxy-2-phenyl-ethyl)amino)-6-
phenylhex-3-yn-2-yl acetate (1d). dH (500 MHz, CDCl3) 7.40e7.25
(10H, m), 5.61 (1H, m), 4.94 (1H, m), 3.54 (2H, m), 3.48 (1H, d,
J¼3.0 Hz), 3.45 (1H, d, J¼3.0 Hz), 2.81 (2H, t, J¼7.5 Hz), 2.48 (2H, td,
J¼7.5, 2.0 Hz), 2.04 (3H, s), 1.51 (9H, s); dC (75 MHz, CDCl3) 169.8,
157.6, 142.4, 140.5, 128.7, 128.6, 127.8, 126.6, 126.0, 87.1, 81.6, 76.5,
74.2, 62.8, 57.6, 52.8, 34.8, 28.5, 21.2, 21.1; nmax (liquid film) 3452,
4. Experimental section
4.1. General experimental
2929, 1744, 1693, 1454, 1409, 1367, 1229, 1164, 1024, 750, 700 cmꢀ1
MS (ESI): MNaþ, found 464.4. C27H33NO5 requires 474.2.
;
Unless otherwise stated, commercially available materials were
used without further purification. All solvents were of HPLC or ACS
grade. Solvents used for moisture-sensitive operations were dried
4.2.5. 1-((tert-Butoxycarbonyl)(2-hydroxyethyl)-amino)-4-phenyl-
but-3-yn-2-yl acetate (1e). dH (400 MHz, CDCl3) 7.43e7.41 (2H, m),
7.32e7.25 (3H, m), 5.85 (1H, m), 3.77 (2H, m), 3.65 (2H, m), 3.53
(2H, m), 2.64 (1H, br s), 2.10 (3H, s), 1.46 (9H, s); dC (75 MHz, CDCl3)
169.9, 157.0, 132.1, 129.1,128.5, 121.9, 86.7, 84.4, 81.4, 63.1, 62.6, 52.6,
52.1, 28.5, 21.2; nmax (liquid film) 3446, 2976, 1747, 1695, 1478, 1410,
1368,1225,1166,1032, 758, 691 cmꢀ1; MS (ESI): MNaþ, found 370.1.
C19H25NO5 requires 370.1.
ꢀ
over molecular sieves (4 A, Aldrich). Pyridine was dried over solid
KOH; anhydrous N,N-dimethylformamide and CH3CN were pur-
chased from commercial sources. Reactions were performed under
an atmosphere of nitrogen with magnetic stirring unless noted
otherwise. Flash chromatography was performed using E. Merck
silica gel 60 (240e400 mesh) according to the protocol of Still
et al.31 TLC was performed using pre-coated plates purchased from
E. Merck (silica gel 60 PF254, 0.25 mm) and were visualized using
a KMnO4 or Ce (IV) stain. NMR spectra were recorded with an in-
ternal deuterium lock and referenced to the residual solvent peak32
on the following instruments: 500 MHz: Varian Inova-500;
400 MHz: Varian Inova-400; 300 MHz Mercury-300 spectrome-
ters. 1H NMR data are presented as follows: chemical shift (in ppm),
integration, multiplicity (s¼singlet, d¼doublet, t¼triplet,
4.2.6. 1-((tert-Butoxycarbonyl)(2-hydroxy-2-phenyl-ethyl)amino)-4-
phenylbut-3-yn-2-yl acetate (1f). dH (400 MHz, CDCl3) 7.41e7.25
(10H, m), 5.86 (1H, m), 4.97 (1H, m), 3.46 (4H, m), 2.68 (1H, br s),
2.09 (3H, s), 1.49 (9H, s); dC (75 MHz, CDCl3) 169.9, 157.4, 142.3,
132.1, 129.1, 128.7, 128.5, 128.4, 127.8, 125.5, 84.4, 81.6, 74.1, 63.0,
57.8, 53.2, 28.5, 28.4, 21.3; nmax (liquid film) 2360, 1747, 1692, 1408,

Q. Liang, J.K. De Brabander / Tetrahedron 67 (2011) 5046e5053
5049
1367, 1223, 1164, 1026, 757 cmꢀ1; MS (ESI): MNaþ, found 446.3.
C25H29NO5 requires 446.2.
m), 1.76 (1H, m), 1.49 (9H, s), 1.01 (3H, d, J¼7.0 Hz), 0.94 (3H, d,
J¼7.0 Hz); dC (125 MHz, CDCl3) 154.7, 140.7, 128.6, 128.5, 126.5, 85.9,
81.1, 80.3, 77.8, 77.4, 67.1, 35.1, 31.3, 28.6, 21.1, 18.8, 18.3; nmax (liquid
film) 3432, 2964, 2929, 1699, 1454, 1366, 1250, 1150, 1082, 886,
699 cmꢀ1; MS (ESI): MNaþ, found 380.1. C22H31NO3 requires 380.2.
4.2.7. 1-((tert-Butoxycarbonyl)(2-hydroxyethyl)-amino)dec-3-yn-2-
yl acetate (1g). dH (400 MHz, CDCl3) 5.60 (1H, m), 3.74 (2H, m), 3.51
(2H, m), 3.48 (2H, m), 2.18 (2H, td, J¼7.2, 2.0 Hz), 2.06 (3H, s),
1.52e1.46 (2H, m), 1.46 (9H, s), 1.38e1.24 (6H, m), 0.88 (3H, t,
J¼7.2 Hz); dC (75 MHz, CDCl3) 169.9, 157.1, 88.0, 81.3, 75.5, 63.1, 62.4,
52.8, 51.9, 31.4, 28.6, 28.4, 22.7, 21.2, 18.8, 14.2; nmax (liquid film)
3463, 2933, 1748, 1697, 1466, 1409, 1367, 1226, 1158, 1023,
775 cmꢀ1; MS (ESI): MNaþ, found 378.1. C19H33NO5 requires 378.2.
4.3.4. tert-Butyl 2-phenyl-6-(4-phenylbut-1-yn-1-yl)morpholine-4-
carboxylate (2d). dH (400 MHz, CDCl3) 7.39e7.18 (10H, m), 4.42 (1H,
dd, J¼10.8, 2.4 Hz), 4.30 (1H, m), 4.10 (2H, m), 2.90 (1H, dd, J¼12.8,
11.2 Hz), 2.84 (2H, t, J¼7.6 Hz), 2.78 (1H, m), 2.52 (2H, td, J¼7.6,
1.2 Hz), 1.49 (9H, s); dC (125 MHz, CDCl3) 154.4, 140.6, 138.7, 128.6,
128.5, 128.4, 126.6, 126.5, 86.5, 80.6, 78.2, 67.3, 60.6, 49.0, 34.9, 28.6,
21.2, 14.4; nmax (liquid film) 3419, 2976, 2929, 2859, 2243, 1694,
1454, 1416, 1366, 1305, 1251, 1168, 1120, 1074, 1029, 886, 750,
699 cmꢀ1; MS (ESI): MNaþ, found 414.2. C25H29NO3 requires 414.2.
4.2.8. 1-((tert-Butoxycarbonyl)(2-hydroxy-3-methyl-butyl)amino)
dec-3-yn-2-yl acetate (1h). dH (400 MHz, CDCl3) 5.61 (1H, m), 3.71
(1H, m), 3.54 (2H, m), 3.29 (2H, m), 2.18 (2H, app. t, J¼7.2 Hz), 2.05
(3H, s),1.52e1.41 (4H, m),1.46 (9H, s),1.38e1.26 (6H, m), 0.96 (3H, t,
J¼7.6 Hz), 0.88 (3H, t, J¼7.2 Hz); dC (75 MHz, CDCl3) 169.8, 157.2,
88.0, 81.1, 75.6, 73.1, 63.1, 55.3, 54.8, 52.8, 31.4, 28.7, 28.5, 28.3, 22.7,
21.2, 18.8, 14.2, 10.0; nmax (liquid film) 2932, 2360, 1747, 1693, 1467,
1410, 1367, 1228, 1156, 1023, 766 cmꢀ1; MS (ESI): MNaþ, found
405.9. C21H37NO5 requires 406.2.
4.3.5. tert-Butyl 2-(phenylethynyl)morpholine-4-carboxylate (2e).
dH (400 MHz, CDCl3) 7.44e7.42 (2H, m), 7.33e7.25 (3H, m), 4.43 (1H,
dd, J¼8.0, 2.8 Hz), 3.98 (1H, app. d, J¼11.2 Hz), 3.89 (1H, br d,
J¼8.0 Hz), 3.65e3.55 (2H, m), 3.36e3.24 (2H, m), 1.46 (9H, s); dC
(125 MHz, CDCl3) 154.6, 132.1, 128.8, 128.4, 122.5, 86.5, 85.4, 80.4,
66.4, 65.2, 48.8, 43.7, 28.6; nmax (liquid film) 2975, 1698, 1490, 1454,
1417, 1366, 1250, 1168, 1127, 1085, 757, 691 cmꢀ1; MS (ESI): MNaþ,
found 310.1. C17H21NO3 requires 310.1.
4.2.9. 1-((tert-Butoxycarbonyl)(2-hydroxyethyl)-amino)oct-3-yn-2-
yl acetate (1i). dH (400 MHz, CDCl3) 5.59 (1H, m), 3.73 (2H, app. t,
J¼2.8 Hz), 3.49e3.43 (4H, m), 2.18 (2H, td, J¼6.8, 2.0 Hz), 2.05 (3H,
s), 1.50e1.43 (2H, m), 1.47 (9H, s), 1.41e1.29 (2H, m), 0.88 (3H, t,
J¼7.2 Hz); dC (75 MHz, CDCl3) 169.9, 157.1, 87.9, 81.3, 75.5, 63.1, 62.4,
52.8, 51.9, 30.5, 28.5, 22.1, 21.2, 18.5, 13.7; nmax (liquid film) 3455,
4.3.6. tert-Butyl 2-phenyl-6-(phenylethynyl)-morpholine-4-carboxy-
late (2f). dH (500 MHz, CDCl3) 7.49e7.27 (10H, m), 4.59 (1H, dd,
J¼3.0, 11.0 Hz), 4.53 (1H, dd, J¼11.0, 2.5 Hz), 4.29 (1H, br d,
J¼11.5 Hz), 4.18 (1H, br d, J¼9.0 Hz), 3.11 (1H, app. t, J¼12.0 Hz), 2.88
(1H, app. t, J¼12.0 Hz),1.49 (9H, s); dC (125 MHz, CDCl3) 154.5,138.8,
132.1, 128.8, 128.6, 128.4, 128.3, 126.6, 122.5, 86.2, 85.4, 80.7, 78.3,
67.7, 49.7, 48.6, 28.6; nmax (liquid film) 2360, 1694, 1413, 1249, 1165,
1125, 1071, 756 cmꢀ1; MS (ESI): MNaþ, found 386.1. C23H25NO3
requires 386.1.
2935, 1747, 1697, 1466, 1409, 1367, 1227, 1160, 1023, 878, 775 cmꢀ1
MS (ESI): MNaþ, found 350.0. C17H29NO5 requires 350.1.
;
4.3. General procedure for the preparation of 2,6-substituted
morpholines 2aei
To a 0.1 M solution of propargylic ester 1aei13 in THF at rt was
added [Cl2Pt(CH2CH2)]2 (2.5 mol %). The resulting yellow solution
was stirred for 0.5e2.0 h13 before being quenched by the addition
of NEt3 (0.5 mL/mmol substrate). The solution was concentrated in
vacuo and the crude material was filtered through a plug of silica
gel to give the title compound 2aei as a colorless oil.
4.3.7. tert-Butyl 2-(oct-1-yn-1-yl)morpholine-4-carboxylate (2g). dH
(500 MHz, CDCl3) 4.17 (1H, m), 3.89 (1H, app. dt, J¼12.0, 4.0 Hz),
3.80 (1H, br d, J¼12.0 Hz), 3.61 (1H, dt, J¼12.0, 3.5 Hz), 3.49 (1H,
ddd, J¼14.5, 11.5, 3.5 Hz), 3.19e3.10 (2H, m), 2.20 (2H, td, J¼7.0,
2.0 Hz), 1.53e1.48 (2H, m), 1.46 (9H, s), 1.44e1.24 (6H, m), 0.88 (3H,
t, J¼7.0 Hz); dC (125 MHz, CDCl3) 154.6, 87.4, 80.2, 76.5, 66.3, 65.2,
49.1, 43.1, 31.4, 28.6, 28.5, 22.6, 18.8, 14.0; nmax (liquid film) 3445,
2931, 2859, 2360, 1702, 1455, 1417, 1250, 1172, 1100, 1015, 869,
767 cmꢀ1; MS (ESI): MNaþ, found 318.2. C17H29NO3 requires 318.2.
4.3.1. tert-Butyl 2-(4-phenylbut-1-yn-1-yl)-morpholine-4-carboxyl-
ate (2a). dH (500 MHz, CDCl3) 7.31e7.27 (2H, m), 7.22e7.19 (3H, m),
4.18 (1H, m), 3.88 (1H, dt, J¼12.5, 4.0 Hz), 3.78 (1H, br d, J¼12.5 Hz),
3.60 (1H, app. dt, J¼13.5, 3.0 Hz), 3.49 (1H, ddd, J¼13.5, 9.0, 3.0 Hz),
3.22e3.14 (2H, m), 2.84 (2H, t, J¼7.5 Hz), 2.52 (2H, td, J¼8.0, 2.0 Hz),
1.49 (9H, s); dC (125 MHz, CDCl3) 154.6, 140.7, 128.6, 128.4, 126.5,
86.5, 80.2, 77.4, 66.2, 65.1, 49.1, 43.6, 35.1, 28.6, 20.9; nmax (liquid
film) 2975, 1698, 1454, 1417, 1250, 1171, 1099, 1016, 868, 748,
699 cmꢀ1; MS (ESI): MNaþ, found 338.1. C19H25NO3 requires 338.1.
4.3.8. tert-Butyl 2-ethyl-6-(oct-1-yn-1-yl)-morpholine-4-carboxyl-
ate (2h). dH (500 MHz, CDCl3) 4.12 (1H, m), 4.03 (1H, br d,
J¼11.0 Hz), 3.91 (1H, br d, J¼11.0 Hz), 3.27 (1H, m), 2.80 (1H, t,
J¼12.0 Hz), 2.50 (1H, t, J¼12.0 Hz), 2.21 (2H, td, J¼7.0, 2.0 Hz),
1.64e1.55 (1H, m), 1.54e1.43 (3H, m),1.47 (9H, s), 1.24e1.41 (6H, m),
0.97 (3H, t, J¼7.5 Hz), 0.89 (3H, t, J¼7.0 Hz); dC (125 MHz, CDCl3)
154.5, 86.9, 80.3, 77.5, 76.8, 67.1, 49.1, 47.7, 31.4, 28.7, 28.6, 28.5, 26.3,
22.6, 18.9, 14.1, 9.7; nmax (liquid film) 2931, 2858, 1703, 1415, 1318,
1235, 1173, 1147, 1083, 882 cmꢀ1; MS (ESI): Mþ, found 323.1.
C19H33NO3 requires 323.2.
4.3.2. tert-Butyl 2-ethyl-6-(4-phenylbut-1-yn-1-yl)-morpholine-4-
carboxylate (2b). dH (500 MHz, CDCl3) 7.31e7.27 (2H, m), 7.22e7.20
(3H, m), 4.12 (1H, m), 4.02 (1H, br d, J¼12.5 Hz), 3.93 (1H, br d,
J¼12.5 Hz), 3.31e3.25 (1H, m), 2.85 (2H, t, J¼7.5 Hz), 2.79 (1H, app.
t, J¼12.5 Hz), 2.53 (2H, app. td, J¼7.5,1.5 Hz), 2.49 (1H, m),1.64e1.57
(1H, m), 1.53e1.47 (1H, m), 1.49 (9H, s), 0.98 (3H, t, J¼7.5 Hz); dC
(125 MHz, CDCl3) 154.5, 140.7, 128.6, 128.5, 126.5, 86.1, 80.3, 77.7,
77.5, 67.0, 49.0, 47.8, 35.1, 28.6, 26.3, 21.1, 9.6; nmax (liquid film)
3449, 2923, 2107,1703,1654, 1453,1419,1365,1232, 1171, 1084, 880,
699 cmꢀ1; MS (ESI): MNaþ, found 366.0. C21H29NO3 requires 366.1.
4.4. Propargylic acetates 3aed
4.4.1. 1-(2-(4-Methylphenylsulfonamido)ethoxy)-4-phenylbut-3-yn-
2-yl acetate (3a). dH (400 MHz, CDCl3) 7.74 (2H, d, J¼8.4 Hz),
7.45e7.42 (2H, m), 7.36e7.27 (5H, m), 5.73 (1H, dd, J¼7.2, 4.0 Hz),
5.05 (1H, m), 3.73e3.63 (2H, m), 3.61e3.53 (2H, m), 3.12 (2H, br dd,
J¼10.0, 5.6 Hz), 2.41 (3H, s), 2.13 (3H, s); dC (75 MHz, CDCl3) 170.2,
143.6, 137.0, 132.1, 129.9, 129.8, 129.1, 128.5, 127.2, 126.5, 121.8, 86.6,
83.3, 72.5, 69.8, 63.3, 42.9, 21.6, 21.2; nmax (liquid film) 3278, 1744,
4.3.3. tert-Butyl 2-isopropyl-6-(4-phenylbut-1-yn-1-yl)morpholine-
4-carboxylate (2c). dH (500 MHz, CDCl3) 7.31e7.27 (2H, m),
7.23e7.20 (3H, m), 4.10 (1H, br d, J¼10.5 Hz), 3.98 (2H, m), 3.06 (1H,
t, J¼7.5 Hz), 2.85 (2H, t, J¼7.5 Hz), 2.77 (1H, t, J¼12.5 Hz), 2.55 (3H,

5050
Q. Liang, J.K. De Brabander / Tetrahedron 67 (2011) 5046e5053
1492, 1371, 1329, 1228,1161, 1093, 815 cmꢀ1; MS (ESI): MNaþ, found
424.5. C21H23NSO5 found 424.2.
J¼11.2, 3.2 Hz), 2.41 (3H, s), 1.79 (2H, d, J¼1.6 Hz), 1.26e1.21 (2H, m),
1.17e1.16 (6H, m), 0.87 (3H, t, J¼7.2 Hz); dC (75 MHz, CDCl3) 143.6,
134.7, 129.4, 128.5, 73.5, 71.6, 68.4, 66.8, 46.7, 41.9, 31.5, 28.7, 28.4,
22.7, 21.7, 18.7, 14.2; nmax (liquid film) 2929, 2858, 1348, 1261, 1167,
1113, 937 cmꢀ1; MS (ESI): MNaþ, found 372.0. C19H27NSO3 requires
372.1.
4.4.2. 1-(2-(4-Methylphenylsulfonamido)ethoxy)-6-phenylhex-3-yn-
2-yl acetate (3b). dH (400 MHz, CDCl3) 7.73 (2H, d, J¼8.4 Hz), 7.27
(4H, app. t, J¼8.0 Hz), 7.21e7.17 (3H, m), 5.45 (1H, m), 4.90 (1H, br t,
J¼5.6 Hz), 3.56e3.44 (4H, m), 3.08 (2H, dd, J¼10.8, 6.0 Hz), 2.80 (2H,
t, J¼7.2 Hz), 2.49 (2H, td, J¼7.6, 2.0 Hz), 2.40 (3H, s), 2.07 (3H, s); dC
(75 MHz, CDCl3) 170.2, 143.6, 140.4, 137.0, 129.9, 128.6, 128.5, 127.2,
126.5, 87.0, 75.5, 72.6, 69.7, 63.2, 42.9, 34.8, 21.7, 21.2, 21.0; nmax
(liquid film) 2360, 1741, 1371, 1329, 1231, 1161, 1092, 1037, 815,
667 cmꢀ1; MS (ESI): MNaþ, found 452.1. C23H27NSO5 requires 452.1.
4.5.4. 3-(Hex-1-yn-1-yl)-4-tosylmorpholine (4d). dH (400 MHz,
CDCl3) 7.69 (2H, d, J¼8.4 Hz), 7.27 (2H, d, J¼8.4 Hz), 4.55 (1H, m),
3.88 (1H, dd, J¼11.6, 2.8 Hz), 3.82 (1H, app. d, J¼10.8 Hz), 3.70 (1H,
dd, J¼11.2, 2.8 Hz), 3.61 (1H, td, J¼11.6, 2.8 Hz), 3.46 (1H, m), 3.05
(1H, td, J¼11.6, 3.2 Hz), 2.41 (3H, s), 1.80 (2H, t, J¼6.8 Hz), 1.24e1.14
(4H, m), 0.81 (3H, t, J¼7.2 Hz); dC (75 MHz, CDCl3) 143.6, 134.7,
129.4, 128.5, 87.5, 73.4, 71.6, 66.9, 46.7, 41.9, 30.5, 22.1, 21.7, 18.4,
13.7; nmax (liquid film) 2929, 2859, 2360, 1598, 1444, 1346, 1261,
1167, 1111, 936 cmꢀ1; MS (ESI): MNaþ, found 344.3. C17H23NSO3
requires 344.2.
4.4.3. 1-(2-(4-Methylphenylsulfonamido)ethoxy)dec-3-yn-2-yl ace-
tate (3c). dH (400 MHz, CDCl3) 7.71 (2H, d, J¼8.4 Hz), 7.27 (2H, app.
t, J¼8.4 Hz), 5.46 (1H, m), 4.96 (1H, br t, J¼6.0 Hz), 3.57e3.45 (4H,
m), 3.07 (2H, m), 2.39 (3H, s), 2.17 (2H, td, J¼7.2, 1.6 Hz), 2.06 (3H, s),
1.49e1.42 (2H, m), 1.36e1.21 (6H, m), 0.86 (3H, t, J¼7.2 Hz); dC
(75 MHz, CDCl3) 170.3, 143.6, 137.1, 129.9, 127.2, 88.0, 74.5, 72.8,
69.7, 63.3, 43.0, 31.4, 28.6, 28.4, 22.7, 21.7, 21.2, 18.8, 14.2; nmax (thin
film) 3288, 2930, 1738, 1599, 1428, 1372, 1329, 130, 1160, 1092, 945,
814, 661 cmꢀ1; MS (ESI): MNaþ, found 432.2. C21H31NSO5 requires
432.1.
4.6. Propargylic acetates 5aeh
4.6.1. 1-(2-Hydroxyethoxy)-6-phenylhex-3-yn-2-yl acetate (5a). dH
(400 MHz, CDCl3) 7.30e7.25 (2H, m), 7.22e7.17 (3H, m), 5.54 (1H,
m), 3.71e3.55 (6H, m), 2.80 (2H, td, J¼7.6, 2.4 Hz), 2.51e2.46 (2H,
m), 2.09 (3H, s); dC (75 MHz, CDCl3) 170.3, 140.5, 128.6, 128.5, 126.5,
86.8, 75.6, 72.8, 72.7, 63.4, 61.8, 34.8, 21.2, 21.1; nmax (liquid film)
3455, 2931, 2239, 1741, 1495, 1454, 1371, 1231, 1131, 1037, 946,
748 cmꢀ1; MS (ESI): MNaþ, found 299.1. C16H20O4 requires 299.1.
4.4.4. 1-(2-(4-Methylphenylsulfonamido)ethoxy)oct-3-yn-2-yl ace-
tate (3d). dH (400 MHz, CDCl3) 7.75e7.71 (2H, m), 7.31e7.25 (2H,
m), 5.47 (1H, m), 4.93 (1H, br t, J¼6.0 Hz), 3.59e3.46 (4H, m),
3.13e3.05 (2H, m), 2.40 (3H, s), 2.18 (2H, td, J¼7.2, 2.0 Hz), 2.07 (3H,
s), 1.49e1.42 (2H, m), 1.40e1.31 (2H, m), 0.88 (3H, t, J¼7.2 Hz); dC
(75 MHz, CDCl3) 170.3, 143.6, 137.1, 129.9, 127.3, 88.0, 74.5, 72.8,
69.7, 63.3, 43.0, 30.5, 22.1, 21.7, 21.2, 18.5, 13.7; nmax (liquid film)
3284, 2933, 2873, 1743, 1431, 1372, 1330, 1231, 1161, 1093, 1037, 944,
815 cmꢀ1; MS (ESI): MNaþ, found 404.2. C19H27NSO5 requires 404.1.
4.6.2. 1-(2-Hydroxyethoxy)-4-phenylbut-3-yn-2-yl acetate (5b). dH
(400 MHz, CDCl3) 7.46e7.43 (2H, m), 7.36e7.26 (3H, m), 5.84 (1H,
dd, J¼4.0, 6.8 Hz), 3.88e3.73 (2H, m), 3.73e3.64 (4H, m), 2.10 (3H,
s); dC (75 MHz, CDCl3) 170.3, 132.1, 129.1, 128.5, 121.9, 86.6, 83.6,
72.9, 72.7, 63.5, 61.9, 21.2; nmax (liquid film) 3432, 2935, 2229, 1742,
1644, 1491, 1443, 1372, 1226, 1131, 1039, 844, 758, 692 cmꢀ1; MS
(ESI): MNaþ, found 271.1. C14H16O4 requires 271.1.
4.5. General procedure for the preparation of 3-substituted
morpholines 4aed
4.6.3. 1-(2-Hydroxyethoxy)dec-3-yn-2-yl acetate (5c). dH (400 MHz,
CDCl3) 5.55e5.53 (1H, m), 3.69e3.54 (6H, m), 2.31 (1H, br s), 2.15
(2H, td, J¼7.2, 2.0 Hz), 2.06 (3H, s), 1.48e1.41 (2H, m), 1.34e1.20 (6H,
m), 0.84 (3H, t, J¼6.0 Hz); dC (75 MHz, CDCl3) 170.2, 87.6, 74.6, 72.8,
72.7, 63.3, 61.6, 31.3, 28.5, 28.3, 22.5, 21.0, 18.7, 14.0; nmax (liquid
film) 3440, 2931, 2240, 1745, 1454, 1371, 1230, 1132, 1036 cmꢀ1; MS
(ESI): MNaþ, found 279.1. C14H24O4 requires 279.1.
To a 0.1 M solution of propargylic ester 3aed in THF at rt was
added [Cl2Pt(CH2CH2)]2 (2.5 mol %). The resulting yellow solution
was stirred for 3e4 h13 before being quenched by the addition of
NEt3 (0.5 mL/mmol substrate). The solution was concentrated in
vacuo and the crude material was filtered through a plug of silica gel.
4.5.1. 3-(Phenylethynyl)-4-tosylmorpholine (4a). dH (500 MHz,
CDCl3) 7.73 (2H, d, J¼8.5 Hz), 7.29e7.20 (5H, m), 6.99 (2H, dd, J¼8.5,
1.0 Hz), 4.79 (1H, m), 3.99 (2H, m), 3.83 (1H, dd, J¼11.0, 3.0 Hz), 3.70
(1H, td, J¼11.0, 3.0 Hz), 3.58 (1H, m), 3.18 (1H, td, J¼12.0, 3.0 Hz),
2.27 (3H, s); dC (75 MHz, CDCl3) 144.0, 134.4, 131.8, 129.6, 128.6,
128.4, 128.2, 122.2, 86.9, 82.8, 71.4, 66.9, 47.2, 42.3, 21.6; nmax (liquid
film) 2933, 1597, 1491, 1443, 1346, 1260, 1165, 1111, 936 cmꢀ1; MS
(ESI): MNaþ, found 364.3. C19H19NSO3 requires 364.1.
4.6.4. 1-(2-Hydroxyethoxy)oct-3-yn-2-yl acetate (5d). dH (400 MHz,
CDCl3) 5.55e5.52 (1H, m), 3.69e3.54 (6H, m), 2.34 (1H, br s),
2.18e2.13 (2H, m), 2.06 (3H, s), 1.47e1.39 (2H, m), 1.38e1.29 (2H,
m), 0.88e0.83 (3H, m); dC (75 MHz, CDCl3) 170.3, 87.7, 74.7, 72.9,
72.8, 63.4, 61.7, 30.5, 22.0, 21.2, 18.5, 13.7; nmax (liquid film) 3448,
2934, 2360, 1743, 1371, 1228, 1131, 1035 cmꢀ1; MS (ESI): MNaþ,
found 251.1. C12H20O4 requires 251.1.
4.5.2. 3-(4-Phenylbut-1-yn-1-yl)-4-tosylmorpholine (4b). dH (400
MHz, CDCl3) 7.65 (2H, d, J¼8.0 Hz), 7.27e7.17 (5H, m), 7.08 (2H, m),
4.55 (1H, m), 3.88e3.80 (2H, m), 3.68 (1H, dd, J¼11.2, 2.8 Hz), 3.60
(1H, td, J¼11.2, 2.8 Hz), 3.41 (1H, m), 2.98 (1H, td, J¼12.0, 3.2 Hz), 2.51
(2H, m), 2.38 (3H, s), 2.11 (2H, m); dC (75 MHz, CDCl3) 143.7, 140.5,
134.7, 129.3, 128.6, 128.5, 126.5, 86.6, 82.6, 74.3, 71.5, 66.8, 46.7, 41.9,
34.7, 21.8, 20.8; nmax (liquid film) 2921, 2858, 1598, 1494, 1453, 1346,
1261, 1166, 1110, 936 cmꢀ1; MS (ESI): MNaþ, found 392.2. C21H23NSO3
requires 392.1.
4.6.5. 1-(2-Hydroxy-2-phenylethoxy)-4-phenylbut-3-yn-2-yl acetate
(5e). dH (400 MHz, CDCl3) 7.45e7.25 (10H, m), 5.84 (1H, m), 4.91
(1H, m), 3.86e3.83 (2H, m), 3.75 (1H, m), 3.62e3.51 (1H, m), 2.93
(1H, m), 2.14 (3H, s); dC (75 MHz, CDCl3) 170.2, 139.9, 132.1, 129.1,
128.6, 128.5, 128.1, 126.3, 121.9, 86.7, 83.6, 77.6, 72.8, 72.7, 63.5, 21.2;
nmax (liquid film) 2913, 1745, 1491, 1443, 1371, 1226, 1129, 1028, 757,
700 cmꢀ1; MS (ESI): MNaþ, found 347.1. C20H20O4 requires 347.1.
4.6.6. 1-(2-Hydroxy-2-phenylethoxy)dec-3-yn-2-yl acetate (5f). dH
(400 MHz, CDCl3) 7.37e7.25 (5H, m), 5.58 (1H, m), 4.86 (1H, m),
3.73e3.69 (2H, m), 3.66 (1H, dd, J¼10.0, 3.2 Hz), 3.49 (1H, m), 2.95
(1H, dd, J¼6.4, 2.0 Hz), 2.18 (2H, m), 2.08 (3H, s), 1.48 (2H, m),
1.37e1.22 (6H, m), 0.87 (3H, t, J¼6.8 Hz); dC (75 MHz, CDCl3) 170.3,
140.0, 128.6, 128.1, 126.3, 88.0, 74.7, 73.0, 72.8, 72.7, 63.4, 31.4, 28.7,
4.5.3. 3-(Oct-1-yn-1-yl)-4-tosylmorpholine (4c). dH (400 MHz,
CDCl3) 7.71e7.68 (2H, m), 7.30e7.25 (2H, m), 4.55 (1H, m), 3.88 (1H,
dd, J¼11.2, 3.2 Hz), 3.83 (1H, m), 3.69 (1H, dd, J¼11.2, 3.2 Hz),
3.65e3.62 (1H, td, J¼11.6, 2.8 Hz), 3.47e3.41 (1H, m), 3.05 (1H, td,

Q. Liang, J.K. De Brabander / Tetrahedron 67 (2011) 5046e5053
5051
28.5, 22.7, 21.2, 18.9, 14.2; nmax (liquid film) 2930, 2858, 1743, 1453,
1371, 1230, 1128, 1028, 757, 700 cmꢀ1; MS (ESI): MHþ, found 333.2.
C20H28O4 requires 333.2.
86.8, 84.1, 78.3, 71.8, 70.0, 67.5; nmax (liquid film) 2962, 2852, 1490,
1450, 1311, 1116, 1075, 909, 756, 698 cmꢀ1; MS (ESI): MHþ, found
265.0. C18H16O2 requires 265.1.
4.6.7. 1-(2-Hydroxybutoxy)dec-3-yn-2-yl acetate (5g). dH (400 MHz,
CDCl3) 5.54 (1H, m), 3.72e3.60 (3H, m), 3.54 (1H, m), 3.32 (1H, m),
2.42 (1H, d, J¼2.8 Hz), 2.17 (2H, m), 2.08 (3H, s), 1.48e1.40 (4H, m),
1.36e1.23 (6H, m), 0.93 (3H, t, J¼6.4 Hz), 0.86 (3H, t, J¼6.4 Hz); dC
(75 MHz, CDCl3) 170.3, 87.9, 75.7, 74.8, 73.0, 71.7, 63.4, 31.4, 28.6,
28.4, 26.1, 22.6, 21.2, 18.8, 14.2, 10.0; nmax (liquid film) 2931, 2858,
1744, 1635, 1457, 1371, 1231, 1118, 1039 cmꢀ1; MS (ESI): Mþ, found
284.2. C16H28O4 requires 284.2.
4.7.6. 2-(Oct-1-yn-1-yl)-6-phenyl-1,4-dioxane (6f). dH (400 MHz,
CDCl3) 7.42e7.20 (5H, m), 4.64 (1H, dd, J¼10.4, 2.8 Hz), 4.54 (1H, ddd,
J¼10.4, 4.4, 2.0 Hz), 3.89 (1H, dd, J¼11.6, 2.8 Hz), 3.82 (1H, dd, J¼11.6,
2.8 Hz), 3.55 (1H, app. t, J¼10.8 Hz), 3.43 (1H, dd, J¼10.8, 10.4 Hz),
2.21 (2H, td, J¼7.2, 2.0 Hz),1.58e1.45 (2H, m),1.44e1.21 (6H, m), 0.88
(3H, t, J¼6.8 Hz); dC (75 MHz, CDCl3) 137.6, 128.6, 128.4, 126.7, 88.0,
78.2, 75.3, 71.7, 70.4, 67.4, 31.4, 28.7, 28.5, 22.7, 18.9, 14.2; nmax (liquid
film) 2957, 2929,1452,1305,1227,1116,1075, 911, 754, 698 cmꢀ1; MS
(ESI): MHþ, found 296.1. C18H24O2 requires 295.1.
4.6.8. 1-(2-Hydroxybutoxy)oct-3-yn-2-yl acetate (5h). dH (400 MHz,
CDCl3) 5.56e5.53 (1H, m), 3.72e3.59 (3H, m), 3.54 (1H, m), 3.2 (1H,
m), 2.42 (1H, br s), 2.18 (2H, m), 2.08 (3H, s), 1.51e1.28 (6H, m), 0.93
(3H, t, J¼7.2 Hz), 0.87 (3H, t, J¼7.2 Hz); dC (75 MHz, CDCl3) 170.3,
87.9, 75.7, 73.0, 72.9, 71.7, 63.5, 30.5, 26.1, 22.0, 21.2, 18.5, 13.7, 10.0;
nmax (liquid film) 2933, 1747, 1464, 1372, 1231, 1119, 1039 cmꢀ1; MS
(ESI): MNaþ, found 279.1. C14H24O4 requires 279.1.
4.7.7. 2-Ethyl-6-(oct-1-yn-1-yl)-1,4-dioxane (6g). dH (400 MHz,
CDCl3) 4.32 (1H, ddd, J¼10.4, 4.4, 2.0 Hz), 3.78 (1H, dd, J¼11.4,
2.8 Hz), 3.72e3.64 (1H, m), 3.51e3.43 (1H, m), 3.39 (1H, app. t,
J¼10.8 Hz), 3.20 (1H, app. t, J¼10.8 Hz), 2.19 (2H, td, J¼7.2, 2.0 Hz),
1.56e1.18 (10H, m), 0.93 (3H, t, J¼7.6 Hz), 0.87 (3H, t, J¼6.8 Hz); dC
(75 MHz, CDCl3) 87.7, 77.1, 75.4, 70.6, 70.5, 67.0, 31.4, 28.7, 28.5, 24.8,
22.7, 18.9, 14.2, 9.8; nmax (liquid film) 2960, 2931, 2853, 1456, 1320,
1101, 1077, 904 cmꢀ1; MS (ESI): MHþ, found 247.1. C14H24O2 re-
quires 247.1.
4.7. General procedure for the preparation of 3,5-substituted-
1,4-dioxanes 6aeh
To a 0.1 M solution of propargylic ester 5aeh in THF at rt was
added [Cl2Pt(CH2CH2)]2 (2.5 mol %). The resulting yellow solution
was stirred for 0.5e1.0 h13 before being quenched by the addition of
NEt3 (0.5 mL/mmol substrate). The solution was concentrated in
vacuo and the crude material was filtered through a plug of silica gel.
4.7.8. 2-Ethyl-6-(hex-1-yn-1-yl)-1,4-dioxane (6h). dH (400 MHz,
CDCl3) 4.32 (1H, d, J¼10.4 Hz), 3.78 (1H, dd, J¼11.2, 2.8 Hz), 3.69
(1H, m), 3.50e3.40 (1H, m), 3.39 (1H, app. t, J¼10.8 Hz), 3.20 (1H, t,
J¼10.8 Hz), 2.20 (2H, t, J¼7.2 Hz), 1.55e1.23 (6H, m), 0.93 (3H, t,
J¼7.5 Hz), 0.88 (3H, t, J¼7.3 Hz); dC (75 MHz, CDCl3) 87.7, 77.1, 75.5,
70.6, 70.5, 67.0, 30.7, 24.8, 22.2, 18.7, 13.8, 9.9; nmax (liquid film)
2961, 2933, 2853, 1464, 1320, 1101, 1077, 909 cmꢀ1; MS (ESI): MHþ,
found 197.0. C12H20O2 requires 197.1.
4.7.1. 2-(4-Phenylbut-1-yn-1-yl)-1,4-dioxane (6a). dH (400 MHz,
CDCl3) 7.30e7.27 (2H, m), 7.26e7.18 (3H, m), 4.31e4.28 (1H, m),
3.87e3.76 (2H, m), 3.70e3.55 (3H, m), 3.54e3.49 (1H, m),
2.86e2.81 (2H, m), 2.54e2.48 (2H, m); dC (75 MHz, CDCl3) 140.6,
128.6, 128.5, 126.6, 87.0, 76.5, 70.8, 66.6, 66.4, 65.9, 35.1, 21.1; nmax
(liquid film) 2962, 2854, 1603, 1453, 1338, 1260, 1119, 1091, 876,
699 cmꢀ1; MS (ESI): MNaþ, found 239.0. C14H16O2 requires 239.1.
4.8. Propargylic acetates 7aeg
4.8.1. 7-Phenyl-1-(sulfamoyloxy)hept-4-yn-3-yl acetate (7a). dH
(500 MHz, CDCl3) 7.33e7.27 (2H, m), 7.25e7.21 (3H, m), 5.49 (1H, t,
J¼7.0 Hz), 5.04 (2H, s), 4.25 (2H, m), 2.83 (2H, t, J¼7.0 Hz), 2.52 (2H,
td, J¼7.5, 1.5 Hz), 2.22e2.07 (2H, m), 2.09 (3H, s); dC (125 MHz,
CDCl3) 170.6, 140.6, 128.8, 128.7, 126.7, 105.0, 86.9, 67.1, 61.3, 34.8,
34.4, 21.3, 21.0; nmax (liquid film) 3335, 3281, 2933, 2246, 1728,
1559, 1372, 1241, 1183, 1020, 931, 751, 700 cmꢀ1; MS (ESI): MNaþ,
found 348.0. C15H19NSO5 requires 348.0.
4.7.2. 2-(Phenylethynyl)-1,4-dioxane (6b). dH (400 MHz, CDCl3)
7.45e7.44 (2H, m), 7.32e7.25 (3H, m), 4.56 (1H, dd, J¼8.8, 3.2 Hz),
3.95e3.89 (2H, m), 3.77e3.65 (4H, m); dC (75 MHz, CDCl3) 132.0,
128.9, 128.5, 122.2, 86.7, 84.5, 70.6, 66.6, 66.5, 66.0; nmax (liquid
film) 2853, 1491, 1443, 1337, 1263, 1119, 1092, 903, 874, 756,
691 cmꢀ1; MS (ESI): Mþ, found 187.9. C12H12O2 requires 188.0.
4.8.2. 1-Phenyl-5-(sulfamoyloxy)pent-1-yn-3-yl acetate (7b). dH
(400 MHz, CDCl3) 7.44e7.41 (2H, m), 7.33e7.25 (3H, m), 5.74 (1H, t,
J¼6.4 Hz), 5.34 (2H, s), 4.36 (2H, m), 2.34e2.23 (2H, m), 2.10 (3H, s);
dC (125 MHz, CDCl3) 170.6, 132.0, 129.1, 128.5, 121.8, 86.4, 85.1, 66.9,
61.3, 34.2, 21.1; nmax (liquid film) 3281, 2234, 1731, 1557, 1491, 1372,
1237, 1183, 1022, 932, 759 cmꢀ1; MS (ESI): MNaþ, found 319.9.
C13H15NSO5 requires 320.0.
4.7.3. 2-(Oct-1-yn-1-yl)-1,4-dioxane (6c). dH (400 MHz, CDCl3) 4.28
(1H, ddd, J¼8.8, 4.8, 2.4 Hz), 3.80 (2H, m), 3.68e3.61 (3H, m), 3.50
(1H, dd, J¼11.2, 8.8 Hz), 2.18 (2H, td, J¼7.2, 2.0 Hz), 1.47 (2H, td,
J¼15.2, 7.2 Hz),1.37e1.20 (6H, m), 0.85 (3H, t, J¼7.2 Hz); dC (75 MHz,
CDCl3) 87.8, 75.5, 70.9, 66.5, 66.0, 31.4, 28.7, 28.6, 22.7, 18.8, 14.2;
nmax (liquid film) 2958, 2885, 2245, 1452, 1337, 1259, 1120, 912,
877 cmꢀ1; MS (ESI): MHþ, found 197.1. C12H21O2 requires 197.1.
4.8.3. 8-Phenyl-2-(sulfamoyloxy)oct-5-yn-4-yl
acetate
(7c). dH
4.7.4. 2-(Hex-1-yn-1-yl)-1,4-dioxane (6d). dH (400 MHz, CDCl3)
4.28 (1H, ddd, J¼8.8, 4.8, 2.4 Hz), 3.86e3.76 (2H, m), 3.69e3.58 (3H,
m), 3.50 (1H, dd, J¼11.2, 8.8 Hz), 2.19 (2H, td, J¼7.2, 2.0 Hz),
1.50e1.45 (2H, m), 1.44e1.34 (2H, m), 0.87 (3H, t, J¼7.2 Hz); dC
(75 MHz, CDCl3) 87.8, 75.5, 70.9, 66.5, 66.0, 30.6, 22.1, 18.5, 13.7;
nmax (liquid film) 2959, 2856, 2359,1451,1336,1259,1119,1092, 915,
874 cmꢀ1; MS (ESI): MHþ, found 169.0. C10H16O2 requires 169.1.
(400 MHz, CDCl3) 7.30e7.25 (2H, m), 7.21e7.18 (3H, m), 5.34e5.29
(1H, m), 5.06e4.98 (1H, m), 4.82 (2H, s), 2.82 (2H, t, J¼7.6 Hz), 2.49
(2H, td, J¼8.0, 2.0 Hz), 2.10 (1H, ddd, J¼10.6, 8.8, 6.4 Hz), 2.02 (3H,
s), 1.81 (1H, ddd, J¼10.6, 8.8, 6.4 Hz), 1.25 (3H, d, J¼6.0 Hz); dC
(75 MHz, CDCl3) 170.7, 140.6, 128.6, 128.5, 126.5, 86.5, 77.7, 68.1,
62.8, 41.2, 34.9, 21.5, 21.1, 20.3; nmax (liquid film) 2360, 1722, 1371,
1243, 1043, 668 cmꢀ1; MS (ESI): MNaþ, found 361.9. C16H21NSO5
requires 362.1.
4.7.5. 2-Phenyl-6-(phenylethynyl)-1,4-dioxane (6e). dH (400 MHz,
CDCl3) 7.49e7.26 (10H, m), 4.80 (1H, dd, J¼10.4, 2.8 Hz), 4.72 (1H,
dd, J¼10.4, 2.6 Hz), 4.03 (1H, dd, J¼11.5, 2.8 Hz), 3.87 (1H, dd, J¼11.7,
2.7 Hz), 3.70 (1H, app. t, J¼10.8 Hz), 3.50 (1H, dd, J¼11.6, 10.8 Hz); dC
(75 MHz, CDCl3) 137.4, 132.1, 128.9, 128.6, 128.5, 128.4, 126.7, 122.2,
4.8.4. 1-Phenyl-5-(sulfamoyloxy)hex-1-yn-3-yl acetate (7d). dH
(400 MHz, CDCl3) 7.45e7.40 (2H, m), 7.35e7.15 (3H, m), 5.73 (1H,
dd, J¼8.0, 6.0 Hz), 5.12 (2H, s), 4.98e4.90 (1H, m), 2.38e2.27 (1H,
m), 2.15e2.03 (1H, m), 2.08 (3H, s), 1.53 (3H, d, J¼6.8 Hz); dC

5052
Q. Liang, J.K. De Brabander / Tetrahedron 67 (2011) 5046e5053
(75 MHz, CDCl3) 170.3,132.1,129.2,128.6,121.7, 86.7, 85.4, 77.6, 61.8,
41.5, 21.3, 21.2; nmax (liquid film) 3277, 2360, 1729, 1491, 1370, 1239,
1183, 1023, 918, 759, 692 cmꢀ1; MS (ESI): MNaþ, found 333.9.
C14H17NSO5 requires 334.1.
(75 MHz, CDCl3) 140.3, 128.6, 126.7, 86.2, 80.2, 76.6, 47.2, 38.5, 34.7,
21.1, 20.8; nmax (liquid film) 2388, 1414, 1360, 1189, 1069, 867,
700 cmꢀ1; MS (ESI): MNaþ, found 301.8. C14H17NSO3 requires 302.0.
4.9.4. 6-Methyl-4-(phenylethynyl)-1,2,3-oxathiazinane 2,2-dioxide
(8d). dH (400 MHz, CDCl3) 7.42e7.37 (2H, m), 7.36e7.25 (3H, m),
4.93e4.85 (1H, m), 4.73 (1H, app. t, J¼10.0 Hz), 4.22 (1H, d,
J¼10.0 Hz), 2.14 (1H, m), 1.86 (1H, dt, J¼14.4, 12.0 Hz), 1.45 (3H, d,
J¼6.4 Hz); dC (75 MHz, CDCl3) 132.0, 129.4, 128.6, 121.5, 86.0, 84.1,
80.3, 47.6, 38.2, 21.2; nmax (thin film) 3254, 2360, 1422, 1365, 1189,
1076, 929, 865, 758 cmꢀ1; MS (ESI): Mþ, found 250.9. C12H13NSO3
requires 251.0.
4.8.5. 2-(Sulfamoyloxy)dodec-5-yn-4-yl acetate (7e). dH (400 MHz,
CDCl3) 5.50e5.45 (1H, m), 4.95 (2H, s), 4.90e4.82 (1H, m),
2.26e2.18 (3H, m), 2.07 (3H, s), 1.95 (1H, ddd, J¼12.4, 8.8, 4.4 Hz),
1.53e1.45 (2H, m), 1.48 (3H, d, J¼6.4 Hz), 1.38e1.24 (6H, m), 0.87
(3H, t, J¼6.4 Hz); dC (75 MHz, CDCl3) 170.3, 88.2, 77.9, 76.8, 61.8,
41.8, 31.4, 28.7, 28.5, 22.7, 21.4, 21.3, 18.8, 14.2; nmax (liquid film)
3374, 2927, 2360, 1729, 1457, 1370, 1239, 1182, 1023, 923, 668 cmꢀ1
MS (ESI): MNaþ, found 342.1. C14H25NSO5 requires 342.1.
;
4.9.5. 6-Methyl-4-(oct-1-yn-1-yl)-1,2,3-oxathiazinane
2,2-dioxide
4.8.6. 1-((tert-Butyldiphenylsilyl)oxy)-2-(sulfamoyloxy)dodec-5-yn-
4-yl acetate (7f). dH (400 MHz, CDCl3) 7.78e7.55 (m, 4H), 7.42 (6H,
m), 5.48 (1H, m), 4.81 (3H, m), 3.87 (2H, d, J¼4.4 Hz), 2.32e2.08
(4H, m), 2.02 (3H, s), 1.56e1.40 (2H, m), 1.43e1.17 (6H, m), 1.06 (9H,
(8e). dH (400 MHz, CDCl3) 4.81 (1H, m), 4.45 (1H, m), 4.06 (1H, d,
J¼10.0 Hz), 2.16 (2H, td, J¼7.2, 2.0 Hz), 2.01 (1H, dt, J¼14.4, 2.4 Hz),
1.69 (1H, dt, J¼14.8, 12.0 Hz), 1.50e1.45 (2H, m), 1.44 (3H, d,
J¼6.8 Hz), 1.37e1.20 (6H, m), 0.88 (3H, t, J¼6.8 Hz); dC (75 MHz,
CDCl3) 87.1, 80.2, 75.6, 47.3, 38.6, 31.4, 28.6, 28.4, 22.7, 21.1, 18.7,
s), 0.87 (3H, t, J¼7.2 Hz); dC (75 MHz, CDCl3)
d170.0, 135.8, 135.7,
133.0, 132.7, 130.25, 130.22, 128.1, 88.1, 80.9, 76.6, 65.4, 61.8, 36.8,
14.2; nmax (liquid film) 2931, 2359, 1415,1363,1190, 1070, 869 cmꢀ1
;
31.4, 28.7, 28.5, 27.0, 22.7, 21.2, 19.4, 18.8, 14.2; nmax (liquid film)
MS (ESI): Mþ, found 259.0. C12H21NSO3 requires 259.1.
3279, 2930, 2857, 1730, 1427, 1370, 1236, 1185, 1112, 933, 702 cmꢀ1
MS (ESI): Mþ, found 573.2. C30H43NO6SSi requires 573.2.
;
4.9.6. 6-(((tert-Butyldiphenylsilyl)oxy)methyl)-4-(oct-1-yn-1-yl)-
1,2,3-oxathiazinane 2,2-dioxide (8f). dH (500 MHz, CDCl3) 7.82e7.59
(4H, m), 7.58e7.35 (6H, m), 4.77 (1H, m), 4.51 (1H, app. t,
J¼10.0 Hz), 4.09 (1H, d, J¼10.0 Hz), 3.79 (2H, d, J¼4.5 Hz), 2.20 (2H,
td, J¼17.0, 8.5 Hz), 2.04 (1H, dt, J¼14.5, 2.5 Hz), 1.92 (1H, dt, J¼14.5,
12.0 Hz),1.56e1.47 (2H, m),1.45e1.22 (6H, m), 1.08 (9H, s), 0.91 (3H,
t, J¼7.0 Hz); dC (125 MHz, CDCl3) 135.8, 135.7, 132.8, 132.7, 130.2,
128.1, 128.0, 87.3, 82.9, 75.8, 65.1, 47.2, 33.5, 31.4, 28.6, 28.4, 26.9,
22.7, 19.4, 18.7, 14.2; nmax (liquid film) 2927, 2855, 1718, 1427, 1374,
1191, 1113, 1067, 823, 702 cmꢀ1; MS (ESI): Mþ, found 513.1.
C28H39NSSiO4 requires 513.2.
4.8.7. 6-((tert-Butyldiphenylsilyl)oxy)-1-phenyl-5-(sulfamoyloxy)
hex-1-yn-3-yl acetate (7g). dH (400 MHz, CDCl3) 7.78e7.57 (4H, m),
7.52e7.20 (11H, m), 5.89e5.62 (1H, dd, J¼6.8, 6.0 Hz), 4.91 (2H, s),
4.88 (1H, dd, J¼7.6 Hz, 4.8 Hz), 3.91 (2H, d, J¼4.8 Hz), 2.45e2.21 (2H,
m), 2.05 (3H, s), 1.08 (9H, s); dC (75 MHz, CDCl3) 170.0, 135.9, 135.7,
133.0, 132.7, 132.1, 130.26, 130.24, 129.1, 128.5, 128.1, 121.9, 86.7,
85.4, 80.6, 65.4, 61.8, 36.6, 27.0, 21.2, 19.4; nmax (liquid film) 3389,
2931, 1731, 1428, 1371, 1233, 1186, 1113, 1022, 922, 758 cmꢀ1; MS
(ESI): MNaþ, found 588.5. C30H35NSiSO6 requires 588.2.
4.9. General procedure for the preparation of cyclic
sulfamates 8aeg
4.9.7. 6-(((tert-Butyldiphenylsilyl)oxy)methyl)-4-(phenylethynyl)-
1,2,3-oxathiazinane 2,2-dioxide (8g). dH (500 MHz, CDCl3) 7.88e7.60
(4H, m), 7.55e7.32 (11H, m), 4.96e4.64 (2H, m), 4.24 (1H, d,
J¼10.5 Hz), 3.81 (2H, br d, J¼4.5 Hz), 2.24e2.12 (1H, m), 2.06 (1H,
m), 1.10 (9H, s); dC (125 MHz, CDCl3) 135.85, 135.81, 132.8, 132.7,
132.09, 132.07, 130.2, 129.4, 128.7, 128.14, 128.13 121.5, 86.1, 84.2,
83.0, 65.2, 47.5, 33.2, 27.0, 19.5; nmax (liquid film) 3272, 2931, 1427,
1377, 1192, 1113, 1072, 873, 824, 702 cmꢀ1; MS (ESI): Mþ, found
505.0. C28H31NSSiO4 requires 505.2.
To a 0.1 M solution of sulfamate 7aeg in THF at rt was added
[Cl2Pt(CH2CH2)]2 (2.5 mol %). The resulting yellow solution was
stirred for 0.5e5.0 h13 before being quenched by the addition of NEt3
(0.5 mL/mmol substrate). The solution was concentrated in vacuo
and the crude material was filtered through a plug of silica gel.
4.9.1. 4-(4-Phenylbut-1-yn-1-yl)-1,2,3-oxathiazinane
2,2-dioxide
(8a). dH (400 MHz, CDCl3) 7.32e7.24 (2H, m), 7.23e7.18 (3H, m),
4.67 (1H, td, J¼12.0, 2.8 Hz), 4.51e4.47 (2H, m), 4.10 (1H, d,
J¼10.4 Hz), 2.80 (2H, t, J¼7.2 Hz), 2.49 (2H, app. td, J¼7.2, 1.6 Hz),
2.04e1.88 (2H, m); dC (75 MHz, CDCl3) 140.3, 128.6, 128.5, 126.6,
86.4, 76.0, 71.4, 47.8, 34.6, 31.2, 20.8; nmax (liquid film) 3268, 2360,
2089, 1651, 1417, 1368, 1188, 1061, 1012, 781 cmꢀ1; MS (ESI): MꢀHꢀ,
found 264.0. C13H15NSO3 requires 264.0.
Acknowledgements
We thank Justin Du Bois (Stanford University) for suggesting our
propargylic substitutions as an entry toward cyclic sulfamates and
Mina Razzak (UTSW) for help with preparing this manuscript. Fi-
nancial support was provided by the Robert A. Welch Foundation
(Grant I-1422), Reata Pharmaceuticals, and the NIH (Grant
CA90349).
4.9.2. 4-(Phenylethynyl)-1,2,3-oxathiazinane 2,2-dioxide (8b). dH
(400 MHz, CDCl3) 7.43e7.41 (2H, m), 7.38e7.30 (3H, m), 4.80e4.71
(2H, m), 4.56 (1H, ddd, J¼12.0, 4.8, 2.0 Hz), 4.49 (1H, d, J¼9.2 Hz),
2.25e2.14 (1H, m), 2.09e2.03 (1H, m); dC (75 MHz, CDCl3) 132.0,
129.4, 128.6, 121.5, 86.1, 84.1, 71.5, 48.2, 30.9; nmax (liquid film) 3263,
2360, 1491, 1420, 1373, 1189, 1064, 1002, 934, 874, 783, 758,
691 cmꢀ1; MS (ESI): MꢀHꢀ, found 235.9. C11H11NSO3 requires
236.0.
Supplementary data
Additional experimental details, spectroscopic data, and copies
of 1H and 13C NMR spectra for new compounds are available.
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2011.03.115.
References and notes
4.9.3. 6-Methyl-4-(4-phenylbut-1-yn-1-yl)-1,2,3-oxathiazinane 2,2-
dioxide (8c). dH (400 MHz, CDCl3) 7.32e7.28 (2H, m), 7.25e7.18 (3H,
m), 4.84e4.76 (1H, m), 4.43 (1H, app. td, J¼10.0, 2.0 Hz), 4.02 (1H, d,
J¼10.4 Hz), 2.80 (2H, t, J¼7.2 Hz), 2.48 (2H, td, J¼7.2, 2.0 Hz), 1.96
(1H, dt, J¼17.5, 2.0 Hz), 1.70e1.58 (1H, m), 1.40 (3H, d, J¼6.4 Hz); dC
1. For selected reviews and examples see: (a) Kumar, K.; Waldmann, H. Angew.
Chem., Int. Ed. 2009, 48, 3224e3242; (b) Nicolaou, K. C.; Chen, J. S. Pure Appl.
Chem. 2008, 80, 727e742; (c) Elliot, M. C. J. Chem. Soc., Perkin Trans. 1 2000,
1291e1318; (d) Sromek, A. W.; Kel’in, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed.
2004, 43, 2280e2282; (e) Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804e16805.

Q. Liang, J.K. De Brabander / Tetrahedron 67 (2011) 5046e5053
5053
2. (a) De Brabander, J. K.; Liu, B.; Qian, M. Org. Lett. 2008, 10, 2533e2536; (b) For
a cycloisomerization strategy towards spiroketals, tetrahydrofuranyl, and tet-
rahydropyranyl acetals from our laboratory, see: Liu, B.; De Brabander, J. K. Org.
Lett. 2006, 8, 4907e4910.
3. In an important precedent, it was demonstrated that replacement of the tet-
rahydropyran B-ring of the bryostatins with a dioxane heterocycle not only
significantly improved synthetic access, but also provided analogs with equal
or superior biological activity, see: Wender, P. A.; DeBrabander, J.; Harran, P. G.;
Jimenez, J.-M.; Koehler, M. F. T.; Lippa, B.; Park, C.-M.; Shiozaki, M. J. Am. Chem.
Soc. 1998, 120, 4534e4535.
(m) Tiecco, M.; Testaferri, L.; Marini, F.; Sternativo, S.; Santi, C.; Bagnoli, L.;
Temperini, A. Tetrahedron: Asymmetry 2003, 14, 2651e2657; (n) Takahata, H.;
Takahashi, S.; Kouno, S.-i.; Momose, T. J. Org. Chem. 1998, 63, 2224e2231; (o)
Lai, J.-Y.; Shi, X.-X.; Gong, Y.-S.; Dai, L.-X. J. Org. Chem. 1993, 58, 4775e4777.
12. For a review see: Wijtmans, R.; Vink, M. K. S.; Schoemaker, H. E.; van Delft, F. L.;
Blaauw, R. H.; Rutjes, F. P. J. T. Synthesis 2004, 641e662.
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