Synthesis of spiroacetals using functionalised titanium carbenoids

Article abstract of DOI:10.1016/j.tetlet.2008.05.094

Alkylidenation of lactones with functionalised titanium carbenoid reagents (Schrock carbenes) followed by acid-induced cyclisation of the resulting enol ethers constitutes a new method for the preparation of [4.4], [4.5] and [5.5] spiroacetals (1,6-dioxaspiro[4.4]nonanes, 1,6-dioxaspiro[4.5]decanes and 1,7-dioxaspiro[5.5]undecanes, respectively, sometimes termed 5,5-, 5,6- and 6,6-spiroketals). The titanium carbenoids are easily generated from readily available thioacetals.

Full text of DOI:10.1016/j.tetlet.2008.05.094

Tetrahedron Letters 49 (2008) 4771–4774
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of spiroacetals using functionalised titanium carbenoids
Calver A. Main a, Shahzad S. Rahman b, Richard C. Hartley a,
*
a WestChem, Department of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK
b GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Alkylidenation of lactones with functionalised titanium carbenoid reagents (Schrock carbenes) followed
by acid-induced cyclisation of the resulting enol ethers constitutes a new method for the preparation of
[4.4], [4.5] and [5.5] spiroacetals (1,6-dioxaspiro[4.4]nonanes, 1,6-dioxaspiro[4.5]decanes and 1,7-dioxa-
spiro[5.5]undecanes, respectively, sometimes termed 5,5-, 5,6- and 6,6-spiroketals). The titanium carbe-
noids are easily generated from readily available thioacetals.
Received 14 April 2008
Revised 8 May 2008
Accepted 20 May 2008
Available online 24 May 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Spiroketal
Spiroacetal
Lactone
Titanium
Schrock carbene
Thioacetal
Spiroacetals have attracted a great deal of interest as synthetic
targets as they are found widely in Nature and have a range of bio-
logical activities.1,2 We envisaged synthesising such compounds 4
by the alkylidenation of lactones 1 using titanium carbenoids 2
bearing a masked hydroxyl group, followed by cyclisation of the
resulting exocyclic enol ethers 3 in acid (Scheme 1).
Exocyclic enol ethers have been used to prepare spiroacetals by
cycloadditions,3–8 or through acid-induced cyclisation of alco-
hols.9–13 Such enol ethers have been prepared by cyclisation of
alcohols onto alkynes bearing an electron-withdrawing group,12
by E2 elimination of hemiacetal derivatives8,14 or b-alkoxyalkyl io-
dides,4 by Ramberg–Bäcklund rearrangement,9 by Wittig reaction
between exocyclic a
-alkoxyphosphorous ylides and aldehydes,10–12
and by methylenation of lactones5–7 using the Tebbe reagent,15
Petasis methylenation16 or Yan’s CH2Cl2–Mg–TiCl4 reagent sys-
tem.17 This last strategy is particularly relevant to our work as it
uses titanium carbenoids,18 but the titanium reagents employed
only introduced a methylene unit. In their pioneering work, Morti-
more and Kocienski used titanium carbenoids bearing THP-pro-
tected alcohols to alkylidenate acyclic esters and then induced
cyclisation to spiroacetals in acid.19 However, the titanium carbe-
noids were prepared from 1,1-dibromoalkanes,20 which were at
the time synthetically difficult to access,21 and alkylidenation of
lactones was reported to be slow and low yielding. Lactones are
attractive starting materials, as they are straightforward to prepare
by ring-closing metathesis,22 Baeyer–Villiger oxidation of cyclic
ketones23 and by oxidation of sugars,24 as well as by methods
which would be appropriate for preparation of acyclic esters.
R2
TiCp2
PGO
OPG
y
y
R2
We have previously shown that using Takeda’s procedure,25
a
O
O
2
R1
R1
O
range of functionalised titanium carbenoids18 can be generated
from easily prepared thioacetals. We had used titanium carbenoids
bearing masked oxygen nucleophiles,26,27 but exclusively for solid-
phase synthesis and never to prepare spiroacetals. As in this earlier
work,26 dithiane 6 was synthesised in two steps from 2-hydroxy-
benzaldehyde, and converted into a titanium carbenoid, presum-
ably titanium benzylidene 7, using low valent titanium reagent 5
(Scheme 2). Similarly, new titanium alkylidenes 9 and 11 were pre-
pared from dithiane 8 and thioacetal 10, respectively (Schemes 1
and 3). Titanium reagents 7, 9 and 11 (1.2 or 3 equiv) were then
used to alkylidenate a range of lactones 12–19 (Fig. 1) in dry THF
overnight to give enol ethers, which were immediately treated
x
3
x
1
H+
O
O
R2
x and y = 1 or 2
PG = acid-labile protecting group
R1
y
x
4
Scheme 1.
* Corresponding author. Tel.: +44 141 330 4398; fax: +44 141 330 4888.
E-mail address: richh@chem.gla.ac.uk (R. C. Hartley).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.05.094

4772
C. A. Main et al. / Tetrahedron Letters 49 (2008) 4771–4774
Table 1
S
4 eq. Cp2Ti[P(OEt)3]2
TiCp2
Entry Lactone Titanium Spiroacetal % Isolated yield
% Isolated yield
using 3 equiv
of titanium
reagent
5
S
reagent
using 1.2 equiv
of titanium
reagent
THF, 4 Å MS
X
OSiMe3
X
OSiMe3
6 X = H
8 X = Cl
7 X = H
9 X = Cl
1
2
3
4
5
6
7
8
9
12
12
13
14
13
14
12
15
16
17
18
19
7
9
9
9
11
11
11
7
20
21
22
23
24
25
26
27
28
29
30
31
46
46
51
33
44a
47
40
32
33a
54
48
49
53
54
62
44
52a
58
51
48
44a
65
57
61
Scheme 2.
4 eq. Cp2Ti[P(OEt)3]2
SPh
SPh
TiCp2
3
TBSO
TBSO
9
THF, 4 Å MS
10
11
12
11
11
7
10
11
Scheme 3.
a
Isolated yield of major diastereomer.
O
Ph
O
O
O
H
O
O
low diastereoselectivity when (+)-sclareolide 13 and
were treated with titanium alkylidene 11 followed by acid (entries
5 and 6). The transformation of sterically hindered -lactone 12
c-lactone 14
Ph
12
13
14
Ph
c
nC5H11
O
BnO
BnO
BnO
15
O
into [4.5] spiroacetal 26 proceeded well (entry 7). Alternatively,
[4.5] spiroacetals could be accessed from d-lactones (entries 8
and 9). Mixtures of anomeric spiroacetals were obtained from glu-
cose-derived lactone 15 and from d-lactone 16: the structures 27
and 28 were presumably the major isomers as they are stabilised
by the anomeric effect. The moderate diastereoselectivities agree
with those in the literature for [4.5] spiroacetals, including glu-
cose-derived [4.5] spiroacetals,8,9 produced in acid.31 [5.5] Spiro-
acetals 29 and 30 were prepared from dihydrocoumarin 17 and
coumarin 18, respectively, by the same method (entries 10 and
O
O
O
O
BnO
16
17
O
O
O
O
18
19
Figure 1.
11). Clearly an
a,b-unsaturated lactone presented no problem.
Cl
O
O
Cl
However, -lactone 19 gave the benzofuran 31 rather than a [5.6]
e
O
O
O
O
H
spiroacetal (entry 12).
The modest yields when using 1.2 equiv of the titanium alkylid-
enes 7, 9 and 11 were improved upon by using 3 equiv, but the
large quantity of triethyl phosphite used under the latter condi-
tions (12 equiv) hampered purification by chromatography. How-
ever, washing the crude spiroacetals with excess saturated
aqueous iron(III) chloride prior to chromatography removed the
triethyl phosphite and expedited purification.
Ph
Ph
Ph
20
21
22 dr = 50:50
Ph
O
O
Ph
O
O
Cl
Ph
O
O
H
23 dr = 50:50
24 dr = 73:27
nC5H11
25 dr = 63:37
In conclusion, we have developed a concise two-step method
for the conversion of c- and d-lactones into spiroacetals.
BnO
BnO
BnO
O
O
O
O
O
BnO
O
Acknowledgements
Ph
Ph
26
27 dr = 60:40
28 dr = 70:30
Cl
The authors gratefully acknowledge the EPSRC and GSK for
financial support.
HO
O
O
O O
References and notes
O
29
30
Figure 2.
31
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2).28,29 The results are summarised in Table 1.
c
-Lactones 12–14 were converted effectively into [4.4] spiro-
acetals 20–23 using titanium benzylidenes 7 and 9 (entries 1–4).
The transformation tolerates quaternary centres both to the car-
bonyl group and to the endocyclic oxygen atom, with no diffi-
a
a
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formation of spiroacetals 22 and 23 under thermodynamic control
are consistent with those reported for similar compounds in the
literature.1,30 [4.5] Spiroacetals 24 and 25 were also isolated with

C. A. Main et al. / Tetrahedron Letters 49 (2008) 4771–4774
4773
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Myers, A. G. J. Am. Chem. Soc. 2004, 126, 5436–5445.
22. Recent examples include: (a) Boxer, M. B.; Yamamoto, H. J. Am. Chem. Soc. 2007,
129, 2762–2763; (b) Canova, S.; Bellosta, V.; Bigot, A.; Mailliet, P.; Mignani, S.;
Cossy, J. Org. Lett. 2007, 9, 145–148; (c) Sakaguchi, H.; Tokuyama, H.;
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387–394; (j) Krishna, P. R.; Reddy, P. S. Tetrahedron 2007, 63, 3995–3999; (k)
4.21 (1H, apparent q, J 8.3 Hz), 4.35 (1H, ddd, J 2.9 Hz, 8.6 Hz and 9.9 Hz), 6.59
(1H, d, J 2.1 Hz), 6.79 (1H, dd, J 2.1 and 8.0 Hz), 7.00 (1H, d, J 8.0 Hz), 7.10–7.14
(4H, m), 7.18–7.27 (6H, m). dC (100 MHz, CDCl3): 36.59 (CH2), 37.97 (CH2),
61.39 (C), 65.54 (CH2), 110.16 (CH), 120.44 (CH), 120.98 (C), 124.01 (C), 124.80
(CH), 126.42 (CH), 126.53 (CH), 127.86 (CH), 127.94 (CH), 128.07 (CH), 128.21
(CH), 133.11 (C), 142.70 (C), 144.96 (C), 158.10 (C). m/z (CI+): 363 [(M+H)+
(
35Cl), 97%], 211 (100). HRMS: 363.1152 and 365.1132. C23H20O235Cl requires
(M+H)+ 363.1151, and C23H20O237Cl requires (M+H)+ 365.1122. (c) 22 (mixture
of epimers A and B), solid. mmax (Golden Gate)/cmꢀ1: 1479, 1610, 2866, 2925.
dH (400 MHz, CDCl3): 0.84 (3HA and B, s), 0.88 (6HB + 3HA, s), 0.91 (3HA, s), 1.20
and
(3HB, s), 1.35 (3HA, s), 0.99–2.12 (13HA
B, m), 2.21 (1HB, dd, J 3.4 and
10.1 Hz), 2.45 (1HA, dd, J 12.8 and 14.1 Hz), 3.20 (2HA, s), 3.23 (2HB, s), 6.76–
6.82 (2HA and B, m), 7.00–7.05 (1HA and B, m). dC (100 MHz, CDCl3): d 12.81 (CH3),
13.13 (CH3), 15.95 (CH2), 15.98 (CH2), 18.13 (CH2), 18.49 (CH2), 18.64 (CH3),
18.67 (CH3), 20.29 (CH3), 20.59 (CH3), 27.35 (CH2), 31.11 (CH3), 33.43 (CH2),
33.98 (CH2), 37.44 (CH2), 37.59 (CH2), 37.73 (CH2), 39.10 (CH2), 40.02 (CH2),
40.05 (CH2), 40.39 (CH2), 54.40 (CH), 54.70 (CH), 56.35 (CH), 58.77 (CH), 81.91
(C), 82.33 (C), 107.73 (CH), 107.77 (CH), 115.70 (C), 116.73 (C), 118.08 (CH),
122.07 (C), 122.26 (C), 122.63 (CH), 122.68 (CH), 130.75 (C), 130.79 (C), 155.97
(C), 156.49 (C). m/z (EI+): 374 [M+
(
35Cl), 78%], 191 (100). HRMS: 374.2013
and 376.1993.
C
23H31O235Cl requires 374.2018, and C23H31O237Cl requires
376.1989. (d) 23 (50:50 mixture of diastereomers A and B), oil. Rf [SiO2, pet.
ether–DCM (1:1)]: 0.76. mmax (Golden Gate)/cmꢀ1: 1451, 1594, 1609, 2915,
or
2950. dH (400 MHz, CDCl3): 2.01 (1HA B, dddd, J 4.4, 5.8, 9.7 and 12.4 Hz),
or
or
or
2.21–2.29 (3HA
B), 2.44–2.53 (3HA
B, m), 2.66 (1HA
B, qd, J 8.3 and
12.4 Hz), 3.29 (1HB, d, J 16.7 Hz), 3.34 (1HB, d, J 16.7 Hz), 3.36 (1HA, d, J
or or
16.6 Hz), 3.45 (1HA, d, J 16.6 Hz), 5.16–5.22 (1HA B, m), 5.34 (1HA B, dd,
J 5.9 and 7.8 Hz), 6.80–6.86 (2HA
B, m), 7.05–7.09 (1HA
B, m), 7.24–7.44
and
and
(5HA and B, m, ArH). dC (100 MHz, CDCl3): 32.28 (CH2), 33.75 (CH2), 35.60 (CH2),
37.62 (CH2), 37.77 (CH2), 37.88 (CH2), 80.61 (CH), 83.07 (CH), 109.58 (CH),
109.72 (CH), 118.73 (C), 118.97 (C), 119.93 (CH), 120.04 (CH), 123.94 (C),
123.96 (C), 124.51 (CH), 125.05 (CH), 125.36 (CH), 125.57 (CH), 126.97 (CH),
127.03 (CH), 127.83 (2xCH), 132.68 (C), 141.41 (C), 141.79 (C), 157.97 (C),
158.06 (C). m/z (CI+): 287 [(M+H)+
(
35Cl), 100%]. HRMS: 287.0839 and
289.0815. C17H16O235Cl requires (M+H)+ 287.0838, and C17H16O237Cl requires
(M+H)+ 289.0816. (e) 24 (major diastereomer), solid. mp: 116 °C (MeOH). ½a 1D8
ꢁ
+49.1 (c 0.1 M, DCM). mmax (Golden Gate)/cmꢀ1: 2931. dH (400 MHz, CDCl3):
0.78 (3H, s), 0.84 (3H, s), 0.86 (3H, s), 0.89–0.95 (2H, m), 1.05–1.12 (1H, m),
1.21 (3H, s), 1.21–1.77 (16H, m), 1.87 (1H, td, J 3.2 Hz and 11.3 Hz), 3.56 (1H, br
d, J 11.6 Hz), 3.89 (1H, dt, J 3.1 Hz and 11.3 Hz). dC (100 MHz, CDCl3): 15.18
(CH3), 18.37 (CH2), 19.62 (CH2), 20.53 (CH2), 21.08 (CH3), 23.07 (CH3), 25.30
(CH2), 33.11 (C), 33.53 (CH3), 36.02 (C), 36.89 (CH2), 37.05 (CH2), 39.75 (CH2),
40.40 (CH2), 42.50 (CH2), 57.10 (CH), 60.24 (CH), 62.74 (CH2), 82.31 (C), 106.04
(C). m/z (EI+): 306 (M+Å, 13%), 291 (M+ÅꢀÅCH3, 37), 111 (100). HRMS: 306.2559.
´
Alcaide, B.; Almendros, P.; del Campo, T. M.; Rodrıguez-Acebes, R. Adv. Synth.
Catal. 2007, 349, 749–758.
23. Recent examples include: (a) Kumar, I.; Rode, C. V. Tetrahedron: Asymmetry
2007, 18, 1975–1980; (b) Vuagnoux-D’Augustin, M.; Kehrli, S.; Alexakis, A.
Synlett 2007, 2057–2060.
24. Recent examples include: (a) Morimoto, N.; Ogino, N.; Narita, T.; Kitamura, S.;
Akiyoshi, K. J. Am. Chem. Soc. 2007, 129, 458–459 (Supplementary data); (b) El-
Badri, M. H.; Willenbring, D.; Tantillo, D. J.; Gervay-Hague, J. J. Org. Chem. 2007,
72, 4663–4672.
C
20H34O2 requires 306.2562. (f) 25 (63:37 mixture of diastereomers A and B),
oil. Rf [SiO2, 100% DCM]: 0.26. mmax (Golden Gate)/cmꢀ1
: 1461, 2894. dH
and
25. Horikawa, Y.; Watanabe, M.; Fujiwara, T.; Takeda, T. J. Am. Chem. Soc. 1997, 119,
1127–1128.
(400 MHz, CDCl3): 1.42–2.09 (9HA
B, m), 2.10–2.18 (1HB, m), 2.33–2.42
(1HA, m), 3.55–3.60 (1HA, m), 3.60–3.65 (1HB, m), 3.81 (1HA, dt, J 2.9 Hz and
11.3 Hz), 3.89 (1HB, dt, J 2.9 Hz and 11.5 Hz), 4.88 (1HB, dd, J 6.6 Hz and 9.6 Hz),
5.10 (1HA, t, J 7.1 Hz), 7.15–7.36 (5HA and B, m, Ph). dC (100 MHz, CDCl3): 20.23
(CH2), 20.27 (CH2), 25.30 (CH2), 25.37 (CH2), 33.17 (CH2), 33.86 (CH2), 33.96
(CH2), 34.40 (CH2), 37.89 (CH2), 39.59 (CH2), 61.89 (CH2), 61.99 (CH2), 79.47
(CH), 83.18 (CH), 105.94 (C), 106.29 (C), 125.84 (CH), 126.74 (CH), 127.43 (CH),
127.56 (CH), 128.44 (CH), 128.50 (CH), 143.29 (C), 143.44 (C). m/z (CI+): 219
[(M+H)+, 100%]. HRMS: 219.1385. C14H19O2 requires (M+H)+ 219.1384. (g) 26:
26. Macleod, C.; McKiernan, G. J.; Guthrie, E. J.; Farrugia, L. J.; Hamprecht, D. W.;
Macritchie, J.; Hartley, R. C. J. Org. Chem. 2003, 68, 387–401.
27. McKiernan, G. J.; Hartley, R. C. Org. Lett. 2003, 5, 4389–4392.
28. General procedure: Cp2TiCl2 (1.84 g, 7.4 mmol, 4.1 equiv), Mg (210 mg,
4.9 equiv, predried at 250 °C overnight) and freshly activated 4 Å molecular
sieves (0.5 g) were heated, gently, under reduced pressure (0.3 mmHg) for
about 1 min and then placed under argon. Dry THF (5 mL) was added followed
by dry P(OEt)3 (2.5 mL, 8.2 equiv). After stirring for 3 h at rt, a solution of
thioacetal 7, 9 or 11 (2.2 mmol, 1.2 equiv) in dry THF (2 mL) was added and
solid. mp: 85 °C. Rf [SiO2, hexane–DCM (1:1)]: 0.14.mmax (Golden Gate)/cmꢀ1
:
1442, 1490, 2941. dH (400 MHz, CDCl3): 1.02 (1H, br d, J 13.1 Hz), 1.50–1.92
(5H, m), 2.80–2.95 (2H, m), 3.72 (1H, br dd, J 4.1 and 11.0 Hz), 3.88 (1H, dt, J 2.6
and 11.1 Hz), 4.09 (1H, ddd, J 4.9, 8.6 and 10.0 Hz), 4.22 (1H, dt, J 6.6 and
8.7 Hz), 6.97–6.99 (2H, m), 7.12–7.36 (6H, m), 7.44–7.46 (2H, m). dC (100 MHz,
CDCl3): 19.14 (CH2), 23.88 (CH2), 29.61 (CH2), 39.11 (CH2), 60.15 (CH2), 60.67
(C), 62.56 (CH2), 105.68 (C), 124.58 (CH), 124.80 (CH), 126.26 (CH), 126.45
(CH), 127.61 (CH), 128.32 (CH), 144.22 (C), 145.38 (C). m/z (CI+): 295 (M+H+,
100%). HRMS: 295.1698. C20H23O2 requires M+H+, 295.1699. (h) 27: oil. Rf
stirring continued for 15 min.
A solution of one of the lactones 12–19
(1.8 mmol, 1 equiv) in dry THF (2 mL) was added, and the resulting mixture
stirred overnight at rt. Aqueous NaOH (1 M, 40 mL) was added and the
resulting suspension filtered through Celite, washing through with diethyl
ether. The mixture was extracted with ether, the combined organics were dried
over K2CO3 and the solvent removed under reduced pressure to give the crude
enol ether. 10% HCl–MeOH solution (1 mL concentrated aqueous HCl, 9 mL of
MeOH) was added and the mixture stirred at rt for 1.5–2 h, before pouring into
aqueous HCl (1 M) and extracting into dichloromethane. The combined
organics were dried over MgSO4 and the solvent removed under reduced
pressure and the mixture separated by column chromatography on silica to
give the corresponding spiroacetal 20–31. When 3 equiv of the titanium
reagent was used, a dichloromethane solution of the crude spiroacetal was
washed with 100 mL of saturated aqueous iron(III) chloride per gramme of
crude material prior to column chromatography.
[SiO2, hexane–ethyl acetate (4:1)]: 0.51. m
max (Golden Gate)/cmꢀ1: 1454, 1496,
1598, 2856, 2925. dH (400 MHz, CDCl3): 2.99 (1HB, d, J 16.3 Hz), 3.13 (1HA, d, J
B
16.4 Hz), 3.17 (1HB, d, J 16.3 Hz), 3.57 (1HA, d, J 16.1 Hz), 3.57–4.26 (6HA and
,
m), 4.41–5.50 (8HA
B, m) 6.71–7.40 (24HA
B, m, ArH). m/z (FAB+): 629
and
and
[(M+H)+, 100%]. HRMS: 629.2824. C41H40O6 requires 629.2821. (i) 28 (major
diastereomer), oil. Rf [SiO2, pet. ether–DCM (4:1)]: 0.36. mmax (Golden Gate)/
cmꢀ1: 1480, 1591, 1610, 2858, 2951. dH (400 MHz, CDCl3): 0.86 (3H, t, J 6.8 Hz),
1.20–1.41 (8H, m), 1.42–1.49 (1H, m), 1.65–1.80 (3H, m), 1.92–2.03 (2H, m),
2.98 (1H, d, J 16.3 Hz), 3.06 (1H, d, J 16.3 Hz), 3.91–3.99 (1H, m), 6.77–6.82 (2H,
m), 7.02 (1H, d, J 7.7 Hz). dC (100 MHz, CDCl3): 13.07 (CH3), 18.76 (CH2), 21.60
(CH2), 23.84 (CH2), 29.07 (CH2), 30.81 (CH2), 33.00 (CH2), 35.02 (CH2), 41.44
(CH2), 71.17 (CH), 109.41 (CH), 110.47 (C), 119.35 (CH), 124.00 (C), 124.40
29. Spectral data for spiroacetals: (a) 20: solid, mp: 142 °C (MeOH). mmax (Golden
Gate)/cmꢀ1: 1480, 1461, 1598, 2899. dH (400 MHz, CDCl3): 2.70 (1H, ddd, J
3.1 Hz, 7.8 Hz and 12.3 Hz), 3.17 (1H, d, J 17.4 Hz), 3.25 (1H, ddd, J 8.5 Hz,
9.9 Hz and 12.3 Hz), 3.57 (1H, d, J 17.4 Hz), 4.22 (1H, apparent q, J 8.2 Hz), 4.35
(1H, ddd, J 3.1 Hz, 8.6 Hz and 9.9 Hz), 6.61 (1H, d, J 8.0 Hz), 6.81 (1H, dt, J 0.7
and 7.5 Hz), 7.03 (1H, t, J 7.5 Hz), 7.10 (1H, d, J 7.3 Hz, H-7), 7.13–7.29 (10H, m,
Ar–H). dC (100 MHz, CDCl3): 37.32 (CH2), 38.39 (CH2), 61.36 (C), 65.42 (CH2),
109.59 (CH), 119.99 (C), 120.48 (CH), 124.43 (CH), 125.38 (C), 126.37 (CH),
126.56 (CH), 127.91 (CH), 128.00 (CH), 128.32 (CH), 128.40 (CH), 143.25 (C),
145.47 (C), 157.52 (C). m/z (EI+): 328 (M+, 6%), 194 (100). HRMS: 328.1463.
(CH), 131.98 (C), 158.17 (C). m/z (CI+): 295 [(M+H)+ 35Cl), 100%]. HRMS:
(
295.1465 and 297.1441. C17 H24O235Cl requires M+H+ 295.1461, and
C17H24O237Cl requires M+H+ 297.1438. (j) 29: oil. Rf [SiO2, pet. ether–DCM
(4:1)]: 0.22.mmax (Golden Gate)/cmꢀ1: 1456, 1491, 2845, 2874. dH (400 MHz,
CDCl3): 1.49–1.65 (4H, m), 1.72 (1H, dt, J 6.1 and 13.2 Hz), 1.77–1.83 (1H, m),
1.89 (1H, ddd, J 2.1, 6.4 and 13.4 Hz), 1.93–2.09 (1H, m), 2.53 (1H, ddd, J 1.9, 6.1
and 16.3 Hz), 2.93 (1H, ddd, J 6.4, 13.1, 16.3 Hz), 3.48–3.55 (1H, m), 3.73 (1H,
dt, J 3.3 Hz and 11.5 Hz), 6.72–6.81 (2H, m), 6.95–7.06 (2H, m). dC (100 MHz,
CDCl3): 18.49 (CH2), 21.04 (CH2), 25.27 (CH2), 31.94 (CH2), 34.83 (CH2), 61.84
(CH2), 95.89 (C), 116.99 (CH), 120.56 (CH), 122.75 (C), 127.08 (CH), 129.25
C
23H20O2 requires 328.1465. (b) 21: solid, mp: 138 °C. Rf [SiO2, pet. ether–DCM
(4:1)]: 0.19. mmax (Golden Gate)/cmꢀ1
:
1445, 1596, 1609, 2889, 2985. dH
(400 MHz, CDCl3): 2.65 (1H, ddd, J 2.9 Hz, 7.6 Hz and 12.1 Hz), 3.16 (1H, d, J
17.7 Hz), 3.25 (1H, ddd, J 8.7 Hz, 9.9 Hz and 12.2 Hz), 3.55 (1H, d, J 17.7 Hz),

4774
C. A. Main et al. / Tetrahedron Letters 49 (2008) 4771–4774
(CH), 152.26 (C). m/z (EI+): 204 (M+Å
13H16O2 requires 204.1151. (k) 30: oil. Rf [SiO2, pet. ether–DCM (4:1)]: 0.24.
max (Golden Gate)/cmꢀ1: 1458, 1488, 1638, 2851, 2923. dH (400 MHz, CDCl3):
1.50–1.73 (4H, m), 2.00–2.18 (2H, m), 3.55 (1H, dd, J 4.6 Hz and 11.0 Hz), 3.93
(1H, dt, J 3.2 and 11.6 Hz), 5.67 (1H, d, J 9.6 Hz), 6.57 (1H, d, J 9.6 Hz), 6.83 (1H,
t, J 7.4 Hz), 6.94 (1H, d, J 7.9 Hz), 7.06 (1H, dd, J 1.5 Hz and 7.5 Hz), 7.14 (1H, dt,
J 1.6 Hz and 7.7 Hz). dC (100 MHz, CDCl3): 18.55 (CH2), 24.77 (CH2), 35.07 (CH2),
61.79 (CH2), 95.38 (C), 116.53 (CH), 121.23 (C), 121.45 (CH), 125.47 (CH),
126.04 (CH), 127.02 (CH), 129.19 (CH), 151.45 (C). m/z (FAB+): 203 [(M+H)+,
100%]. HRMS: 203.1072. C13H15O2 requires M+H+ 203.1071. (l) 31: oil. Rf [SiO2,
hexane–DCM (4:1)]: 0.21. mmax (Golden Gate)/cmꢀ1: 1432, 1587, 2859, 2937,
,
89%), 131 (100). HRMS: 204.1150.
3387. dH (400 MHz, CDCl3): 1.33 (1H, s), 1.33–1.38 (2H, m), 1.46–1.53 (2H, m),
C
m
1.68 (2H, quin, J 7.6 Hz), 2.76 (2H, t, J 7.6 Hz), 3.51 (2H, t, J 6.6 Hz), 6.37 (1H, s),
7.04–7.13 (2H, m), 7.31 (1H, d, J 7.4 Hz), 7.38 (1H, dd, J 1.9 Hz and 7.8 Hz). dC
(100 MHz, CDCl3): 25.31 (CH2), 27.47 (CH2), 28.38 (CH2), 32.42 (CH2), 62.78
(CH2), 101.92 (CH), 110.69 (CH), 120.17 (CH), 122.38 (CH), 123.07 (CH), 128.93
(C), 154.58 (C), 159.32 (C). m/z (CI+): 205 [(M+H)+, 100%]. HRMS: 205.1229.
C
13H17O2 requires M+H+ 205.1225.
30. For example: Brimble, M. A.; Bryant, C. J. Chem. Commun. 2006, 4506–4508.
´
31. Doubsky, J.; Streinz, L.; Saman, D.; Zednık, J.; Koutek, B. Org. Lett. 2004, 6, 4909–
4911.