A rearrangement-cycloaddition approach to spiro-fused indanones

Article abstract of DOI:10.1016/j.tetlet.2010.12.086

Spiro-fused indanones were constructed using a [4 + 2]-cycloaddition approach from α-methylene indanone dienophiles, which were elaborated from 4-chromanone in a number of steps including a key rearrangement process. This type of spiro-fused structure for

Full text of DOI:10.1016/j.tetlet.2010.12.086

Tetrahedron Letters 52 (2011) 960–963
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A rearrangement–cycloaddition approach to spiro-fused indanones
⇑
William P. D. Goldring , Samira Bouazzaoui, John F. Malone
School of Chemistry and Chemical Engineering, Queen’s University Belfast, David Keir Building, Stranmillis Road, Belfast, Northern Ireland BT9 5AG, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
Spiro-fused indanones were constructed using a [4 + 2]-cycloaddition approach from a-methylene inda-
none dienophiles, which were elaborated from 4-chromanone in a number of steps including a key rear-
rangement process. This type of spiro-fused structure forms the central core ring system found in natural
products such as coleophomone A. The cycloaddition reactions using an a-methylene indanone dieno-
Received 16 November 2010
Revised 3 December 2010
Accepted 17 December 2010
Available online 24 December 2010
phile led to the exo diastereoisomer as the major cycloadduct, whereas the 1,4-dione based dienophile
predominantly led to the endo diastereoisomer.
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
Coleophomone
Diels–Alder cycloaddition
Rearrangement
Indanone
Spiro-fused ring system
The spiro-fused indanone unit, such as 2, is a structurally
unique ring system found at the core of the natural products cole-
ophomone A (1)1 and fredericamycin A.2 The construction of these
complex structures represents a synthetic challenge,3 which could
be achieved via a cycloaddition approach using a-methylene inda-
nones. Reports of the hetero-Diels–Alder based assembly of spiro-
get synthesis, we describe preliminary studies which have led to a
rearrangement–cycloaddition approach to spiro-fused indanones.
The antibacterial natural product coleophomone A (1), isolated
from the plant fungus Coleophoma sp.,1,6,7 possesses an 11-mem-
bered cyclic ether with an embedded spiro-fused indanone. Simpli-
fication of this intriguing natural structure reveals the core ring
system 2 (Scheme 1). Next, a retro-cycloaddition disconnection
on 2 leads to the dienophile 3 and the diene 4. Finally, the substi-
tuted indanone 3 could be elaborated from the indenone 5. Thus,
our retrosynthetic analysis reveals a unique opportunity for the
development of a [4 + 2]-cycloaddition approach to the spiro-fused
indanone core found in coleophomone A (1).
fused heterocyclic structures analogous to 2 have been limited to
reactions between
1,3-dienes,4 or 2-hydroxymethylene indanones and either
or
-azo-styrene.5
Therefore, based on this precedent and our interest in the devel-
opment of a synthesis of these structures, with applications in tar-
a-oxo sulfine derivatives of indanones and
a-nitro-
a
Our plan for the construction of spiro-fused indanone structures
demanded the preparation of
a-methylene substituted indanone-
based dienophiles, such as 9, which could be elaborated from
commercially available 4-chromanone (6). The first step in our
OH
O
O
O
O
O
O
O
HO
HO
OR
OBn
O
O
O
2
coleophomone A (1)
i, ii
iii
O
OH
OH
O
6
7, R = H
9
O
OH
8, R = Bn
OBn
OBn
O
O
5
3
4
OH
iv
HO
+
Scheme 1. Retrosynthetic analysis of coleophomone A (1) and the embedded spiro-
fused indanone core structure 2.
10
11
12
(1:3.6)
Scheme 2. Reagents and conditions: (i) AlCl3, 180 °C, 20 min; then 200 °C, 30 min,
75% (7); (ii) BnBr, TBAI, K2CO3, DMF, 99% (8); (iii) (CH2O)n, morpholine, AcOH, 80 °C,
93%; (iv) cyclopentadiene (10), toluene, 120 °C, 79% combined yield (11:12, 1:3.6).
⇑
Corresponding author. Tel.: +44 0 28 9097 4414; fax: +44 0 28 9097 6524.
E-mail address: w.goldring@qub.ac.uk (W.P.D. Goldring).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.12.086

W. P. D. Goldring et al. / Tetrahedron Letters 52 (2011) 960–963
961
NHPh
N
OBn
OBn
OBn
O
O
O
OBn
O
3' 4'
i
ii
TMSO
18
toluene
120 ºC, 53%
8
9
PhHNN
14
15
RO
O
13
H
19a, R = TMS
19b, R = H
O
O
OBn
O
O
iii
OBn
O
OTMS
OH
3' 4'
3'
4'
+
16
17
(6.1:1)
HO
20
21
22
Scheme 3. Reagents and conditions: (i) 13, MeONa, MeOH, 32%; (ii) CH2O(aq), 1,4-
dioxane, 46%; (iii) cyclopentadiene (10), toluene, 120 °C, 37% combined yield
(16:17, 6.1:1).
Scheme 4. Construction of the spiro-fused indanone 19a.
yield,17,18 together with 9% recovery of the starting dienophile 9
(Scheme 4). Based on our synthetic strategy (see Scheme 1) the
spiro-fused indanone 19a was formed with the appropriate regio-
chemistry for elaboration of coleophomone A (1).
The structures of the major cycloadducts 12, 16 and 19a were
determined using either single-crystal X-ray diffraction or 1D, 2D
and NOE NMR spectroscopy. For example, on the basis of COSY,
HMQC and NOE NMR data, the major adduct 16 was determined
to be the endo diastereoisomer. This assignment was based on
synthetic route involved the rearrangement of 6 into the indanone
7.2a,8 This was accomplished by heating a solvent-free melt of 6
and anhydrous aluminium chloride at 180 °C for 20 min, and then
at 200 °C for 30 min, to give 7-hydroxyindanone (7) in 75% yield
(Scheme 2). The yield of this reaction significantly depended on
the reaction time and temperature. For example, the product yield
decreased when the reaction time at either temperature was
increased. The phenol in 7 was alkylated using benzyl bromide in
the presence of tetrabutylammonium iodide and potassium car-
bonate in DMF to give the protected indanone 8 in quantitative
yield.2a Installation of the exocyclic alkene was achieved by treat-
ment of 8 with para-formaldehyde and morpholine in glacial acetic
acid to give the dienophile 9 in 93% yield.9,10 We were pleased to
discover the cycloaddition reaction between the enone 9 and
cyclopentadiene (10),11 conducted in refluxing toluene over 18 h,
gave a 1:3.6 mixture of the cycloadducts 11 and 12 in 79% com-
bined yield.
We next set our sights on the construction of the ene-dione 15,
which could be derived from the indanone 8, and the subsequent
[4 + 2]-cycloaddition studies. Our synthesis of 15 began with the
preparation of aldehyde 13 from phenylhydrazine and methylgly-
oxal 1,1-dimethyl acetal.12,13 Treatment of indanone 8 with so-
dium methoxide in methanol, followed by the aldehyde 13 gave
the enone 14 (Scheme 3). The ketone was then unmasked using
aqueous formaldehyde in 1,4-dioxane to give the ene-dione 15.
The structures 14 and 15 were assigned the Z-alkene geometry
based on the allylic coupling constants measured in the proton
NMR spectra (ca. 2.4 Hz).14 The cycloaddition reaction between
the ene-dione 15 and cyclopentadiene (10) was conducted in
refluxing toluene over 18 h to give a 6.1:1 mixture of the cycload-
ducts 16 and 17 in 37% combined yield.15
0
0
NOE NMR enhancements observed between H7a and H3b, H2 and
0
the geminal proton H7b (Fig. 1), and supported by selected proton
NMR coupling constants. The minor adduct 17 was tentatively as-
signed as the exo diastereoisomer. In contrast, the major adduct 12
was determined to be the exo diastereoisomer based on a single-
crystal X-ray structure (Fig. 2).19 The minor adduct 11 was tenta-
tively assigned as the endo diastereoisomer. The differences we ob-
served in the diastereoselectivity of the cycloaddition reactions
using the dienophiles 9 and 15 presumably reflects the product
stability in the case of exo-12 (from 9) or the degree of orbital over-
lap between the diene 10 and dienophile 15, as in the case of endo-
16. The substitution pattern of the dienophile is known to govern
the diastereoselectivity of the reaction.20
The adduct 19a was determined to be the exo diastereoisomer,
with pseudo-ortho regiochemistry, which was consistent with the
electron-withdrawing properties of the dienophile and the elec-
tron-donating properties of the diene. The regiochemical assign-
ment was based on COSY and HMQC NMR data recorded for 19a.
For example, the strong COSY correlations between all the protons
on C-30 and C-40 clearly indicated the two methylene groups were
adjacent. It is unlikely these correlations would be observed for the
regioisomer 22. Furthermore, selected carbon NMR data reported
for the isomeric cyclohexenols 20 and 21 supported our regio-
chemical assignment.21 For example, the strong correlation be-
tween the chemical shift values reported for the carbons C-30 and
C-40 in 20 and the corresponding values recorded for the adduct
19a supported our assignment (Table 1). The relative stereochem-
ical assignment of the adduct 19a, as the exo diastereoisomer, was
Based on the success of these preliminary cycloaddition studies
we attempted to employ the enone 14 as the dienophile in a
reaction with the diene 10. Unfortunately, none of the desired
cycloadduct was isolated, and only the starting dienophile was
recovered. Furthermore, our attempts to employ furan as a diene
in cycloaddition reactions using the dienophiles 9 and 15 met with
similar frustration.
0
based on the NOE NMR enhancements observed between H1 and
The success of the cycloaddition reactions using cyclopentadi-
ene (10) and the dienophiles 9 and 15, led us to study the regiose-
lectivity of this reaction using a non-symmetrical diene substrate.
For example, we chose to investigate the cycloaddition reaction
between the dienophile 15 and the diene 18, which was prepared
from crotonaldehyde and chlorotrimethylsilane using zinc chloride
and triethylamine.16 Unfortunately, only the starting ene-dione 15
was recovered when the reaction was performed in a sealed tube,
or under the conditions described earlier. However, we were
pleased to discover the cycloaddition reaction between the enone
9 and the diene 18 led exclusively to the adduct 19a in 53%
H3a'
O
H1'
OBn
H
OBn
H
O
O
H5'
H
1'
H6'
H2'
H3b
H
H3b
3b' OTMS
H7b'
H7a'
16
19a
Figure 1. Selected NOE NMR enhancements observed for the cycloadducts 16 and
19a.

962
W. P. D. Goldring et al. / Tetrahedron Letters 52 (2011) 960–963
Acknowledgements
We gratefully acknowledge the Nuffield Foundation and
Queen’s University Belfast for their financial support.
References and notes
1. (a) Wilson, K. E.; Tsou, N. N.; Guan, Z.; Ruby, C. L.; Pelaez, F.; Gorrochategui, J.;
Vicente, F.; Onishi, H. R. Tetrahedron Lett. 2000, 41, 8705–8709; (b) Kamigaichi,
T.; Nakajima, M.; Tani, H. Japanese Patent JP 10101666 A, 1998; Chem. Abstr.
1998, 129, 236773.
2. (a) Boger, D. L.; Jacobson, I. C. J. Org. Chem. 1990, 55, 1919–1928; (b) Pandey, R.
C.; Toussaint, M. W.; Stroshane, R. M.; Kalita, C. C.; Aszalos, A. A.; Garretson, A.
L.; Wei, T. T.; Byrne, K. M.; Geoghegan, R. F., Jr.; White, R. J. J. Antibiot. 1981, 34,
1389–1401.
3. For examples of the construction of spiro-fused indan-1,3-diones from 3-
ylidenephthalides, see: Watanabe, M.; Morimoto, H.; Tomoda, M.; Iwanaga, U.
Synthesis 1994, 1083–1086.
4. (a) Morita, H.; Takeda, M.; Yoshimura, T.; Fujii, T.; Ono, S.; Shimasaki, C. J. Org.
Chem. 1999, 64, 6730–6737; (b) Rewinkel, J. B. M.; Zwanenburg, B. Recl. Trav.
Chim. Pays-Bas 1990, 109, 190–196; (c) Lenz, B. G.; Regeling, H.; Zwanenburg, B.
Tetrahedron Lett. 1984, 25, 5947–5948.
5. (a) Hegazi, S.; Titouani, S. L.; Soufiaoui, M.; Tahdi, A. Tetrahedron 2004, 60,
10793–10798; (b) Salaheddine, H.; Titouani, S. L.; Soufiaoui, M.; Tahdi, A.
Tetrahedron Lett. 2002, 43, 4351–4353.
6. For the isolation of related members of this family of natural products, see:
Kamigaichi, T.; Nakajima, M.; Tani, H. Japanese Patent JP 11158109 A, 1999;
Chem. Abstr. 1999, 131, 378444.
7. For the syntheses of related members of this family of natural products,
including coleophomones B, C and D, see: (a) Nicolaou, K. C.; Montagnon, T.;
Vassilikogiannakis, G.; Mathison, C. J. N. J. Am. Chem. Soc. 2005, 127, 8872–
8888; (b) Nicolaou, K. C.; Montagnon, T.; Vassilikogiannakis, G. Chem. Commun.
2002, 2478–2479; (c) Nicolaou, K. C.; Vassilikogiannakis, G.; Montagnon, T.
Angew. Chem., Int. Ed. 2002, 41, 3276–3281.
8. (a) Deady, L. W.; Desneves, J.; Kaye, A. J.; Thompson, M.; Finlay, G. J.; Baguley, B.
C.; Denny, W. A. Bioorg. Med. Chem. 1999, 7, 2801–2809; (b) Hauser, F. M.; Zhou,
M. J. Org. Chem. 1996, 61, 5722; (c) Loewenthal, H. J. E.; Schatzmiller, S. J. Chem.
Soc., Perkin Trans. 1 1975, 2149–2157; (d) Loudon, J. D.; Razdan, R. K. J. Chem.
Soc. 1954, 4299–4303.
Figure 2. ORTEP representation of the cycloadduct exo-12 at the 50% probability
level.
9. (a) Milagre, C. D. F.; Milagre, H. M. S.; Santos, L. S.; Lopes, M. L. A.; Moran, P. J. S.;
Eberlin, M. N.; Rodrigues, J. A. R. J. Mass Spectrom. 2007, 42, 1287–1293; (b)
Kim, M. Y.; Lim, G. J.; Lim, J. I.; Kim, D. S.; Kim, I. Y.; Yang, J. S. Heterocycles 1997,
45, 2041–2043.
Table 1
Selected carbon NMR chemical shift data for the cyclohexenes 19a, 20 and 21a
19a
20
21
10. For a synthesis of
a-methylene indanones and related structures, see: (a)
C-30
C-40
29.0
22.8
32.4
22.4
44.8
38.8
Chatani, N.; Kamitani, A.; Oshita, M.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc.
2001, 123, 12686–12687; (b) Bhattacharya, A.; Segmuller, B.; Ybarra, A. Synth.
Commun. 1996, 26, 1775–1784; (c) Muckensturm, B.; Diyani, F. J. Chem. Res. (M)
1995, 2544–2556; (d) Gras, J.-L. Tetrahedron Lett. 1978, 19, 2111–2114.
11. For the preparation of cyclopentadiene (10) from the corresponding dimer, see:
Magnusson, G. J. Org. Chem. 1985, 50, 1998, and references cited therein.
12. Severin, T.; Adam, R. Chem. Ber. 1975, 108, 88–94.
a
The 13C NMR (25 MHz) data for compounds 20 and 21 were recorded in CDCl3
(see Ref. 21c).
13. For a related method to access the ene-dione 15, see: Severin, T.; Kullmer, H.
Chem. Ber. 1971, 104, 440–448.
0
0
H3a , and between H3b and H3b (see Fig. 1), and supported by se-
lected proton NMR coupling constants.
14. Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. Spectrometric Identification of
Organic Compounds, 5th ed.; John Wiley & Sons: New York, 1991, p 221.
15. Purification of the mixture using flash column chromatography gave the major
isomer 16 and an inseparable 1:1 mixture of the isomers 16 and 17. In our
hands, the minor isomer 17 could not be separated from the mixture.
16. (a) Gaonac’h, O.; Maddaluno, J.; Chauvin, J.; Duhamel, L. J. Org. Chem. 1991, 56,
4045–4048; (b) Paterson, I.; Price, L. G. Tetrahedron Lett. 1981, 22, 2833–2836.
In summary, the indanone-based dienophiles 9 and 15 were
constructed and successfully employed in [4 + 2]-cycloaddition
reactions leading to the spiro-fused indanone structures exo-12,
endo-16 and exo-19a. The structures of the major adducts endo-
16 and exo-19a were assigned based on COSY, HMQC and NOE
NMR data, and that of exo-12 was based on a single-crystal X-ray
structure determination. The cycloaddition reactions using the
-methylene indanone 9 preferentially formed the exo adducts,
for example, 12 and 19a, while in contrast, the reaction which
employed the -methylene indanone 15 preferentially formed
the endo adduct, for example, 16. To the best of our knowledge,
the results of these preliminary studies represent the first cycload-
dition-based approach to carbocyclic spiro-fused indanones, and
have established the precedent for future applications in synthesis.
Work is now underway to optimize the reaction conditions,
evaluate different methods, and expand this synthetic approach
to include other substrates. Furthermore, we plan to exploit the
regio- and diastereoselective cycloaddition reaction between 9
and the diene 18, leading to the adduct 19a, in the construction
of a spirocyclic system, cf. 2, for elaboration of coleophomone A
(1). A full account of our cycloaddition approach to spiro-fused
indanones, together with our progress towards the natural prod-
uct, will be disclosed in due course.
17.
A
neat sample of the silyl ether 19a, stored at 5 °C over 40 weeks, was
quantitatively converted into the secondary alcohol 19b.
18. Satisfactory spectroscopic data were recorded for all synthesised compounds
reported in this Letter.
a
Data recorded for the endo-adduct 11: colourless film; Rf = 0.67 (2% Et2O in
toluene); mmax (film/cmꢀ1) 3048, 2951, 2926, 2856, 1700, 1599, 1475, 1275,
736; dH (400 MHz, CDCl3) 7.53–7.51 (2H, m, 2 ꢁ ArH), 7.45 (1H, dd, J 8.0 and
7.5, ArH), 7.39–7.35 (2H, m, 2 ꢁ ArH), 7.31–7.27 (1H, m, ArH), 6.97 (1H, dd, J 7.5
and 0.6, ArH), 6.81 (1H, d, J 8.1, ArH), 6.40 (1H, dd, J 5.5 and 3.0, CH@CH), 6.07
(1H, dd, J 5.5 and 3.0, CH@CH), 5.22 (2H, s, PhCH2O), 3.29 (1H, d, J 17.0, CHH),
3.16 (1H, d, J 17.0, CHH), 3.02–3.01 (1H, m, CH), 2.60 (1H, dd, J 2.5 and 1.5, CH),
1.75 (2H, m, CH2), 1.60–1.58 (1H, m, CHH), 1.55–1.52 (1H, m, CHH); dC
(100 MHz, CDCl3) 205.7 (s), 156.8 (s), 154.7 (s), 137.9 (d), 136.6 (s), 135.6 (d),
133.0 (d), 128.6 (d), 127.6 (d), 126.7 (d), 125.6 (s), 118.2 (d), 110.8 (d), 70.0 (t),
55.5 (s), 54.7 (d), 50.2 (t), 44.1 (t), 43.6 (d), 40.0 (t); m/z (ES) 339.1343 (M++Na,
100%, C22H20O2Na requires 339.1361).
Data recorded for the exo-adduct 12: colourless solid; mp 91–92 °C (EtOAc);
Rf = 0.77 (2% Et2O in toluene); mmax (KBr/cmꢀ1) 3067, 2954, 2930, 1701, 1590,
1498, 1298, 1030, 733; dH (500 MHz, CDCl3) 7.54–7.52 (2H, m, ArH), 7.43 (1H,
dd, J 8.1 and 7.6, ArH), 7.40–7.37 (2H, m, 2 ꢁ ArH), 7.31–7.27 (1H, m, ArH), 6.92
(1H, dd, J 7.5 and 0.7, ArH), 6.79 (1H, d, J 8.1, ArH), 6.42 (1H, dd, J 5.6 and 3.0,
CH@CH), 6.23 (1H, dd, J 5.6 and 3.0, CH@CH), 5.27 (2H, s, PhCH2O), 3.02 (1H, d, J
17.5, CHH), 3.00–2.98 (1H, m, CH), 2.79–2.78 (1H, m, CH), 2.78 (1H, d, J 17.5,
CHH), 2.40 (1H, br d, J 8.6, CHH), 2.34 (1H, dd, J 11.5 and 3.6, CHCHHCH), 1.37
a

W. P. D. Goldring et al. / Tetrahedron Letters 52 (2011) 960–963
963
(1H, dq, J 8.4 and 1.5, CHH), 1.15 (1H, dd, J 11.5 and 2.9, CHCHHCH); dC
(125 MHz, CDCl3) 208.0 (s), 157.0 (s), 155.1 (s), 140.7 (d), 136.6 (s), 135.8 (d),
135.6 (d), 128.6 (d), 127.7 (d), 126.7 (d), 125.1 (s), 118.1 (d), 110.6 (d), 70.1 (t),
55.7 (s), 51.3 (d), 47.0 (t), 43.4 (d), 41.5 (t), 41.1 (t); m/z (ES) 339.1353 (M++Na,
100%, C22H20O2Na requires 339.1361).
Data recorded for the endo-adduct 16: brown solid; mp 96–98 °C (EtOAc);
Rf = 0.37 (20% EtOAc in pentane); mmax (KBr/cmꢀ1) 3064, 2960, 2924, 2853,
1700, 1600, 1456, 1261, 1096, 802; dH (500 MHz, CDCl3) 7.55 (2H, m, 2 ꢁ ArH),
7.47 (1H, t, J 7.8, ArH), 7.42–7.39 (2H, m, 2 ꢁ ArH), 7.33–7.30 (1H, m, ArH), 6.93
(1H, dd, J 7.5 and 0.6, ArH), 6.83 (1H, d, J 8.2, ArH), 6.60 (1H, dd, J 5.5 and 3.0,
CH@CH), 6.25 (1H, dd, J 5.5 and 3.0, CH@CH), 5.28 (2H, s, OCH2Ph), 3.77 (1H, d, J
2.9, CHCOCH3), 3.15 (1H, d, J 1.0, CH), 2.83–2.82 (3H, m, C(4°)CH2 and CH),
2.30–2.28 (1H, m, CHH), 1.91 (3H, s, CH3), 1.33 (1H, dt, J 8.7 and 1.6, CHH); dC
(125 MHz, CDCl3) 209.3, 205.4, 157.1, 155.1, 139.8, 136.3, 136.2, 135.3, 128.5,
127.7, 126.5, 118.0, 110.6, 69.9, 62.0, 53.0, 46.4, 45.1, 36.2, 31.6; m/z (ES)
381.1487 (M++Na, 100%, C24H22O3Na requires 381.1467).
2920, 2851, 1677, 1597, 1480, 1270, 1056, 779; dH (400 MHz, CDCl3) 7.55–7.52
(2H, m, ArH), 7.48 (1H, t, J 7.8, ArH), 7.41–7.37 (2H, m, 2 ꢁ ArH), 7.32–7.30 (1H,
m, ArH), 7.01 (1H, dd, J 8.2 and 0.6, ArH), 6.79 (1H, d, J 8.2, ArH), 5.81–5.76 (1H,
m, CH@CH), 5.81 (1H, dq, J 10.1 and 2.0, CH@CH), 5.24 (2H, s, PhCH2O), 4.77–
4.76 (1H, m, CHOH), 3.33 (1H, d, J 17.3, CHH), 2.82 (1H, d, J 17.3, CHH), 2.21–
2.17 (2H, m, C(4°)CH2CH2), 2.01–1.93 (1H, m, C(4°)CHHCH2), 1.59–1.55 (1H, m,
C(4°)CHHCH2); dC (100 MHz, CDCl3) 207.9 (s), 157.1 (s), 156.9 (s), 136.6 (s),
136.5 (d), 130.8 (d), 118.7 (d), 110.4 (d), 70.1 (t), 70.0 (d), 54.2 (s), 31.6 (t), 29.1
(t), 22.9 (t); m/z (ES) 343.1308 (M++Na, 100%, C21H20O3Na requires 343.1310).
19. Crystal data for 12:
b = 15.715(7), c = 18.402(10) Å, U = 1612.8(2) Å3, T = 150(2) K, Mo-K
radiation, k = 0.71073 Å, space group P212121 (no. 19), Z = 4, F(0 0 0) = 672,
Dx = 1.303 g cmꢀ3 = 0.082 mmꢀ1
measured/independent reflections:
C22H20O2, M = 316.4, orthorhombic, a = 5.577(2),
a
,
l
,
12,324/2734, Rint = 0.084, direct methods solution, full-matrix least squares
refinement on F2o, anisotropic displacement parameters for non-hydrogen
atoms; all hydrogen atoms located in
a difference Fourier synthesis but
Data recorded for the exo-adduct 19a: colourless film; Rf = 0.68 (50% EtOAc in
included at positions calculated from the geometry of the molecules using the
riding model, with isotropic vibration parameters. R1 = 0.045 for 2319 data
petroleum ether);
m
max (film/cmꢀ1) 3048, 3024, 2968, 2927, 2839, 1733, 1699,
1600, 1227, 1069, 737; dH (500 MHz, CDCl3) 7.53–7.51 (2H, m, 2 ꢁ ArH), 7.43
with Fo > 4r(Fo), 217 parameters, xR2 = 0.123 (all data), GoF = 1.13,
(1H, t, J 7.8, ArH), 7.39–7.35 (2H, m, 2 ꢁ ArH), 7.30–7.27 (1H, m, ArH), 6.97 (1H,
D
q
min,max = ꢀ0.39/0.37 e Åꢀ3. The racemic sample is a spontaneously resolved
br dt,
J
7.5 and 0.7, ArH), 6.74 (1H, d,
J
8.1, ArH), 5.74–5.72 (1H, m,
conglomerate comprising individual crystals that are enantiopure (R,R,R) and
(S,S,S). Crystallographic data (excluding structure factors) for this structure
have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 797032. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK, (fax: +44 (0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
20. Berson, J. A.; Hamlet, Z.; Mueller, W. A. J. Am. Chem. Soc. 1962, 84, 297–304.
21. (a) Donaldson, L. R.; Haigh, D.; Hulme, A. N. Tetrahedron 2008, 64, 4468–4477;
(b) Liotta, D.; Zima, G.; Saindane, M. J. Org. Chem. 1982, 47, 1258–1267; (c)
Magnusson, G.; Thorén, S. J. Org. Chem. 1973, 38, 1380–1384.
CH(OH)CH@CH), 5.55–5.52 (1H, m, CH(OH)CH@CH), 5.26 (2H, d,
PhCH2O), 4.65–4.62 (1H, m, CHOSi(CH3)3), 3.34 (1H, d, J 17.2, CHH), 2.73 (1H,
d, 17.2, CHH), 2.17–2.13 (2H, m, C(4°)CH2CH2), 2.04–1.98 (1H, m,
J 5.1,
J
C(4°)CHHCH2), 1.59–1.55 (1H, m, C(4°)CHHCH2), ꢀ0.10 (9H, s, C(CH3)3); dC
(125 MHz, CDCl3) 208.1 (s), 157.6 (s), 156.9 (s), 136.9 (s), 136.2 (d), 132.2 (d),
128.7 (d), 127.7 (d), 127.4 (d), 126.7 (d), 125.8 (s), 118.5 (d), 110.3 (d), 71.0 (d),
70.0 (t), 54.3 (s), 32.3 (t), 29.0 (t), 22.8 (t), 0.0 (q).
Data recorded for the alcohol 19b: pale yellow solid; mp = 193–195 °C (EtOAc);
Rf = 0.29 (80% EtOAc in petroleum ether); mmax (KBr/cmꢀ1) 3469, 3032, 2952,