A general, concise, 'collective' approach to eudesmanolide sesquiterpenoids: Total synthesis of bioactive atractylenolides I-IV and related natural products

Article abstract of DOI:10.1016/j.tetlet.2015.08.045

Total synthesis of seven bioactive atractylenolide-type eudesmanolides from Hagemann's ester, following, a short, scalable, adaptable, and diversity oriented protocol, has been accomplished. This effort opens a gateway to access through synthesis an exceptionally potent and promising group of natural products and their congeners of contemporary interest.

Full text of DOI:10.1016/j.tetlet.2015.08.045

Tetrahedron Letters 56 (2015) 5545–5548
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Tetrahedron Letters
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A general, concise, ‘collective’ approach to eudesmanolide
sesquiterpenoids: total synthesis of bioactive atractylenolides
I–IV and related natural products
⇑
Subburethinam Ramesh, Goverdhan Mehta
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Total synthesis of seven bioactive atractylenolide-type eudesmanolides from Hagemann’s ester, follow-
ing, a short, scalable, adaptable, and diversity oriented protocol, has been accomplished. This effort opens
a gateway to access through synthesis an exceptionally potent and promising group of natural products
and their congeners of contemporary interest.
Received 28 July 2015
Revised 11 August 2015
Accepted 16 August 2015
Available online 21 August 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Sesquiterpenoid synthesis
Eudesmanolides
Atractylenolides
RCM
c
-lactone annulation
Dried root and stem of Atractylis ovata and Atractylodes japonica
Indeed, atractylenolides in general and ATL I–IV 2–5 in particu-
lar pack a remarkably impressive range of bioactivity attributes
which have witnessed a massive resurgence of interest in recent
years evidenced through a spate of observations and publications.3
A few notable examples: in vivo study on lung carcinoma cell line
(A549), ATL-I 2, and ATL-III 4 effectively suppressed tumor growth
with up-regulation of caspase-3, caspase-9, and Bax and down-reg-
ulation of Bcl-2 and Bcl-XL and activated the mitochondria-medi-
ated death pathway, respectively.3g,c Similarly, ATL-I 2 induces
apoptosis by inactivating Notch1, Jagged1, and its downstream
Hes1/Hey1 and attenuating gastric cancer stem cell traits.3j
Powerful neuroprotection activity of ATL-III 4 manifests through
inhibition of glutamate-induced neuronal apoptosis3h and
preventing learning and memory loss induced by high
homocysteine levels in experimental animals.3n Thus, it is quite
evident that atractylenolides I–IV or their close structural siblings
are poised to evolve into therapeutic candidates for a variety of
disorders of contemporary concern like cancer and
neurodegeneration.
(known in Chinese as cangzhu) and from a related plant species
Atractylodes macrocephala koidz (known in Chinese as baizhu) are
part of the traditional Chinese medicine (TCM) and used in diverse
disorders like chronic asthenia, spleen qi deficiency, anorexia, dys-
pepsia, and excessive perspiration among others.1,2 Following the
first isolation of a eudesmane sesquiterpene atractylon 1,1 from
these plant species over half a century ago, a steady stream of
bioactive eudesmanolides like atractylenolides (ATL) I 2, II 3, and
III 4 have been unraveled from the same sources. Emergent
world-wide interest in TCM with the intent to scientifically explore
new therapeutic possibilities, while validating their efficacy in pre-
viously observed indications, through modern biology probes has
rekindled interest in atractylenolides I–IV 2–5 (Fig. 1) which are
regarded as the main bioactive constituents of Atractylodes macro-
cephala responsible for anti-tumor, anti-inflammatory, anti-bacte-
rial, and anti-aging properties.
More recently, bioactivity assay guided fractionation of the
extracts of Atractylodes macrocephala and other plants like Sarcan-
dra glabra, Lindera strychnifolia, and some Chloranthus species have
led to the isolation of several eudesmanolides 6–9 closely related
to atractylenolides and are presented in Figure 1.2
These developments underscore the need for accessing ATLs
I–IV through enabling total syntheses which will concurrently
facilitate full exploration of chemical space around their scaffold.
However, it was quite surprisingly to find that synthesis efforts
toward atractylenolides have been sporadic although the first syn-
thesis was accomplished nearly five decades ago. Minato and
Nagasaki were the first to achieve a total synthesis of atractylon
⇑
Corresponding author. Tel.: +91 40 23134848; fax: +91 40 23010785.
E-mail address: gmehta43@gmail.com (G. Mehta).
1
and atractylenolide II 3 from a-tetralone precursor 10,
http://dx.doi.org/10.1016/j.tetlet.2015.08.045
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

5546
S. Ramesh, G. Mehta / Tetrahedron Letters 56 (2015) 5545–5548
H
O
RCM
O
O
O
O
H
O
O
O
O
H2
H
H
H
O
O
O
1
2
3
Atractylon
Atractylenolide I
Atractylenolide II
H
H
H
H
16
3
O
15
14
lactone
Wittig rxn.
Atractylenolide II
annulation
OH
O
H
O
OH
O
O
O
O
1,4-addition
O
O
HO
HO
HO
O
H
H
H
6
4
5
N
MeO
H
EtO2C
Hydroxy
Atractylenolide III Atractylenolide IV
O
atractylenolide III
O
12
13
Hagemann's
Ester
Grignard rxn.
OH
OH
OH
H
H
O
O
O
O
O
Scheme 2. Retrosynthetic analysis for atractylenolide II.
O
O
H
HO
H
H
O
7
8
9
side arms with requisite stereodisposition through 1,4-vinyl addi-
tion, carbonyl protection, conversion of the ester moiety into
Weinreb amide (12 ? 13) and allylation (13 ? 14), respectively.
Further advance toward the target required implementation of
RCM protocol (14 ? 15), a few routine interventions including a
Wittig olefination would lead to 16, Scheme 2. Finally, a direct
Chlorantholide B
LinderolideH
Serralactone C
Figure 1. Representative examples of eudesmanolide sesquiterpenoids.
Scheme 1.4a Honan achieved a synthesis of 1 from
a
-tetralone 114b
regioselective Tanabe5
c-lactone annulation was to be imple-
and most recently Baldwin group reported
a
synthesis of
atractylenolides I–III also from
a-tetralone 10 following a
mented on 16 to furnish atractylenolide II 3, Scheme 2.
modified/shortened version4c of the Minato protocol, Scheme 1.
To operationalize the theme delineated in Schemes 2, 1,4-vinyl-
cuprate addition on Hagemann’s ester 12 was carried out to install
the quaternary center in a stereoselective manner as described
previously6a to deliver 17, Scheme 3. The carbonyl group in 17
was protected as ketal 18 and the ester moiety in it was
activated as Weinreb amide 13.6b Addition of allylmagnesium
bromide to 13 led to the allylketone 14 and set the stage to
execute the RCM protocol. Exposure of 14 to UMICORE M2
catalyst7 smoothly and efficiently delivered the trans-decalone
15, Scheme 3 which was to serve as the key common intermediate
in the diverse syntheses reported here.8
In the light of the prevailing scenario of limited options for gain-
ing synthetic access to eudesmanolides 1–9, we ventured to devise
a de novo approach to this family of natural products which
embraces the elements of brevity, flexibility, and is intrinsically
diversity oriented. In this Letter, we divulge our strategy which
enables amplification of chemical space around this bioactive scaf-
fold and has culminated in the total syntheses of as many as seven
atractylenolides and related natural products.
Contours of our proposed synthetic strategy were unveiled
through the retrosynthetic analysis directed toward atractyleno-
lides II 3 depicted in Scheme 2 and could be traced to versatile,
commercially available Hageman’s ester 12. Evolution of 12
toward the projected objective envisaged setting-up of the quater-
nary carbon center and installation of two terminal olefin bearing
In the initial foray toward the synthesis of atractylenolides I–III,
unsaturated decalone 15 was catalytically hydrogenated to 19 and
further Wittig olefination with the ylide derived from methyltriph-
enylphosphonium bromide led quite smoothly to 20.8 Ketal depro-
tection in 20 gave 16 and was subjected to Ti+4 mediated
regioselective one pot Tanabe c
-lactone annulation5 to furnish nat-
ural product atractylenolide II 39 quite uneventfully, Scheme 4.8 To
fully reaffirm the structure of 3 we also carried out a routine X-ray
crystal structure determination on it.10 Atractylenolides I 2 and III
4 were prepared from synthetic natural product 3. For this
1. Minato and Nagasaki synthesis (1966)4a - 20 steps
H
CN O
OMe
O
O
O
H
H
3
O 10
NC
Atractylenolide II
O
2. Honan'ssynthesis (1985)4b - 14 steps
O
O
c
a
b
O
O
O
EtO2C
EtO2C
EtO2C
OMe
O
12
18
O
17
OMe
H
H
1
CO2H
MeO2C
Atractylon
O
O
O
11
e
d
O
2003 4c 12 steps
) -
O
O
3.
Baldwin et. al synthesis (
OMe
N
MeO
H
O
H
H
H
O
O
O
O
O
13
14
15
H
H
O
3
Scheme 3. (a) VMB, CuBrÁMe2S, THF, À78 °C, 92%; (b) ethylene glycol, pTSA,
benzene, reflux, 8 h, 95%; (c) MeNHOMeÁHCl, BuLi, HMDS, THF, À10 °C to rt, 94%; (d)
allylmagnesium bromide, À78 °C, THF, 1 h, 86%; (e) UMICORE M2 (3 mol %), rt, 7 h,
92%.
10
Atractylenolide II
Scheme 1. Earlier synthetic approaches to atractylenolides.

S. Ramesh, G. Mehta / Tetrahedron Letters 56 (2015) 5545–5548
5547
O
O
H
O
O
O
O
b
c
a
d
b
c
a
d
O
O
O
O
O
O
O
H
O
H
H
H
H
H
H
H
H
HO
O
O
O
O
O
15
16
19
3
20
22
23
15
e
O
O
O
O
O
e
O
O
O
H
H
H
ORTEP of 3
Atractylenolide II
7
25
24
Chlorantholide B
OH
O
Scheme 6. Reagents and conditions: (a) DBU (0.5 equiv), DCM, 0 °C–rt, 12 h, 93%;
(b) MeLi, THF, À78 °C, 1 h, 89% (dr ratio = 8:2); (c) PCC, DCM, rt, 12 h, 74%; (d) pTSA/
O
Si
O
g
f
O
O
O
acetone, rt, 5 h, 90%; (e) TiCl4, Bu3N, DCM,
46%.
a,a-dimethoxyacetone, À78 °C to rt, 17 h,
H
H
H
21
2
4
Atractylenolide III
AtractylenolideI
As the last example of the present total synthesis campaign, we
selected linderolide H 8 as an important objective to test our plat-
form for targeted functionalization and functional group compati-
bility, necessary for chemical space exploration. In the event, we
reverted to the precursor 14 and stereoselective carbonyl reduction
led to the diastereomer 26 (dr = 9:1). Carbonyl deprotection to 27
Scheme 4. Reagents and conditions: (a) H2/Pd on C (10 mol %), EtOAc, rt, 5 h, 93%;
(b) PPh3CH3Br, tBuOK, toluene, reflux, 2 h, 87%; (c) pTSA, acetone, rt, 9 h, 97%; (d)
TiCl4, Bu3N, DCM,
a,a-dimethoxyacetone, À78 °C to rt, 17 h, 63%; (e) TBDMSOTf,
Et3N, DCM, 0 °C–rt, 48 h; (f) mCPBA, DCM, rt, 2 h, 63% (overall 2 steps); (g) MsCl,
Et3N, 0 °C–rt, 1 h, 82%.
and Tanabe c
-lactone annulation gave 28, Scheme 7.8 RCM in 28 pro-
transformation, 3 was converted4c to TBDMS protected tricyclic
hydroxyfuran 21 and further peracid oxidation readily delivered
natural product 49 which was dehydrated in methanesulfonyl
chloride–TEA milieu to install the double bond and deliver
atractylenolide I 2,9 Scheme 4.8
For the amplification of our atractylenolides synthesis theme,
natural products atractylenolide IV 5 and hydroxyatractylenolide
6, which are very scarce in Nature, were chosen as next targets
for synthesis. Our one step preparation of 5 and 6 from readily
available synthetic precursors 3 and 4, respectively, confirms their
formulation and makes them available for further biological evalu-
ation. Thus, catalytic OsO4-mediated dihydroxylation of 3 deliv-
ered 59 quite efficiently.8 Similarly, SeO2 allylic oxidation in 4
was regio- and stereoselective and led to 6,9 Scheme 5.8
We now turned attention to more functionally embellished
atractylenolide-type natural product chlorantholide B 7, recently
isolated from Chloranthus elatior.2d Toward this end, multi-
purpose intermediate 15 came quite handy. DBU mediated
double bond isomerization in 15 to conjugated enone 22 and
chemoselective 1,2-addition of methyllithium led to the tertiary
alcohol 23. An oxidative transposition in 23 employing PCC
delivered the enone 24, Scheme 6.8
ceeded well with low loading of UMICORE M2 catalyst7 and 29 was
readily obtained and its stereostructure was secured through single
crystal X-ray structure determination.10 Oxidation of the secondary
hydroxyl group in 29 to enone 30 and chemoselective mCPBA oxida-
tion furnished epoxide stereoselectively. Silica-gel promoted epox-
ide opening in 31 delivered natural product linderolide H 8.8,9 It was
considered appropriate at this stage to reconfirm the structure of 8
through X-ray crystal structure determination.10
In summary, we have outlined the total synthesis of seven
atractylenolide-type natural products through an approach which
is short, sleek, and efficacious and provides access to a precious
group of bioactive natural products by circumventing tedious iso-
lation procedures. Our strategy is eminently geared to scale-up
and analoging for exploring the full biological potential of these
exceptional chemical entities. Lastly, as Hagemann’s ester is avail-
able in both its enantiomeric forms, the approach delineated here
is well poised to deliver the chiral variants of the natural products.
O
H
O
O
a
c
b
O
14
O
O
H
H
H
H
HO
Carbonyl deprotection in 24 to 25 and regio- and chemoselec-
HO
HO
O
27
28
30
tive Tanabe c
-lactone annulations5 delivered the natural product
26
(dr ratio 9:1)
chlorantholide B 79 quite uneventfully.8
H
H
O
O
e
d
O
OsO4 (10 mol %)
H
H
O
O
NMO(2 equiv)
H
OH
O
O
O
29
ORTEP of 29
Dioxane/H2O (4:1)
12h, 50 oC, 77%
H
HO
H
OH
3
5
OH
H
H
Atractylenolide II
Atractylenolide IV
O
O
f
g
O
O
H
OH
O
OH
O
H
H
SeO2
O
O
8
O
O
Dioxane, 80 oC
1h, 74%
ORTEP of 8
31
Linderolide H
HO
H
H
6
4
Scheme 7. Reagents and conditions: (a) NaBH4, CeCl3Á7H2O, MeOH, 5 h, 0 °C–rt,
87%; (b) pTSA (10 mol %), acetone, rt, 6 h, 93% (c) TiCl4, Bu3N, DCM, À78 °C to rt,
62%; (d) UMICORE M2 (1.5 mol %), DCM, rt, 7 h, 89%; (e) PCC, MS, DCM, rt, 91%; (f)
mCPBA (2.5 equiv), DCM, 0 °C–rt; (g) SiO2, EtOAc, 50 °C, 10 h, 72%, (overall 2 steps).
hydroxyatractylenolide III
Atractylenolide III
Scheme 5. Synthesis of atractylenolide IV and hydroxyatractylenolide III.

5548
S. Ramesh, G. Mehta / Tetrahedron Letters 56 (2015) 5545–5548
Acknowledgments
8. All compounds reported here are racemic and were fully characterized on the
basis of IR, 1H NMR, 13C NMR and HRMS spectral data. Spectral data of final
compounds are given here while the rest are included in the Supplementary
material.
S.R. wishes to thank the University Grants Commission (UGC,
India) for the award of Dr. D. S. Kothari post-doctoral fellowship.
G.M. acknowledges the research support from Eli Lilly and Jubi-
lant-Bhartia Foundations. We also acknowledge the cooperation
of Indo-French joint laboratory at Indian Institute of chemical
Technology, Hyderabad in this endeavor.
Compound 2. IR (KBr): 2945, 1739, 1287, 1025, 1260, 1106, 724 cmÀ1 1H NMR
;
(400 MHz, CDCl3) 5.63 (s, 1H), 4.94 (s, 1H), 4.65 (s, 1H), 2.69–2.74 (m, 1H),
2.51–2.59 (m, 1H), 2.35–2.42 (m, 2H), 2.04–2.09 (m, 1H), 1.93 (s, 3H), 1.67–
1.75 (m, 4H), 0.96 (s, 3H); 13C NMR (400 MHz, CDCl3) 171.2, 148.2, 148.0, 147.9,
120.3, 119.0, 107.3, 48.3, 39.0, 38.0, 36.1, 22.9, 22.5, 18.4, 8.3; HRMS (ESI-MS)
calcd for C15H18O2; 231.1385 (M+H), found 231.1381. Compound 3. IR (KBr):
2926, 2854, 1753, 1682, 1435, 1331, 1227, 1084, 882 cmÀ1 1H NMR (400 MHz,
;
CDCl3) 4.86 (s, 1H), 4.80–4.85 (m, 1H), 4.59 (s, 1H), 2.71 (dd, J = 13.8 & 3.4 Hz,
1H), 2.35–2.38 (m, 1H), 2.26–2.33 (m, 2H), 1.93–2.00 (m, 1H), 1.84–1.88 (m,
1H), 1.81 (s, 3H), 1.56–1.63 (m, 3H), 1.26–1.34 (m, 1H), 1.12 (t, J = 11.9 Hz, 1H),
0.88 (s, 3H); 13C NMR (100 MHz, CDCl3) 174.9, 162.6, 148.6, 120.3, 107.0, 78.1,
50.1, 47.7, 41.0, 37.1, 36.4, 25.8, 22.5, 16.5, 8.3; HRMS (ESI-MS) calcd for
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.08.
045.
C
15H20O2; 255.1361 (M+Na), found 255.1363. Compound 4. IR (KBr): 3347,
2947, 2926, 1742, 1693, 1435, 1232, 1117, 893 cmÀ1 1H NMR (400 MHz,
;
CDCl3) 4.89 (s, 1H), 4.62 (s, 1H), 3.45 (s, 1H), 2.62–2.66 (m, 1H), 2.38–2.49 (m,
2H), 2.29 (d, J = 13.8 Hz, 1H), 1.95–2.03 (m, 1H), 1.86–1.90 (m, 1H), 1.84 (s, 3H),
1.66–1.72 (m, 2H), 1.62–1.64 (m, 1H), 1.54–1.58 (m, 1H), 1.21–1.30 (m, 1H),
1.05 (s, 3H); 13C NMR (100 MHz, CDCl3) 172.5, 161.1, 148.5, 122.0, 106.7, 103.7,
51.6, 51.1, 41.2, 36.6, 36.0, 24.5, 22.2, 16.5, 8.1; HRMS (ESI-MS) calcd for
References and notes
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C
15H20O3; 271.1310 (M+Na), found 271.1309. Compound 5. IR (KBr): 2958,
2920, 2854, 1742, 1682, 1254, 1106, 1030, 794 cmÀ1 1H NMR (500 MHz,
;
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CD3OD) 4.91–4.94 (m, 1H), 3.70 (d, J = 11.5 Hz, 1H), 3.58 (d, J = 11.4 Hz, 1H),
3.20 (dd, J = 13.9 & 3.3 Hz, 1H), 2.33 (t, J = 13.8 Hz, 1H), 2.17–2.33 (m, 2H), 1.81
(s, 3H), 1.57–1.63 (m, 3H), 1.42 (dd, J = 13.6 & 3.3 Hz, 1H), 1.19–1.27 (m, 1H),
1.14–1.18 (m, 1H), 1.10 (s, 3H), 1.02 (t, J = 11.7 Hz, 1H); 13C NMR (125 MHz,
CD3OD) 177.4, 166.3, 120.0, 79.9, 74.6, 63.7, 55.4, 52.1, 41.5, 37.3, 36.7, 23.5,
20.2, 19.4, 8.0; HRMS (ESI-MS) calcd for C15H22O4; 289.1416 (M+Na), found
289.1418. Compound 6. IR (KBr): 2953, 2920, 1742, 1457, 1375, 1260, 1106,
794 cmÀ1 1H NMR (400 MHz, CD3OD) 5.06 (s, 1H), 4.76 (s, 1H), 4.24–4.25 (m,
;
1H), 2.60–2.64 (m, 1H), 2.37–2.40 (m, 2H), 2.22 (d, J = 13.2 Hz, 1H), 1.78–1.84
(m, 4H), 1.63–1.72 (m, 2H), 1.48 (d, J = 12.8 Hz, 1H), 1.30 (d, J = 12.1 Hz, 1H), 1.0
(s, 3H); 13C NMR (400 MHz, CD3OD) 174.4, 163.0, 151.6, 122.5, 109.8, 105.4,
73.4, 52.0, 47.1, 37.6, 36.5, 30.1, 25.1, 16.3, 8.0; HRMS (ESI-MS) calcd for
C
15H20O4; 287.1260 (M+Na), found 287.1255. Compound 7. IR (KBr): 2958,
2920, 1747, 1556, 1260, 1106, 1035, 800 cmÀ1 1H NMR (400 MHz, DMSO-d6)
;
5.88 (s, 1H), 5.04–5.08 (m, 1H), 3.15–3.20 (m, 1H), 2.57–2.60 (m, 1H), 2.35–2.41
(m, 2H), 2.17–2.27 (m, 2H), 2.04 (s, 3H), 1.83 (s, 3H), 1.29–1.32 (m, 1H), 1.01 (s,
3H); 13C NMR (100 MHz, DMSO-d6) 197.3, 174.0, 162.4, 161.4, 126.0, 119.8,
77.2, 52.5, 46.9, 45.2, 38.2, 24.5, 21.6, 16.7, 8.2; HRMS (ESI-MS) calcd for
C
15H18O3; 269.1154 (M+Na), found 269.1147. Compound 8. IR (KBr): 3052,
2849, 1731, 1682, 1452, 1260, 734, 701 cmÀ1 1H NMR (500 MHz, CDCl3) 6.89–
;
6.92 (m, 1H), 6.09 (d, J = 10.0 Hz, 1H), 4.87–4.91 (m, 1H), 4.04 (t, J = 5.5 Hz, 1H),
3.36–3.37 (m, 1H), 3.19 (dd, J = 15.0 & 4.6 Hz, 1H), 2.86 (dd, J = 12.3 & 4.6, 1H),
2.38 (t, J = 13.7 Hz, 1H), 2.15–2.19 (m, 1H), 1.88–1.93 (m, 1H), 1.86 (s, 3H), 1.06
(s, 3H); 13C NMR (400 MHz, CDCl3) 198.5, 175.3, 161.4, 144.6, 129.3, 121.3,
78.3, 70.8, 47.4, 41.4, 41.3, 22.1, 18.0, 8.4; HRMS (ESI-MS) calcd for C14H16O4;
271.0947 (M+Na), found 271.0943.
9. All the natural products obtained here by synthesis were spectroscopically (1H
and 13C NMR) compared with the data for natural products and their identities
were unambiguously matched.
4. (a) Minato, H.; Nagasaki, T. J. Chem. Soc. C 1966, 1866–1872; (b) Honan, M. C.
Tetrahedron Lett. 1985, 26, 6393–6396; (c) Bagal, S. K.; Adlington, R. M.;
Baldwin, J. E.; Marquez, R.; Cowley, A. Org. Lett. 2003, 5, 3049–3052.
5. (a) Tanabe, Y.; Mitarai, K.; Higashi, T.; Misaki, T.; Nishii, Y. Chem. Commun.
2002, 2542–2543; (b) Ramesh, S.; Mehta, G. Tetrahedron Lett. 2015, 56, 3941–
3944.
6. (a) Kametani, T.; Tsubuki, M.; Nemoto, H. J. Org. Chem. 1980, 45, 4391–4398; (b)
Yue, G.; Yang, L.; Yuan, C.; Jiang, X.; Liu, B. Org. Lett. 2011, 13, 5406–5408.
7. UMICORE M2 catalyst
10. Single crystal X-ray data for 3, 29, 8 was collected on Oxford CCD X-ray
diffractometer (Yarnton, Oxford, UK) equipped with Cu-K radiation
a
(k = 1.54 Å) source. The data were reduced by SAINTPLUS; an empirical
absorption correction was applied using the package SADABS and XPREP was
used to determine the space group. The crystal structure was solved by direct
methods using SIR92 and refined by the full-matrix least-squares method on F2
using SHELXL97. Crystal data for 3: (CCDC 1414561), C15H20O2, M = 232.31,
triclinic, P-1, a = 10.3618(10) Å, b = 11.1340(10) Å, c = 12.2599(11) Å,
V = 1290.9(2) Å3, Z = 4,
q
calcd = 1.195 g/cm3, 7089 reflections measured, 3522
unique (R(int) = 0.0273), R1 = 0.0599 and wR2 = 0.1872; Crystal data for 29:
(CCDC 1414562), C14H18O3, M = 234.28, monoclinic, C2/c, a = 19.4230(9) Å,
CH3
CH3
N
b = 9.7292(5) Å, c = 13.1532(5) Å, V = 2481.9(2) Å3, Z = 8, calcd = 1.254 g/cm3,
q
N
4608 reflections measured, 2365 unique (R(int) = 0.0267), R1 = 0.0718 and
wR2 = 0.2280; Crystal data for 8: (CCDC 1414563), C14H16O4, M = 248.27,
orthorhombic, Pbcn, a = 15.1100(8) Å, b = 12.1055(7) Å, c = 13.3644(11) Å,
H3C
CH3
CH3
H3C
V = 2444.5(3) Å3, Z = 8,
q
calcd = 1.349 g/cm3, 5249 reflections measured, 2326
unique (R(int) = 0.0316), R1 = 0.0604 and wR2 = 0.1881.
Cl
Cl
Ru
P