Ti(III)-mediated radical cyclization of β-aminoacrylate containing epoxy alcohol moieties: synthesis of highly substituted azacycles

Article abstract of DOI:10.1016/j.tetlet.2009.02.063

Ti(III)-mediated radical cyclization of β-aminoacrylate containing 2,3-epoxy alcohol moieties led to the formation of highly substituted piperidine and pyrrolidine rings. The pyrrolidine ring system was then transformed into an indolizidine framework pres

Full text of DOI:10.1016/j.tetlet.2009.02.063

Tetrahedron Letters 50 (2009) 3306–3310
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ti(III)-mediated radical cyclization of b-aminoacrylate containing epoxy
alcohol moieties: synthesis of highly substituted azacycles q
b
b
b
Tushar Kanti Chakraborty a,b, , Rajarshi Samanta , Saumya Roy , Balasubramanian Sridhar
*
a Central Drug Research Institute, CSIR, Lucknow 226 001, India
b Indian Institute of Chemical Technology, CSIR, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Ti(III)-mediated radical cyclization of b-aminoacrylate containing 2,3-epoxy alcohol moieties led to the
formation of highly substituted piperidine and pyrrolidine rings. The pyrrolidine ring system was then
transformed into an indolizidine framework present in many natural products.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 12 January 2009
Revised 6 February 2009
Accepted 10 February 2009
Available online 13 February 2009
Keywords:
Piperidine
Pyrrolidine
Indolizidine
Ti(III)-mediated epoxide opening
Radical cyclization
b-Aminoacrylates
Piperidine, pyrrolidine, and indolizidine/quinolizidine are
important structural scaffolds of several natural products.1 In the
literature, radical cyclization of b-alkoxyacrylates and b-aminoac-
rylates has been extensively used as versatile tools for the con-
struction of oxacyclic2,3 and azacyclic4 rings with the latter
having applications in the synthesis of many alkaloids. Recently,
we have reported that radicals formed during the opening of 2,3-
epoxy alcohols 1 and 3 with Cp2Ti(III)Cl5 could be trapped intramo-
stabilized ylide Ph3P@CHCOCH3 led to an
compound 7.
a,b-unsaturated keto
A Luche reduction9 of 7 followed by a Sharpless kinetic resolu-
tion10 of the resultant racemic allylic alcohol afforded chiral epoxy
alcohol 8 >92% ee as determined using the Mosher ester method11
in 45% yield. With this epoxide in our hand, we turned our atten-
tion to carry out the crucial epoxide ring opening reaction followed
by cyclization. Accordingly, when epoxy alcohol 8 was treated with
Cp2Ti(III)Cl, generated in situ from Cp2TiCl2, Zn dust and freshly
fused ZnCl2, it underwent epoxide opening at the C-2 position from
lecularly by a suitably positioned a,b-unsaturated ester moiety in
the same molecule giving rise to a cyclohexane ring system 2,6 tet-
rahydrofurans, and tetrahydropyrans 4 (see Scheme 1).7
Focusing on our work on the synthesis of carbocycles, oxacycles,
and azacycles via Ti(III)-mediated radical cyclization reactions, we
wish to report here the cyclization reaction of b-aminoacrylates
through epoxide opening followed by 5-exo and 6-exo cyclizations.
The details of the process are outlined in Schemes 2–4. Scheme 2
describes the synthesis of a highly substituted piperidine moiety.
The synthesis started from the commercially available compound
5. Tosylation of 5 with tosyl chloride followed by treatment with
methyl propiolate in the presence of N-methylmorpholine
(NMM) gave the ‘b-aminoacrylate’ intermediate 6.8 Cleavage of
the acetal 6 with formic acid followed by Wittig olefination with
H
CO2Et
CH3
CO2Et
CH3
Cp2TiCl
(ref 6)
O
H
OH
OH OH
1
2
H
O
O
CO2Me
CH3
CO2Me
CH3
Cp2TiCl
(ref 7)
nO
n
H
HO
OH
OH
[n = 1,2]
q
3
4
CDRI Communication No. 7694.
* Corresponding author. Tel.: +91 522 2623405; fax: +91 522 2623405/2623938.
E-mail address: chakraborty@cdri.res.in (T.K. Chakraborty).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.063

T. K. Chakraborty et al. / Tetrahedron Letters 50 (2009) 3306–3310
3307
Ts
N
EtO
EtO
NH2
EtO
EtO
iii, iv
i, ii
CO2Me
vii, viii
5
6
Ts
Ts
N
H
H
Ts
N
O
N
v, vi
CO2Me
Me
CO2Me
Me
CO2Me
Me
O
O
O
OH
8
7
9
Scheme 2. Reagents and conditions. (i) TsCl, Et3N, DMAP (cat.), CH2Cl2, 0 °C to rt, 2 h; (ii) methyl propiolate, NMM, CH2Cl2, rt, 1 h, 76% over two steps; (iii) 20% HCO2H,
pentane, 0 °C, 0.5 h; (iv) Ph3P@CHCOCH3, CH2Cl2, rt, 8 h, 85% over two steps; (v) NaBH4, CeCl3, MeOH, 0 °C, 15 min; (vi)
0.5 h, 45% over two steps; (vii) Cp2TiCl2, ZnCl2, Zn, THF, ꢀ20 °C to rt, 8 h; (viii) 2,2-dimethoxypropane, CSA (cat.), CH2Cl2, 2 h, 40% in two steps.
L
-(+)-DIPT, Ti(OiPr)4, TBHP, MS (4 Å), CH2Cl2, ꢀ20 °C,
Ts
N
Ts
N
CO2Me
OH
i, ii
CO2Me
CHO
iii
iv
6
11
10
Ts
N
Ts
N
O
Ts
N
O
H
H
CO2Me
2
v
vi
CO2Me
OTBDPS
CO2Me
OH
OTBDPS
14
4
OH
13
12
vii
+
CO2Me
H
O
2
3
O
4
viii, ix
MeOOC
TsHN
Ts
MeOOC
NH
OTBDPS
OAc
OTBDPS
17
16
TsN
Ac
15
OH
Scheme 3. Reagents and conditions. (i) 20% HCO2H, pentane, 0 °C, 0.5 h; (ii) Ph3P@CHCHO, C6H6, reflux, 6 h, 60% in two steps; (iii) NaBH4, CeCl3, MeOH, rt, 24 h, 55%; (iv) L-
(+)-DIPT, Ti(OiPr)4, TBHP, MS (4 Å), CH2Cl2, ꢀ20 °C, 2 h, 85%; (v) TBDPSCl, Et3 N, CH2Cl2, DMAP (cat.), 0 °C to rt, 4 h, 95%; (vi) Cp2TiCl2, ZnCl2, Zn, THF, ꢀ20 °C to rt, 6 h; (vii) 15,
K2CO3, MeOH, 0 °C, 2 h, 69% (combined yield) over two steps; (viii) TBAF, THF, 0 °C to rt, 2 h, 85%; (ix) Ac2O, Et3N, DMAP, CH2Cl2, 0 °C to rt, 0.5 h, 90%.
Ts
N
Ts
N
H
H
CO2Me
OR
CO2Me
OH
v, vi
i
ii, iii
14
H
H
OH
19: R = H
18
iv
20: R = TBDPS
Ts
N
Ts
N
H
N
H
H
H
H
OH
OH
OTBDPS
CO2Et
OTBDPS
vii
viii
2
3
OTBDPS
H
H
23
22
21
N
ix
H
H
OTBDPS
24
Scheme 4. Reagents and conditions. (i) TBAF, THF, 0 °C, 1 h; (ii) NaIO4, THF/H2O (1:1) 0 °C, 15 min; (iii) NaBH4, MeOH, rt, 10 min; (iv) TBDPSCl, Et3N, CH2Cl2, DMAP (cat.), 0 °C
to rt, 4 h, 70% over four steps; (v) DIBAL-H, CH2Cl2, ꢀ78 °C, 15 min; (vi) Ph3P@CHCO2Et, CH2Cl2, rt, 8 h, 80% in two steps; (vii) LiBH4, THF/H2O (20:1), 0 °C to rt, 24 h,
quantitative; (viii) NaþC10H8 DME, ꢀ60 °C, 10 min, 85%; (ix) Ph3P, CBr4, Et3 N, CH2Cl2, 24 h, 60%.
ꢀ

3308
T. K. Chakraborty et al. / Tetrahedron Letters 50 (2009) 3306–3310
the hydroxy side12 and gave a radical intermediate that underwent
facile intramolecular trapping by the acrylate moiety leading to the
formation of the six-membered piperidine as the only isolable
product along with some unidentified complex mixture of com-
pounds. Next, the resulting diol was protected as an acetonide to
furnish the bicyclic compound 9 as a white crystalline solid.13
The absolute stereochemistry of 9 was established unequivo-
cally from its single-crystal X-ray analysis14, which confirmed the
assigned structure (Fig. 1).
Next, we wanted to test this reaction in a substrate containing
primary epoxy alcohol. For this, we started from compound 6 as
shown in Scheme 3. Cleavage of the acetal protection with formic
acid followed by the Wittig reaction of the resulting aldehyde with
as R as it was in the chiral epoxide 12. The C-5 protons decoupled
1H NMR spectrum of 17 showed a doublet (J = 1.62 Hz) at 5.03 ppm
for C4–H signal indicating that the C3–H and C4–H had a trans-
relationship and that the absolute stereochemistry of C-3 in 17,
and hence in 14, was S. The absolute stereochemistry of C-2 in
14 was established at a later stage.
Next, we wanted to transform the pyrrolidine moiety to an ind-
olizidine frame work, which is a very important building block for
many natural products.1e–k For the synthesis of the indolizidine
frame work, shown in Scheme 4, we started from 14 which was
treated with TBAF to provide diol 18. Further oxidative cleavage
of the resulting diol with NaIO4 gave an aldehyde that was treated
with NaBH4 to form primary alcohol 19. The protection of the pri-
mary alcohol of 19 as a TBDPS ether gave 20 as a single isomer after
removing the minor isomer via silica gel column chromatography.
The treatment of 20 with 1 equiv of DIBAL-H followed by Wittig
Ph3P@CHCHO in refluxing benzene furnished the
aldehyde 10 in 60% yield over two steps.
a,b-unsaturated
The Luche reduction9 of 10 provided the allylic alcohol 11,
which was subjected to Sharpless asymmetric epoxidation10 using
olefination with stabilized ylide Ph3P@CHCO2Et gave a,b-unsatu-
L
-(+)-DIPT to furnish chiral epoxy alcohol 12. However, treatment
rated ester compound 2117 as a white crystalline compound. The
stereochemistry of 21 was determined by the 3J values of the
C2–H proton. It appeared as a ddd at 3.62 ppm with coupling con-
stants of 7.8, 3.7, and 3.5 Hz. One of the CH2–CH@CH–CO2Et pro-
tons appeared as a ddd at 2.67 ppm with coupling constants
14.5, 7.4, and 3.7 Hz. The other one appeared as a td at 2.58 ppm
with coupling constants 14.5 and 7.8 Hz. So the coupling constant
between C2–H and C3–H is 3.5 Hz, which indicates that the rela-
tionship between C2–H and C3–H was trans. The absolute stereo-
chemistry of 21 was, finally, unequivocally established from the
single-crystal X-ray analysis18 which clearly showed the assigned
structure (Fig. 2). Consequently, it also proved that the absolute
stereochemistry at C-2 in 14 was R.
Next, the reduction of 21 with LiBH4 gave saturated primary
alcohol 22, which on treatment with sodium naphthalenide19 pro-
vided the detosylated product 23. The transformation of primary
alcohol to the corresponding alkyl bromide followed by cycliza-
tion20 gave the desired indolizidine framework 24. The spectral
and analytical data of 2421 were in good agreement with those re-
ported in the literature.
of the primary epoxy alcohol with Cp2Ti(III)Cl gave only an allylic
alcohol15 and no cyclization product was obtained. The primary
hydroxyl group was then protected as a silyl ether and when this
epoxide 13 was treated with Ti(III) reagent, it opened the epoxy
ring at the C-3 position and the radical at C-3 was trapped intramo-
lecularly by the acrylate moiety furnishing a mixture of the desired
cyclized pyrrolidine 1416 (minor product, 20%) and a ring opened
acyclic product 15 (major one, 70%), which was probably formed
by in situ opening of the pyrrolidine 14. Both 14 and 15 were found
to have isomeric products at C3-H in a 4:1 ratio. Compound 15
could, however, be transformed back into the same pyrrolidine
14 in 70% yield on treatment with K2CO3 in methanol taking its
overall yield to 69%. In this process, we also obtained another
highly substituted tetrahydrofuran 16 (ꢁ4:1 diastereomeric mix-
ture) in 20% yield from 15. To know the absolute stereochemistry
of 14 (major isomer), we first assigned the stereochemistry of 17,
which was obtained from 16 in two steps. During the course of rad-
ical-mediated epoxide opening and subsequent base-catalyzed
cyclization, the absolute stereochemistry at C-4 of 14 was retained
Figure 1. X-ray crystal structure of 9. Perspective view of the two independent molecules showing the atom-numbering schemes. Displacement ellipsoids are drawn at the
30% probability level, and H atoms are shown as small spheres of arbitrary radii.

T. K. Chakraborty et al. / Tetrahedron Letters 50 (2009) 3306–3310
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13. Analytical and spectral data of compound 9: Rf = 0.4 (silica gel, 30% EtOAc in
hexane); ½a 3D1
+25.8 (c 0.53 in CHCl3); IR (neat): mmax 2985, 2934, 1735, 1332,
ꢂ
1154 cmꢀ1 1H NMR (200 MHz, CDCl3): d 7.71 (d, J = 8.0 Hz, 2H), 7.28 (d,
;
J = 8.0 Hz, 2H), 4.17–3.98 (m, 2H), 3.65 (s, 3H), 3.58 (m, 1H), 3.37 (m, 1H), 3.18
(td, J = 11.6, 5.1 Hz, 1H), 2.54–2.46 (m, 2H), 2.43 (s, 3H), 2.16–1.81 (m, 2H), 1.60
(dd, J = 9.4, 6.5 Hz, 1H), 1.24 (s, 3H), 1.15 (d, J = 6.5 Hz, 3H), 1.14 (s, 3H); 13C
NMR (75 MHz, CDCl3): d 170.7, 143.4, 137.0, 129.6, 127.0, 99.3, 64.8, 62.9, 51.8,
48.9, 46.4, 39.8, 37.8, 26.5, 26.4, 24.7, 21.4, 18.9; MS (ESI): m/z (%) 412 (15)
[M+H]+, 434 (35) [M+Na]+; HRMS (ESI): calcd for C20H29NO6NaS [M+Na]+
434.1613, found 434.1609.
Figure 2. X-ray crystal structure of 21. Displacement ellipsoids are drawn at 30%
probability level, and H atoms are shown as small spheres of arbitrary radii.
14. X-ray Crystal data for compound 9: Crystal data, C20H29NO6S, M = 411.5,
orthorhombic, space group P212121, a = 8.2570(6) Å, b = 18.0755(14) Å,
c = 28.902(2) Å, V = 4313.6(5) Å3, dcalcd = 1.267 Mg mꢀ3. Data were collected
at room temperature using a Bruker Smart Apex CCD diffractometer with
In conclusion, we have demonstrated the Ti(III)-mediated radi-
cal cyclization of ‘b-aminoacrylate’ containing 2,3-epoxy alcohols,
and this method can be extended to the synthesis of many natural
products containing piperidine, pyrrolidine, and indolizidine/quin-
olizidine moieties.
graphite-monochromated MoKa radiation (k = 0.71073 Å) with x-scan
method.22 Preliminary lattice parameters and orientation matrices were
obtained from four sets of frames. Unit cell dimensions were determined
from the setting angles of 9359 reflections for compound 9. Integration and
scaling of intensity data were accomplished using SAINT program.22 The
structure was solved by Direct Methods using SHELXS9723 and refinement was
carried out by full-matrix least-squares technique using SHELXL97.23 All the
hydrogen atoms were positioned geometrically and were treated as riding on
their parent carbon atoms, with C–H distance of 0.93–0.98 Å and an O–
H = 0.82 Å, with Uiso(H) = 1.2Ueq (C) or 1.5Ueq(methyl C and O). The structure
Acknowledgments
The authors wish to thank DST, New Delhi for the Ramanna Fel-
lowship (SR/S1/RFOC-06/2006; T.K.C.) and CSIR, New Delhi for re-
search fellowships (R.S. and S.R.).
was refined with R1 = 0.0373, wR2 = 0.0972 for 986 reflections with I > 2r(I).
Crystallographic data has been deposited for compound 9 with the Cambridge
Crystallographic Data Centre [CCDC No. 696654]. Copies of the data can be
obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from
the Cambridge Crystallographic Data Centre (CCDC), 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44(0) 1223 336 033; email:
deposit@ccdc.cam.ac.uk].
References and notes
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Findlay, J. A.. In The Alkaloids; Brossi, A., Ed.; Academic Press: London, 1985; Vol.
26, pp 89–183; (c) Schneider, M. J.. In Alkaloids: Chemical and Biological
Perspectives; Pelletier, S. W., Ed.; Pergamon: Oxford, UK, 1996; Vol. 10, pp 155–
299; (d) Pinder, A. R. Nat. Prod. Rep. 1986, 6, 447–455. and references cited
therein; (e) Kinghorn, A. D.; Balandrin, M. F.. In Alkaloids: Chemical and
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105–148; (f) Daly, J. W.; Spande, T. F.. In Alkaloids: Chemical and Biological
Perspectives; Pelletier, S. W., Ed.; Wiley: New York, 1986; Vol. 4, pp 1–274; (g)
Daly, J. W.; Garraffo, H. M.; Spande, T. F.. In The Alkaloids; Cordell, G. A., Ed.;
Academic Press: London, UK, 1993; Vol. 43, pp 185–288; (h) Takahata, H.;
Momose, T.. In The Alkaloids; Cordell, G. A., Ed.; Academic Press: San Diego, CA,
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16. Analytical and spectral data of compound 14 (major isomer): Rf = 0.6 (silica gel,
30% EtOAc in hexane); IR (neat): mmax 2932, 1735, 1431, 1341, 1159,
1104 cmꢀ1 1H NMR (200 MHz, CDCl3): d 7.77–7.19 (m, 14H), 3.71 (m, 1H);
;
3.57 (s, 3H), 3.54–3.28 (m, 2H), 3.24–2.99 (m, 3H), 2.93 (dd, J = 16.1, 3.6 Hz,
1H), 2.53 (dd, J = 16.1, 8.8 Hz, 1H), 2.38 (s, 3H), 2.01 (m, 1H), 1.80–1.63 (m, 2H),
1.03 (s, 9H); 13C NMR (75 MHz, CDCl3): d 171.4, 143.5, 135.4, 134.1, 132.7,
129.9, 129.6, 127.8, 127.6, 70.2, 66.2, 58.6, 51.5, 48.0, 46.7, 40.8, 26.7, 24.3,
21.5, 19.1; MS (ESI): m/z (%) 596 (45) [M+H]+, 618 (30) [M+Na]+; HRMS (ESI):
calcd for C32H41NO6NaSiS [M+Na]+ 618.2321, found 618.2300.
17. Analytical and spectral data of compound 21: Rf = 0.5 (silica gel, 30% EtOAc in
hexane); ½a 3D1
ꢂ
ꢀ22.9 (c 0.63 in CHCl3);IR (neat): mmax 2937, 2862, 1718, 1344,
1161, 1103 cmꢀ1
;
1H NMR (500 MHz, CDCl3): d 7.65 (d, J = 8.2 Hz, 2H), 7.49–
7.38 (m, 6H), 7.36–7.30 (m, 4H), 7.17 (d, J = 8.2 Hz, 2H), 6.90 (td, J = 15.6,
7.5 Hz, 1H), 5.85 (d, J = 15.6 Hz, 1H), 4.16 (q, J = 6.7 Hz, 2H), 3.62 (ddd, J = 7.8,
3.7, 3.5 Hz, 1H), 3.37 (m, 1H), 3.05 (ddd, J = 9.7, 8.2, 7.4 Hz, 1H), 2.93 (d,
J = 7.4 Hz, 2H), 2.67 (ddd, J = 14.5, 7.4, 3.7 Hz, 1H), 2.58 (td, J = 7.8, 14.5 Hz, 1H),
2.36 (s, 3H), 2.04 (m, 1H), 1.82 (m, 1H), 1.43 (m, 1H), 1.28 (t, J = 7 Hz, 3H), 0.98
(s, 9H); 13C NMR (75 MHz, CDCl3): d 166.1, 144.3, 143.4, 135.4, 134.0, 133.1,
129.8, 129.6, 127.7, 127.4, 124.3, 63.4, 60.7, 60.3, 47.5, 45.1, 38.9, 26.7, 25.8,
21.5, 19.0, 14.2; MS (ESI): m/z (%) 606 (15) [M+H]+, 623 (100) [M+NH4]+; HRMS
(ESI): calcd for C34H43NO5NaSiS [M+Na]+ 628.2528, found 628.2498.
18. (a) X-ray Crystal data for compound 21: Crystal data, C34H43NO5SSi, M = 605.84,
3. For further developments, see the following references. Use of acyl radicals: (a)
Evans, P. A.; Roseman, J. D.; Garber, L. T. J. Org. Chem. 1996, 61, 4880–4881. and
the references cited therein; Formation of oxepanes in the presence of a Lewis
acid: (b) Yuasa, Y.; Sato, W.; Shibuya, S. Synth. Commun. 1997, 27, 573–585;
Photosensitized electron-transfer cyclization of aldehydes: (c) Pandey, G.;
Hajra, S.; Ghorai, M. K.; Kumar, K. R. J. Org. Chem. 1997, 62, 5966–5973; SmI2-
induced cyclization of aldehydes: (d) Hori, N.; Matsukura, H.; Matsuo, G.;
monoclinic,
c = 19.9503(14) Å, b = 97.939(1)°, V = 1661.3(2) Å3, dcalcd = 1.211 Mg mꢀ3. Data
were collected at room temperature using Bruker Smart Apex CCD
diffractometer with graphite-monochromated MoK radiation
(k = 0.71073 Å) with
-scan method.22 Preliminary lattice parameters and
space
group
P21,
a = 10.2220(7) Å,
b = 8.2252(6) Å,
a
a
x
orientation matrices were obtained from four sets of frames. Unit cell
dimensions were determined from the setting angles of 5835 reflections for

3310
T. K. Chakraborty et al. / Tetrahedron Letters 50 (2009) 3306–3310
compound 21. Integration and scaling of intensity data were accomplished
Crystallographic Data Center (CCDC), 12 Union Road, Cambridge CB2 1EZ,
UK; fax: +44(0) 1223 336 033; email: deposit@ccdc.cam.ac.uk].; (b) Flack, H.
D.; Bernardinelli, G. J. Appl. Crystallogr. 2000, 33, 1143–1148.
using the SAINT program.22 The structure was solved by Direct Methods using
SHELXS97,23 and refinement was carried out by full-matrix least-squares
technique using SHELXL97.23 The side chain atoms C30/C31/C32/C33/O6 are
disordered over two sites with occupancies of 0.711(14) and 0.289(14). The
geometries of the disordered atoms were refined with distance constraints. The
displacement parameters of the disordered atoms were restrained. All the
hydrogen atoms were positioned geometrically and were treated as riding on
their parent carbon atoms, with C–H distance of 0.93–0.98 Å and an O–
H = 0.82 Å, with Uiso(H) = 1.2Ueq (C) or 1.5Ueq (methyl C and O). The structure
19. Ji, S.; Gortler, L. B.; Waring, A.; Battisti, A. J.; Bank, S.; Closson, W. D.; Wriede, P.
A. J. Am. Chem. Soc. 1967, 89, 5311–5312.
20. Dressel, M.; Restorp, P.; Somfai, P. Chem. Eur. J. 2008, 14, 3072–3077.
21. Analytical and spectral data of compound 24: Rf = 0.3 (silica gel, 10% MeOH in
CHCl3); ½a 3D1
ꢂ
+31.1 (c 0.37 in CHCl3); IR (neat): mmax 2930, 2858, 1464, 1430,
1108 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d 7.74–7.30 (m, 10H), 3.63 (d, J = 4.4 Hz,
2H), 3.23–3.04 (m, 2H), 2.30–1.14 (m, 12H), 1.05 (s, 9H); 13C NMR (75 MHz,
CDCl3): d 135.6, 133.6, 129.6, 127.6, 67.4, 64.5, 53.3, 52.9, 45.1, 29.6, 29.3, 26.8,
24.4, 23.9, 19.2; MS (ESI): m/z (%) 394 (100) [M+H]+; HRMS (ESI): calcd for
C25H36NOSi [M+H]+ 394.2566, found 394.2549.
was refined with R1 = 0.0672, wR2 = 0.1777 for 5199 reflections with I > 2r(I).
The structure is shown in Figure 2. The absolute stereochemistry was
confirmed by refinement of the absolute structure parameters {Flack
parameter = 0.08(13)}. Crystallographic data have been deposited for
compound 21 with the Cambridge Crystallographic Data Center [CCDC No.
696653]. Copies of the data can be obtained free of charge at
22. SMART
& SAINT. Software Reference manuals. Versions 6.28a and 5.625, Bruker
Analytical X-ray Systems Inc., Madison, Wisconsin, U.S.A., 2001.
23. Sheldrick, G. M. SHELXS97 and SHELXL97, Programs for crystal structure solution and
refinement; University of Gottingen: Germany, 1997.
www.ccdc.cam.ac.uk/conts/retrieving.html
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from
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Cambridge