A simple and stereodivergent strategy for the synthesis of 3′-C-branched 2′,3′-dideoxynucleosides exploiting (Z)-but-2-en-1,4-diol and (R)-2,3-cyclohexylideneglyceraldehyde

Article abstract of DOI:10.1016/j.tetlet.2006.04.120

Barbier type additions of allylic bromide 4, derived from (Z)-but-2-en-1,4-diol 2 to (R)-2,3-cyclohexylideneglyceraldehyde 1 were performed through mediation with Zn employing Luche's procedure and also with low valent Cu, Co, and Fe which were produced v

Full text of DOI:10.1016/j.tetlet.2006.04.120

Tetrahedron Letters 47 (2006) 4701–4705
A simple and stereodivergent strategy for the synthesis of
30-C-branched 20,30-dideoxynucleosides exploiting
(Z)-but-2-en-1,4-diol and (R)-2,3-cyclohexylideneglyceraldehyde
Angshuman Chattopadhyay,* Dibakar Goswami and Bhaskar Dhotare
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India
Received 15 February 2006; revised 20 April 2006; accepted 26 April 2006
Available online 19 May 2006
Abstract—Barbier type additions of allylic bromide 4, derived from (Z)-but-2-en-1,4-diol 2 to (R)-2,3-cyclohexylideneglyceraldehyde
1 were performed through mediation with Zn employing Luche’s procedure and also with low valent Cu, Co, and Fe which were
produced via bimetal redox strategy in THF to afford 5c,d as the major products. From these, 5a,b were prepared following an oxi-
dation–reduction protocol. Compound 5c was exploited as a representative starting material to develop a simple and inexpensive
strategy toward the synthesis of 30-C-branched 20,30-dideoxynucleosides having stereodiversity at 30- and 40-positions.
Ó 2006 Elsevier Ltd. All rights reserved.
From the time of the finding that a number of 20,30-dide-
oxynucleosides like ddI, ddC, AZT, etc. are effective
therapeutic agents for the treatment of AIDS,1a the syn-
thesis of nucleoside analogs has become a topic of ever
increasing attention.1 Various modifications of natural
nucleosides of physiological and pharmaceutical interest
were designed with the aim of attaining improved bio-
logical efficiency with minimal toxic effects. Incidentally,
cellular kinases are more tolerant to modification in the
sugar units than in the base moieties. Interest in the
branched chain nucleosides2 has been stimulated by
their potential as antitumor and antiviral agents and a
number of (20- or 30-)-C-branched-(20- or 30-)-deoxy
and 20,30-dideoxy nucleoside analogs have been synthe-
sized and evaluated in biological systems.3 Moreover,
in view of the current attention on antisense oligonu-
cleotide therapeutics4 of varied activities viz. antiviral,
anticancer, antibacterial, etc., 30-methylene branched
nucleosides are used as building blocks for the prepara-
tion of the 30-methylene-modified oligonucleotides with
a view to attaining better enzymatic stability against
exo/endo nucleases and also enhancing membrane per-
meability.5 Hence, preparation of 30-C-branched dide-
oxynucleoside analogs with varied stereochemical
features drew attention.6
For the synthesis of a nucleoside analog, a convergent
approach1 involving the base coupling of a sugar unit
with a nucleoside base using various established proce-
dures,7 has an inherent advantage since it provides an
opportunity to carry out a desired chemical/stereochem-
ical modification in the sugar unit prior to the coupling.
Thus, designing and developing efficient syntheses of su-
gar units assumes considerable importance. The present
work describes our endeavors to develop a very simple,
efficient, and stereochemically flexible strategy for the
synthesis of 3-C-branched sugars of the corresponding
nucleosides through combined exploitation of easily
accessible (R)-2,3-cyclohexylideneglyceraldehyde 18a
and commercially available (Z)-but-2-en-1,4-diol 2.
Monosilylation of 2 with TBDPS-chloride following a
simple procedure used by us earlier8b afforded 3 in good
yield (77%). The hydroxyl of 3 was brominated effi-
ciently in two steps via mesylation and treatment of
the mesylate with NaBr to produce allylic bromide 4
in a good yield. Zinc-mediated Barbier type addition
of 4 to 1 was first performed following Luche’s proce-
dure9 to obtain a mixture of all possible diasteromers
(5a–d) of the homoallylic alcohol product, with 4,5-
anti-3,4-syn5c10 and 4,5-anti-3,4-anti5d11 being the ma-
jor products, separable by column chromatography.
Compounds 5a and 5b were produced only in very small
Keywords: (R)-2,3-Cyclohexylideneglyceraldehyde; (Z)-But-2-en-1,4-
diol; Crotylation; Bimetal redox strategy; Oxidation potential (E0);
30-C-Branched 20,30-dideoxynucleosides; Convergent; Stereodiversity.
*
Corresponding author. Tel.: +91 22 25595422; fax: +91 22
25505151; e-mail: achat@apsara.barc.ernet.in
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.120

4702
A. Chattopadhyay et al. / Tetrahedron Letters 47 (2006) 4701–4705
quantities and could not be separated from each other
chromatographically (Table 1, entry 1). The same croty-
lation reaction was performed using three other metals
(Co, Cu, Fe) as the promoters. The active metals were
generated in situ according to bimetal redox strategy.
The reactions were carried out by the addition of zinc
powder to a stirred mixture of 1, 4 and any one of the
commercially available salts (CoCl2Æ8H2O, CuCl2Æ2H2O,
and FeCl3) in distilled THF and following an operation-
ally simple procedure.12 In each case, the overall
reaction is likely to take place via reduction of the metal
salt with zinc to produce the metal (Fe or Co or Cu) in
any of their low valent states due to the fact that
mechanism,14 the production of different reduction
products 5a or 5b from the substrates 5c or 5d clearly
establishes the 4,5-anti relationship originally present
in the latter.
Thus, the preparation of substantial amounts of all the
four possible diastereomers 5a–d could be accomplished.
To determine their relative 3,4-stereochemistry, one of
them, 5d was benzoylated and then deketalized by stir-
ring its CH2Cl2 solution with aqueous CF3COOH at
0 °C, to afford diol 9. This was monosilylated at the pri-
mary hydroxyl and then ozonolyzed following a re-
1
ported procedure17 to produce c-lactone 11.18 The H
E0Zn¼Zn
þ0:761 V; E0Co¼Co
þ0:280 V; E0Fe¼Fe
þ
NMR spectrum of 11 showed a doublet of doublets at
5.97 (J = 13.7, 2.4 Hz) indicating the syn (J = 2.4 Hz)
and anti (J = 13.7 Hz) relationship of H-3 with its two
neighboring protons H-2 and H-4, respectively, which
in turn proves the anti–anti relationship of the corre-
sponding H-4 in 5d. Accordingly, the stereochemistry
of all other diastereomers (5a–c) could be ascertained
as shown in Scheme 1.
2þ
2þþ2e
2þþ2e
2þþ2e
0:441 Vþ2e and EF0 e2þ
ꢀ 0:771 V;
E0Cu¼Cu
ꢀ
¼Fe3þþe
0:337 V. This was followed by the addition of 4 to
1 mediated by the low valent metal. The comparative
results of all these metal mediated additions are shown
in Table 1.
All the reactions yielded exclusively c-addition products.
For Cu and Co mediated additions (entries b and c),
yields were comparable with that applying Luche’s pro-
cedure (entry a); however, the reactions took place at a
much slower rate. In contrast, Fe mediated addition (en-
try d) took place at a considerably faster rate and gave a
better yield of the product. The good rate of the Fe-
promoted reaction was presumably due to the high
DE0FeðIIIÞ–Zn. However, the copper-mediated reaction
was slow despite a high DE0Cu–Zn, as active copper tends
to form larger sized beads on prolonged stirring which
causes good loss of its reactivity. All the new metal-medi-
ated reactions (entries b–d) were favored in ordinary
THF (distilled only) due to appreciable solubility of
the salts in the somewhat moist solvent.13 In all cases,
the freshly generated metals (Co, Cu, and Fe) remained
active enough to promote the crotylation reaction even
in such moist conditions. In all cases the metal/metal
salts were taken in excess for total consumption of 1.
Moreover, the reactions were made faster by using Zn
in powdered form ensuring the availability of more sur-
face area. All these reactions (entries a–d) were associ-
From a mechanistic viewpoint, very high 4,5-anti selec-
tivity in all the cases suggests that all the crotylations
took place predominantly via a Felkin Anh model,19
thereby reducing the possibility of a-chelate attack
which was apparently not favored due to hydration of
metals in the moist reaction environment. Interestingly,
of the four cases, copper-mediated addition produced a
higher amount of the 3,4-anti product. The formation of
significant amounts of both 3,4-syn- and 3,4-anti-prod-
ucts gave ample evidence of a considerable amount of
E,Z equilibration of allylic bromide 6 during carbon–
carbon bond formation in all cases.
Benzoylation of 5c and transformation of the terminal
olefin 12 applying boron chemistry20 afforded primary
alcohol 13. This was oxidized with PCC21 to give alde-
hyde 14 in good overall yield. Debenzoylation of 14 un-
der alkaline conditions directly produced furanose 15
possessing a protected hydroxymethyl at the 3-C posi-
tion. This was acetylated to produce the acetate 16.22 Fi-
nally, coupling of the latter with silylated thymine
following a reported procedure7a furnished the corre-
sponding 30-C branched nucleoside 17.23 (Scheme 2).
Compound 17, rather than a hydroxymethyl functional-
ity at C0-5 as observed normally, has a functionalized
chiral substituent comprising a primary and a secondary
hydroxyl which are suitable for versatile chemical and
stereochemical manoeuvres independently of each other.
ated with
a similar pattern of stereoselectivities
producing 5c and 5d as the major products and only a
very small amount of the other two diastereomers (5a
and b). Among them, Cu-mediated additions produced
more 5d in contrast with the other additions. There
was a good improvement in the formation of 5c for
the Co-mediated reaction. Subsequently, the prepara-
tions of 5a and 5b were improved employing an oxida-
tion–reduction strategy.14 Thus PCC oxidation of 5c
or 5d and reduction of the resulting ketones 6 or 7 with
K-selectride14a furnished 2,3-syn products 5a15 or 5b,16
respectively, almost exclusively. As is evident from its
Thus, a very simple, efficient and stereochemically flexi-
ble strategy for the synthesis of 30-C branched 20,30-dide-
oxynucleosides was established through judicious
Table 1. Metal mediated addition of 4 to (R)-2,3-cyclohexylideneglyceraldehyde 1
Entry
Metal/salt
Solvent
1:Zn:Metal salt
Reaction time
Product ratio 5a/5b:5c:5d
Overall yield (%)
A
B
C
D
Zn/aq NH4Cl
Zn/CoCl2Æ8H2O
Zn/CuCl2Æ2H2O
Zn/FeCl3
THF
THF
THF
THF
1:3.5:—
1:3.5:3.5
1:3.5:3.5
1:3:3
5 h
3:52:45
2:70:28
2:33:65
2:50:48
73
72.1
70
20 h
20 h
30 min
83

A. Chattopadhyay et al. / Tetrahedron Letters 47 (2006) 4701–4705
4703
i
ii, iii
Br
OTBDPS
HO
OH
HO
OTBDPS
4
2
3
iva-d
+
O
O
R'
O
O
+
O
+
O
R'
O
O
R'
O
O
R'
CHO
1
5c
5b
5a
5d
OH
OH
OH
OH
R'
R
O
O
v
vi
5c, 5d
5a, 5b
O
6: R', H ; R, CH OTPS
2
7: R, H ; R', CH OTPS
2
RO
R'
RO
OH
O
R'
O
vii
O
O
ix
viii, i
5d
R, TBDPS
8
OBz
R', CH OTBDPS
2
OBz
9: R, H
OBz
11
R'
10: R, TBDPS
Scheme 1. Reagents and conditions: (i) TBDPS-Cl (1 equiv), Im, THF, rt, 77%; (ii) MesCl, TEA; (iii) NaBr, acetone, 86% (two steps); (iva) Zn, aq
NH4Cl, THF; (ivb) CoCl2Æ8H2O, Zn, THF, rt; (ivc) CuCl2Æ2H2O, Zn, THF, rt; (ivd) FeCl3, Zn, THF, rt; (v) PCC, CH2Cl2, rt, 73%; (vi) K-selectride,
THF, ꢀ78 °C, 93%; (vii) BzCl, Py, 0 °C, 95%; (viii) CF3CO2H, H2O, 0 °C, 87%; (ix) O3, MeOH, NaOH, ꢀ15 °C, 72%.
i
O
O
R'
O
O
ii
R'
iii
O
O
R'
5c
CHO
OH
12
13
14
OBz
OBz
OBz
O
O
O
O
OR
vi
O
R'
Th
O
R'
iv, v
R', CH OTBDPS
2
Th, Thyminyl
15, R = H
16, R = Ac
17
Scheme 2. Reagents and conditions: (i) BzCl, Py, 0 °C, 95%; (ii) Me2S–BH3, hexane, H2O2–NaOH, 90%; (iii) PCC, CH2Cl2, 71%; (iv) K2CO3,
MeOH, rt, 75%; (v) Ac2O, Py, 90%; (vi) thymine, HMDS, NH4SO4; TMSOTf, CH2Cl2, 72%.
exploitation of easily available 1 and 2. To establish the
viability of our strategy, compound 17 was synthesized
as a representative target molecule. In this context, a
practically viable method for crotylation of aldehydes
has been developed and applied successfully for the reac-
tion between 1 and 4. This new procedure could be of
considerable significance in view of the current attention
on crotylation of aldehydes,24 a valuable alternative to
aldol reactions and having versatile synthetic applica-
tion. The stability of the cyclohexylidene moiety in 1
allowed all these metal-mediated crotylations to be per-
formed simply by stirring under somewhat moist condi-
tions in the presence of metal salts (Table 1, entries b
and c). Moreover, the bulky ketal moiety was responsi-
ble for the stereoselective conversion of 5c/d to 5a/b via
an oxidation–reduction protocol.14 With hindsight, the
poor 3,4-stereoselectivity for all these crotylation reac-
tions 1 has ultimately been exploited to our advantage
to have access to all four diastereomers 5a–d starting
from the same combination of substrates 1 and 2. Our

4704
A. Chattopadhyay et al. / Tetrahedron Letters 47 (2006) 4701–4705
(m, 8H), 2.26 (m, 1H), 3.02 (br s, 1H), 3.81 (dd, J = 10.0,
4.1 Hz, 1H), 3.88–4.0 (m, 5H), 5.0–5.2 (m, 2H), 5.8–6.0
(m, 1H), 7.41 (m, 6H), 7.68 (m, 4H). Anal. Calcd
for C29H40O4Si: C, 72.46; H, 8.39. Found, C, 72.29; H,
8.64.
strategy was established by exploiting 5c as a representa-
tive precursor to produce nucleoside 17. Employing a
similar strategy, the other stereochemical variations at
C-3 and C-4 in the sugar units could be introduced start-
ing from 5a,b,d.
25
11. Compound 5d: ½aꢁD ꢀ 4:68 (c 1.8, CHCl3); 1H NMR
(200 MHz, CDCl3): d 1.05 (s, 9H), 1.4 (m, 2H), 1.55–1.62
(m, 8H), 2.53 (m, 1H), 2.84 (br s, 1H), 3.84 (m, 2H), 3.9–
4.0 (m, 4H), 5.1–5.2 (m, 2H), 5.7–6.0 (m, 1H), 7.41 (m,
6H), 7.66 (m, 4H). Anal. Calcd for C29H40O4Si: C, 72.46;
H, 8.39. Found, C, 72.69; H, 8.61.
References and notes
1. (a) Huryn, D. M.; Okabe, M. Chem. Rev. 1992, 92, 1745–
1768, and references cited therein; (b) Duelhom, K. L.;
Pedersen, E. B. Synthesis 1992, 1–22, and references cited
therein; (c) Wilson, L. J.; Hager, M. W.; El-Kattan, Y. A.;
Liotta, D. C. Synthesis 1992, 1465–1479, and references
cited therein; (d) Yokoyama, M.; Momotake, A. Synthesis
1999, 1541–1554; (e) Yokoyama, M. Synthesis 2000, 1637–
1655; (f) Ludel, O. R.; Meier, C. Synthesis 2003, 2101–
2109.
2. (a) Shuto, S.; Kanazaki, M.; Ichikawa, S.; Minakawa, N.;
Matsuda, A. J. Org. Chem. 1998, 63, 746–754, and
references cited therein; (b) Harry-Okuru, R. E.; Smith,
J. M.; Wolfe, M. S. J. Org. Chem. 1997, 62, 1754–1789,
and references cited therein; (c) Ton-That, T. Nucleosides
Nucleotides 1999, 18, 731–732; (d) Takatori, S.; Kanda, H.
J. Med. Chem. 1999, 42, 2901–2908.
3. (a) Ichikawa, S.; Shuto, S.; Minakawa, N.; Matsuda, A. J.
Org. Chem. 1997, 62, 1368–1375; (b) Garg, N.; Plavec, J.;
Chattopadhyaya, J. Tetrahedron 1993, 49, 5189–5202; (c)
Ogawa, A.; Tanaka, M.; Sasaki, T.; Matsuda, A. J. Med.
Chem. 1998, 41, 5094–5107; (d) Vanheusden, V.; Munier-
Lehman, H.; Froeyen, M.; Dugue, L.; Heyerick, A.; De
Keukeleire, D.; Pochet, S.; Busson, R.; Herdewijn, P.; Van
Calenbergh, S. J. Med. Chem. 2003, 46, 3811–3821.
4. (a) Uhlmann, E.; Peyman, A. Chem. Rev. 1990, 90, 543–
584; (b) Mesmaekar, A. D.; Haner, R.; Martin, P.; Moser,
E. H. Acc. Chem. Res. 1995, 28, 366–374; (c) Kurreck, J.;
Wyszko, E.; Clemens, G.; Erdmann, V. A. Nucleic Acids
Res. 2002, 30, 1911–1918; (d) Stein, C. A. J. Clin. Invest.
2001, 108, 641–644; (e) Crooke, S. T. Methods Enzymol.
2000, 313, 3–45.
12. To a well stirred mixture of 1 (0.01 mol), 4 (0.012 mol) and
metal salt [CoCl2Æ6H2O (8.4 g, 0.035 mol) or CuCl2Æ2H2O
(6.0 g, 0.035 mol) or FeCl3 (4.9 g, 0.03 mol)] in THF
(70 mL) was added Zn dust ( 2.25 g, 0.035 mol for Co and
Cu; 1.95 g, 0.03 mol for Fe) in portions over a period of
15 min. The mixture was stirred at ambient temperature
for the period as shown in Table 1. The reaction mixture
was then treated successively with water (50 mL) and
EtOAc (100 mL), stirred for 10 min more and then
filtered. The filtrate was treated with 2% aqueous HCl to
dissolve a small amount of suspended particles. The
organic layer was separated. The aqueous layer was
extracted with EtOAc. The combined organic layer was
washed with water, brine and then dried. Solvent removal
and column chromatography of the residue (silica gel, 0–
15% EtOAc in petroleum ether) afforded 5a/5b as an
inseparable mixture, and 5c and 5d in pure form.
13. The partial (Co and Cu) to good (Fe) solubility of the
metal salts in distilled THF which always contains some
moisture, plays a role in facilitating bimetal redox reac-
tions and subsequent crotylation. It has been observed,
that in anhydrous THF no crotylation reaction took place
presumably due to the very poor solubility of these metal
salts.
14. (a) Dhotare, B.; Salaskar, A.; Chattopadhyay, A. Synthe-
sis 2003, 2571–2575; (b) Dhotare, B.; Chattopadhyay, A.
Tetrahedron Lett. 2005, 46, 3103–3105.
25
15. Compound 5a: ½aꢁD ꢀ 2:0 (c 0.9, CHCl3); 1H
NMR(200 MHz, CDCl3): d 1.04 (s, 9H), 1.4 (m, 2H),
1.55–1.62 (m, 8H), 2.25–2.5 (m, 1H), 2.84 (br s, 1H), 3.6–
3.7 (m, 1H), 3.75–4.0 (m, 4H), 4.1–4.2 (m, 1H), 5.0–5.2 (m,
2H), 5.7–6.0 (m, 1H), 7.40 (m, 6H), 7.65 (m, 4H). Anal.
Calcd for C29H40O4Si: C, 72.46; H, 8.39. Found, C, 72.24;
H, 8.11.
5. Heinemann, U.; Rudolph, L. N.; Alings, C.; Morr, M.;
Heikens, W.; Frank, R.; Blocker, H. Nucleic Acids Res.
1991, 19, 427–433.
6. (a) Svansson, L.; Kvarnstrom, I. J. Org. Chem. 1991, 56,
2993–2997, and references cited therein; (b) Hossain, N.;
Plavec, J.; Chattopadhyay, J. Tetrahedron 1994, 50, 4167–
4178; (c) Aguste, S. P.; Young, D. W. J. Chem. Soc.,
Perkin Trans. 1 1995, 395–404; (d) Herradon, B. Tetrahe-
dron: Asymmetry 1991, 2, 191–194; (e) Robins, M. J.;
Doboszewski, B.; Timoshchuk, V. A.; Peterson, M. A. J.
Org. Chem. 2000, 65, 2939–2945; (f) Nomura, M.; Sato,
T.; Washinosu, M.; Tanaka, M.; Shuto, S.; Matsuda, S.
Tetrahedron 2002, 58, 1279–1288.
7. (a) Vorbruggen, H. Acc. Chem. Res. 1995, 28, 509–520; (b)
Martin, P. Helv. Chim. Acta 1996, 79, 1930; (c) Saneyoshi,
M.; Satoh, E. Chem. Pharm. Bull. 1979, 27, 2518–2521; (d)
Mukaiyama, T.; Ishikawa, T.; Uchino, H. Chem. Lett.
1997, 389; (e) Vorbruggen, H.; Krolikiewicz, K.; Bennua,
B. Chem. Ber. 1981, 114, 1234–1255.
25
16. Compound 5b: ½aꢁD ꢀ7.2 (c 1.0, CHCl3); 1H
NMR(200 MHz, CDCl3): d 1.03 (s, 9H), 1.4 (m, 2H),
1.56–1.62 (m, 8H), 1.90 (br s, 1H), 2.2–2.4 (m, 1H), 3.5–4.0
(m, 5H), 4.1–4.2 (m, 1H), 5.0–5.2 (m, 2H), 5.8–6.0 (m,
1H), 7.39 (m, 6H), 7.64 (m, 4H). Anal. Calcd for
C29H40O4Si: C, 72.46; H, 8.39. Found, C, 72.68; H, 8.30.
17. Marshall, J. A.; Garofalo, A. W. J. Org. Chem. 1993, 58,
3675–3680.
18. 1H NMR data of 11 (200 MHz, CDCl3): d 0.97 (s, 9H), 1.1
(s, 9H), 3.4–3.5 (m, 1H, H-2), 3.9–4.2 (m, 4H, H-5 and
CH2OTBDPS at H-2), 4.63 (m, 1H, H-4), 5.96 (dd,
J = 13.7 and 2.4 Hz, 1H, H-3), 7.1–7.9 (m, 25H). For
C45H50O6Si2: C, 72.74; H, 6.78. Found, C, 72.96; H, 7.01.
19. (a) Cherest, M.; Felkin, H. Tetrahedron Lett. 1968, 2205;
(b) Anh, N. T. Top. Curr. Chem. 1980, 88, 145–170.
20. Lane, C. F. J. Org. Chem. 1974, 39, 1437–1438.
21. Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 2647–
2650.
8. (a) Chattopadhyay, A.; Mamdapur, V. R. J. Org. Chem.
1995, 59, 585–587; (b) Chattopadhyay, A.; Dhotare, B.
Tetrahedron: Asymmetry 1998, 9, 2715–2723.
25
22. Compound 16: ½aꢁD 2.3 (c 1.4, CHCl3; 1H NMR
9. (a) Petrier, C.; Luche, J. L. J. Org. Chem. 1985, 50, 910–
912; (b) Einhorn, C.; Luche, J. L. J. Organomet. Chem.
1987, 322, 177; (c) Petrier, C.; Einhorn, J.; Luche, J. L.
Tetrahedron Lett. 1985, 26, 1449–1452.
(200 MHz, CDCl3): 1.05 (s, 9H), 1.4–1.6 (m, 10H), 1.96
and 2.04 (2s, 3H), 2.1–2.3 (m, 2H, H-2), 2.6 (m, 1H, H-3),
3.6–3.8 (m, 2H), 3.9–4.1 (m, 4H), 6.24 (m, 1H, H-1), 7.40
(m, 6H), 7.65 (m, 4H). Anal. Calcd for C31H42O6Si: C,
69.11; H, 7.86. Found, C, 69.29; H, 8.04.
25
10. Compound 5c: ½aꢁD 20.75 (c 1.6, CHCl3); 1H NMR
(200 MHz, CDCl3): d 1.07 (s, 9H), 1.4 (m, 2H), 1.56–1.62

A. Chattopadhyay et al. / Tetrahedron Letters 47 (2006) 4701–4705
4705
25
23. Compound 17: ½aꢁD ꢀ15.03 (c 0.9, CHCl3); 1H NMR
Commun. 1997, 411–418, and references cited therein; (c)
Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763–2793,
and references cited therein; (d) Hoffmann, R. W. Angew.
Chem., Int. Ed. Engl. 1982, 21, 555, and references cited
therein; (e) Roush, W. R.; Halterman, P. L. J. Am. Chem.
Soc. 1986, 108, 294–296; (f) Buse, C. T.; Heathcock, C. H.
Tetrahedron Lett. 1978, 19, 1685–1688; (g) Marshall, J. A.
Chem. Rev. 1996, 96, 31–47; (h) Kennedy, J. W. J.;
Hall, D. G. Angew. Chem. Int. Ed. 2003, 42, 4732–
4739.
(200 MHz, CDCl3): 1.05 (s, 9H), 1.4–1.7 (m, 10H, over-
lapped with a s at 1.7, 3H), 1.9–2.6 (m, 3H, H-20, H-30),
3.6–4.0 (m, 3H), 4.1–4.3 (m, 2H), 4.45 (m, 1H, H-40), 6.38
(m, 1H, H-10), 7.3–7.5 (m, 6H, phenyl), 7.6–7.7 (m, 5H, 4
phenyl and H-6), 8.1 (br s, 1H, NH). Anal. Calcd for
C34H44N2O6Si: C, 67.52; H, 7.33; N, 4.63. Found, C,
67.35; H, 7.54; N, 4.77.
24. (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207–
2293, and references cited therein; (b) Thomas, E. J. Chem.