Stereoselective synthesis of chiral tertiary alcohol building blocks via neighbouring group participation from tri-substituted olefins

Article abstract of DOI:10.1016/j.tetlet.2007.12.046

A regio- and stereoselective preparation of chiral quaternary 1,2/1,3-diols from acyclic tri-substituted alkenes is disclosed. Optically active tertiary alcohols are the constituents of several bioactive natural products, pharmaceuticals and a general met

Full text of DOI:10.1016/j.tetlet.2007.12.046

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1169–1174
Stereoselective synthesis of chiral tertiary alcohol building blocks
via neighbouring group participation from tri-substituted olefins
Sadagopan Raghavan *, T. Sreekanth
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 9 November 2007; revised 4 December 2007; accepted 10 December 2007
Available online 15 December 2007
Abstract
A regio- and stereoselective preparation of chiral quaternary 1,2/1,3-diols from acyclic tri-substituted alkenes is disclosed. Optically
active tertiary alcohols are the constituents of several bioactive natural products, pharmaceuticals and a general method for their
preparation is desirable. A sulfinyl moiety has been utilized as an intramolecular nucleophile.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Chiral quaternary 1,2/1,3-diols; Tri-substituted alkenes; Sulfoxide
The introduction of a chiral quaternary carbon centre
poses a considerable challenge to synthetic organic chem-
ists.1 Optically active tertiary alcohols are the constituents
of several bioactive natural products,2 pharmaceuticals and
employed as versatile building blocks. Much effort has
therefore been devoted to the synthesis of chiral tertiary
alcohols, these include (a) asymmetric oxidation3 (b)
desymmetrization of prochiral tertiary alcohols4 (c) enantio-/
diastereoselective nucleophilic addition to ketones5 and (d)
stereospecific insertion of carbene into secondary alcohols.6
Since most of the reported methods have their limitation in
terms of the substrate diversity, new methods applicable to
a variety of substrates are needed. In this context, we
report herein, a highly regio- and stereoselective prepara-
tion of chiral 1,2/1,3 diols possessing a quaternary stereo-
genic centre from acyclic tri-substituted allyl alcohols.7
We also present the utility of one of the building blocks
for the synthesis of C7–C11 fragment of fostriecin.
The olefinic substrates 6–9 were prepared as an equimo-
lar mixture of epimers by condensing the lithium anion of
methyl p-tolyl sulfoxide8 1 and unsaturated aldehydes9 2–5,
Scheme 1. The anti-(6a–9a) and syn-isomers10 (6s–9s) were
R2
R3
R2
R2
O
S
O
S
OH
OH
LDA, THF, -78 ºC
70-75%
O
S
OHC
R3
R3
p
-Tol
p-Tol
+
+
p
-Tol
Me
R1
6a-9a
R1
6s-9s
R1
2-5
1
2, 6; R1 = H, R2 = CH2OPMB, R3 = Me
3, 7; R1 = H, R2 = Me, R3 = CH2OPMB
4, 8; R1 = Me, R2 = CH2OBPS, R3 = H
5, 9; R1 = Me, R2 = H, R3 = CH2OBPS
Scheme 1.
*
Corresponding author. Tel.: +91 040 27160123; fax: +91 040 27160512.
E-mail address: sraghavan@iict.res.in (S. Raghavan).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.046

1170
S. Raghavan, T. Sreekanth / Tetrahedron Letters 49 (2008) 1169–1174
Table 1
Regio- and stereoselective chiral tertiary alcohol preparationa
S. No
Substrate
Product
Anti C2,C3
Yield % (Syn:Anti)
Derivative
Syn C2,C3
Ph
O
H
O
O
S
HO HO
Me
O
S
OPMB
Me
O
S
OH
Me
80 (>95:<5)b
1
p
p
-Tol
-Tol
p
-Tol
p
p
-Tol
-Tol
Br OPMB
11
Br OPMB
6a
25
O
S
HO HO
O
S
Me
HO HO
OPMB
Me
Me
O
S
OH
78 (1:2)c
p
p
-Tol
-Tol
2
3
Br OPMB
13
Br OPMB
12
6s
O
S
HO HO
Me
O
S
OH
Me
Me
78 (<5:>95)b
OPMB
p
p
-Tol
-Tol
Br OPMB
7a
14
PMP
O
H
O
S
HO HO
Me
O
S
OH
O
S
O
Me
76 (<5:>95)b
p
-Tol
OPMB
OBPS
4
p
-Tol
Br OPMB
15
7s
Br OH
26
O
S
OH Br
O
S
OH Br
O
S
OH
O
O
O
S
Me
OBPS
p
-Tol
-Tol
p
-Tol
-Tol
p
p
-Tol
-Tol
5
6
80 (1:1)
p
-Tol
HO Me
HO Me
OBPS
OBPS
OBPS
OBPS
Me
Br
27
16
17
8a
OBPS
O
S
OH Br
O
S
OH Br
O
S
OH
79 (2:1)c
p
p
HO Me
HO Me
18
Me
19
8s
O
S
OBPS
O
S
OH Br
OBPS
OBPS
OBPS
Br
O
S
p
-Tol
p-Tol
7
81 (>95:<5)b
p
-Tol
-Tol
HO Me
HO Me
OBPS
OBPS
Me
10a
20
16
OBPS
O
S
OBPS
O
S
OBPS
Br
Br
O
S
82 (3:1)c
p-Tol
p
-Tol
-Tol
8
9
p
HO Me
HO Me
21
OBPS
OBPS
Me
10s
22
O
S
OH
O
S
OH
Br
O
O
O
S
Me
OBPS
OBPS
OBPS
82 (>95:<5)b
p
p
-Tol
-Tol
p
p
-Tol
HO Me
Me
OBPS
Br
28
9a
23
O
S
OH
Br
O
S
OH
p
-Tol
10
80 (>95:<5)b
Me
HO Me
24
OBPS
9s
a
All reactions were carried out on a 0.5 mmol scale using 1.2 equiv of NBS, 1.5 equiv of H2O in toluene as solvent (0.2 M).
Crude product NMR did not reveal peaks for other isomers.
The isomers were inseparable by column chromatography.
b
c

S. Raghavan, T. Sreekanth / Tetrahedron Letters 49 (2008) 1169–1174
1171
separated and subjected to a reaction with freshly recrystal-
lized N-bromosuccinimide (NBS) in toluene in the presence
of water to afford tertiary alcohols (Table 1) regio- and ste-
reoselectively in good yield.
selectivity can be improved so as to get one isomer exclu-
sively. Syn 1,2- and 1,3-diols with a quaternary stereo-
genic centre are thus readily obtained regio- and stereo-
selectively. It is worthwhile to note that by the reduction
of the b-ketosulfoxide, obtained for instance, by reacting
the lithium anion of methyl p-tolylsulfoxide with the esters
corresponding to 2–5, with DIBAL-H or DIBAL-H/
ZnCl2,15 the anti- or syn-isomers, respectively, can be
obtained diastereoselectively. The presence of functional
groups like bromine, sulfoxide and hydroxy groups pro-
vides a wide scope for manipulations, further carbon–
carbon and carbon–heteroatom bond formations by
intermolecular reactions. Also the bromohydrins can be
readily transformed into chiral epoxides which are impor-
tant intermediates,16 using either the secondary or tertiary
hydroxy group. Also the hydroxymethyl and sulfinyl
groups provide suitable handles for further elaboration at
either ends of the molecule. As an illustration of the utility
of the methodology we describe the synthesis of the C7–
C11 fragment 31, of fostriecin,17 Scheme 3. It was envis-
aged to construct (i) the C6–C7 double bond by a Julia
olefination18 between subunits 30 and 31 and (ii) the lac-
tone ring via a RCM reaction. In the resulting product,
an aldehyde group at C11 was envisioned to be introduced
by a selective hydroboration followed by oxidation. Fur-
ther, the 1,3-asymmetric induction due to C9 substituent
was to be capitalized on for introducing the C11 stereo-
centre selectively while forming the C11–C12 bond using
32. Cadiotz–Chodkiewicz coupling19 using enyne 33 and
further routine transformations were expected to furnish
fostriecin. Compound 31 was envisioned to be derived
from 1,3-diol 15.
A perusal of the table reveals that the reaction is general,
high yielding and obeys Markonikov’s rule11 to afford
products regiospecifically, wherein the nucleophile is linked
to the more substituted carbon or the most electrophilic
centre.12 The structures were assigned by NMR (and
NOE) study on the acetonides13 derived from diols 11,
15, 16 and 23. Deprotection of the silyl groups in 20
followed by selective reprotection of the primary hydroxy
group yielded 16, thereby confirming the structure assigned
to 20. The enantiomeric relationship at C2–C4 between 14
and 15 was apparent after individually oxidizing them to
the corresponding sulfones, whose 1H NMR were identical.
A similar oxidation proved the enantiomeric relationships
at carbon atoms of 11/12, 16/18 and 23/24. The regio-
and stereochemical outcome14 (illustrated only for anti
series) of the reaction in entry 1 can be rationalized by
invoking intermediate I, resulting from the rate-determin-
ing nucleophilic attack by the sulfinyl moiety onto a P-
complexed bromonium ion, wherein A(1,3) interactions
are minimized. Intermediate II, arising similarly would
account for the only product in entries 3,7,9 and product
16 in entry 5. Product 17 in entry 5 could be arising via
intermediate III. The strong destabilizing A(1,2) steric
interactions that would be encountered between the siloxy
and the methyl (R1) substituent in III would account
for the exclusive formation of 20 from 10a via II (entry
7), Scheme 2.
The relative stereochemistry at sulfur and carbon atoms
influences the stereoselectivity (compare entries 1/2, 5/6
and 7/8). By an appropriate choice of the anti/syn-isomers
(compare entries 1/2 and 7/8) or by suitably protecting the
allylic hydroxyl group (compare entries 5/7), the stereo-
Epoxide formation by the selective participation of the
secondary hydroxy group in 15 followed by the reductive
elimination of sulfinyl moiety was expected to furnish the
required allyl alcohol. In the event, the treatment of 1520
OPMB
O
S
OPMB
Me
HO HO
Me
O
S
OH
H2O
p-Tol
S
O
p-Tol
p
-Tol
Me
Br
Br OPMB
11
6a
HO
I
b
OP
R2
HO HO
2
bR2
Br
O
S
OP
O
S
Br
R3
R
O
a
R3
p
a
-Tol
p-Tol
R3
p
-Tol
HO R1
Br
S
R1
R1
H2O
II
16, 20, 23
14
R2
R3
O
S
OP
p-Tol
R2 Br
R3
R1
R1
H2O
R2
R3
Br
O
S
HO
p
-Tol
S
p-Tol
R
1, R2, R3 as in Scheme 1
P = H/BPS
HO R1
O
OP
17
III
Scheme 2.

1172
S. Raghavan, T. Sreekanth / Tetrahedron Letters 49 (2008) 1169–1174
3
15
NaHO3PO
OP
PO
18
7
11
OH
12
OHC
1
7
+
OH
TMS
PO
30
+
+
5
O
O
11
18
Me OP
31
SO2Ar
Me OH
14
29
33
32
Scheme 3.
PMP
O
H
O
O
S
O
S
HO HO
O
S
HO
O
Me
Me
K2CO3, CH3CN
DDQ, CH2Cl2
Me
p
-Tol
p
-Tol
p
-Tol
Br OPMB
15
Br OH
26
OPMB
34
Scheme 4.
PMP
OTBS
HO
OTBS
Me
NBS, H2O
Toluene
H
OP
O
O
S
O
S
O
S
Me
DDQ, CH2Cl2
Me
O
OPMB
p-Tol
p
-Tol
p
-Tol
35
Br OPMB
36
Br
37, P = TBS
38, P = H
TBAF/AcOH
THF
PMP
PMP
DIBAL-H
Toluene
Na-Hg, Na2HPO4
MeOH
H
H
O
Me
O
O
S
X
O
K2CO3, CH3CN
Me
O
O
p-Tol
OP
39, X =
41, P = H
42, P = BPS
40, X = O
Me
OPMB
OH
Me
OPMB
O
DMP, CH2Cl2
OBPS
43
OBPS
31
Scheme 5.
with anhydrous potassium carbonate in acetonitrile affor-
ded epoxide 34 (89% yield) as the only product. The ter-
tiary hydroxyl group therefore needed to be protected.
Treatment of 15 with DDQ21 did not afford the 1,2-aceto-
nide but the rearranged 1,3-acetonide 26 (76% yield) as the
only product, Scheme 4.
Silyl ether 35 (90% yield) derived from 7s was reacted
with NBS to furnish bromohydrin 36 (76% yield, 9:1 dr,
minor isomer not depicted). 1,2-Acetonide formation with
DDQ proceeded without an incident to yield 37 as an epi-
meric mixture (75% yield). Deprotection of the silyl group
using buffered TBAF and epoxide formation by base treat-
ment yielded 39 (81% for two steps). Reductive elimina-
tion22 of epoxy sulfoxide proceeded less cleanly in
comparison to the corresponding sulfone 40 to yield allyl
alcohol 41 (64% overall yield), which was protected as its
silyl ether 42 (92% yield). Regioselective reduction of the
acetonide with DIBAL-H furnished primary alcohol 43
as a 9:1 mixture of regioisomers (76% yield). Oxidation
of 43 with DMP23 proceeded cleanly to yield aldehyde 31
(95% yield), Scheme 5.
In conclusion, we have disclosed a highly regio- and
stereoselective method for the preparation of 1,2- and
1,3-diols possessing a quaternary chiral centre. The meth-
odology is general, high yielding and affords building
blocks useful for the natural products synthesis. The syn-
thesis of few natural products is presently underway and
these would form subjects for later communications from
our laboratory.
Acknowledgements
S.R. is thankful to Dr. J. M. Rao, Head, Org. Div. I and
Dr. J. S. Yadav, Director, I.I.C.T, for constant support
and encouragement. T.S is thankful to CSIR, New Delhi
for a fellowship. Financial assistance from DST (New

S. Raghavan, T. Sreekanth / Tetrahedron Letters 49 (2008) 1169–1174
1173
Asymmetry 2004, 15, 565; (k) Raghavan, S.; Tony, K. A. Tetrahedron
Lett. 2004, 45, 2639; (l) Raghavan, S.; Ramakrishna Reddy, S.
Tetrahedron Lett. 2004, 45, 5593.
Delhi) is gratefully acknowledged. We thank Dr. A. C.
Kunwar for the NMR spectra and Dr. M. Vairamani for
the mass spectra.
8. Drago, C.; Caggiano, L.; Jackson, R. F. W. Angew. Chem., Int. Ed.
2005, 44, 7221.
Supplementary data
9. The unsaturated aldehydes were obtained from the corresponding
esters in two steps, (a) reduction using DIBAL-H to furnish the allyl
alcohols followed by (b) oxidation using Swern protocol. The esters
themselves were prepared using procedures reported in the literature,
ester corresponding to 2, refer: Koppisch, A. T.; Blagg, B. S. J.;
Poulter, C. D. Org. Lett. 2000, 2, 215. For ester corresponding to 3
refer: Baldwin, I. R.; Whitby, R. J. Chem. Commun. 2003, 2786; For
ester corresponding to 4 refer: Nicolaou, K. C.; Liu, J.-J.; Yang, Z.;
Ueno, H.; Sorensen, E. J.; Claiborne, C. F.; Guy, R. K.; Hwang, C.-
K.; Nakada, M.; Nantermet, P. G. J. Am. Chem. Soc. 1995, 117, 634;
For ester corresponding to 5 refer: Marshall, J. A.; Trometer, J. D.;
Blough, B. E.; Crute, T. D. J. Org. Chem. 1988, 53, 4274.
10. The configuration of anti- and syn-isomers were assigned by
comparison of coupling constants for the methylene protons directly
bonded to the carbon of the b-hydroxy sulfoxide moiety and the
chemical shift of the b-methine proton. Refer: Carreno, M. C.; Garcia
Ruano, T. L.; Martin, A. M.; Pedregal, C.; Rodrigues, J. H.; Rubio,
A.; Sanchez, J.; Solladie, G. J. Org. Chem. 1990, 55, 2120; and
references cited therein.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.12.046.
References and notes
1. (a) Ramon, D. J.; Yus, M. Challenges and Solution for Organic
Synthesis. In Christoffers, J., Baro, A., Eds.; Wiley-VCH, 2005.
Chapter 8; (b) Christoffers, J.; Baro, A. Angew. Chem., Int. Ed. 2003,
42, 1688; (c) Denissova, I.; Barriault, L. Tetrahedron 2003, 59, 10105;
(d) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37,
388.
2. Representative examples of tertiary carbinol containing bioactive
compounds: Cinatrin C, Integerrimine, Harringtonine, K-252-a,
Fostriecin, Viridofungin, Erythromycin and Zaragozic acid.
11. (a) Markovnikov, V. Liebigs Ann. Chem. 1870, 153, 256. For a
modern interpretation, see: (b) Isenberg, N.; Grdinic, M. J. Chem.
Educ. 1969, 46, 601.
12. De la Mare, P. B. D.; Bolton, O. Electrophilic Addition to Unsaturated
Systems; Elsevier: Amsterdam, 1982.
3. Asymmertic epoxidation: (a) Katsuki, T. In Comprehensive Asym-
metric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: Heidelberg, 1999; Vol. 2, Chapter 18.1 (b) Jacobsen, E. N.;
Wu, M. F. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Heidelberg, 1999; Vol. 2,
Chapter 18.2 (c) Murray, R. W. Chem. Rev. 1989, 89, 1187;
Asymmetric hydroxylation: (d) Marko, I. E.; Svensen, J. S. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Heidelberg, 1999; Vol. 2, Chapter 20
(e) Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483; Biological methods: (f) Takagi, M.; Uemura, N.;
Furuhashi, K. Ann. N. Y Acad. Sci. 1990, 613, 697; (g) Subramanaian,
V. J. Ind. Micobiol. 1986, 1, 119; (h) Rossiter, J. T.; Williams, S. R.;
Cass, A. E. G.; Ribbons, D. W. Tetrahedron Lett. 1987, 28, 5173.
4. Jung, B.; Kang, S. H. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 1471.
5. Cyanohydrin formation: (a) Fuerst, D. E.; Jacobsen, E. N. J. Am.
Chem. Soc. 2005, 127, 8964; (b) Riu, D. H.; Corey, E. J. J. Am. Chem.
Soc. 2005, 127, 5384; (c) Tian, S.-K.; Hong, R.; Deng, L. J. Am.
Chem. Soc. 2003, 125, 9990; (d) Chen, F.; Feng, X.; Qin, B.; Zhang,
G.; Jiang, Y. Org. Lett. 2003, 5, 949. and references cited therein;
Organometallic addition: (e) Forrat, V. J.; Prieto, O.; Ramon, D. J.;
Yus, M. Chem. Eur. J. 2006, 12, 4431; (f) Chen, C.; Hong, L.; Xu, Z.-
Q.; Zhao-Qing, V.; Liu, L.; Wang, R. Org. Lett. 2006, 8, 2277; (g)
Canales, E.; Prasad, K. G.; Soderquist, J. A. J. Am. Chem. Soc. 2005,
127, 11572; (h) Li, H.; Walsh, P. J. J. Am. Chem. Soc. 2005, 127, 8355;
Aldol reaction: (i) Moreau, X.; Bazan-Tezeda, B.; Campagne, J.-M. J.
Am. Chem. Soc. 2005, 127, 7288; (j) Denmark, S. E.; Fan, Y. J. Am.
Chem. Soc. 2002, 124, 4233; (k) Johnson, J. S.; Evans, D. A. Acc.
Chem. Res. 2000, 33, 325.
6. (a) Masaki, Y.; Arasaki, H.; Iwata, M. Chem. Lett. 2003, 32, 4; (b)
Masaki, Y.; Arasaki, H.; Shiro, M. Chem. Lett. 2000, 29, 1180.
7. For the oxidative functionalization of di-substituted alkenes refer: (a)
Raghavan, S.; Rasheed, M. A.; Joseph, S. C.; Rajender, A. Chem.
Commun. 1999, 1845. For the application of this methodology in the
synthesis of bioactive target molecules refer: (b) Raghavan, S.;
Ramakrishna Reddy, S. J. Org. Chem. 2003, 68, 5754; (c) Raghavan,
S.; Joseph, S. C. Tetrahedron: Asymmetry 2003, 14, 101; (d)
Raghavan, S.; Rasheed, M. A. Tetrahedron: Asymmetry 2003, 14,
1371; (e) Raghavan, S.; Rajender, A.; Yadav, J. S. Tetrahedron:
Asymmetry 2003, 14, 2093; (f) Raghavan, S.; Joseph, S. C. Tetra-
hedron Lett. 2003, 44, 6713; (g) Raghavan, S.; Rajender, A. J. Org.
Chem. 2003, 68, 7094; (h) Raghavan, S.; Rasheed, M. A. Tetrahedron
2003, 59, 10307; (i) Raghavan, S.; Joseph, S. C. Tetrahedron Lett.
2003, 44, 8237; (j) Raghavan, S.; Sreekanth, T. Tetrahedron:
13. See Electronic Supplementary data.
14. The inversion of sulfoxide configuration expected from neighbouring
group participation has been conclusively proven in earlier work by
labelling studies using H218O and X-ray crystallography, refer: (a)
Raghavan, S.; Ramakrishna Reddy, S.; Tony, K. A.; Naveen Kumar,
Ch.; Varma, A. K.; Nangia, A. J. Org. Chem. 2002, 67, 5838; (b)
Raghavan, S.; Rajender, A.; Joseph, S. C.; Rasheed, M. A.;
Ravikumar, K. Tetrahedron: Asymmetry 2004, 15, 365; (c) Raghavan,
S.; Naveen Kumar, Ch.; Tony, K. A.; Ramakrishna Reddy, S.;
Ravikumar, K. Tetrahedron Lett. 2004, 45, 7231; Ref. 7l. Also refer:
(d) Dalton, D. R.; Dutta, V. P.; Jones, D. C. J. Am. Chem. Soc. 1968,
90, 5498. The positive optical rotation for the substrates and the
negative rotation for the products also support inversion of sulfoxide
configuration, refer: Electronic Supplementary data.
15. (a) Solladie, G.; Demailly, G.; Greck, C. Tetrahedron Lett. 1985, 26,
435; (b) Solladie, G.; Frechou, C.; Demailly, G.; Greck, C. J. Org.
Chem. 1986, 51, 1912;; (c) Carreno, M. C.; Garcia Ruano, J. L.;
Martin, A.; Pedregal, C.; Rodrigues, J. H.; Rubio, A.; Sanchez, J.;
Solladie, G. J. Org. Chem. 1990, 55, 2120.
16. (a) Zhao, H.; Engers, D. W.; Morales, C. L.; Pagenkopf, B. L.
Tetrahedron 2007, 63, 8774; (b) Lautens, M.; Maddess, M. L.; Sauer,
E. L. O.; Ouellet, S. G. Org. Lett. 2002, 4, 83; (c) Jung, M. E.; Lee, C.
P. Org. Lett. 2001, 3, 333; (d) Jung, M. E.; Lee, W. S.; Sun, D. Org.
Lett. 1999, 2, 307; (e) Jung, M. E.; D’Amico, D. C. J. Am. Chem.
Soc. 1997, 119, 12150; (f) Jung, M. E.; Marquez, R. Tetrahedron
Lett. 1999, 40, 3129; (g) Shimazaki, M.; Hara, H.; Suzuki, K.;
Tsuchihashi, G. Tetrahedron Lett. 1987, 28, 5891; (h) Maruoka, K.;
Ooi, T.; Nagahara, S.; Yamamoto, H. Tetrahedron 1991, 47,
6983.
17. (a) Boger, D. L.; Ichikawa, S.; Zhong, W. J. Am. Chem. Soc. 2001,
123, 4161; (b) Chavez, D. E.; Jacobsen, E. N. Angew. Chem., Int. Ed.
2001, 40, 3667; (c) Cossy, J.; Pradaux, F.; BouzBouz, S. Org. Lett.
2001, 3, 2233; (d) Reddy, Y. K.; Falck, J. R. Org. Lett. 2002, 4, 969;
(e) Wang, Y. G.; Kobayashi, Y. Org. Lett. 2002, 4, 4615; (f)
Miyashita, K.; Ikejiri, M.; Kawasaki, H.; Maemura, S.; Imanishi, T.
Chem. Commun. 2002, 742; (g) Esumi, T.; Okamoto, N.; Hatakeyama,
S. Chem. Commun. 2002, 3042; (h) Miyashita, K.; Ikejiri, M.;
Kawasaki, H.; Maemura, S.; Imanishi, T. J. Am. Chem. Soc. 2003,
125, 8238; (i) Fujii, K.; Maki, K.; Kanai, M.; Shibasaki, M. Org. Lett.

1174
S. Raghavan, T. Sreekanth / Tetrahedron Letters 49 (2008) 1169–1174
2003, 5, 733; (j) Trost, B. M.; Frederiksen, M. U.; Papillon, J. P. N.;
Harrington, P. E.; Shin, S.; Shireman, B. T. J. Am. Chem. Soc. 2005,
127, 3666.
20. Compound 15 was obtained from 7s prepared in two steps
(i. formation of b-keto sulfoxide and ii. stereoselective reduction of
keto sulfoxide, 53% overall yield) as depicted.
LDA, THF, -40 ºC,
add 46 at 0 ºC
Me
O
S
OH
Me
O
S
EtO2C
p
-Tol
+
p
-Tol
Me
DIBAL-H/ZnCl2, THF
-78 ºC
OPMB
OPMB
1
46
7s
18. Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett
1998, 26–28.
21. Hanessian, S.; Cooke, N. G.; DeHoff, B.; Sakito, Y. J. Am. Chem.
Soc. 1990, 112, 5276.
19. (a) Cadiotz, P.; Chodkiewicz, W. In Chemistry of Acetylenes; Viehe,
H. G., Ed.; Marcel Deker: New York, 1969; pp 597–647; (b)
Chodkiewicz, W. Ann. Chim. (Paris) 1957, 2, 819; (c) Siemsen, P.;
Livingstone, R. C.; Diedrich, F. Angew. Chem., Int. Ed. 2000, 39,
2632.
22. Trost, B. M.; Arndt, H. C.; Strege, P. E.; Verhoeven, T. R.
Tetrahedron Lett. 1976, 3477.
23. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.