Expeditious stereoselective synthesis of L-iminosugar precursors via a mitsunobu reaction

Article abstract of DOI:10.1055/s-0028-1088209

An efficient stereoselective synthesis of L-imino-C-gulosides is disclosed. Starting from the 2,3:4,6-di-O-isopropylidene-D- mannopyranose the synthetic pathway involves first a Wittig reaction with CMPP to introduce the carbon at the pseudo-anomeric posi

Full text of DOI:10.1055/s-0028-1088209

978
LETTER
Expeditious Stereoselective Synthesis of L-Iminosugar Precursors via a
Mitsunobu Reaction
Stereoselective
Sy
n
nthesis of
L
-
I
t
minosu
o
gars ine Bussière, Véronique Barragan-Montero,* Khalid Oumzil, Jean-Yves Winum, Jean-Louis Montero*
Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron,
Ecole Nationale Supérieure de Chimie de Montpellier, 8 Rue de l¢Ecole Normale, 34296 Montpellier Cedex, France
Fax +33(4)67144343; E-mail: jean-louis.montero@univ-montp2.fr; E-mail: vbarragan@univ-montp2.fr
Received 19 December 2008
(cyanomethylene)trimethylphosphorane (CMMP) for the
synthesis of carba-C-glycosides.22 However, in order to
prepare azahexopyranoses using a comparable approach,
a one-pot reaction could not be envisaged, and the conver-
Abstract: An efficient stereoselective synthesis of L-imino-C-gulo-
sides is disclosed. Starting from the 2,3:4,6-di-O-isopropylidene-D-
mannopyranose the synthetic pathway involves first a Wittig reac-
tion with CMPP to introduce the carbon at the pseudo-anomeric po-
sition, followed by a Michael reaction under ultrasound activation sion had to be separated into three sequential steps. The
to introduce the nitrogen center, and finally a Mitsunobu reaction
for the ring closure leading to the C-iminosugar from the L-series.
reaction involves (a) a ring-opening process with the aim
to free the hemiacetal hydroxyl group; (b) nucleophile ad-
Key words: carbohydrates, azasugars, stereoselective, Mitsunobu
reaction, glycosidase
dition at the anomeric position in order to introduce the ni-
trogen with a variety of substituents, and (c) a ring closure
(Scheme 1 and Scheme 2).
Among carbohydrate mimetics, iminosugars (or azasug-
ars), in which the endocyclic oxygen of the sugar is re-
placed by a nitrogen atom, attract considerable attention.
Nojirimycin, a natural azasugar isolated from Streptomy-
ces filtrate, was found to inhibit a- and b-glucosidase.1
Extended researches have enlarged the range of biological
activities of azasugars and demonstrated that those low-
molecular-weight compounds are powerful inhibitors of a
variety of glycosidases. As a consequence, the therapeuti-
cal potentials of natural or synthetic azasugars are remark-
able.2–5 Compared to azasugars, aza-C-glycosides, which
possess a C-linked aglycon, have shown to improve the
selectivity of the inhibitors. Moreover, they offer the pos-
sibility of further functionalization and/or elongation in
search of improved biological activities, inhibitory prop-
erties depending also on the nature of the substituents on
the nitrogen atom. Since several decades, various synthet-
ic methods focusing on azasugars and aza-C-glycosides
have been developed.6–15 Interest in finding simple and
general ways to synthesize such carbohydrate mimetics
has, of course, been prompted by their remarkable proper-
ties.
13
14
6
12
Ph3P
CMPP
O
5O
O
CN
O
O
OH
4
CN
3
O
O
O
O
8
2
9
10
1
7
benzene
80 °C, 3 h
OH
11
1
2
Scheme 1
To access the L-azahexopyranose system, we focused the
methodology on mannose, using 2,3:4,6-di-O-isopropy-
lidene-D-mannopyranose (1) as starting material. In order
to achieve the ring opening, a Wittig reaction between
(cyanomethylene)triphenylphosphorane (CMPP, more
stable than CMMP) and the protected sugar – but free at
the anomeric position – was performed under reflux in
benzene for 3 hours. An improved and easy procedure to
synthesize CMPP was previously described by Wasser-
man et al.23 The equilibrium between the open and cyclic
forms allowed CMPP to react on the aldehyde. The Z-
isomer 2 was obtained as the main product24 (Z/E = 7:3)
with no ring closure being observed during the reaction
nor during the purification.25 In this compound, the conju-
gation of the alkene with the nitrile group allowed an in-
termolecular Michael addition of nucleophiles. In this
case, three different amines were used to explore the reac-
tion as described in Scheme 2. Michael addition of amines
without an activating system gives very low yields, and
many methods have been reported in the literature such as
the use of amberlyst 15,26 b-cyclodextrin,27 cerium(IV)
ammonium nitrate,28 borax,29 and ultrasound irradiation.30
Our thought was to find a better procedure in order to
achieve the reaction under more convenient conditions
with a low rate of byproducts and subsequent ease of pu-
rification. Therefore, ultrasound activation seemed highly
promising (Scheme 2). The Z-isomer and the amine were
placed in an ultrasound bath for 10 hours to give exclu-
sively (according to the amine involved in the reaction)
The second aspect of our research deals with L-sugars.
While D-sugars are abundant, L-sugars are rare and expen-
sive. Moreover, the latter play important roles in therapy,
and efforts are needed to develop the synthesis of these
valuable sugars.16–21 In this work, we were interested to
find a direct and potentially general approach to aza-C-
glycosides from the L-series using a strategy developed by
our group. Thus, as part of our program devoted to devel-
op new synthetic routes to sugar derivatives, we have re-
cently published a powerful cascade sequence using
SYNLETT 2009, No. 6, pp 0978–0980
x
x.
x
x.
2
0
0
9
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088209; Art ID: G39508ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Stereoselective Synthesis of L-Iminosugars
979
compounds 3, 4, and 5 in high yields.31 These resulting
compounds presented a free hydroxy group on the pseu-
do-C5 position and a secondary amine at the pseudo-
anomeric center. At this stage, the stereochemistry of C1
could not be assigned. The two entities were engaged in
an intramolecular Mitsunobu reaction which allowed the
ring closure. The substitution of the activated hydroxyl
group by the amine proceeded with a complete inversion
of configuration. Thus, the L-enantiomer, a L-gulose de-
rivative, was selectively obtained in 70% yield
(Scheme 2) in each case.32 It is worth pointing out that
compounds 6, 7, and 8 are a-anomers, as indicated by
NMR experiments (J1–2 close to 2 Hz). This implies that
compounds 3, 4, and 5 possess an S-configuration for C1.
(12) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1966, 5, 495.
(13) Behr, J.-B.; Plantier-Royon, R. Recent Res. Dev. Org. Chem.
2006, 10, 23.
(14) Afarinkia, K.; Bahar, A. Tetrahedron: Asymmetry 2005, 16,
1239.
(15) Ruiz, M.; Ruanova, T. M.; Blanco, O.; Nunez, F.; Pato, C.;
Ojea, V. J. Org. Chem. 2008, 73, 2240.
(16) Aguilar, M.; Diaz-Perez, P.; Garcia-Moreno, M. I.;
Ortiz Mellet, C.; Garcia Fernandez, J. M. J. Org. Chem.
2008, 73, 1995; and references cited therein.
(17) Takahashi, H.; Shida, T.; Hitomi, Y.; Iwai, Y.; Miyama, N.;
Nishiyama, K.; Sawada, D.; Ikegami, S. Chem. Eur. J. 2006,
12, 5868.
(18) Joseph, C. C.; Regeling, H.; Zwanenburg, B.; Chittenden,
G. J. F. Carbohydr. Res. 2002, 337, 1083.
(19) Pandey, G.; Bharadwaj, K. C.; Khan, M. I.; Shashidhara,
K. S.; Puranik, V. G. Org. Biomol. Chem. 2008, 6, 2587.
(20) Pearson, M. S. M.; Mathé-Allainmat, M.; Fargeas, V.;
Lebreton, J. Eur. J. Org. Chem. 2005, 2159.
(21) Shitara, E.; Nishimura, Y.; Kojima, F.; Takeuchi, T. Bioorg.
Med. Chem. 2000, 8, 343.
(22) Bussiere, A.; Barragan-Montero, V.; Toupet, L.; Clavel, C.;
Montero, J.-L. Lett. Org. Chem. 2006, 3, 654.
(23) Wasserman, H. H.; Petersen, A. K. Tetrahedron Lett. 1997,
38, 953; and references cited therein.
10
13
12
11
14
6
R
O
9
O
O
5
DEAD
Ph3P
OH
CN
N
CN
4
4
R
NH2
10 h
3
O
5
1
O
1
8
2
O
O
2
2
7
3
12 O
toluene
9
6
HN
14
10
11
13
R
3 R = Bn
4 R = Bu
5 R = allyl
6 R = Bn
7 R = Bu
8 R = allyl
(24) Synthesis of Compound 2
Scheme 2
To a solution of 2,3:4,6-Di-O-isopropylidene-D-manno-
pyranose (1 equiv, 23 mmol, 6 g) in anhyd benzene was
added(cyanomethylene) triphenylphosphorane (3 equiv, 69
mmol, 21 g). The mixture was stirred and refluxed under
argon atmosphere for 3 h. The reaction mixture was diluted
with CH2Cl2 (200 mL) and washed twice with brine (50 mL).
The organic layer was dried over anhyd Na2SO4 for 30 min
and concentrated under vacuum to give pale yellowish oil.
The crude was chromatographed on SiO2 (PE–Et2O, 5:5) to
afford the two isomers (6.5 g, 70% for Z-isomer) as colorless
oils. Rf = 0.16 (Z-isomer, major), 0.08 (E-isomer, minor;
PE–Et2O, 5:5). 1H NMR (400 MHz, acetone-d6):
d (Z-isomer) = 6.81 (dd, J1–7 = 11.26 Hz, J1–2 = 8.00 Hz, H1),
5.77 (dd, J7–1 = 11.27 Hz, J7–2 = 1.30 Hz, H7), 5.16 (dt,
J2–1 = 7.85 Hz, J2–3 = 7.80 Hz, J2–7 = 1.27 Hz, H2), 4.72 (dd,
J3–2 = 7.48 Hz, J3–4 = 1.45 Hz, H3), 4.29 (d, JOH–5 = 6.01 Hz,
–OH), 3.81–3.70 (m, H5, H6a), 3.58 (dd, J = 10.16, 9.07 Hz,
H6a), 3.48 (dd, J4–5 = 9.17 Hz, J4–3 = 1.43 Hz, H4), 1.48, 1.41,
1.37, 1.31 (4 s, 12 H, H10, H11, H13, H14). 13C NMR (100
MHz, acetone-d6): d (Z-isomer) = 153.45 (C1), 117.16 (C8),
111.70 (C9), 102.34 (C7), 99.90 (C12), 77.87 (C2), 77.64 (C3),
74.44 (C4), 66.48 (C6), 63.94 (C5), 30.09, 27.90, 26.89, 19.96
(C10, C11, C13, C14). MS (ESI+): m/z = 306.22 [M + Na]+.
(25) Nicotra, F.; Ronchetti, F.; Russo, G.; Toma, L. Tetrahedron
Lett. 1984, 25, 5697.
In summary, we have developed a simple and efficient
stereoselective synthesis of aza-C-gulosides of the L-
series starting from a D-sugar. Compared to published
methodologies, our strategy allows in few steps the prep-
aration of a L-iminosugar with a variety of substituents on
the nitrogen atom and an aglycon moiety that can be mod-
ified. The application of this methodology is currently be-
ing extended to other monosaccharides, with emphasis on
the preparation of new heterosugars.
Acknowledgment
We thank the Ministère de l¢Enseignement Supérieur et de la
Recherche for a Doctoral fellowship (A. B.).
References and Notes
(1) Inouye, S.; Tsuruoka, T.; Nida, T. J. Antibiot. 1966, 19, 288.
(2) Borges de Melo, E.; da Silveira Gomes, A.; Carvalho, I.
Tetrahedron 2006, 62, 10277.
(3) Suganuma, R.; Walden, C. M.; Butters, T. D.; Platt, F. M.;
Dwek, R. A.; Yanagimachi, R.; Van der Spoel, A. C. Biol.
Reprod. 2005, 72, 805.
(4) Zou, W. Curr. Top. Med. Chem. 2005, 5, 1363.
(5) Iminosugars: From Synthesis to Therapeutic Applications;
Compain, P.; Martin, O. R., Eds.; John Wiley and Sons, Ltd.:
Chichester, 2007.
(26) Das, B.; Chowdhury, N. J. Mol. Catal. A.: Chem. 2007, 263,
212.
(27) Surendra, K.; Krishnaveni, N. S.; Sridhar, R.; Rao, K. R.
Tetrahedron Lett. 2006, 47, 2125.
(28) Duan, Z.; Xuan, X.; Li, T.; Yang, C.; Wu, Y. Tetrahedron
Lett. 2006, 47, 5433.
(29) Hussain, S.; Bharadwaj, S. K.; Chaudhuri, M. K.; Kalita, H.
Eur. J. Org. Chem. 2007, 374.
(30) Yang, J.-M.; Ji, S.-J.; Gu, D.-G.; Shen, Z.-L.; Wang, S.-Y.
J. Organomet. Chem. 2005, 690, 2989.
(31) Typical Procedure for the Synthesis of Compounds 3–5
Compound 2 (1 equiv) was dissolved in dry amine in excess.
The mixture was placed in an ultrasound bath under an argon
atmosphere for 10 h. The unreacted amine was removed
under reduced pressure and the byproducts removed by flash
chromatography on SiO2 (PE–Et2O, 8:2) to afford
(6) McDonnell, C.; Cronin, L.; O¢Brien, J. L.; Murphy, P. V.
J. Org. Chem. 2004, 69, 3565.
(7) Songa, X.; Hollingsworth, R. I. Tetrahedron Lett. 2007, 48,
3115.
(8) La Ferla, B. L.; Bugada, P.; Cipolla, L.; Peri, F.; Nicotra, F.
Eur. J. Org. Chem. 2004, 2451.
(9) Myers, W. H.; Robertson, G. J. J. Am. Chem. Soc. 1943,
65, 8.
(10) Jones, J. K. N.; Szarek, W. A. Can. J. Chem. 1963, 41, 636.
(11) Hanessian, S.; Haskell, T. H. J. Org. Chem. 1963, 28, 2604.
Synlett 2009, No. 6, 978–980 © Thieme Stuttgart · New York

980
A. Bussière et al.
LETTER
Compound 6: Rf = 0.2 (PE–Et2O, 7:3); [a]D +5.86 (c 1,
compounds 3, 4, or 5 as colorless oils in 80% yield.
Compound 3: Rf = 0.11 (PE–Et2O, 8:2). 1H NMR (400 MHz,
acetone-d6): d = 7.46–7.19 (m, 5 H, Hc, Hd, He), 4.48 (dd,
J3–2 = 6.29 Hz, J3–4 = 1.55 Hz, H3), 4.28 (dd, J2–1 = 8.85 Hz,
J2–3 = 6.29 Hz, H2), 4.22 (d, JOH–5 = 5.88 Hz, OH), n0 = 3.82
(ABq, 2 H, nA = 4.03, nB = 3.87, Dn = 64.2 Hz, JAB = 14.0
Hz, Ha), 3.79–3.68 (m, H5, H6a), 3.63–3.50 (m, H6b), 3.61
(dd, J4–5 = 8.93 Hz, J4–3 = 1.57 Hz, H4), 3.33 (ddd, J1–2 = 8.92
HCCl3, 25 °C). 1H NMR (400 MHz, acetone d6): d = 7.42
(m, 2 H, Hc), 7.30 (m, 2 H, Hd), 7.23 (m, 1 H, He), 4.43 (dd,
J3–4 = 2.5 Hz, J3–2 = 8.0 Hz, H3), 4.25 (dd, J4–3 = 2.7 Hz,
J4–5 = 5.6 Hz, H4), 4.23 (dd, J2–1 = 2.1 Hz, J2–3 = 8.1 Hz, H2),
n0 = 3.99 (ABq, 2 H, nA = 4.13, nB = 3.85, Δn = 112.3 Hz,
JAB = 14.3 Hz, Ha), 3.85 (ddd, J1–2 = 2.2 Hz, J1–7b = 7.3 Hz,
J1–7a = 7.4 Hz, H1), 3.38 (dd, J6a–5 = 6.1 Hz, J6a–6b = 11.7 Hz,
H6a), 3.33 (dd, J6b–5 = 6.4 Hz, J6b–5 = 11.8 Hz, H6b), 2.99 (dd,
J7a–1 = 7.7 Hz, J7a–7b = 17.0 Hz, H7a), 3.00 (ddd, J5–6a = 6.3
Hz, J5–6b = 6.4 Hz, J5–4 = 5.7 Hz, H5), 2.91 (dd, J7b–1 = 7.2
Hz, J7b–7a = 17.0 Hz, H7b), 1.61 (s, CH3), 1.38 (d, J = 0.4 Hz,
CH3), 1.30 (s, CH3), 1.30 (s, CH3). 13C NMR (100 MHz,
acetone-d6): d = 143.17 (Cb), 130.49, 129.94 (Cortho/meta),
128.71 (Cpara), 120.32 (C8), 110.60 (C9), 101.23 (C12), 75.99
(C3), 73.64 (C4), 65.87 (C2), 63.77 (C6), 56.87 (Ca), 56.15
(C5), 53.49 (C1), 27.67, 27.25, 24.44, 22.68 (C10, C11, C13,
C14), 19.81 (C7). MS (ESI+): m/z = 373.32 [M + H]+, 395.28
[M + Na]+, 411.18 [M + K]+, 767.57 [2 M + Na]+.
Hz, J1–7b = 5.18 Hz, J1–7a = 4.49 Hz, H1), 2.81 (dd, J7a–7b
=
17.39 Hz, J7a–1 = 4.44 Hz, H7a) 2.58 (dd, J7b–7a = 17.40 Hz,
J7b–1 = 5.29 Hz, H7b), 1.48, 1.33, 1.23, 1.20 (4 s, 12 H, H10,
H11, H13, H14). 13C NMR (100 MHz, acetone-d6): d = 142.55
(Cb), 130.07 and 129.87 (2 C, Cc, Cd), 128.55 (Ce), 119.67
(C8), 110.31 (C9), 99.82 (C12), 80.65 (C2), 75.79 (C3), 74.44
(C4), 66.48 (C6), 63.92 (C5), 53.73 (C1), 52.16 (Ca), 29.98,
27.75, 27.20, 20.03 (4C, C10, C11, C13, C14), 22.03 (C7). MS
(ESI+): m/z = 391.13 [M + H]+, 413.13 [M + Na]+. MS (ESI–
): m/z = 425.46 [M + Cl]–.
Compound 4: Rf = 0.28 (Et2O). 1H NMR (400 MHz,
acetone-d6): d = 4.48 (dd, J3–2 = 6.26 Hz, J3–4 = 1.56 Hz, H3),
4.20 (dd, J2–1 = 8.53 Hz, J2–3 = 6.26 Hz, H2), 3.84–3.67 (m,
H4, H5, H6a), 3.64–3.56 (m, H6b), 3.28 (ddd, J1–2 = 8.52 Hz,
J1–7b = 5.54 Hz, J1–7a = 4.52 Hz, H1), 2.73 (dd, J7a–7b = 17.31
Compound 7: Rf = 0.6 (PE–Et2O, 8:2); [a]D +6.52 (c 1,
HCCl3, 25 °C). 1H NMR (400 MHz, acetone-d6): d = 4.38
(dd, J3–4 = 26.0 Hz, J3–2 = 8.0 Hz, H3), 4.26 (dd, J4–3 = 2.6
Hz, J4–5 = 5.6 Hz, H4), 4.15 (dd, J2–1 = 2.2 Hz, J2–3 = 8.0 Hz,
H2), 3.78 (dd, J6a–5 = 6.2 Hz, J6a–6b = 11.7 Hz, H6a), 3.69
(ddd, J1–2 = 2.2 Hz, J1–7a = 7.7 Hz, J1–7b = 8.4 Hz, H1), 3.56
Hz, J7a–1 = 4.53 Hz, H7a), 2.55 (dd, J7b–7a = 17.32 Hz, J7b–1
=
5.54 Hz, H7b), 2.78–2.70 (m, H9a), 2.68–2.61 (m, H9b), 1.49–
1.32 (m, H10, H11), 1.50, 1.48, 1.33, 1,32 (4 s, 12 H, H14, H15,
(dd, J6b–5 = 6.6 Hz, J6b–6a = 11.7 Hz, H6b), 3.05 (q, J5–4
=
H17, H18), 0.91 (t, J12–11a = 7.20, J12–11b = 7.20 Hz, H12). 13
C
J5–6a = J5–6b = 6.1 Hz, H5), 2.86–2.64 (m, 4 H, H7a, H7b, H9a,
NMR (100 MHz, acetone-d6): d = 119.83 (C8), 110.15 (C13),
99.91 (C16), 80.26 (C2), 75.83 (C3), 74.45 (C4), 66.57 (C6),
64.07 (C5), 55.36 (C1), 48.30 (C9), 34.09 (C10), 30.15, 27.75,
27.13, 20.45 (4 C, C14, C15, C17, C18), 21.95 (C11), 15.25
(C12). MS (ESI+): m/z = 357.31 [M + H]+, 379.33 [M + Na]+.
MS (ESI–): m/z = 355.36 [M – H]–, 391.28
H9b), (s, 3 H, CH3), 1.41–1.20 (m, 4 H, H10a, H10b, H11a, H11b),
1.47, 1.36, 1.33, 1.30 (4 s, 12 H, H14, H15, H17, H18). 13
C
NMR (100 MHz, acetone-d6): d = 120.20 (C8), 110.46 (C13),
101.13 (C16), 75.97 (C3), 73.47 (C2), 65.69 (C4), 64.57 (C6),
57.07 (C5), 53.58 (C1), 52.66 (C9), 35.35 (C10), 27.60, 27.08,
24.47, 22.85 (C14, C15, C17, C18), 21.60 (C11), 19.81 (C7),
15.38 (C12). MS (ESI+): m/z = 339.36 [M + H+], 361.26
[M + Na]+, 699.47 [2 M + Na]+.
[M + Cl]–.
Compound 5: Rf = 0.08 (PE–Et2O, 9:1). 1H NMR (400 MHz,
acetone-d6): d = 5.90 (dddd, J10–11trans = 17.29 Hz, J10–11cis
=
=
Compound 8: Rf = 0.28 (PE–Et2O, 8:2); [a]D +8.34 (c 1,
10.33 Hz, J = 6.15 Hz, J = 5.19 Hz, H10), 5.25 (qd, J11trans–10
HCCl3, 25 °C). 1H NMR (400 MHz, acetone-d6): d = 5.76
17.29 Hz, J = 1.80, 1.80, 1.79 Hz, H11trans), 5.08 (ddd, J11cis–
10 = 10.34 Hz, J = 3.42 Hz, J = 1.48 Hz, H11cis), 4.48 (dd,
J3–2 = 6.28 Hz, J = 1.57 Hz, H3), 4.24 (dd, J = 8.68 Hz, J2–3
(dddd, J10–11trans = 17.19 Hz, J10–11cis = 10.07 Hz, J10–9b =
7.99 Hz, J10–9a = 4.40 Hz, H10), 5.15 (dtd, J11trans–10 = 17.21
Hz, J = 2.03 Hz, J11trans–11cis = 1.11 Hz, H11trans), 5.00 (dtd,
J10–11cis = 10.07 Hz, J = 1.88 Hz, J11cis–9a = 1.87 Hz, J11cis–
11trans = 0.92 Hz, H11cis), 4.37 (dd, J3–2 = 7.94 Hz, J3–4 = 2.60
Hz, H3), 4.25 (dd, J4–5 = 5.27 Hz, J4–3 = 2.60 Hz, H4), 4.17
(dd, J2–3 = 7.95 Hz, J2–1 = 2.12 Hz, H2), 3.78 (td, J = 8.17
Hz, J1–2 = 1.94 Hz, J = 1.94 Hz, H1), 3.74 (dd, J6a–6b = 11.82
=
6.27 Hz, H2), 3.82–3.55 (m, 4 H, H4, H5, H6a, H6b), 3.47–3.29
(m, 3 H, H1, H9a, H9b), 2.75 (dd, J7a–7b = 17.35 Hz, J = 4.49
Hz, H7a), 2.55 (dd, J7b–7a = 17.35 Hz, J = 5.41 Hz, H7b), 1.48,
1.32 (2 d, 12 H, H13, H14, H16, H17). 13C NMR (100 MHz,
acetone-d6): d = 139.48 (C10), 119.76 (C8), 116.70 (C11),
110.26 (C12), 99.90 (C15), 80.52 (C2), 75.85 (C3), 74.52 (C4),
66.54 (C6), 63.96 (C5), 53.15 (C1), 51 (C9), 30.16, 27.74,
27.74, 20.34 (C13, C14, C15, C17), 22.26 (C7). MS (ESI+):
m/z = 341.27 [M + H]+, 363.29 [M + Na]+.
Hz, J = 5.63 Hz, H6a–6b), 3.60 (tdd, J9a–9b = 14.88 Hz, J9a–10
4.12 Hz, J9a–11cis = 1.87 Hz, J = 1.87 Hz, H9a), 3.57 (dd,
=
J6b–6a = 11.76 Hz, J = 5.85 Hz, H6a–6b), 3.26 (tdd, J9b–9a
=
14.88 Hz, J9b–10 = 7.99 Hz, J = 1.04, 1.04 Hz, H9b), 2.99 (q,
J5–4 = 5.59 Hz, J5–6a = 5.59 Hz, J5–6b = 5.59 Hz, H5), 2.84 (d,
J = 0.65 Hz, H7a), 2.82 (s, H7b), 1.50, 1.37, 1.34, 1.30 (4 d,
12 H, J = 0.58 Hz, H13, H14, H16, H17). 13C NMR (100 MHz,
acetone-d6): d = 140.93 (C10), 120.04 (C8), 116.88 (C11),
110.53 (C12), 101.04 (C15), 75.88 (C3), 73.75 (C2), 66.04
(C4), 64.51 (C6), 55.81 (C9), 55.67 (C5), 53.38 (C1), 28.07,
27.20, 24.50, 22.38 (C14, C13, C16, C17), 19.77 (C7). MS
(ESI+): m/z = 323.27 [M + H]+, 345.21 [M + Na]+, 361.20
[M + K]+.
(32) Typical Procedure for the Synthesis of Compounds 6–8
Compounds 3, 4, or 5 (1 equiv) and Ph3P (2 equiv) were
dissolved in a minimum amount of dry toluene. The mixture
was stirred under argon at r.t. DEAD (2 equiv, 2.56 mmol,
1.2 mL) was added dropwise, and the mixture was stirred
further 3 h. The crude product was purified by chromatog-
raphy on SiO2 (PE–Et2O, 7:3) to afford compounds 6, 7, or
8 in 70% yield.
Synlett 2009, No. 6, 978–980 © Thieme Stuttgart · New York