Mild and efficient methodology for installation of gem-diallyl functionality on carbohydrate synthons

Article abstract of DOI:10.1039/b008184l

A versatile approach to construct gem-diallyl functionality has been described.

Full text of DOI:10.1039/b008184l

Mild and efficient methodology for installation of gem-diallyl functionality on
carbohydrate synthons
Mukund K. Gurjar,* S. V. Ravindranadh and Sukhen Karmakar
National Chemical Laboratory, Pune 411008, India. E-mail: gurjar@dalton.ncl.res.in
Received (in Cambridge, UK) 10th October 2000, Accepted 27th November 2000
First published as an Advance Article on the web 17th January 2001
A versatile approach to construct gem-diallyl functionality
Cyclopropanation of 2 was effected with Me2SOCH3I–NaH in
dry DMSO to give 3, as a single diastereomer.6 Although the
stereochemical identification of 3 was of no consequence to the
present study, we believe the approach of the ylide occurs from
the b-face due to the stereo-controlling effect of the adjacent
1,2-O-isopropylidene group. In the 1H NMR spectrum of 3, the
protons of the cyclopropyl group, as expected, appeared in the
high field region. Conversion of the ester function in 3 into the
hydroxymethyl group was accomplished by using DIBAL-H at
278 °C to produce 4 in 85% yield. Compound 4 on treatment
with CBr4–PPh3 in CH2Cl2 at rt gave the bromo derivative (5)
in 90% yield. The 1H, 13C NMR and MS studies substantiated
the assigned structure 4. Treatment of 5 with allyltri-n-
butylstannane in the presence of a catalytic amount of AIBN in
refluxing benzene under argon atmosphere for 12 h gave the
gem-diallyl compound 6 in 80% yield.† In the 1H NMR
has been described.
As a part of our ongoing efforts directed toward synthesis of
natural products containing a spiro-ring system,1 we were
confronted with a need to synthesize a geminal (gem) diallyl
containing carbohydrate backbone (Fig. 1). The gem-diallyl
groups can undergo ring closing metathesis to produce the
spiro-ring system.2 Such gem-diallyl systems are not reported in
carbohydrate chemistry, although they can form valuable
synthons for many chemical transformations leading to func-
tionalised products.
Incorporation of gem-diallyl groups is usually achieved by
base catalyzed dialkylation of active methylene groups with
allyl halides.3 However, we realized that this approach may not
be appropriate for carbohydrate molecules because of side
reactions resulting from various hydroxy groups. We were
particularly interested in the application of Keck’s one electron
C–C bond-forming reaction4 to generate a gem-diallyl system in
a carbohydrate unit by quenching the allylic radical generated
in situ, with allyltri-n-butylstannane.
Table 1 Compounds 5a–e were prepared essentially by the route shown in
Scheme 1 and their structures elucidated by spectral data. Yields are given
for isolated products.
In accordance with our plan, 5-O-tert-butyldiphenylsilyl-
1,2-O-isopropylidene-a- -xylofuranose (1) was oxidized with
D
IBX–DMSO (IBX = o-iodoxybenzoic acid) and then the
resulting 3-ulose derivative was treated with PPh3NCHCO2Et in
refluxing benzene to give the a,b-unsaturated product (2).5
Fig. 1
Scheme 1 Reagents and conditions: (a) (i) IBX (1.5 eq.), DMSO, rt, 10 h;
(ii) PPh3NCHCOOEt, (1.5 eq.), benzene, 80 °C, 3 h, 70% after two steps; (b)
Me2SOCH3I (1.1 eq.), NaH (1.1 eq.), DMSO, rt, 3 h, 60%; (c) DIBAL-H
(2.5 eq.), 278 °C, 0.5 h, 85%; (d) PPh3 (2.0 eq.), CBr4 (2.2 eq.), pyridine
(2.5 eq.), 0 °C, 90%; (e) allyltri-n-butylstannane (2 eq.), AIBN (5 mol %),
benzene, 80 °C,12 h, 80%.
DOI: 10.1039/b008184l
Chem. Commun., 2001, 241–242
This journal is © The Royal Society of Chemistry 2001
241

2 K. Undheim and J. Efskind, Tetrahedron, 2000, 56, 4857 and reference
cited therein.
3 R. K. Singh, Synthesis, 1985, 54; S. Kotha and N. Sreenivaschary,
Bioorg. Med. Chem. Lett., 1998, 8, 257; S. Kotha and E. Brahmachary,
Tetrahedron Lett., 1997, 3, 3561.
4 G. E. Keck, E. J. Enholm, J. B. Yates and M. R. Wiley, Tetrahedron,
1984, 41, 4079.
5 J. M. Trouchet and B. Gentile, Carbohydr. Res., 197, 44, 23.
6 M. K. Gurjar, B. V. N. B. S. Sharma and B. V. Rao, J. Carbohydr. Chem.,
1998, 17, 1107.
Scheme 2
7 R. H. Grubbs and S. Chang, Tetrahedron, 1998, 54, 4413; R. H. Grubbs,
S. J. Miller and G. C. Fu, Acc. Chem. Res., 1995, 28, 446.
8 Compound 6: 1H NMR (200 MHz) data: d 1.08 (s, 9 H, tBu), 1.29, 1.54
(2s, 6 H, 2 3 Me, 1.87–2.54 (m, 4H, 2 3 CH2-CHN), 3.82 (m, 2 H, H-5
and H-5A), 4.03 (t, 1 H, J = 6.4 Hz, H-4), 4.25 (d, 1 H, J = 3.4 Hz, H-2),
5.0 (m, 4 H, 2 3 CH2N), 5.70 (d, 1 H, J = 3.4 Hz, H-1), 5.80 (m, 2 H, 2
3 CHN), 7.35–7.77 (m, 10 H, 2 3 Ph); 13C NMR (50.32 MHz) data: d
19.3, 26.5, 27.0, 35.6, 36.5, 50.0, 62.9, 84.7, 85.6, 104.2, 111.0, 117.7,
127.8, 129.8, 133.3, 133.5, 134.5, 135.0, 135.7.
spectrum of 6, the characteristic olefinic proton signals of two
allylic groups appeared in in the region of 5.0 and 5.7 ppm while
the allylic methylene protons were located in the region of
2.2 ppm. In addition, the assigned structure of 6 was further
suggested by the 13C NMR, MS and elemental analysis. Table 1
provides other examples in this series which substantiates the
versatility of this methodology. Only entry 5 describes an
aliphatic example.
1
Compound 6a: H NMR (200 MHz) data: d 1.31, 1.53 (2s, 6 H, 2 3
Me), 1.91–2.50 (m, 4 H, 2 3 CH2-CHN), 3.35 (s, 3 H, OMe), 3.52 (m, 2
H, H-5 and H-5A), 4.06 (dd, 1H, J = 3.9, 7.3 Hz, H-4), 4.26 (d, 1 H, J =
3.9 Hz, H-2), 5.06 (m, 4 H, 2 3 CH2N), 5.70 (d, 1 H, J = 3.9, H-1), 5.84
(m, 2 H, 2 3 CHN); 13C NMR (75.47 MHz) data: d 26.3, 26.8, 35.3, 35.8,
49.8, 59.2, 71.7, 83.2, 85.3, 104.2, 112.2, 118.0, 134.0, 134.4.
Compound 6b: 1H NMR (500 MHz) data: d 1.58 (m, 10 H, 5 3 CH2),
2.05- 2.4 (m, 4 H, 2 3 CH2-CHN), 3.31 (s, 3 H, OMe), 3.9 (d, 1 H, J =
4.4 Hz, H-3), 3.95 (dd, 1 H, J = 5.9, 8.3 Hz, H-4), 4.08 (m, 2 H, H-6 and
H-6A), 4.31 (m, 1 H, H-5), 4.49, 4.74 (2d, 2 H, J = 11.0 Hz, CH2Ph), 4.71
(s, 1 H, H-1), 5.06 (m, 4 H, 2 3 CH2N), 5.77 (m, 2 H, 2 3 CHN); 13C NMR
(125.75 MHz) data: d 23.9, 24.1, 25.2, 35.0, 35.3, 36.5, 52.6, 55.9, 67.2,
73.2, 74.2, 80.4, 84.4, 109.2, 109.6, 117.5, 117.7, 127.6, 128.0, 128.3,
135.0, 138.5.
The ring closing metathesis reaction of 6c with Grubbs
catalyst in CH2Cl2 at rt gave the spiro-ring compound 7 in 80%
yield.7 The structure of 7 was established based on H, 13C
1
NMR and MS (Scheme 2).8
In summary this communication describes a mild and
efficient methodology to construct gem-diallylic substituted
carbohydrate synthons as precursors for spiro-cyclic systems.
The preparation of unsymmetrical gem-diallyl substituents at
the quaternary carbon will be the next endeavour of this
methodology.
Authors (S. V. R. and S. K.) are grateful to CSIR, New Delhi
for the award of research fellowships.
Compound 6c: 1H NMR (200 MHz) data: d 1.27, 1.33, 1.45, 1.50 (4s,
12 H, 4 3 Me), 2.15–2.45 (m, 4 H, 2 3 CH2-CHN), 3.72 (m, 1 H, H-4),
3.78 (m, 1 H, H-5), 4.09 (m, 2 H, H-6 and H-6A), 4.24 (d, 1 H, J = 3.4 Hz,
H-2), 5.03 (m, 4 H, 2 3 CH2N), 5.57 (d, 1 H, J = 3.4 Hz, H-1), 5.9 (m,
2 H, 2 3 CHN); 13C NMR (50.32 MHz) data: d 25.5, 26.4, 26.8, 27.1,
36.1, 37.0, 50.6, 69.0, 73.5, 85.2, 86.0, 104.4, 109.5, 111.3, 117.6, 134.8,
135.5.
Notes and references
† Typical experimental procedure: A solution of the cyclopropylmethyl
bromide derivative 5a–e (0.4 mmol), allyltri-n-butylstannane (0.8 mmol)
and AIBN (5 mol %) in dry benzene (3 mL) was degassed by bubbling argon
for 30 min. The reaction mixture was heated under reflux for 12 h and
concentrated in vacuo. A KF solution (5 mL) and diethyl ether (10 mL) were
added, stirred for 1 h, filtered and washed with ether. The ether layer was
separated, dried over anhydrous Na2SO4 and concentrated. The crude
product was purified on silica gel using ethyl acetate–hexane to afford the
desired diallyl product.
Compound 6d: 1H NMR (200 MHz) data: d 1.30 (m, 8 H, 4 3 CH2),
1.92–2.30 (m, 4 H, CH2-CHN), 2.94 (dd, 1 H, J = 3.4, 7.8 Hz, CH), 3.27
(s, 3 H, OMe), 4.94 (m, 4 H, 2 3 CH2N), 5.77 (m, 2 H, 2 3 CHN); 13
C
NMR (50.32 MHz) data: d 21.0, 22.9, 24.1, 31.4, 36.8, 39.8, 40.9, 56.3,
82.3, 117.0, 117.2, 135.1.
1
Compound 6e: H NMR (200 MHz) data: d 1.76 (m, 1 H, methine),
2.10 (m, 4 H, 2 3 CH2-CHN), 3.33 (dd, 2 H, J = 5.9, 11.2 Hz, CH2O),
4.46 (d, 2 H, J = 11.7 Hz, CH2Ph), 5.00 (m, 4 H, 2 3 CH2N), 5.73 (m,
2 H, 2 3 CHN), 7.26 (m, 5 H, Ph); 13C NMR (50.32 MHz) data: d 35.4,
38.3, 72.4, 73.1, 116.3, 127.5, 128.3, 136.7.
1 M. Sannigrahi, Tetrahedron, 1999, 55, 9007; A. P. Krapcho, Synthesis,
1974, 383; E. J. Corey and A. Guzman-Perez, Angew. Chem., Int. Ed.
Engl., 1998, 37, 389.
242
Chem. Commun., 2001, 241–242