Molecular iodine-promoted N- and C-glycosylation of 1-C-alkyl (or phenyl)-glycopyranoses

Article abstract of DOI:10.1016/j.tetlet.2010.09.124

Molecular iodine efficiently promoted the N- and C-glycosylation of hemiketals with Me₃SiN₃ and Me₃SiCN, respectively. Using this method we have prepared diverse functional N- and C-ketosides, which could serve as useful s

Full text of DOI:10.1016/j.tetlet.2010.09.124

Tetrahedron Letters 51 (2010) 6334–6337
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Molecular iodine-promoted N- and C-glycosylation of 1-C-alkyl
(or phenyl)-glycopyranoses
⇑
A. P. John Pal, Asadulla Mallick, Y. Suman Reddy, Yashwant D. Vankar
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Molecular iodine efficiently promoted the N- and C-glycosylation of hemiketals with Me3SiN3 and
Me3SiCN, respectively. Using this method we have prepared diverse functional N- and C-ketosides, which
could serve as useful synthons for the preparation of unnatural glycosyl amino acids or glycopeptides.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 19 August 2010
Revised 23 September 2010
Accepted 25 September 2010
Available online 18 October 2010
Keywords:
Molecular iodine
Ketoses
Glycosylation
N-Ketosides
C-Ketosides
Synthetic manipulations at the anomeric center lead to useful
and interesting transformations in carbohydrate chemistry.1
Among the reactions at the anomeric center, particularly, O-, C-
and N-glycosylations2–4 have gained significant importance in
the field of carbohydrate chemistry and biochemistry. Recently,
C-glycosides have received much attention from the biological
and synthetic standpoints. These are the stable mimics of naturally
occurring O- and N-glycosides. Consequently, this class of com-
pounds is currently receiving much interest because of their bio-
logical activity and these are potent antitumor, antiviral, or
antibiotic agents.5 Therefore, various effective methods have been
reported for the stereoselective synthesis of C-glycosides.6
Further, 1-C-alkyl-sugars, also called as artificial ketoses, or
hemiketals, are a novel class of C-glycosides having an alkyl group
at the anomeric center, which mimics naturally occurring aldoses
and have also gained considerable importance7–9 in synthetic car-
bohydrate chemistry. The O- or C- or N-glycosylation of these 1-C-
alkyl-sugars leads to 1-C-alkyl-glycosides, also called as O- or C- or
N-ketosides,7–9 which are considered as a new class of C-glycoside
analogs and these are expected to possess biological activities dif-
ferent from those of natural molecules9a,10 and thus allow the
structure-activity relationship to be studied. Because of their phar-
macological importance, together with the diverse structural fea-
tures, several groups are currently working to develop the
chemistry of 1-C-alkyl-sugars.11
For the past few years, we have been interested in developing
newer methodologies for functionalizing 2,3-glycals4a,b,12 and their
derivatives en route to some useful carbohydrate synthons. More
recently, we have developed a method for the direct conversion
of unstable amino precursors viz. 1-C-alkyl-1-nitro sugars into
stable amino precursors viz. 1-C-alkyl-1-azido sugars.13 This
methodology gave an easy access for the synthesis of 6,5-fused spi-
roaminals (fused N-ketosides), which are moderate glycosidase
inhibitors. In continuation of our interest in exploring the chemical
and biological properties of ketosides,13 we hereby report on
R2
OBn
O
2 OBn
R
R1
BnO
R1
RMgX or RLi
O
BnO
R
O
BnO
OBn
OH
1 R1 = OBn, R2 = H
2 R1 = H, R2 = OBn
4a-4d R1 = OBn, R2 = H
6a-6d R1 = H, R2 = OBn
R = alkyl or phenyl
OBn
OBn
E, TBAF, 0 ºC
O
BnO
BnO
30 min
O
BnO
BnO
R
BnO
Column
BnO
NO2
OH
Chromatography
5a, 5b
3
CH2=CHCO2Me
or CH2=CHCN
E = electrophile =
⇑
Corresponding author. Tel.: +91 512 259 7169; fax: +91 512 259 0007.
E-mail address: vankar@iitk.ac.in (Y.D. Vankar).
Scheme 1. Preparation of hemiketals from d-lactones 1, 2 and 1-nitro sugar 3.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.09.124

A. P. John Pal et al. / Tetrahedron Letters 51 (2010) 6334–6337
6335
N- and C-glycosylation of 1-C-alkyl-sugars using molecular iodine
as a promoter.
toxic, nonmetallic, and readily available Lewis acid catalyst for
effecting various carbohydrate14 as well as non-carbohydrate15
organic transformations. Herein, we wish to report a simple and
efficient method for the preparation of N- and C-ketosides using
molecular iodine as promoter.
Usually glycosylation of 1-C-alkyl-sugars is carried out using
few Lewis acids such as BF3ꢀOEt2,11f Sc(OTf)3,7d and Me3SiOTf.11g
However, some of these reagents are associated with drawbacks
such as high cost, corrosive nature, moisture sensitive, toxic, and
difficulty in handling. Therefore, the development of simple, effi-
cient, and inexpensive reagents, which can provide convenient
procedures with good yields, is necessary. Recently, molecular
iodine has gained considerable attention as an inexpensive, non-
For the synthesis of 1-C-alkyl-sugars we have chosen
D-glucon-
o-1-5-loctone 1, -galactono-1-5-lactone 2, and glucose derived
D
1-nitro sugar 3 as the starting materials. The addition reaction of
organometallic reagent (RMgX or RLi) to lactones 1 and 2 produced
hemiketals 4a–d11g,16 and 6a–d,6d,16 respectively (Scheme 1). The
Table 1
Azidation of hemiketals in the presence of TMSN3 and I2 (ꢁ40 °C to rt)
OBn
OBn
Me3SiN3, CH2Cl2
O
O
BnO
BnO
BnO
BnO
R
R
I2 (1.0eq), 3-4 h
BnO
BnO
OH
N3
4a-4d, 5a, 5b and 6a-6d
7a-7d, 8a,8b and 9a-9d
Entry
1
Hemiketals
OBn
N-Ketaosides
Yield (%)
7911g
OBn
O
O
BnO
BnO
BnO
BnO
Ph
Ph
4a
BnO
BnO
OH
N3
7a
OBn
OBn
O
O
BnO
BnO
BnO
BnO
2
3
7511g
BnO
BnO
OH
N3
7b
4b
OBn
OBn
O
O
BnO
BnO
BnO
BnO
89
CO2Et
4c
CO2Et
7c
BnO
BnO
OH
N3
OBn
O
OBn
O
BnO
BnO
BnO
BnO
Ph
Ph
N3 7d
4
5
7711g
BnO
BnO
OH
4d
5a
OBn
O
OBn
O
BnO
BnO
BnO
BnO
8013
CO2Me
CN
CO2Me
8a
BnO
BnO
O
N3
N3
OBn
O
OBn
O
BnO
BnO
BnO
BnO
CN
6
7
8
7313
BnO
BnO
OH
8b
5b
OBn
OBn
BnO
BnO
BnO
BnO
O
O
95
CO2Et
CO2Et
N3
9a
BnO
BnO
OH
6a
OBn
OBn
O
BnO
BnO
BnO
BnO
O
Ph
76
Ph
9b
BnO
BnO
OH
OH
N3
N3
N3
6b
OBn
O
OBn
O
BnO
BnO
BnO
BnO
9
72
96
BnO
BnO
9c
6c
OBn
OBn
O
BnO
BnO
BnO
BnO
O
Ph
6d
Ph
9d
10
BnO
BnO
OH

6336
A. P. John Pal et al. / Tetrahedron Letters 51 (2010) 6334–6337
Table 2
also produced azido ester 8a and azido cyanide 8b in 80% and
73% yield, respectively13 (Table 1).
Cyanation of hemiketals in the presence of TMSCN and I2 (ꢁ40 °C to rt)
The optimized reaction conditions were also effective for the
cyanation of 1-C-alkyl-sugars. Thus, the treatment of 1-nitro sugar
derived hemiketal 5a with Me3SiCN in the presence of 1 equiv of
molecular iodine in CH2Cl2 under similar conditions produced cya-
no-ester 11a (Table 2) in excellent yield (93%), which could serve
as a novel, useful synthon for the preparation of artificial glycopep-
tides.17 The formation of the product was confirmed through its
spectral data. Thus, 1H NMR spectrum of compound 11a showed
a characteristic peak of –OMe at d 3.65 as a singlet and 13C NMR
spectrum showed the CN group carbon peak at d 116.8. Further,
hemiketals 4a, 4b and 6a–d also furnished glycosyl cyanides 10a,
10b,11g and 12a–d in good to moderate yields.18
OBn
O
OBn
O
Me3SiCN, CH2Cl2
I2 (1.0eq), 3-4 h
BnO
BnO
BnO
BnO
R
R
BnO
BnO
CN
OH
4a, 4b, 5a and 6a-6d
10a, 10b, 11a and 12a-12d
Entry
Hemiketals
C-Ketosides
OBn
Yield (%)
O
BnO
BnO
1
4a
6711g
Ph
10a
BnO
CN
OBn
O
Interestingly, all the products were obtained as single isomers
BnO
BnO
viz.
acid catalyzed glycosylations of glucose derived ketoses, formation
of a single -isomer has been well demonstrated in the litera-
a-isomers. This is not surprising as in similar types of Lewis
2
3
4
4b
5a
6a
6311g
BnO
CN
10b
a
ture.11g,13 In the case of galactose series, the configuration at the
anomeric center was established based on NOE experiments
(Fig. 1). In ketoside 9b irradiation of H-30 methylene proton at d
3.18 enhanced the signal for H-3 proton at d 3.89 (3.1% NOE) and
did not enhance the signal for H-4 proton at d 3.94, clearly indicat-
ing that the azide group occupies the axial position. In the case of
phenyl ketoside 9d, irradiation of ortho protons at d 7.65 enhanced
the signal for H-3 proton at d 3.92 (7.4% NOE) also clearly indicat-
ing the formation of axial azide. Similarly NOE was observed be-
tween H-3 and H-30 protons of compound 12b (see
Supplementary data). We have also further confirmed the axial ori-
entation of cyanide moiety in galactose derived ketosides from the
single-crystal X-ray data19 of compound 12d.
OBn
O
BnO
BnO
CO2Me
93
BnO
11a
CN
OBn
BnO
BnO
O
71
CO2Et
12a
BnO
CN
OBn
BnO
BnO
O
5
6
7
6b
6c
6d
65
69
84
Ph
BnO
CN
CN
12b
OBn
O
BnO
BnO
In conclusion, we have developed a simple, inexpensive, and
efficient method for providing a-N- and C-ketosides using molecu-
lar iodine as promoter. The procedure is experimentally simple and
using this method we prepared diverse functional glycosyl azides
and cyanides, which are useful synthons for the synthesis of pep-
tide mimetics.
BnO
12c
OBn
BnO
BnO
O
Ph
12d
BnO
CN
Acknowledgments
We thank the Council of Scientific and Industrial Research, New
Delhi for the financial support [Grant No. 01(2298)/09/EMR-II]. We
thank the U.G.C., New Delhi for the fellowship to A.P.J.P. and we
also thank the CSIR, New Delhi for the fellowship to A.M. and Y.S.R.
3.1%
7.4%
BnO
BnO
BnO
H
H
H
BnO
O1
5
H
5
6
O1
6
3
2
3
3'
2
BnO 4
Ph
BnO 4
BnO
BnO
N3
N3
Supplementary data
9b
9d
Figure 1. NOE correlations of compound 9b and 9d.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.09.124.
other glucose derived hemiketals 5a and 5b were prepared by
utilizing the chemistry of anomeric nitro sugar 3. Thus, reaction
of nitro sugar 3 with methyl acrylate or acrylonitrile in the pres-
ence of a catalytic amount of n-tetrabutylammonium fluoride
(TBAF) at 0 °C gave hemiketal 5a or 5b.13
As a preliminary study hemiketal 4a was treated with azidotri-
methylsilane (Me3SiN3) in CH2Cl2 in the presence of molecular
iodine. The reaction proceeded smoothly at room temperature
and afforded the desired glycosyl azide 7a11g as a single isomer
in good yield (Table 1). Best results were obtained by using 1 equiv
of molecular iodine in CH2Cl2 at ꢁ40 °C to room temperature.
Reduction in catalyst loading was ineffective as it led to longer
reaction time and lowering of chemical yield. Similarly, the glucose
derived hemiketals 4b–d and the galactose derived hemiketals
6a–d reacted smoothly to afford glycosyl azides 7b–d11g and 9a–
d in good yield. The 1-nitro sugar derived hemiketals 5a and 5b
References and notes
1. (a) Glycoscience: Chemistry and Chemical Biology; Fraser-Reid, B., Tatsuta, K.,
Thiem, J., Eds.; Springer: Berlin, 2001; (b) Carbohydrates in Chemistry and
Biology; Ernst, B., Hart, G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim, 2000; (c)
Preparative Carbohydrate Chemistry; Hanessian, S., Ed.; Marcel Dekker: New
York, 1997.
2. For reviews on O-glycosylation: (a) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982,
21, 155–173; (b) Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 25, 212–235;
(c) Kunz, H. Angew. Chem., Int. Ed. Engl. 1987, 26, 294–308; (d) Toshima, K.;
Tatsuta, K. Chem. Rev. 1993, 93, 1503–1531; (e) Boons, G.-J. Tetrahedron 1996,
52, 1095–1121; (f) Davies, B. G. J. Chem. Soc., Perkin Trans. 1 2000, 2137–2160;
(g) Nicolaou, K. C.; Mitchell, H. J. Angew. Chem., Int. Ed. 2001, 40, 1576–1624.
3. For reviews on C-glycosylation: (a) Postema, M. H. D. Tetrahedron 1992, 40,
8545–8599; (b) Jaramillo, C.; Knapp, S. Synthesis 1994, 1–20; (c) Levy, D. E.;
Tang, C. The Chemistry of C-Glycosides; Pergamon: Oxford, 1995; (d) Du, Y.;
Linhardt, R. J. Tetrahedron 1998, 54, 9913–9959; (e) Postema, M. H. D.
C-Glycoside Synthesis; CRC Press: London, UK, 1995.
4. Papers regarding N-glycosylation or N-glycopeptides: (a) Rawal, G. K.; Kumar,
A.; Tawar, U.; Vankar, Y. D. Org. Lett. 2007, 9, 5171–5174; (b) Gopal Reddy, B.;

A. P. John Pal et al. / Tetrahedron Letters 51 (2010) 6334–6337
6337
Madhusudanan, K. P.; Vankar, Y. D. J. Org. Chem. 2004, 69, 2630–2633; (c) He,
Y.; Hinklin, R. J.; Chang, J.; Kiessling, L. L. Org. Lett. 2004, 6, 4479–4482. also see
the references in this paper; (d) Nakano, J.; Ichiyanagi, T.; Ohta, H.; Ito, Y.
Tetrahedron Lett. 2003, 44, 2853–2856.
review, see: (e) Wang, H. S.; Miao, J. Y.; Zhao, L. F. Chin. J. Org. Chem. 2005, 25,
615–618; (f) Wu, J.; Xia, H. G.; Gao, K. Org. Biomol. Chem. 2006, 4, 126–129. and
references cited therein; (g) Phukan, P. J. Org. Chem. 2004, 69, 4005–4006.
16. Yang, W.-B.; Yang, Y.-Y.; Gu, Y.-F.; Wang, S.-H.; Chang, C.-C.; Lin, C.-H. J. Org.
Chem. 2002, 67, 3773–3782.
5. (a) Cavezza, A.; Boulle, C.; Guéguiniat, A.; Pichaud, P.; Trouille, S.; Ricard, L.;
Dalko-Csiba, M. Bioorg. Med. Chem. Lett. 2009, 19, 845–849; (b) Sanhueza, C. A.;
Mayato, C.; Garcia-Chicano, M.; Diaz-Penate, R.; Dorta, R. L.; Vazquez, J. T.
Bioorg. Med. Chem. Lett. 2006, 16, 4223–4227; (c) Yang, G.; Schmieg, J.; Tsuji,
M.; Franck, R. W. Angew. Chem., Int. Ed. 2004, 43, 3818–3822; (d) Hacksell, U.;
Daves, G. D. Prog. Med. Chem. 1985, 22, 1–65; (e) Suzuki, K. Pure Appl. Chem.
1994, 66, 2175–2178; (f) Hanessian, S. Total Synthesis of Natural Products: The
Chiron Approach; Pergamon Press: Oxford, 1984.
6. (a) Yahiro, Y.; Ichikawa, S.; Shuto, S.; Matsuda, A. Tetrahedron Lett. 1999, 40,
5527–5531; (b) Shuto, S.; Yahiro, Y.; Ichikawa, S.; Matsuda, A. J. Org. Chem.
2000, 65, 5547–5557; (c) Abe, H.; Shuto, S.; Matsuda, A. J. Am. Chem. Soc. 2001,
123, 11870–11882; (d) Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982,
104, 4976–4978; (e) Tamura, S.; Abe, H.; Matsuda, A.; Shuto, S. Angew. Chem.,
Int. Ed. 2003, 42, 1021–1023; (f) Lancelin, J.-M.; Zollo, P. H. A.; Sinay, P.
Tetrahedron Lett. 1983, 24, 4833–4836; (g) Dondoni, A.; Marra, A.; Scherrmann,
M.-C. Tetrahedron Lett. 1993, 34, 7323–7326; (h) Xie, J.; Durrat, F.; Valery, J.-M.
J. Org. Chem. 2003, 68, 7896–7898.
7. References for (O-ketosides): (a) Li, X. L.; Ohtake, H.; Takahashi, H.; Ikegami, S.
Tetrahedron 2001, 57, 4297–4309; (b) Heskamp, B. M.; Veeneman, G. H.; van
der Marel, G. A.; van Boeckel, C. A. A.; van Boom, J. H. Tetrahedron 1995, 51,
5657–5670; (c) Dondoni, A.; Marra, A.; Rojo, I.; Scherrmann, M.-C. Tetrahedron
1996, 52, 3057–3074; (d) Yamanoi, T.; Oda, Y.; Matsuda, S.; Yamazaki, I.;
Matsumura, K.; Katsuraya, K.; Watanabe, M.; Inazu, T. Tetrahedron 2006, 62,
10383–10392.
8. References for bis-C,C-glycosides (C-ketosides): (a) Tam, T. F.; Fraser-Reid, B. J.
Org. Chem. 1980, 45, 1344–1346; (b) Paquette, L. A.; Kinney, M. J.; Dullweber, U.
J. Org. Chem. 1997, 62, 1713–1722; (c) Dupuis, J.; Giese, B.; Hartung, J.; Leising,
M.; Korth, H.-G.; Sustmann, R. J. Am. Chem. Soc. 1985, 107, 4332–4333; (d)
RajanBabu, T. V.; Reddy, G. S. J. Org. Chem. 1986, 51, 5458–5461; (e) Lay, L.;
Nicotra, F.; Panza, L.; Russo, G.; Cavena, E. J. Org. Chem. 1992, 57, 1304–1306; (f)
Tomooka, K.; Yamamoto, H.; Nakai, T. J. Am. Chem. Soc. 1996, 118, 3317–3318;
(g) Streicher, H.; Geyer, A.; Schmidt, R. R. Chem. Eur. J. 1996, 2, 502–510; (h)
Carrel, F.; Vogel, P. Tetrahedron: Asymmetry 2000, 11, 4661–4680.
17. Schweizer, F.; Hindsgaul, O. Carbohydr. Res. 2006, 341, 1730–1736.
18. Experimental data of selected compounds: General procedure for N- and
C-glycosylation of 1-C-alkyl-sugars: To
a stirred solution of hemiketal
(0.07 mmol) in 1.0 mL dry dichloromethane, iodine (0.07 mmol, dissolved in
0.5 mL CH2Cl2) was added. To this reaction mixture TMSN3 or TMSCN
(0.21 mmol) was added slowly dropwise at ꢁ40 °C and allowed to stir at
room temperature for 3–4 h. After complete conversion as indicated by TLC,
the reaction mixture was quenched with 15% solution of sodium thiosulfate
(1.5 mL) and extracted with dichloromethane (2 ꢂ 15 mL). The combined
extracts was concentrated in vacuo. The resulting product was purified by
column chromatography on silica gel to afford the pure N- or C-ketoside.
(2S,3R,4S,5S,6R)-2-Allyl-2-azido-3,4,5-tris(benzyloxy)-6-
(benzyloxymethyl)tetrahydro-2H-pyran (9c): Rf: 0.65 (hexane/ethyl acetate, 9:1)
Oil. Yield: 72% ½a D28
ꢃ
+72.65 (c 0.89, CH2Cl2). IR (neat) mmax: 2114, 1596, 1385,
1362 cmꢁ1 1H NMR (500 MHz, CDCl3): d 7.36–7.25 (m, 20H, Ar-H), 5.94–5.89
.
(m, 1H, –CH@CH2), 5.18–5.14 (m, 2H, –CH@CH2), 4.98 (d, 1H, J = 10.9 Hz,
PhCH), 4.97 (d, 1H, J = 11.7 Hz, PhCH), 4.75–4.68 (m, 3H, 3 ꢂ PhCH), 4.60 (d, 1H,
J = 11.6 Hz, PhCH), 4.51 (d, 1H, J = 12.0 Hz, PhCH), 4.45 (d, 1H, J = 11.7 Hz,
PhCH), 4.03–3.99 (m, 3H), 3.92 (dd, 1H, J = 2.7, 9.6 Hz), 3.62 (dd, 1H, J = 7.5,
9.3 Hz), 3.56 (dd, 1H, J = 5.5, 9.3 Hz), 2.80 (dd, 1H, J = 6.5, 14.4 Hz,
-
CHaHbCH@CH2), 2.70 (dd, 1H, J = 7.5, 14.4 Hz, CHaHbCH@CH2). 13C NMR
(125 MHz, CDCl3): d 138.9, 138.3, 138.0, 131.6, 128.5–127.6 (m, Ar-C), 119.5,
94.4, 81.2, 78.4, 75.6, 74.5, 74.1, 73.6, 72.7, 72.3, 68.5, 40.3. HRMS calcd for
C
37H39N3O5 [M + NH4]+ 623.3233, Found: 623.3234.
(2S,3R,4S,5S,6R)-2-Azido-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-2-
phenyltetrahydro-2H-pyran (9d): Rf: 0.7 (hexane/ethyl acetate, 9:1) Oil. Yield:
96% ½a 2D8
ꢃ
+2.16 (c 0.925, CH2Cl2). IR (neat) m .
max: 2918, 2111, 1590, 1097 cmꢁ1
1H NMR (500 MHz, CDCl3): d 7.65 (d, 2H, J = 6.9 Hz, Ar-H), 7.41–7.19 (m, 21H,
Ar-H), 7.03–7.02 (m, 2H, Ar-H), 4.99 (d, 1H, J = 11.4 Hz, PhCH), 4.78–4.72 (ABq,
2H, J = 11.7 Hz, PhCH2), 4.63 (d, 1H, J = 11.4 Hz, PhCH), 4.53 (d, 1H, J = 11.4 Hz,
PhCH), 4.49–4.45 (m, 2H, 2 ꢂ PhCH), 4.25–4.23 (m, 1H, H-6), 4.10 (br s, 1H, H-
5), 3.96 (dd, 1H, J = 2.7, 10.1 Hz, H-4), 3.92 (d, 1H, J = 9.6 Hz, H-3), 3.89 (d, 1H,
9. References for (N-ketosides): (a) Czifrak, K.; Kovacs, L.; Kover, K. E.; Somsak, L.
Carbohydr. Res. 2005, 340, 2328–2334; (b) Dondoni, A.; Marra, A. Chem. Rev.
2000, 100, 4395–4421. see the references of fused glycosyl glycines; (c)
Schweizer, F. Angew. Chem., Int. Ed. 2002, 41, 230–253.
J = 10.5 Hz, PhCH) 3.80 (dd, 1H, J = 7.8, 8.8 Hz), 3.69 (dd, 1H, J = 5.5, 9.1 Hz). 13
C
NMR (125 MHz, CDCl3): d 138.9, 138.8, 138.4, 137.8, 137.4, 128.7–126.9 (m, Ar-
C), 96.3, 80.7, 75.9, 75.8, 74.9, 74.8, 73.5, 73.0, 72.7, 68.5. HRMS calcd for
C
40H39N3O5 [M+Na]+ 664.2787, found: 664.2787.
10. Brockhaus, M.; Lehmann, J. Carbohydr. Res. 1977, 53, 21–31.
Methyl3-((2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-2-
11. (a) Waldscheck, B.; Streiff, M.; Notz, W.; Kinzy, W.; Schmidt, R. R. Angew. Chem.,
Int. Ed. 2001, 40, 4007–4011; (b) Schweizer, F.; Otter, A.; Hindsgaul, O. Synlett
2001, 1743–1746; (c) Yamamoi, T.; Oda, Y. Heterocycles 2002, 57, 229–234; (d)
Scheizer, F.; Lohse, A.; Otter, A.; Hindsgaul, O. Synlett 2001, 1434–1436; (e)
Gomez, A. M.; Uriel, C.; Valverde, S.; Jarosz, S.; Lopez, J. C. Tetrahedron Lett.
2002, 43, 8935–8940; (f) Gomez, A. M.; Uriel, C.; Jarosz, S.; Valverde, S.; Lopez,
J. C. Eur. J. Org. Chem. 2003, 4830–4837; (g) Oda, Y.; Yamamoi, T. Synthesis 2007,
3021–3031; (h) Penner, M.; Schweizer, F. Carbohydr. Res. 2007, 342, 7–15.
12. (a) Pachamuthu, K.; Vankar, Y. D. J. Org. Chem. 2001, 66, 7511–7513; (b)
Pachamuthu, K.; Das, J.; Gupta, A.; Schmidt, R. R.; Vankar, Y. D. Eur. J. Org. Chem.
2002, 1479–1483; (c) Agarwal, A.; Rani, S.; Vankar, Y. D. J. Org. Chem. 2004, 69,
6137–6140; (d) Gopal Reddy, B.; Vankar, Y. D. Angew. Chem., Int. Ed. 2005, 44,
2001–2004; (e) Jayakanthan, K.; Vankar, Y. D. Org. Lett. 2005, 7, 5441–5444; (f)
Jayakanthan, K.; Vankar, Y. D. Tetrahedron Lett. 2006, 47, 8667–8671; (g)
Kumar, A.; Doddi, V. R.; Vankar, Y. D. J. Org. Chem. 2008, 73, 5993–5995.
13. John Pal, A. P.; Vankar, Y. D. Tetrahedron Lett. 2010, 51, 2519–2524.
14. (a) Malik, S.; Shah, K. J.; Kartha, K. P. R. Carbohydr. Res. 2010, 345, 867–871; (b)
Yadav, J. S.; Reddy, B. V. S.; Reddy, A. V.; Reddy, C. S.; Raju, S. S. Tetrahedron Lett.
2009, 50, 6631–6634; (c) Yadav, J. S.; Reddy, B. V. S.; Reddy, P. K.; Swamy, T.
Tetrahedron Lett. 2005, 46, 2687–2690; (d) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.;
Reddy, M. S. Synthesis 2003, 247–250; (e) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.;
Chand, P. K.; Prasad, A. R. Synlett 2001, 1638–1640.
cyanotetrahydro-2H-pyran-2-yl) propanoate (11a): Rf: 0.5 (hexane/ethyl
acetate, 4:1) Oil. Yield: 93% ½a D28
ꢃ
+29.19 (c 0.605, CH2Cl2). IR (neat) mmax
:
2919, 1739, 1598, 1496, 1092 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d 7.35–7.17 (m,
20H, Ar-H), 4.94 (d, 1H, J = 11.2 Hz, PhCH), 4.91–4.84 (m, 2H, PhCH2), 4.79 (d,
1H, J = 11.7 Hz, PhCH), 4.73 (d, 1H, J = 11.2 Hz, PhCH), 4.61–4.54 (m, 2H,
2 ꢂ PhCH), 4.48 (d, 1H, J = 12.2 Hz, PhCH), 3.93 (t, 1H, J = 9.2 Hz), 3.82–3.64 (m,
4H), 3.65 (s, 3H, OCH3), 3.35 (d, 1H, J = 9.5 Hz), 2.55–2.51 (m, 2H), 2.40–2.33
(m, 1H), 1.99–1.92 (m, 1H). 13C NMR (125 MHz, CDCl3): d 172.7, 138.1, 137.9,
137.8, 137.2, 128.6–127.9 (m, Ar-C), 116.8, 84.6, 81.1, 77.9, 76.9, 76.7, 75.9,
75.6, 75.2, 73.5, 68.1, 51.9, 31.8, 28.5. HRMS calcd for C39H41NO7 [M+H]+
636.2961, found: 636.2963.
(2R,3R,4S,5S,6R)-2-Benzyl-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)tetrahydro-
2H-pyran-2-carbonitrile (12b): Rf: 0.7 (hexane/ethyl acetate, 4:1) Oil. Yield: 65%
½ ꢃ +18.88 (c 0.3, CH2Cl2). IR (neat) m .
a 2D8 max: 2924, 1496, 1454, 1265, 1101 cmꢁ1
1H NMR (500 MHz, CDCl3): d 7.36–7.23 (m, 25H, Ar-H), 5.04 (d, 1H, J = 11.7 Hz,
PhCH), 4.91 (d, 1H, J = 11.5 Hz, PhCH), 4.75–4.67 (m, 3H, 3 ꢂ PhCH), 4.56 (d, 1H,
J = 11.4 Hz, PhCH), 4.44–4.41 (ABq, 2H, J = 11.7 Hz, 2 ꢂ PhCH), 4.04–4.03 (m,
1H, H-5), 3.97–3.94 (m, 1H, H-6), 3.92 (dd, 1H, J = 2.6, 9.75 Hz, H-4), 3.84 (d, 1H,
J = 9.7 Hz, H-3), 3.63 (dd, 1H, J = 7.75, 9.45 Hz, CHaHbOBn), 3.55 (dd, 1H, J = 5.4,
9.2 Hz, CHaHbOBn), 3.25 (d, 1H, J = 14.0 Hz, CHaHbPh)), 2.98 (d, 1H, J = 14.3 Hz,
CHaHbPh)). 13C NMR (125 MHz, CDCl3): d 138.6, 138.0, 137.9, 134.1, 130.9,
128.6–127.4 (m, Ar-C), 117.3, 82.5, 79.8, 75.4, 74.9, 74.7, 73.5, 72.8, 68.1, 42.2.
HRMS calcd for C42H41NO5 [M+H]+ 640.6063, found: 640.6063.
15. (a) Jin, G.; Zhao, J.; Han, J.; Zhu, S.; Zhang, J. Tetrahedron 2010, 66, 913–917; (b)
Davies, S. G.; Nicholson, R. L.; Price, P. D.; Roberts, P. M.; Russell, A. J.; Savory, E.
D.; Smith, A. D.; Thomson, J. E. Tetrahedron: Asymmetry 2009, 20, 758–772; (c)
Zymitek, K.; Zupan, M.; Stavber, S.; Iskra, J. Org. Lett. 2006, 8, 2491–2494; (d)
Varala, R.; Nuvula, S.; Adapa, S. R. J. Org. Chem. 2006, 71, 8283–8286; For a
19. CCDC 784656 (for 12d) contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.