LETTER
Phenyl 2,3,4-tri-O-acetyl-6-O-[methyl-O-(6-O-tert-
Study of the Regioselectivity of Mannoside Diol Acceptors
1099
6.0 Hz, H6¢), 4.77 (d, 1 H, J = 2.7 Hz, H1), 4.67 (d, 1 H,
J = 1.6 Hz, H1¢), 4.49 (dd, 1 H, J = 15.0, 2.7 Hz, H2), 4.22
(dd, 1 H, J = 16.0, 2.7 Hz, H6¢), 3.88 (ddd, 1 H, J = 13.3, 5.9,
3.8 Hz, H5), 3.73 (m, 2 H, 2 H6), 3.71 (dd, 1 H, J = 4.2, 1.6
Hz, H2¢), 3.59 (s, 3 H, OMe), 3.53 (dd, 1 H, J = 13.5, 13 Hz,
H4¢), 3.46 (s, 3 H, OMe), 3.44 (s, 3 H, OMe), 3.43 (s, 3 H,
OMe), 3.44–3.37 (m, 1 H, H5¢), 3.19 (dd, 1 H, J = 13.0, 4.2,
H3¢), 1.96 (s, 3 H, Me), 1.02 (s, 9 H, t-Bu). 13C NMR (75
MHz, CDCl3): d = 169.9 (CO), 168.8 (CO), 167.4 (CO),
136.0 (2 CH), 136.0 (2 CH), 134.2, 133.6, 131.9, 131.6,
130.6, 130.1, 128.5, 128.1 (2 CH), 128.0 (2 CH), 99.3 (C1,
JC-H = 168 Hz), 98.6 (C1¢, JC-H = 156 Hz), 83.1 (C3¢), 76.0
(C4¢, C2¢), 73.3 (C5¢), 71.9, 71.8, 71.6 (C3, C2 and C5), 67.6
(C4), 63.4 (C6), 62.0 (C6¢), 61.4 (OMe), 61.1 (OMe), 57.3
(OMe), 55.2 (OMe), 27.0 (3 Me), 21.1 (Me), 19.6 (C). MS
(ES): m/z (%) = 809(7) [M + 1], 826 (100) [M + 18], 831
(63) [M + 23].
butyldimethylsilyl-a-D-mannopyranos-3-yloxy)-2-
carbonylbenzoyl]-1-thio-a-D-mannopyranoside (8b):
[a]D +32.2 (c 0.5, CHCl3). 1H NMR (400 MHz, CDCl3): d =
7.75 (d, 1 H, J = 7.8 Hz, Ar), 7.68–7.51 (m, 7 H, Ar), 7.45–
7.19 (m, 9 H, Ar), 7.14–7.11 (m, 2 H, Ar), 5.43–5.41 (m, 2
H, H1¢, H2¢), 5.35 (t, 1 H, J = 9.9 Hz, H4¢), 5.26 (m, 1 H, H3),
5.22 (dd, 1 H, J = 9.9, 3.1 Hz, H3¢), 4.65 (d, 1 H, J = 1.5 Hz,
H1), 4.54 (ddd, 1 H, J = 9.9, 7.8, 3.5 Hz, H5¢), 4.35 (dd, 1 H,
J = 7.8, 3.5 Hz, H6¢a and H6¢b), 4.20 (m, 1 H, H2), 4.0 (dt, 1 H,
J = 9.7, 2.8 Hz, H4), 3.91 (dd, 1 H, J = 10.7, 4.7 Hz, H6a),
3.85 (dd, 1 H, J = 10.7, 5.3 Hz, H6b), (m, 1 H, H5) 3.41 (s, 3
H, OMe), 3.14 (d, 1 H, J = 2.9 Hz, C4-OH), 2.88 (d, 1 H,
J = 4.7 Hz, C2-OH), 2.02 (s, 3 H, Me), 1.94 (s, 3 H, Me), 1.93
(s, 3 H, Me), 0.98 (s, 9 H, t-Bu). 13C NMR (50 MHz, CDCl3):
d = 170.0 (CO), 169.7 (2 ꢀ CO), 167.6 (CO), 167.1 (CO),
135.6, 131.8, 130.7, 129.7, 129.5, 129.4, 129.2, 128.0,
127.7, 100.7, 86.6, 77.0, 71.9, 70.9, 69.4, 69.2, 68.6, 66.9,
66.5, 64.9 (C-6), 63.9 (C-6), 54.8 (OMe), 26.8 (t-Bu), 20.7
(2 ꢀ Me), 20.6 (Me), 19.2. ESI+ [M + Na]+: 983.6; ESI– [M
+ Cl]–: 995.4.
Methyl O-(2¢,3¢,4¢-tri-O-methyl-a-d-mannopyranosyl)-
(1-4)-2-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside-3,6¢-phthalate (12a): 1H NMR (300
MHz, CDCl3): d = 7.96 (dd, 1 H, J = 7.4, 1.1 Hz, Ar), 7.75–
7.35 (m, 13 H, Ar), 5.89 (dd, 1 H, J = 10.7, 3.6 Hz, H3), 5.68
(t, 1 H, J = 2.2 Hz, H2), 5.19 (d, 1 H, J = 3.7 Hz, H1¢), 5.04
(d, 1 H, J = 9.3 Hz, H6 or H6¢), 4.72 (d, 1 H, J = 2.2 Hz, H1),
5.58 (t, 1 H, J = 10.3 Hz, H4), 4.04 (dd, 1 H, J = 10.7, 3.0, H6
or H6¢), 3.96–3.85 (m, 5 H, 2 H6 or 2 H6¢, H5¢ H5 and H4¢), 3.51
(s, 3 H, OMe), 3.42 (s, 3 H, OMe), 3.41 (s, 3 H, OMe), 3.30
(m, 1 H, H2¢), 3.27 (s, 3 H, OMe), 3.19 (dd, 1 H J = 9.3, 5.5
Hz, H3¢), 2.17 (s, 3 H, Me), 1.05 (s, 9 H, t-Bu). 13C NMR (75
MHz, CDCl3): d = 170.3 (CO), 168.2 (CO), 165.5 (CO),
135.7 (2 CH), 135.6 (2 CH), 135.2, 133.5, 133.3, 132.4,
131.2, 130.0, 129.7, 129.6, 127.6 (2 CH), 127.6 (2 CH), 98.2
(C1, JC-H = 172 Hz), 92.6 (C1¢, JC-H = 160 Hz), 79.2 (C2¢),
77.1 (C3¢), 71.1, 69.8, 69.7, 69.2, 68.8 (H4), 64.9 (CH2), 62.3
(CH2), 59.2 (OMe), 58.2 (OMe), 57.9 (OMe), 55.3 (OMe),
26.7 (3 Me), 20.7 (Me), 19.4 (C). After desilylation of 12
with TBAF and treatment with pyridine–Ac2O: 13C NMR
(75 MHz, CDCl3): d = 98.6 (C1, JC-H = 177 Hz), 93.3 (C1¢,
JC-H = 166 Hz). MS (ES): m/z (%) = 809 (2) [M + 1], 826
(100) [M + 18], 831 (40) [M + 23].
(11) Procedure for Intramolecular Glycosylation Reactions.
Method A: diester 8a was co-evaporated 3 times with
toluene, 4 Å molecular sieves were added, and the residue
was dried under vacuum for 3 h. The mixture was dissolved
in CH2Cl2 under argon, and NIS (3 equiv) was added as solid
under a stream of argon at r.t. The reaction mixture was
stirred for 48 h, then NaHCO3 and Na2S2O3 were added as
solids. The mixture was stirred at r.t. for 30 min, then filtered
through a short pad of celite, the solvent was evaporated, and
the crude product was purified by flash chromatography.
Method B: as for method A, but with the addition of 0.1
equiv of TfOAg after the addition of NIS. In this case the
reaction mixture was stirred at –40 °C for 2 h, was left to
reach r.t. over a period of 12 h, and was then stirred at r.t. for
a further 4 h.
Method C: as for method A, but with the addition of 1 equiv
of TfOAg after the addition of NIS and stirring the reaction
mixture at 0 °C for 10 min.
Methyl O-(2¢,3¢,4¢-tri-O-methyl-a-D-mannopyranosyl)-
(1-2)-6-O-tert-butyldiphenylsilyl-a-D-mannopyranoside-
3,6¢-phthalate (10a): [a]D +43 (c 0.21, CHCl3). 1H NMR
(300 MHz, CDCl3): d = 7.88 (dd, 1 H, J = 6.6, 2.2 Hz, Ar),
7.58–7.33 (m, 13 H, Ar), 5.57 (d, 1 H, J = 4.4, H1¢), 5.32 (dd,
1 H, J = 10.2, 3.4 Hz, H3), 4.78–4.74 (m, 2 H, H1 and H6¢),
4.58 (m, 1 H, H2), 4.43–4.33 (m, 2 H, H6¢ and H4), 4.12 (m,
2 H, 2 H6), 3.83 (m, 1 H, H5¢), 3.78 (dt, J = 9.3, 4.1 Hz, 1 H,
H5), 3.53–3.51 (m, 1 H, H2¢), 3.50 (s, 3 H, OMe), 3.45–3.35
(m, 2 H, H4¢ and H3¢), 3.41 (s, 3 H, OMe), 3.37 (s, 3 H, OMe),
3.36 (s, 3 H, OMe), 2.82 (d, 1 H, J = 3.5 Hz, C4OH), 1.08 (s,
9 H, t-Bu). 13C NMR (75 MHz, CDCl3): d = 168.1 (CO),
168.0 (CO), 136.1 (4 CH), 133.5, 133.4, 132.9, 132.8, 132.0,
131.4, 130.5, 130.1, 129.7, 128.8, 128.1 (2 CH), 128.0 (2
CH), 101.4 (C1, JC-H = 166 Hz), 98.0 (C1¢, JC-H = 175 Hz),
80.6 (C2¢), 78.9 (C4¢), 77.6 (C3), 76.0 (C3¢), 74.6 (C5¢), 73.0
(C5), 71.8 (C2), 66.8 (C4), 66.3 (C6), 64.8 (C6¢), 60.5 (OMe),
59.1 (OMe), 58.0 (OMe), 55.1 (OMe), 28.9 (C), 27.2 (3Me).
After treatment with pyridine–Ac2O: 1H NMR (300 MHz,
CDCl3): d = 5.55 (t, 1 H, J = 10.0 Hz, H4). MS (ES): m/z
(%) = 809 (14) [M + 1], 826 (100) [M + 18], 831 (28) [M +
23].
Methyl O-(2¢,3¢,4¢-tri-O-methyl-b-D-mannopyranosyl)-
(1-4)-2-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside-3,6¢-phthalate (13a): [a]D –15 (c 0.17,
CHCl3), 1H NMR (300 MHz, CDCl3): d = 7.70–7.30 (m, 14
H, Ar), 5.69 (dd, 1 H, J = 6.3, 3.7 Hz, H3), 5.46 (t, 1 H,
J = 3.7 Hz, H2), 4.95 (dd, 1 H, J = 11.5, 2.7 Hz, H6¢), 4.78 (d,
1 H, J = 4.7 Hz, H1), 4.41 (s, 1 H, H1¢), 4.28 (dd, 1 H, J = 9.8,
6.3 Hz, H4), 4.12 (dd, 1 H, J = 11.5, 6.6 Hz, H6¢), 4.00–3.88
(m, 2 H, 2 H6), 3.85–3.78 (m, 1 H, H5), 3.52 (s, 3 H, OMe),
3.46 (s, 3 H, OMe), 3.44 (s, 3 H, OMe), 3.43 (s, 3 H, OMe),
3.50–3.26 (m, 2 H, H5¢ and H2¢), 3.34 (t, 1 H, J = 8.8 Hz, H4¢),
3.01 (dd, 1 H, J = 8.8, 2.9 Hz, H3¢), 2.07 (s, 3 H, Me), 1.09
(s, 9 H, 3 Me). 13C NMR (75 MHz, CDCl3): d = 170.7 (CO),
167.8 (CO), 167.1 (CO), 136.4 (2 CH), 136.1 (2 CH), 134.3,
133.6, 133.1, 131.8, 131.7, 131.3, 130.4, 129.6, 128.3 (2
CH), 128.2 (2 CH), 102.4 (C1¢, JC-H = 157 Hz), 99.1 (C1,
JC-H = 172 Hz), 83.8 (C3¢), 77.1 (C4¢), 76.8 (C5¢), 74.9 (C4),
74.0 (C3), 73.8 (C2¢), 72.1 (C5), 70.2 (C2), 64.1 (C6¢), 63.7
(C6), 61.8 (OMe), 61.2 (OMe), 57.9 (OMe), 55.7 (OMe),
27.1 (3 Me), 21.4 (Me), 19.7 (C). MS (ES): m/z (%) = 809
(5) [M + 1], 826 (100) [M + 18], 831 (16) [M + 23].
Methyl O-(2¢,3¢4¢-tri-O-acetyl-a-d-mannopyranosyl)-(1-
2)-a-D-mannopyranoside-3,6¢-phthalate: formed by
treatment of 10b with TBAF. 1H NMR (400 MHz, CDCl3):
d = 7.94–7.93 (m, 1 H, Ar), 7.55–7.50 (m, 3 H, Ar), 5.69 (d,
1 H, J = 4.7 Hz, H1¢), 5.33 (dd, 1 H, J = 10.6, 3.7 Hz, H3),
5.24 (dd, 1 H, J = 7.0, 3.8 Hz, H3¢), 5.06–5.00 (m, 2 H, H2¢,
Methyl O-(2¢,3¢,4¢-tri-O-methyl-b-D-mannopyranosyl)-
(1-2)-4-O-acetyl-6-O-tert-butyldiphenylsilyl-a-D-
mannopyranoside-3,6¢-phthalate (11a): [a]D –19 (c 1.07,
CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.78–7.62 (m, 5
H, Ar), 7.56–7.28 (m, 9 H, Ar), 5.45 (dd, 1 H, J = 16.0, 4.8
Hz, H3), 5.36 (t, 1 H, J = 15.0, H4), 5.07 (dd, 1 H, J = 16.0,
Synlett 2005, No. 7, 1095–1100 © Thieme Stuttgart · New York