Synthesis of glycosyl boranes and glycosyl borinates

Article abstract of DOI:10.1039/a906400a

Insertion of glycosylidene carbenes into a B-C bond of BEt₃ leads to unstable glycosyl boranes, while insertion into a B-C bond of borinic esters yields stable anomeric glycosyl borinates.

Full text of DOI:10.1039/a906400a

Synthesis of glycosyl boranes and glycosyl borinates†
Andrea Vasella,* Wolfgang Wenger and Thennati Rajamannar
Laboratorium für Organische Chemie, ETH-Zentrum, Universitätstrasse 16, CH–8092 Zürich, Switzerland.
E-mail: vasella@sugar.org.chem.ethz.ch
Received (in Liverpool, UK) 5th August 1999, Accepted 17th September 1999
Insertion of glycosylidene carbenes into a B–C bond of BEt3
leads to unstable glycosyl boranes, while insertion into a B–C
bond of borinic esters yields stable anomeric glycosyl
borinates.
was rapidly converted into the hemiacetal 5 (isolated in ca.
75%) by exposure to air, storage in oxygen–containing CDCl3,
or treatment with alkaline H2O2. The 11B NMR of air-stable
mixtures of 7 and 2 equiv. of PPh3 shows a broad signal at d
1
56.5, typical for dialkyl borinic acids.8 The H NMR shows a
Insertion of glycosylidene carbenes, generated by thermolysis
or photolysis of glycosylidene diazirines, into HX bonds leads
to O-, C- and N-glycosides,1 glycosyl phosphines2 and glycosyl
stannanes.3 We speculated that reaction of a borane with the
carbene 2 would lead to a zwitterion such as 3; migration of a B-
substituent—as proposed for the reaction of methoxycarbene
with trialkylboranes4—should lead to the as yet unknown
glycosyl boranes (Scheme 1).
broad singlet of an exchangeable H at d 8.16, corresponding to
B–OH, two doublets of quintets at d 1.8 and 1.6 (2 H), a triplet
at d 0.9 (3 H) for the C-ethyl and a multiplet at d 1.0–0.9 (5 H)
of the B–Et group. The 13C NMR signal for the boron
substituted anomeric carbon is missing, as expected.9
The intermediate formation of a glycosyl borane was further
evidenced by treating the product of thermolysis of 1 and BEt3
in degassed THF with excess TFA, followed by aqueous work-
up (Scheme 3). The resulting cyclic borinic ester 8, isolated in
45%, showed a 11B signal at d 51, typical for O-alkyl
borinates.10
Scheme 3
Scheme 1
1
The H NMR spectrum of 8 shows signals for a BC(Et)2
Thermolysis of the diazirine 15 in degassed THF in the
presence of 1.5 equiv. of BEt3 at 25 °C, followed by treatment
with excess 30% alkaline H2O2 and aqueous work-up, yielded
55% of hemiacetal 5 and 13% of the C-ethylglucal 6. These
products suggest the intermediate formation of anomeric
glycosyl boranes 4. Treatment with alkaline H2O2 leads either
(depending on the borane configuration?) to oxidation6 and
(after anomerisation?) to the hemiacetal 5, or to elimination of
the C(1) boron substituent and the vicinal benzyloxy group.7
trans-Elimination is suggested by the observation (13C NMR)
that 6 is only formed after additon of alkaline H2O2.
Thermolysis of the diazirine 1 in the presence of 1.5 equiv. of
BEt3 in oxygen-containing THF yielded 25% of the borinic acid
7 after rapid chromatography (Scheme 2). The borinic acid 7
moiety and a multiplet at d 0.9–0.7 for a BEt group. H–C(7) is
strongly shifted downfield due to the R2BO substituent [H–C(5)
in 6 at d 4.02, H–C(7) in 8 at d 4.77].
The formation of 8 is rationalised by protonation of the ring
oxygen of 4, nucleophilic attack of trifluoroacetate at boron,
1,2-migration of an ethyl substituent with concomitant ring-
opening, and nucleophilic attack of HO–C(7) at boron.
Treatment of 8 with alkaline H2O2 in THF leads to the diol 9
(37%) and the alkene 10 (39%) (Scheme 4).
To prepare glycosyl borinates, we exposed the diazirine 1 to
the exceptionally stable borinates 11–1211 derived from
10-bora-9-oxabicyclo[3.3.2]decane (Scheme 5). This led to
Scheme 2
† Glycosylidene Carbenes Part 28. For Part 27, see ref. 1(b).
Scheme 4
Chem. Commun., 1999, 2215–2216
This journal is © The Royal Society of Chemistry 1999
2215

(hexane–AcOEt–CH2Cl2 18+1+1) gave 17/18 (61 mg, 55%, 45+55), which
were separated by preparative HPLC (hexane–AcOEt 12+1; 9 ml min21).
Selected data for 17: Rf (hexane–AcOEt–CH2Cl2 4+1+1) 0.36; [a]2D5 +51.4
(c 1.16, CH2Cl2); nmax(CH2Cl2)/cm21 3032w, 2927m, 2963m, 1604w,
1493m, 1453m, 1420m, 1364m, 1092s, 1027s; dH(300 MHz, CDCl3)
7.62–7.11 (m, 20 arom. H), 4.87 (d, J 10.6, PhCH), 4.85 (d, J 10.9, PhCH),
4.83 (d, J 10.9, PhCH), 4.77 (d, J 10.9, PhCH), 4.71 (d, J 12.1, PhCH),
4.70–4.66 (m, BOCH), 4.68 (d, J 10.9, PhCH), 4.66 (d, J 10.9, PhCH), 4.64
(d, J 12.1, PhCH), 3.91 [t, J 8.7, H–C(5)], 3.74 [dd, J 11.2, 4.0, H–C(8)],
3.73 [dd, J 11.2, 1.9, HA–C(8)], 3.68 [d, J 9.0, irrad. at 3.91 ? d, J ≈ 4, H–
C(4)], 3.67–3.63 [m, H–C(7)], 3.58 [t, J 8.4, irrad. at 3.91 ? dd, J ≈ 9, 3,
H–C(6)], 2.65–2.56 [m, 2 H–C(1)], 2.37–2.27 [m, irrad. at 2.6 ? d, J ≈ 10,
H–C(2)], 2.22–2.18 (m, BCH), 2.01–1.91 [m, irrad. at 2.6 ? d, J ≈ 10, HA–
C(2)], 2.01–1.46 (m, 12 H); dC(75 MHz, CDCl3, assignment based on 1H/
13C COSY) 142.03 (s), 139.00 (2s), 138.69, 138.29, 131.12 (3s),
129.79–127.12 (several d), 84.42 [d, C(5)], 81.57 [d, C(4)], 79.53 [d, C(6)],
75.60, 75.13, 74.73 (3t, 3 PhCH2), 74.19 (d, BOCH), 73.51 (t, PhCH2),
72.24 [d, C(7)], 69.99 [t, C(8)], 32.41 (t), 30.63 (t), 30.19 [t, C(1)], 28.91 [t,
C(2)], 27.54 (t), 25.63 (t), 22.89 (t), 21.91 (t), 21.30 (small br d, HCB),
signal of C(3) hidden by noise; dB(160 MHz, CDCl3) 52.02 (br s); m/z
(FAB) 821 ( < 1%, [M + Na]+), 799 ( < 1, [M + H]+), 599 (38), 553 (43, [M
2 BnOBOC8H14 + H]+), 447 (44), 181 (100). For 18: Rf (hexane–AcOEt–
CH2Cl2 10+1+1) 0.32; [a]2D5 +12.0 (c 0.65, CH2Cl2); nmax(CH2Cl2/cm21
3032w, 2927m, 1492m, 1453m, 1418w, 1364m, 1093s, 1027m, 1015m;
dH(300 MHz, CDCl3) 7.38–6.99 (m, 20 arom. H), 4.98 (d, J 11.8, PhCH),
4.85 (d, J 10.9, PhCH), 4.84 (s, PhCH2), 4.70 (d, J 11.8, PhCH), 4.71–4.67
(m, HCOB), 4.68 (d, J 12.1, PhCH), 4.62 (d, J 10.9, PhCH), 4.60 (d, J 12.1,
PhCH), 3.96 [dt, J ≈ 9.6, 4.0, H–C(7)], 3.78–3.70 [m, H–C(5), 2 H–C(8)],
3.60 [t, J 9.6, irrad. at 3.96 ? d, J ≈ 9, H–C(6)], 3.50 [d, J 9.4, H–C(4)],
2.74–2.67 [m, 2 H–C(1)], 2.25–2.21 (m, BCH), 2.05–1.95 [m, irrad. at 2.70
Scheme 5
diastereoisomeric mixtures 13/14 (31%; 35:65), 15/16 (42%;
40+60) and 17/18 (55%; 45:55) that were isolated by flash
chromatography. The isomers 15/16 and 17/18 were separated
by HPLC. The glycosyl borinates 13–18 were characterized by
FAB-MS, 11B NMR, 1H NMR, 13C NMR and IR spectroscopy.
They were stable at 210 °C for several weeks and not affected
by air.
The configuration of 17 and 18 was deduced from NOE
experiments (Fig. 1), with 17 showing NOEs between H–C(2)
and H–C(5), H–C(2) and H–C(7), and H–C(1A) and H–C(4),
indicating an axial orientation of the anomeric alkyl group. In
contradistinction, a small NOE between H–C(1A) and H–C(5)
and the lack of other NOEs > 1% for 18 indicate an equatorial
orientation of the anomeric alkyl group.
? d, J
≈ 12, H–C(2)], 1.99–1.26 (m, 13 H); dC(75 MHz, CDCl3,
assignment based on 1H/13C COSY) 141.75 (s), 139.26 (2s), 138.2, 137.8,
133.6 (3s), 129.9–127.14 (several d), 85.93 [d, C(5)], 84.90 [d, C(3)], 79.54
[d, C(6)], 76.00 [d, C(7)], 75.37, 75.09, 74.80 (3t, 3 PhCH2); 74.06 (d,
BOCH), 73.22 (t, PhCH2), 69.93 [t, C(8)], 37.14 [t, C(2)], 31.82 (t), 30.91
(t), 29.33 [t, C(1)], 26.79 (t), 25.77 (t), 23.38 (small br d, BCH), 22.48 (t),
21.92 (t), signal of C(3) hidden by noise; dB(160 MHz, CDCl3) 53.8 (br s);
m/z (FAB) 821 ( < 1%, [M + Na]+), 799 ( < 1, [M + H]+), 553 (43, [M 2
BnOBOC8H14 + H]+), 461 (28), 401 (41), 325 (60), 281 (87), 181 (100).
1 (a) A. Vasella, Glycosylidene Carbenes, in Bioorganic Chemistry, Vol.
3, Carbohydrates, ed. S. Hecht, OUP, New York, 1999, p. 56 and
references therein; (b) M. Weber, A. Vasella, M. Textor and N. D.
Spencer, Helv. Chim. Acta, 1998, 81, 1359; (c) K. Briner and A. Vasella,
Helv. Chim. Acta, 1992, 75, 621; (d) P. Uhlmann and A. Vasella, Helv.
Chim. Acta, 1992, 75, 1979; (e) A. Vasella and C. A. A. Waldraff, Helv.
Chim. Acta, 1991, 74, 585; (f) A. Vasella, P. Dhar and C. Witzig, Helv.
Chim. Acta, 1993, 76, 1767; (g) T. Rajamannar and A. Vasella,
unpublished results on the synthesis of N-glycosylsulfonamides.
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151.
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77, 1430.
4 A. Suzuki, S. Nozawa, N. Miyaura and M. Itoh, Tetrahedron Lett., 1969,
2955.
Fig. 1
5 K. Briner and A. Vasella, Helv. Chim. Acta, 1989, 72, 1371.
6 G. Zweifel and H. C. Brown, Org. React., 1963, 13, 1.
7 D. J. Pasto and S. R. Snyder, J. Org. Chem., 1966, 31, 2777; D. S.
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We thank the Swiss National Science Foundation and F
Hoffmann-La Roche, Basel, for generous financial support.
Notes and references
‡ Synthesis of 17 and 18: at 25 °C, a solution of 12 (R,RA = H, 4-ClC6H4,
116 mg, 0.42 mmol) in abs. THF (3 ml) was treated portionwise with a
cooled (dry ice, ca. 260 °C) solution of 1 (77 mg, 0.14 mmol) in dry CH2Cl2
(0.8 ml) within 140 min, stirred for 2 h at 25 °C until complete
disappearance of 1. Evaporation at 20 °C and flash chromatography
11 J. A. Soderquist and M. R. Najafi, J. Org. Chem., 1986, 51, 1330.
Communication 9/06400A
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Chem. Commun., 1999, 2215–2216