8200
V. Di Bussolo et al. / Tetrahedron 64 (2008) 8188–8201
epoxides 1
conformation, with the oxirane and the endocyclic oxygen on the same side of
the molecular plane. Corresponding conformers 1
00-OMe, 1 00, 1 00-Tr and 8b00
(not present) and 1
00-OMe, 1a00 and 8a00 (less stable) have the two oxygens on
the opposite side of the molecular plane. All the results obtained in this theo-
retical conformational study are the subject of a manuscript from our labo-
ratory: Crotti, P.; Di Bussolo, V.; Pomelli, C. S.; Favero, L. Theor. Chem. Acc.,
submitted for publication.
b-OMe, 1b, 1b-Tr, 8b, 1a-OMe, 1a and 8a contain the same ring
AcOEt mixture yielded pure (2S,5R,6R)-5-hydroxy-2,6-dimethyl-2H-
5,6-diihydropyran (38
(1:1 hexane/AcOEt); FTIR (film)
1H NMR
6.02 (ddd, 1H, J¼10.0, 7.4, 2.3 Hz), 5.81 (dd, 1H, J¼10.0,
b
) (0.012 g, 39% yield), as a liquid: Rf¼0.45
b
b
b
n
3427, 1643, 1446, 1375, 1085 cmꢀ1
.
a
d
1.2 Hz), 4.09–4.27 (m, 1H), 3.54–3.75 (m, 2H), 1.29 (d, 3H, J¼5.8 Hz),
1.26 (d, 3H, J¼6.3 Hz). 13C NMR
d 135.4, 127.3, 73.9, 71.8, 65.2,
21.3,17.0. Anal. Calcd for C7H12O2: C, 65.60; H, 9.44. Found: C, 65.43;
H, 9.67.
9. In the reaction carried out under protocol A, trans-hydroxy mesylate 17 (or 21)
was treated with t-BuOK (1 equiv) in the glycosyl acceptor (MeOH, EtOH, i-
PrOH or t-BuOH), as the solvent. In the reaction carried out under protocol B,
a
solution of trans-hydroxy mesylate 17 (or 21) in an anhydrous solvent
6.5.2. Reaction of epoxide 8a with MeLi in anhydrous Et2O
(protocol B)
(benzene, Et2O, MeCN or THF) was treated with t-BuOK (1 equiv). After the
TLC analysis showed that the starting material was completely consumed
(15–30 min), the glycosyl acceptor (O-, C-, N- or S-nucleophile, 3–4 equiv) was
added.
Following the typical procedure, treatment of a solution of
trans-hydroxy mesylate 21 (0.050 g, 0.24 mmol) in anhydrous Et2O
(3 mL) with t-BuOK (0.029 g, 0.26 mmol) and 1.6 M CH3Li in Et2O
(0.45 mL, 0.72 mmol, 4 equiv) afforded, after 1 h stirring at 0 ꢁC,
a crude product essentially consisting of (2R, 5S, 6R)-5-hydroxy-2,6-
10. For the completeness of the comparison between the 6-deoxy- (8
and 6-OR-substituted allyl oxirane systems (1 , 1 and 1 -Tr), also some
previously unreported results with TMSCN, TMSN3, TMGA and thiols from
epoxide are described, too: see entry 5, Table (TMSCN), Scheme
(TMSN3), Schemes 10–13 (TMGA), Scheme 15 (thiols) and related discussion.
All the other results from epoxide [alcohols and partially protected
a and 8b)
a
b
b
1
a
3
9
1
a
dimethyl-2H-5,6-dihydropyran (33
a) (0.020 g, 65% yield), pure, as
20
monosaccharides (O-nucleophiles) and alkyl lithium compounds (C-nucleo-
a liquid: Rf¼0.45 (1:1 hexane/AcOEt); [
a
]
D
þ43.3 (c 1.3, CHCl3);
philes)]1c and all the results from epoxides 1
b and 1b-Tr have been previously
FTIR (film) n d 5.79 (s, 2H), 4.30 (q, 1H,
3427 cmꢀ1. 1H NMR (CDCl3)
described.1a,b,d
J¼6.8 Hz, H-1), 3.68–3.81 (m, 2H), 1.28 (d, 6H, J¼6.7 Hz). 13C NMR
11. Achmatowicz, O., Jr.; Szechner, B. Carbohydr. Res. 1976, 50, 23–33. See also:
Achmatowicz, O., Jr.; Bukowski, P.; Szechner, B.; Zwierzchowska, Z.; Zamojski, A.
Tetrahedron 1971, 27, 1973–1996.
12. (a) Ramnauth, J.; Poulin, O.; Rakhit, S.; Maddaford, S. P. Org. Lett. 2001, 3, 2013–
2015; (b) Hayashi, M.; Kawabata, H.; Nakayama, S.-Z. Chirality 2003, 15, 10–16;
(c) Pudlo, P.; Thiem, J.; Vill, V. Chem. Ber. 1990, 123, 1129–1135.
(CDCl3)
d 133.2, 128.5, 71.5, 68.3, 66.8, 30.5, 18.2. Anal. Calcd for
C7H12O2: C, 65.60; H, 9.44. Found: C, 65.78; H, 9.59. MS (m/z) 91,
102, 112, 122, 129 (MþH)þ.
13. The proposed oxirane oxygen–nucleophile coordination appears at the mo-
ment as the only rationalization able to justify the regio- and stereoselectivity
obtained both with coordinating and non-coordinating nucleophiles. However,
at least in principle, the occurrence of other effects cannot be ruled out.
14. On the basis of the evidences found by Woerpel,15 the required activation of
TMSCN by a nucleophile, with the formation of a pentacoordinate siliconate
such as TMSCN-PS, the actual reacting species (Scheme 7), could arise by the
reaction of TMSCN with MeSOꢀ3 Kþ, formed in the base-catalyzed cyclization of
Acknowledgements
`
This work was supported by the Universita di Pisa and MIUR
(Ministero dell’Istruzione, della Universita e della Ricerca) Roma.
We thank Dr. Alessandra Bertoli of our Department for performing
mass spectra of selected compounds. P.C. gratefully acknowledges
Merck Research Laboratories for the generous financial support
deriving from the 2005 ADP Chemistry Award.
`
trans-hydroxy mesylate 17 to the epoxide 8
b. The same can be said for the
corresponding reaction of epoxides 8 , 1 and 1
a
a
b
-Tr. In the case of 1 -Tr, the
b
rationalization previously proposed in order to justify the complete regio- and
stereoselectivity observed in its reaction with TMSCN should be appropriately
modified.1d
15. Shenoy, S. R.; Smith, D. M.; Woerpel, K. A. J. Am. Chem. Soc. 2006, 128, 8671–
8677 and references therein.
Supplementary data
16. (a) Among the four diastereoisomeric 6-deoxy azido alcohols, cis-azido alcohol
50 has not been previously described. (b) For the 4-OBz derivative of the en-
Supplementary data associated with this article can be found in
antiomer of 48b, see: Kirschning, A.; Domann, S.; Dra¨ger, G.; Rose, L. Synlett
1995, 767–769. For the 4-OAc or 4-OBz derivative of 54, 56, 60 and 62, see: (c)
Boivin, J.; Montagnac, A.; Monneret, C.; Pais, M. Carbohydr. Res. 1980, 85, 223–
242; (d) Boivin, J.; Pais, M.; Monneret, C. Carbohydr. Res. 1980, 79, 193–204.
References and notes
17. The previously described result for the reaction of epoxide 1
indicated 16:39:45 mixture of trans-azido alcohol 59 (anti-1,2-addition
product), cis-azido alcohol 49 (syn-1,2-addition product) and 4-OTMS-derived
-glycosyl azide 48 -OTMS (
-1,4-addition product, coordination product).1d
18. The 55-Ac/53 -Ac ratio slightly decreased on standing in solution (CDCl3): after
two days 55-Ac/53
-Ac¼67:33.
19. The syn-1,2-addition product (56)/coordination product (54
b-Tr with TMSN3
a
1. (a) Di Bussolo, V.; Caselli, M.; Pineschi, M.; Crotti, P. Org. Lett. 2002, 4, 3695–
3698; (b) Org. Lett. 2003, 5, 2173–2176; (c) Di Bussolo, V.; Caselli, M.; Romano,
M. R.; Pineschi, M.; Crotti, P. J. Org. Chem. 2004, 69, 7383–7386; (d) J. Org. Chem.
2004, 69, 8702–8708.
b
b
b
a
a
a
-OTMS) ratio in-
2. Methyl O-glycoside 9a is the intermediate for the formal synthesis of D ring of
calicheamicin gI1
;
ethyl O-glycoside 10a is the 2,3-unsaturated glycoside nec-
3a
creased from about 1.25:1 after 10 min to about 5.3:1 after 30 min.
20. For examples of [3,3]-sigmatropic rearrangement by the azido group, see: (a)
Heyns, K.; Hohlweg, R. Chem. Ber. 1978, 111, 1632–1645; (b) Paulsen, H.; Heiker,
F. R. Carbohydr. Res. 1982, 102, 83–98; (c) Takasu, H.; Tsuji, Y.; Sajiki, H.; Hirota,
K. Tetrahedron 2005, 61, 11027–11031.
essary for the synthesis of (ꢀ)-methyl ravidosaminide;3b,c tert-butyl O-glycoside
11a
is the key intermediate for the synthesis of the antifungal agent GM222712.3d
3. (a) Clive, D. L. J.; Tao, Y.; Bo, Y.; Hu, Y.-Z.; Selvakumar, N.; Sun, S.; Daigneault, S.;
Wu, Y.-J. Chem. Commun. 2000, 1341–1350; (b) Knapp, S.; Lal, G. S.; Sahai, D. J.
Org. Chem. 1986, 51, 380–383; (c) Yunker, M. B.; Tam, S. Y.-K.; Hicks, D. R.;
21. The reaction of epoxide 1a with TMGA was repeated in CD3CN in an NMR tube.
´
The 1H NMR spectra of the reaction mixture registered at different reaction
times indicated the presence of a mixture of trans-azido alcohol 61, as the main
reaction product (84%), accompanied by a mixture (overall 16%) of cis-azido
Fraser-Reid, B. Can. J. Chem. 1976, 54, 2411–2416; (d) Bueno, J. M.; Coteron, J. M.;
Chiara, J. L.; Ferna´ndez-Mayoralas, A.; Fiandor, J. M.; Valle, N. Tetrahedron Lett.
2000, 41, 4379–4382.
alcohol 55 and
action times from 55/53
NMR analysis indicated only the presence of trans-azido alcohol 61 (85%) and
cis-azido alcohol 55 (15%).
a-glycosyl azide 53a in a ratio, which increased with the re-
4. (a) Di Bussolo, V.; Favero, L.; Macchia, F.; Pineschi, M.; Crotti, P. Tetrahedron
2002, 58, 6069–6091; (b) Fraser-Reid, B.; Kelly, D. R.; Tulshian, D. B.; Ravi, P. S.
J. Carbohydr. Chem. 1983, 2, 105–114; (c) Pihko, A. J.; Nicolaou, K. C.; Koskinen,
A. M. P. Tetrahedron: Asymmetry 2001, 12, 937–942.
a
¼6:1 after 5 min to 40:1 after 50 min. After 2 h, 1H
22. Bonner, O. D. J. Phys. Chem. 1979, 83, 1218–1220.
23. Moss, R. A.; Terpinski, J.; Cox, D. P.; Denny, D. Z.; Krogh-Jespersen, K. J. Am.
Chem. Soc. 1985, 107, 2743–2748.
5. Epoxides 8a and 8b are not isolable, and can only be prepared in situ by cy-
clization of the corresponding stable precursors, the trans-hydroxy mesylates
17 and 21, respectively, and left immediately to react with a nucleophile.
24. The addition reactions of EtSH and MeSNa to epoxide 1b-Tr are completely
6. For a recently described synthesis of 6-deoxy-D-gulal (18), see: Engstrom, K. M.;
1,2-regioselective with the exclusive formation of the corresponding non-
coordination product. In the case of PhSH, a small amount (15%) of the corre-
Mendoza, M. R.; Navarro-Villalobos, M.; Gin, D. Y. Angew. Chem., Int. Ed. 2001,
40, 1128–1130.
sponding phenyl
25. As previously admitted for the corresponding reaction with TMGA, the larger
amount of coordination product ( -thioglycoside, 1,4-addition product) found in
the reaction with thiols of epoxide 1 with respect to 8 (Schemes 14 and 15)
and 1 to react through conformer 1
-Tr1d,24 is due to the possibility for 1 0, in
b
-thioglycoside, the coordination product, was obtained.1d
7. Alternatively, trans-diol 18 could be prepared by reaction of epoxide 8
b with
commercially available tetrabutylammonium acetate (Bu4NþAcOꢀ). In this re-
action, contrary to expectations, trans-diol 18 was the only reaction product:
a saponification process on the primary reaction product, the monoacetate
18-Ac, reasonably occurred under the slightly alkaline reaction conditions
(Scheme 3).
a
a
b
b
a
a
which the coordinated attack on C(1) corresponds to a more favourable pseu-
doaxial attack (structure 7800, route a, Scheme 15). As they exist in only con-
8. It is interesting to note that the unique (1
b
0-OMe, 1
b b b
0, 1 0-Tr and 8 0) and the
8
0-Tr and
8
b0
,
respectively, the same attack in
1
b-Tr and
8
b
more stable conformer (1
a
0-OMe, 1a0 and 8
a
0) present at the equilibrium in
former
1
b