Synthesis of all four isomers of (E)-4,5-dihydroxydec-2-enal using osmium-catalysed asymmetric dihydroxylation (original) (raw)
The Journal of Organic Chemistry, 1991
A stereochemically general strategy for the synthesis of 2-deoxyhexoses is described. This new approach involves the asymmetric allylboration of epoxy aldehydes 12 and 13, prepared via the Sharpless asymmetric epoxidation reaction, as a means of establishing the stereochemistry of the sugar backbone. Thus, the matched double asymmetric allylborations of 12 and 13 using tartrate allylboronates (R,R)and (S,S)-7, respectively, provide erythro epoxy alcohols 14 and 16 with excellent diastereoselectivity (>96:4) and enantioselectivity (296% ee). The mismatched double asymmetric reactions of 12 and 13 using (S,S)-and (R,R)-7, respectively, provided the diastereomeric threo epoxy alcohols 15 and 17 with lower (ca. 7525) but still synthetically useful selectivity. The enantiomeric purity of the major diastereomer in each of these reactions was determined to be greater than that of the epoxy aldehyde precursors. Epoxy alcohols 14 and 16 were converted with excellent selectivity to the 1-urubino (21) and I-xylo (26) tetrols via neighboring group assisted a-substitution reactions of the derived phenylurethane derivatives 18 and 23. Stereochemically complementary 0-opening reactions were accomplished by treating primary alcohols 38,40,42, and 44 [prepared from 14-17, respectively, by ethoxyethylation of C(4)-OH and removal of the C(7)-tert-butyldiphenylsilyl (TBDPS) ethers] with NaOH in aqueous t-BuOH at reflux. Acid-catalyzed hydrolysis of the C(4)-ethoxyethyl ethers then provided tetrols d-35 (from 14), d-21 (from 15), d-30 (from 161, and d-26 (from 17), each with excellent stereoselectivity. These tetrols were isolated and fully characterized as the tetraacetate derivatives 36,22,31, and 27, respectively. These @-opening reactions proceed by way of an epoxide migration (29 to 33) that inverts the stereochemistry at C(6) and activates C(7) toward nucleophilic attack. It is necessary that the C(4) hydroxyl be protected in three of the four stereoisomeric series to minimize competitive epoxide migration pathways (cf. 29 to 32a). arabino tetrol21 and lyxo tetrol30 were converted to 2-deoxyglucose and 2-deoxygalactose, respectively, by a standard ozonolytic sequence and then to 2-deoxyglucitol pentaacetate (45) and 2-deoxygalactitol pentaacetate (46) via NaBH, reduction of the 2-deoxy sugars, thereby confirming all stereochemical assignments. The epoxide 0-opening technology was also applied to epoxy benzyl ether 47 (prepared from 14) and epoxy BOM ether 49 (deriving from 16). These reactions provide tetrol derivatives 48 and 50, respectively, in which the C(4)-and C(5)-hydroxyl functionality are suitably differentiated for use in subsequent synthetic sequences.
The Journal of Organic Chemistry, 2001
Codacovi, L. M.; Wang, X. C.; Kohlbrenner, W. E.; Wideburg, N. E.; Saldivar, A.; Vasavanonda, S.; March, K. C.; Bryant, P.; Sham, H. L.; Green, B. E.; Betebenner, D. A.; Erickson, J. J.; Norbeck, D. W. J. Med. Chem. 1993, 36, 320. (c) Erickson, J. J.; Neidhart, D. J.; Van Drie, J.; Kempf, D. J.; Wang, X. C.; Norbeck, D. W.; Pattner, J. J.; Rittenhouse, J. W.; Turon, M.; Wideburg, N. E.; Kohlbrenner, W. E.; Simmer, R.; Helfrich, R.; Paul, D. A.; Knigge, M. Science 1990, 249, 527. (4) For several classes of compounds with C 2 symmetry, see (a) Aguilar, N.; Moyano, A.; Pericà s, M. A.; Riera, A. Tetrahedron Lett. 1999, 40, 3913. (b) Aguilar, N.; Moyano, A.; Pericà s, M. A.; Riera, A. Tetrahedron Lett. 1999, 40, 3917. (c) Ettmayer, P.; Hü bner, M.; Gstach H. Tetrahedron Lett. 1994, 35, 3901. (d) Lam, P. Y. S.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bacheler, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, Y. N.; Chang, C. H.; Weber, P. C.; Jackson, D. A.; Sharpe, T. R.; Erickson-Vitanen, S. Science 1994, 263, 380. (e) Rossano, L. T.; Lo, Y. S.; Anzalone, L.; Lee, Y. C.; Meloni, D. J.; Moore, J. R.; Gale, T. M.; Arnett, J. F. Tetrahedron Lett. 1995, 36, 4967. (f) Hulten, J.; Bonham, N. M.; Nillroth, U.; Hansson, T.; Zuccarello, G.; Bouzide, A.; Aqvist, J.; Classon, B.; Danielson, U. H.; Karlén, A.; Kvarnström, I.; Samuelsson, B.; Hallberg, A. J. Med. Chem. 1997, 40, 885. (g) Nugiel, D. A.; Jacobs, K.; Cornelius, L.; Chang, C. H.; Jadhav, P. K.; Holler, E. R.; Klabe, R. M.; Bacheler, L. T.; Cordova, B.; Garber, S.; Reid, C.; Logue, K. A.; Gorey-Feret, L. J.; Lam, G. M.; Erikson-Vitanen, S.; Seitz, S. P. J. Med. Chem. 1997, 40, 1465. (h) Lam, P. Y. S.; Ru, Y.; Jadhav, P. K.; Aldrich, P. E.; DeLucca, G. V.; Eyermann, C. J.; Chang, C. H.; Emmet, G.; Holler, E. R.; Daneker, W. F.; Li, L.; Confalone, P. N.; McHugh, R. J.; Han, Q.; Li, R.; Markwalder, J. A.; Seitz, S. P.; Sharpe, T. R.; Bacheler, L. T.; Rayner, M. M.; Klabe, R. M.; Shum, L.; Winslow, D. L.; Kornhauser, D. M.; Jackson, D. A.; Erikson-Vitanen, S.; Hodge, C. N. J. Med. Chem. 1996, 39, 3514. (i) Nugiel, D. A.; Jackson, K.; Worley, T.; Patel, M.; Kaltenbach, R. F.; Meyer, D. T.; Jadhav, P. K.; Delucca, G. V.; Smyser, T. E.; Klabe, R. M.; Bacheler, L. T.; Rayner, M. M.; Seitz, S. P. J. Med. Chem. 1996, 39, 2156. (j) Pierce, M. E.; Harris, G. D.; Islam, Q.; Radesca, L. A.; Storace, L.; Waltermire, R. E.; Wat, E.; Jadhav, P. K.; Emmet, G. C.
European Journal of Organic Chemistry, 2013
An improved and convenient preparation of protected (S)-isoserinal on a large scale is reported. This key intermediate was reacted through organocatalyzed aldol reaction or Wittig based chain extension and functionalization to give enantiopure 1,5,6-trideoxy-1,5-imino-hexitols such as 10a (L-manno) and 10b (D-gluco). These two compounds are of interest as glycosidase inhibitors. The elaborated organocatalytic process includes diastereoselective syn aldol reaction of (S)-isoserinal hydrate and hydroxyacetone or 1-hydroxy-2-octanone and is promoted by various amino acid-based catalysts. Diastereoselectivities of up to 8:1 were achieved, thus establishing a new, efficient synthetic route to these important carbohydrate mimics.
Journal of Organic Chemistry, 2001
We describe for the first time the free radical cyclization of enantiomerically pure alkyne-tethered aldehydes obtained from a carbohydrate (6, 7). The synthesis of compounds 6 and 7 obtained from a derivative of D-ribose is reported. These radical precursors have been submitted to cyclization with tributyltin hydride plus azobisisobutyronitrile to yield, after ring closure, two carbocycles, respectively. These carbocycles have been obtained as mixtures of E and Z vinyltin isomers, but with excellent diastereoselection at the new stereocenter formed during the ring closure. After protodestannylation, only one diastereomer was detected and isolated. The absolute configuration at the new stereocenter formed during the carbocyclization has been established by detailed 1 H NMR analysis. The specific transformation of 7-methoxymethoxy-2,2-dimethyl-4-methylene-5-tertbutyldimethylsilyloxy-(3aR,5S,7S,7aS)-perhydrobenzo[d][1,3]dioxole into optically pure (+)-alloquercitol and (+)-talo-quercitol is described. From these results, we conclude that under an appropriate choice of radical precursors and conditions, the synthesis of highly functionalized cyclohexane derivatives of biological interest is now available.