Synlett 2014; 25(09): 1312-1318
DOI: 10.1055/s-0033-1341266
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Tricyclic Precursors of Cyclitols

Johannes Aucktor
Chiara Anselmi
Reinhard Brückner*
Manfred Keller
Further Information

Publication History

Received: 21 February 2014

Accepted after revision: 27 March 2014

Publication Date:
29 April 2014 (online)


Stereoselective syntheses of three tricyclic cyclohexenones are described. These compounds were conceived as novel precursors of synthetic conduritols, quercitols, and inositols because they allow diastereoselective C=O reductions, C=C osmylations, and C=C epoxidations to be performed. These functionalizations created up to three uniformly configured oxygen-bearing stereocenters. One of the follow-up products was a tricycle that was amenable to successive cleavages of its 1,4-dioxane and 1,3-dioxane rings. This rendered the pentaesters of neo-quercitol, which contain five stereogenic C–O bonds, with ds = 85:15.

Supporting Information

  • References and Notes

  • 1 New Address: Istituto CNR di Scienza e Technologie Molecolari, c/o Dipartimento di Chimica, Università degli Studi di Perugia, via Elce di Sotto 8, 06123 Perugia, Italy.
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  • 26 The enantiomeric excess (ee) of the diol 28 was determined by chiral HPLC [Chiralcel OD-H; 0.8 mL/min, n-heptane/ EtOH (80:20); λdetection = 275 nm, tret ,ent-28 = 13.3 min, tret ,28 = 15.3 min].
  • 27 The oxidation of the diol 27 delivered, besides the six-membered-ring ketal 30, the isomeric seven-membered-ring ketal (8%; not depicted in Scheme 5), i.e. a PMP-substituted analogue of the seven-membered-ring ketal 15. It was separated by flash chromatography on silica gel (ref. 19).
  • 28 The inversion of configuration of a benzylic C–O bond in a syn-configured arylethane-1,2-diol was described if the non-benzylic oxygen was incorporated in a OMEM group: Ramachandran PV, Liu H, Reddy MV. R, Brown HC. Org. Lett. 2003; 5: 3755
  • 29 For the oxidation of benzylic alcohols to aromatic ketones by DDQ, see: Peng K, Chen F, She X, Yang C, Cui Y, Pan X. Tetrahedron Lett. 2005; 46: 1217
  • 30 The enantiomeric excess (ee) of the hydroxy ketone 29 was determined by chiral HPLC [Chiralpak AD-3; 1.0 mL/min, n-heptane/EtOH (25:75); λdetection = 275 nm, tret ,29 = 28.3 min, tret ,ent-29 = 34.2 min].
  • 31 Zn(BH4)2 in THF solution was prepared from Zn(OMe)2 and BH3·THF as described by: Nöth H, Wiberg E, Winter RP. Z. Anorg. Allg. Chem. 1969; 370: 209
    • 32a For anti-selective reductions of racemic α-hydroxy ketones giving 1,2-diols, see: Nakata T, Tanaka T, Oishi T. Tetrahedron Lett. 1983; 24: 2653
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  • 33 The enantiomeric excess (ee) of the diol epi-27 was determined by chiral HPLC [Chiralpak OD-3; 1.0 mL/min, n-heptane/EtOH (85:15); λdetection = 275 nm, tret ,ent-epi-27 = 11.8 min, tret ,epi-27 = 14.4 min].
  • 34 The oxidation of the diol epi-27 delivered, besides the six-membered-ring ketal epi-30, the isomeric seven-membered-ring ketal (10%; not depicted in Scheme 5), i.e. another (ref. 27) PMP-substituted analogue of the seven-membered-ring ketal 15. It was separated by flash chromatography on silica gel (ref. 19).
  • 35 Acetylation of the cyclohexenols endo-31 and exo-31 gave the corresponding acetates endo-32 and exo-32, respec-tively. Both were isolated isomerically pure.
  • 36 Procedure: Chae HI, Hwang G.-S, Jin MY, Ryu DH. Bull. Korean Chem. Soc. 2010; 31: 1047
  • 37 The triacetate 36 was processed further as disclosed in Scheme 8.
  • 38 Rücker G, Hörster H, Gajewski W. Synth. Commun. 1980; 623
  • 39 For the method, see: Mehta G, Pujar SR, Ramesh SS, Islam K. Tetrahedron Lett. 2005; 46: 3373
    • 40a A neighboring participation of an acetate group is a plausible inaugural step for carrying on the epoxide 39 towards the triacetate 40 (Scheme 9). The resulting carboxonium ion picks up H2O at the dioxygenated C atom (followed by decay of the dialkyl orthocarboxylate intermediate to a mixture of two regioisomeric glycol monoacetates 47a and 47b), not at the monooxygenated C atom (by an SN2 attack). This chemoselectivity is known from the carboxonium ion intermediate of the Woodward (= aqueous) diacetoxylation as opposed to the Prevost (= anhydrous) diacetoxylation of C=C bonds. The former is a cis-diacetoxylation (while the latter is a trans-diacetoxylation; it includes an SN2-opening by an acetate ion, not by H2O).
    • 40b All tricyclic compounds prepared in the present study, which were not analyzed stereochemically by X-ray crystallography (cf. Figure 1) were conceived as cyclohexane-based chair conformers or as cyclohexene-based half-chair conformers. Whether their substituents were equatorially or axially disposed was inferred from the magnitudes of the vicinal H,H coupling constants in the respective substructures similarly as exemplified in the bottom-line of Scheme 9 for telling apart the diastereomers 40 (which we had obtained) and iso-40 (which we had not obtained)].
  • 41 For the method, see: Ma Z, Hu H, Xiong W, Zhai H. Tetrahedron 2007; 63: 7523
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  • 43 An analogous acetate migration in the initially formed reduction product would have passed unnoticed. We never worked up the reduction product properly, but subjected it to an in-situ acetylation before we worked it up.
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  • 45 The crystallographic data of the tricyclic cyclohexenone 8 are contained in CCDC 987664 (ref. 54).
  • 46 The crystallographic data of the tricyclic cyclohexenol 16 are contained in CCDC 987666 (ref. 54).
  • 47 The crystallographic data of the tricyclic dihydroxy-cyclohexanone 18 are contained in CCDC 987665 (ref. 54).
  • 48 The crystallographic data of the tricyclic cyclohexenone endo-9 are contained in CCDC 987667 (ref. 54).
  • 49 The crystallographic data of the tricyclic cyclohexenone exo-9 are contained in CCDC 987668 (ref. 54).
  • 50 The crystallographic data of the tricyclic dihydroxy-cyclohexanone endo-33 are contained in CCDC 987669 (ref. 54).
  • 51 The crystallographic data of the tricyclic dihydroxy-cyclohexanone exo-33 are contained in CCDC 987670 (ref. 54).
  • 52 The crystallographic data of the tricyclic cyclohexenyl acetate exo-32 are contained in CCDC 987671 (ref. 54).
  • 53 The crystallographic data of the tricyclic epoxycyclohexyl acetate 39 are contained in CCDC 987672 (ref. 54).
  • 54 These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via the link