A s y m m e t r i c S y n t h e s i s o f P r o t e c t e d 2 -K e t o -1 , 3 -dAbstract: The asymmetric synthesis of protected 2-keto-1,3-diols 5 and 1,2,3-triols 6 bearing a quaternary stereogenic center starting from 2,2-dimethyl-1,3-dioxan-5-one (1) is described. The stereogenic centers are generated by sequential a-alkylation of 1 using the SAMP/RAMP hydrazone method and stereoselective reduction of ketones 5 with L-selectride. The products are obtained in good yields and high diastereomeric and enantiomeric excesses.A common structural feature of a large variety of polyoxygenated biologically active compounds is a tertiary alcohol moiety with a methyl group as one of the substituents. For example, it is found in many nucleosides, such as trachycladine A and B 1 or in sugars such as L-mycarose, 2 part of the antibiotic erythromycin, 3 or L-vancosamine, 4 part of glycopeptide vancomycin. 5 General procedures for the enantioselective formation of this characteristic moiety 6 are the 1,2-addition to a prochiral ketone, 7 the Jacobsen epoxidation of alkenes 8 with subsequent cleavage or the Sharpless-dihydroxylation 9 of trisubstituted alkenes. A common drawback of these reactions is the need to synthesize pure E-or Z-alkenes and further, the reductive opening of an epoxide or the removal of a hydroxy group.We now describe an efficient diastereo-and enantioselective synthesis of protected 2-keto-1,3-diols and 1,2,3-triols starting from the readily available dihydroxy acetone equivalent 1,3-dioxan-5-one (1) 10 employing the SAMP/ RAMP-hydrazone method. 11,12 As shown in Scheme 1, our synthesis starts from 1,3-dioxan-5-one 1, which was synthesized according to a literature procedure. 13 In the first step, this ketone was transformed to the corresponding RAMP-hydrazone 2.Two alkylations at the a-and a'-position with methyl iodide led to the RAMP-hydrazone 3 with the two methyl substituents in a trans-relationship. The key step in our synthesis was a subsequent third metalation and alkylation of 3 to install the quaternary stereocenter. The smooth metalation of 3 was achieved with tert-butyllithium; and the alkylation with various electrophiles led to the a-quaternary hydrazones 4 in excellent yields and diastereomeric excesses ( Table 1). One of the hydrazones 4g was a colorless crystalline solid and could be analyzed by X-ray diffraction (Figure). 14 The structure showed the twist-boat conformation of the six-membered dioxane ring, and the two methyl groups in cis-position. This meant that the electrophilic attack is again from the lithium-coordinated side and therefore consistent with a metallo-retentive mechanism. 11 Further, NOE data showed this to apply also for hydrazones 4a, c-f. The alkylation of 3 with isopropyl iodide lead to a nearly 1:1 mixture of both possible epimers 4b at position 4, the metallo-retentive and the inverse one (Table 1), which could be separated by column chromatography. Apparently, a sterically hindered electrophile leads to a diminished stereo differentiation.Scheme 1 Reagents and c...

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The asymmetric synthesis of (1S,3R,5R,7S)‐(+)‐sordidin and 7‐epi‐(1S,3R,5R,7R)‐(–)‐sordidin, both components of the natural male‐produced aggregation pheromone of the banana weevil Cosmopolites sordidus (Germar), starting from 2,2‐dimethyl‐1,3‐dioxan‐5‐one is described. Two of the stereogenic centers were generated by three α‐alkylations of the corresponding RAMP‐hydrazone. Diastereoselective epoxide opening as another key step of the synthesis employing the aza‐enolate of 3‐pentanone SAEP‐hydrazone as nucleophile and subsequent acidic intramolecular acetalisation furnished the sordidin C‐7 epimers in good overall yield (39 %) as a 1.5:1 diastereomeric mixture. The epimers could be separated by preparative GC and thus, each of them could be obtained in high diastereomeric and enantiomeric purity (de ≥ 97 %, ee ≥ 98 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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The absolute configuration of the conformationally flexible six membered ring system 2-methyl- and 2,6-dimethyl-l,4-cyclohexanedione monoethylene acetal was determined by comparison of measured and calculated CD spectra. The rotational strengths were calculated by means of the CNDO/S-method assuming R at the stereogenic center. The results were compared with the predictions made by the octant rule. The enantiomerically pure material was synthesized via the corresponding SAMP- and RAMP-hydrazones.