Diols stereochemistry

The cleavage reaction occurs in three steps O protonation of the epoxide, Sn2 nucleophilic attack on the protonated epoxide, and deprotonation of the ring-opened product. Draw the complete mechanism. How many intermediates are there Which step determines diol stereochemistry ... 

One way in which the Z-a,P-unsaturated carbonyl functionality could be exploited would be via its incorporation into lactone 17. It could be predicted with some confidence that external reagents would attack the bicyclic lactonic system from its convex face. Such an a attack by osmium tetroxide would provide the correct 7,8-erythro diol stereochemistry required to reach NeuSAc. This anticipation turned out to be well founded. 

This approach is very popular because all that is left to control is the 1,3-diol stereochemistry between C-6 and C-8. 

Disulfonate esters of vicinal diols sometimes undergo reductive elimination on treatment with sodium iodide in acetone at elevated temperature and pressure (usually l(X)-200°). This reaction derived from sugar chemistry has been used occasionally with steroids, principally in the elimination of 2,3-dihy-droxysapogenin mesylates. The stereochemistry of the substituents and ring junction is important, as illustrated in the formation of the A -olefins (133) and (134). 

Diols can be prepared either by direct hydroxylation of an alkene with 0s04 followed by reduction with NaHSOj or by acid-catalyzed hydrolysis of an epoxide (Section 7.8). The 0s04 reaction occurs with syn stereochemistry to give a cis diol, and epoxide opening occurs with anti stereochemistry to give a trans diol. 

It is worth pointing out that the stereochemistry of intermediate 147 at C-9 and C-10 is inconsequential since both positions will eventually bear trigonal carbonyl groups in the final product. The synthetic problem is thus significantly simplified by virtue of the fact that any or all C9-C10 diol stereoisomers could be utilized. A particularly attractive means for the construction of the C9-C10 bond and the requisite C8-C10 functionality in 147 is revealed by the disconnection shown in Scheme 41. It was anticipated that the venerable intermolecular aldol reaction could be relied upon to accomplish the union of aldehyde 150 and methyl glycolate (151) through a bond between carbons 9 and 10. 

The synthesis of the key intermediate aldehyde 68 is outlined in Schemes 19-21. The two hydroxyls of butyne-l,4-diol (74, Scheme 19), a cheap intermediate in the industrial synthesis of THF, can be protected as 4-methoxybenzyl (PMB) ethers in 94% yield. The triple bond is then m-hydrostannylated with tri-n-butyl-tin hydride and a catalytic amount of Pd(PPh3)2Cl238 to give the vinylstannane 76 in 98 % yield. Note that the stereospecific nature of the m-hydrostannylation absolutely guarantees the correct relative stereochemistry of C-3 and C-4 in the natural product. The other partner for the Stille coupling, vinyl iodide 78, is prepared by... 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

In a recent total synthesis of the novel neurotrophic agent merrilactone A (22, Scheme 4) by Inoue and Hirama [24], key intermediate 21 with the cis-bicyclo[3.3.0] octane framework embedded within the caged pentacycle 22 was elaborated from cyclobutane 18 by a sequence of RCM and immediate cleavage of the resulting bicyclic vicinal diol 19 to raeso-diketone 20. Cyclooctenedione 20 then underwent regioselective transannular aldol reaction at low temperature (LHMDS, THF, -100 °C) to produce a 3 1 mixture of isomers in 85% combined yield. The major isomer 21 with the required stereochemistry was then converted into the racemic natural compound ( )-22 in 19 steps. 

Aspects of Stereochemistry. Part III. Acidic and Basic Hydrolysis of Some Diol Cyclic Sulphates and Related Compounds, J. S. Brimacombe, A. B. Foster, E. B. Hancock, W. G. Overend, and... 

During the course of the development of our group s alkylation/reductive decyanation strategy, a very reliable method for distinguishing between syn-and anfz-l,3-diols was discovered [17,18]. The acetonide methyl groups reliably display diagnostic C-NMR chemical shifts, allowing for stereochemistry to be determined simply by inspection (Fig. 1). Evans later extended the C-NMR chemical correlation to polypropionate chains [19,20]. 

In a study of stereochemistry, the half ether (5) of an unsymmetrical diol (6) was required. There is little prospect of making (5) from (6) as chemoselectlvity presents a formidable problem. Grignard disconnection from the tertiary alcohol would leave o-methoxyl ketones (7) or (8). 

Akhtar MN, DR Boyd, NJ Thompson, M Koreeda, DT Gibson, V Mahadevan, DM Jerina (1975) Absolute stereochemistry of the dihydroanthracene-ci - and -fra 5,l,2-diols from anthracene by mammals and bacteria. J Chem Soc Perkin I 2506-2511. 

The catalytic enantioselective desymmetrization of meso compounds is a powerful tool for the construction of enantiomerically enriched functionalized products." Meso cyclic allylic diol derivatives are challenging substrates for the asymmetric allylic substitution reaction owing to the potential competition of several reaction pathways. In particular, S 2 and 5n2 substitutions can occur, and both with either retention or inversion of the stereochemistry. In the... 

Both the regiochemistry and stereochemistry of Wacker oxidation can be influenced by substituents that engage in chelation with Pd. Whereas a single y-alkoxy function leads to a mixture of aldehyde and ketone, more highly oxygenated systems such as the acetonide or carbonate of the diol 1 lead to dominant aldehyde formation.107 The diol itself gives only ketone, which perhaps indicates that steric factors are also important. 

The three fragments were then coupled. The C(16)—C(17) bond was established by addition of the lithium enolate of the aryl ester in the C(9)—C(16) fragment with the aldehyde group of the C(17)-C(24) fragment. The stereochemistry is consistent with the cyclic aldol addition TS. The adduct was immediately reduced to the diol 14 by LiAlH4. 

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