Dihydroxylation stereospecificity

Perhaps the madness of needing to have another diastereomer of a starting material in order for a reaction to be stereospecific is more obvious in the next example. Heptene 106 may be dihydroxylated stereospecifically to give 107. But the reaction of cycloheptene 108 would not be a stereospecific reaction because there is no such thing as a trans cycloheptene. Clearly this is crazy - both reactions are stereospecific. But see what your friends think. 

Lee K, DT Gibson (1996a) Stereospecific dihydroxylation of the styrene vinyl group by purified naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4. J Bacteriol 178 3353-3356. 

Disubstituted-3,6-dihydro-l,2-dioxines can be dihydroxylated readily with OsOa to furnish the 4,5-diols 73 in yields of 33-98% and with de values not less than 90%. Subsequent reduction of the peroxy bond allowed the stereospecific synthesis of tetraols 74 without the use of protecting groups <2006JOC7236>. 

Stereospecific conversion of vinylsilanes to silyl enol ethers This conversion can be effected by dihydroxylation with 0s04 in combination with (CH3)3NO and pyridine followed by anti p-elimination with NaH via an a-oxidosilane. The overall process converts vinylsilanes into silyl enol ethers with preservation of the geometry of the double bond. 

There are other stereospecific olefin addition processes which occur with cis or syn stereochemistry. Common examples include catalytic hydrogenation, hydroboration/oxidation, and dihydroxylation using osmium tetroxide. The stereospecificity of these syn additions requires that die facial properties of the olefinic bond be maintained throughout die addition process and that both new bonds are formed to the same face of the olefin. This is normally accomplished by a concerted syn addition to the n system. 

Pseudomonas putida mediated cis-dihydroxylation of bromo or chlorobenzene supplied the requisite chiral starting material 44 for a second synthesis of (+)-7-deoxynarciclasine reported by Hudlicky [18,19]. Subsequent to protection of the diol as the acetonide45 (Scheme 8), its cycloaddition reaction with the N-acylnitroso compound derived from benzyl-N-hydroxycarbamate 46 by in situ oxidation, occurred with complete regio and stereospecificity togive the bromo adduct 47. In a similar fashion, the chloro compound 48 was obtained. 

Draw the products formed when both c/s- and frans-2-butene are treated with a peroxyacid followed by "OH (in H2O). Explain how these reactions illustrate that anti dihydroxylation is stereospecific. 

In summary, these studies demonstrated that in CTX the impaired synthesis of bile acids is due to a defect in the biosynthetic pathway involving the oxidation of the cholesterol side-chain. As a consequence of the inefficient side-chain oxidation, increased 23, 24 and 25-hydroxylation of bile acid precursors occurs with the consequent marked increase in bile alcohol glucuronides secretions in bile, urine, plasma and feces (free bile alcohols). These compounds were isolated, synthesized and fully characterized by various spectroscopic methods. In addition, their absolute stereochemistiy determined by Lanthanide-Induced Circular Dichroism (CD) and Sharpless Asymmetric Dihydroxylation studies. Further studies demonstrated that (CTX) patients transform cholesterol into bile acids predominantly via the 25-hydroxylation pathway. This pathway involves the 25-hydroxylation of 5P-cholestane-3a,7a, 12a-triol to give 5P-cholestane-5P-cholestane-3a,7a,12a,25- tetrol followed by stereospecific 24S-hydroxylation to yield 5P-cholestane-3a,7a,12a,24S,25-pentol which in turn was converted to cholic acid. 

The property that the stereochemical result of an electrocyclic reaction is absolutely predictable is called stereospecificity. A stereospecific reaction will give you one stereochemical result when a cis starting material is used, and the opposite result when a trans starting material is used. Other examples of stereospecific reactions include Sn2 substitutions, catalytic hydrogenation of alkynes or alkenes, and dihydroxylation and bromination of alkenes. 

When an alkene is treated with OSO4, an osmate ester containing two new C-O bonds is formed. The osmate ester is hydrolyzed, usually with aqueous NaHSC>3, to give a 1,2-diol. The overall dihydroxylation reaction is stereospecifically syn. 

Asymmetric dihydroxylation of trifluoromethylalkenes is also useful for construction of enantio-enriched trifluoromethylated diols usable for trifluoromethylated amino acids with chiral hydroxyl group. Thus, Sharpless AD reaction of 16 provides diol 17 with excellent enantioselectivity. Regioselective and stereospecific replacement of the sulfonate moiety in 18 with azide ion enables the introduction of nitrogen functionality. A series of well-known chemical transformation of 19 leads to 4,4,4-trifluorothreonine 20 (see Scheme 9.6) [16]. Dehydroxylative-hydrogenation of 21 by radical reaction via thiocarbonate and subsequent chemical transformation synthesize enantio-enriched (S)-2-amino-4,4,4-trifluoro-butanoic acid 22 [16]. Both enantiomers of 20 and 22 were prepared in a similar manner from (2R,3S)-diol of 17. 

Finally the remaining alkene is dihydroxylated with catalytic Os04and stoichiometric iV-methyl-morpholine (NMO) as oxidant to give the diol 56 that cyclises to the THF 57 stereospecifically. The aldehyde 58 was used to make (-)-dysiherbane. 

The relative configurations at the asymmetric carbons were decided through the stereospecific synthesis of ( )-viridifloric acid, again on the assumption of CLXVIl as the structure of the precursor a-isopro-pylcrotonic acid. Traws-dihydroxylation of a-isopropylcrotonic acid was effected by Dry and Warren (184) by conversion with perbenzoic acid to the epoxide (not isolated), which was hydrolyzed with aqueous sulfuric acid to ( )-er2/phenacyl ester, m.p. 123-124°) by pertungstic acid oxidation of a-isopropylcrotonic acid. The... 

Some of the most pertinent virtues of asymmetric epoxidations and dihydroxylations were already present in their classical versions. Both reactions are highly chemo-selective and can be carried out in the presence of many other functional groups. More important with respect to stereochemistry, each reaction is stereospecific in that the product faithfully reflects the E or Z configuration of the starting olefin (the nucleophilic epoxidation of a,P-unsaturated carbonyl compounds is an important exception). And one should not underestimate the importance of experimental simplicity in most cases, one can carry out these reactions by simply adding the often commercially available reagents to a substrate in solvent, without extravagant precautions to avoid moisture or air. 

The alcohol was protected as its TMS ether, and the C-15,16 alkene stereospecifically dihydroxylated to give compound 50. The diol was then converted to its cyclic sulfate derivative according to the Sharpless protocol.29 Attempted base-catalyzed elimination of the sulfate to introduce the C-14,15 alkene was plagued by side-reactions involving epoxide formation by displacement of the sulfate by the adjacent TMS ether, perhaps aided by enolization of the methyl ketone. Instead, displacement of the sulfate by iodide ion occurred uneventfully to provide 51 as its tetrabutylammonium salt. 

With regard to the biomimetic non-heme iron complexes, the work devoted to develop catalysts that perform catalytic alkane hydroxylation has resulted in a large number of iron complexes, which generate Fe =0 iron-oxo species characterized by different spectroscopic techniques. There is now direct evidence that the involvement of high-valent iron-oxo species leads to stereospecific alkane hydroxylation, while hydroxyl radicals contribute to non-selective oxidations. The impressive work performed by Que and co-workers has demonstrated that olefin epoxidation and cis-dihydroxylation are different facets of the reactivity of a common Fe -OOH intermediate, whose spin state can be modulated by the electronic and steric properties of... 

This methodology [94TL3601] was used to construct the optically active erythro-diol 8, which was then stereospecifically converted to (+)- disparlure (9), the sex attractant pheromone of the female gypsy moth. This transformation represents a formal asymmetric epoxidation across a nonfunctionalized olefin, not a direct option with traditional Sharpless asymmetric epoxidation technology. This clever variation using initial Sharpless dihydroxylation (applicable to nonfunctionalized olefins) and subsequent epoxide formation is starting to be recognized as a useful indirect method for asymmetric epoxidation. 

A new approach to construction of 3-aminosugar moieties by stereospecific intramolecular addition of a carbon-free radical to hydrazone 125 derived from crotonaldehyde was recently demonstrated by Friestad. This synthesis, comprising asymmetric dihydroxylation, PhS radical-induced C = N bond alkylation (C-vinylation) and subsequent Wacker oxidation [88] of terminal olefin 128, which afforded L-daunosaminide derivative 129, in overall 32% yield, is outlined in Scheme 23 [89]. 

Because OSO4 adds two hydroxyl groups to an alkene in a syn fashion, the overall product depends on the geometry of the alkene starting material it is stereospecific. It is similar to bromination (p. 439) in that respect, although of course bromination is an anti addition. You can see how two different diastereoisomers are produced from different alkenes in these two examples both dihydroxylations are mechanistically syn, but redrawing the product from the Z alkene in its more extended form reveals anti stereochemistry. 

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