Oxygen stereoselective

The large sulfur atom is a preferred reaction site in synthetic intermediates to introduce chirality into a carbon compound. Thermal equilibrations of chiral sulfoxides are slow, and parbanions with lithium or sodium as counterions on a chiral carbon atom adjacent to a sulfoxide group maintain their chirality. The benzylic proton of chiral sulfoxides is removed stereoselectively by strong bases. The largest groups prefer the anti conformation, e.g. phenyl and oxygen in the first example, phenyl and rert-butyl in the second. Deprotonation occurs at the methylene group on the least hindered site adjacent to the unshared electron pair of the sulfur atom (R.R. Fraser, 1972 F. Montanari, 1975). 

Open-chain 1,5-polyenes (e.g. squalene) and some oxygenated derivatives are the biochemical precursors of cyclic terpenoids (e.g. steroids, carotenoids). The enzymic cyclization of squalene 2,3-oxide, which has one chiral carbon atom, to produce lanosterol introduces seven chiral centres in one totally stereoselective reaction. As a result, organic chemists have tried to ascertain, whether squalene or related olefinic systems could be induced to undergo similar stereoselective cyclizations in the absence of enzymes (W.S. Johnson, 1968, 1976). 

When the 2-hydroxy group of a monosaccharide reacts with (diethylamino)sulfur trifluoride (DAST), quantitative and stereoselective rearrangements are observed (K.C Nico-laou, 1986). This reaction may simultaneously introduce fluorine to C-1 and a new oxygen, sulfur, or nitrogen residue to C-2 with inversion of configuration. 

Cyclopentene derivatives with carboxylic acid side-chains can be stereoselectively hydroxy-lated by the iodolactonization procedure (E.J. Corey, 1969, 1970). To the trisubstituted cyclopentene described on p. 210 a large iodine cation is added stereoselectively to the less hindered -side of the 9,10 double bond. Lactone formation occurs on the intermediate iod-onium ion specifically at C-9ot. Later the iodine is reductively removed with tri-n-butyltin hydride. The cyclopentane ring now bears all oxygen and carbon substituents in the right stereochemistry, and the carbon chains can be built starting from the C-8 and C-12 substit""" ... 

In order to make these oxidative reactions of 1,3-dienes catalytic, several reoxidants are used. In general, a stoichiometric amount of benzoquinone is used. Furthermore, Fe-phthalocyanine complex or Co-salen complex is used to reoxidize hydroquinone to benzoquinone. Also, it was found that the reaction is faster and stereoselectivity is higher when (phenylsulflnyl)benzoquinone (383) is used owing to coordination of the sulfinyl group to Pd, Thus the reaction can be carried out using catalytic amounts of PdfOAcji and (arylsulfinyl)benzoquinone in the presence of the Fe or Co complex under an oxygen atmosphere[320]. Oxidative dicyanation of butadiene takes place to give l,4-dicyano-2-butene(384) (40%) and l,2-dicyano-3-butene (385)[32l]. 

Stereoselective All lations. Ben2ene is stereoselectively alkylated with chiral 4-valerolactone in the presence of aluminum chloride with 50% net inversion of configuration (32). The stereoselectivity is explained by the coordination of the Lewis acid with the carbonyl oxygen of the lactone, resulting in the typ displacement at the C—O bond. Partial racemi2ation of the substrate (incomplete inversion of configuration) results by internal... 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

Gluconolactone shows no exchange. The reason is that the tetrahedral intermediate is formed and breaks down stereoselectively. Even though proton exchange can occur in the tetrahedral intermediate, the anomeric effect leads to preferential loss of the axial oxygen. 

In transforming bis-ketone 45 to keto-epoxide 46, the elevated stereoselectivity was believed to be a consequence of tbe molecular shape — tbe sulfur ylide attacked preferentially from tbe convex face of the strongly puckered molecule of 45. Moreover, the pronounced chemoselectivity was attributed to tbe increased electropbilicity of the furanone versus the pyranone carbonyl, as a result of an inductive effect generated by tbe pair of spiroacetal oxygen substituents at tbe furanone a-position. ... 

The powerful influence of an oxygen substituent on the rate and stereoselectivity of cyclopropanation augured well for the development of a chiral auxiliary based approach to asymmetric synthesis [54]. The design of the chiral auxiliary would take into account ... 

Stereoselective addition of cuprates to ji-alkoxy enoates of type 49 [17] isee Sdiemes 6.8 and 6.9) bas been used in die crrnstruction of polypropionate-type structures. Tlius, a sequence of diastereoselective cuprate addition, etiolate for-ruabon, and diastereoselective oxygenation widi Davis s reagent bas been applied iteratively to provide a Cio segment of Rifaruycin S i60) [ 17c, d]. 

In 1999, Bob Atkinson wrote [1] that aziridination reactions were epoxida-tion s poor relation , and this was undoubtedly true at that time the scope of the synthetic methods available for preparation of aziridines was rather narrow when compared to the diversity of the procedures used for the preparation of the analogous oxygenated heterocycles. The preparation of aziridines has formed the basis of several reviews [2] and the reader is directed towards those works for a comprehensive analysis of the area this chapter presents a concise overview of classical methods and focuses on modern advances in the area of aziridine synthesis, with particular attention to stereoselective reactions between nitrenes and al-kenes on the one hand, and carbenes and imines on the other. 

Nonperpendicular attack of the nucleophile explains Felkin s hypothesis for the predominance of interactions involving R1 and R2 over interactions involving the carbonyl oxygen. Additionally, as R1 increases in bulk, the nucleophile is pushed towards the stereogenic center and can better feel" the difference between the substituents, resulting in an increase in stereoselectivity. 

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