Asymmetric synthesis alkene dihydroxylation

The growing interest manifested by synthetic chemists towards the use of the asymmetric dihydroxylation of olefins has resulted in so many varied apphca-tions that it is beyond the scope of this limited review to enumerate them all. Throughout this concise review, the specificities of the catalytic AD of alkenes have been discussed and the salient features of the almost limitless transformations of the resulting chiral diols have been illustrated through the use of selected examples. Whilst the AD of olefins is now considered as one of the most important tools in asymmetric synthesis, let us not forget that the enantioselectiv-ity displayed by the asymmetric dihydroxylation process can depend upon subtle steric, electronic or conformational effects that are far less pronounced in other asymmetric catalytic reactions. Such is the case in our last example [141], featuring an elegant approach towards vitamin E by Tietze and coworkers... 

From Achiral Non-carbohydrates. — 3-Deoxy-3-guanidino-D-threose 48 equilibrates with 49. a transition state inhibitor for galactosidase. It was synthesized as shown in Scheme 12 from epoxide 47, which was obtained by porcine pancreatic lipase catalysed enantioselective esterification of the racemic epoxy-alcohol precursor. 6-Deoxy-L-talonolactone 50 was synthesized by an asymmetric aldol condensation - dihydroxylation sequence (Vol.24, p.lS2) in improved diastereoselectivity and was converted into 2-acetamido-2,6-dideoxy-L-fucose (shown as its furanose isomer 51 in Scheme 13), 3-acetamido-3,6Hlideoxy-L-idose and 5-acetamido-S,6-dideoxy-D-allose by S 2 displacements of triflate with azide ion. 4-Amino-4-deoxy-DL-erthrose 53 was obtained from the hetero-Diels-Alder adduct 52 by a sequence of reactions including cis-dihydroxylation (OSO4, NMNO) of the alkene moiety (Scheme 14). The synthesis of a racemic branched-chain lactam is covered in Chapter 16. 

Preparation of enantiopure chiral molecules by transformation of prochiral substrates can offer the most elegant of available approaches, especially when the source of chirality is a man-made chemical catalyst rather than a reagent used in stoichiometric quantitites. Tremendous effort has been devoted to the development of asymmetric synthesis methodology, with notable success in the fields of asymmetric hydrogenation [98], hydride reduction of ketones [99], epoxidation [100] and dihydroxylation [101] of alkenes. In constrast to the enzymes which are used in organic synthesis, man-made chiral catalysts [102] are much simpler molecular entities and are routinely available in both enantiomeric forms. Since reactions employing such catalysts usually follow a predictable course, the correct form can be chosen for the desired product configuration. 

More recently, in light of the development of the Sharpless asymmetric dihydroxylation protocol [20], we have approached the synthesis of diols such as 14 (Scheme 2) from the alkene. Thus, treatment of the alkenyl D-glucosides 15 vmder the conditions of the Sharpless dihydroxylation gave a range of diols 16 with varying diastereoisomeric excesses (Table 1). One of these mixtures of diols, upon recrystallization, yielded the pure diastereoisomer, namely the diol 14. This procedure now gives a very rapid and efficient entry into one of the precursor diols for the synthesis of the optically-pure epoxides [21]. 

Osmium-catalysed dihydroxylation of olefins is a powerful route towards enantioselective introduction of chiral centers into organic substrates [82]. Its importance is remarkable because of its common use in organic and natural product synthesis, due to its ability to introduce two vicinal functional groups into hydrocarbons with no functional groups [83]. Prof. Sharpless received the 2001 Nobel Prize in chemistry for his development of asymmetric catalytic oxidation reactions of alkenes, including his outstanding achievements in the osmium asymmetric dihydroxylation of olefins. 

Unlike epoxides, these five-membered heterocyclics have received scant attention from organic chemists. But the recent catalytic asymmetric dihydroxylation of alkenes (14, 237-239), which is now widely applicable (this volume), and the ready access to optically active natural 1,2-diols has led to study of these compounds, including a convenient method for synthesis. They are now generally available by reaction of a 1,2-diol with thionyl chloride to form a cyclic sulfite of a 1,2-diol, which is then oxidized in the same flask by the Sharpless catalytic Ru04 system, as shown in equation I.1... 

Jacobsen epoxidation turned out to be the best large-scale method for preparing the cis-amino-indanol for the synthesis of Crixivan, This process is very much the cornerstone of the whole synthesis. During the development of the first laboratory route into a route usable on a very large scale, many methods were tried and the final choice fell on this relatively new type of asymmetric epoxidation. The Sharpless asymmetric epoxidation works only for allylic alcohols (Chapter 45) and so is no good here. The Sharpless asymmetric dihydroxylation works less well on ris-alkenes than on trans-alkenes, The Jacobsen epoxidation works best on cis-alkenes. The catalyst is the Mn(III) complex easily made from a chiral diamine and an aromatic salicylaldehyde (a 2-hydroxybenzaldehyde). 

Sharpless asymmetric dihydroxylation One-pot enantioselective synthesis of vicinal diols from simple alkenes. 406... 

The cinchona alkaloids have opened up the field of asymmetric oxidations of alkenes without the need for a functional group within the substrate to form a complex with the metal. Current methodology is limited to osmium-based oxidations. The power of the asymmetric dihydroxylation reaction is exemplified by the thousands (literally) of examples for the use of this reaction to establish stereogenic centers in target molecule synthesis. The usefulness of the AD reaction is augmented by the bountiful chemistry of cyclic sulfates and sulfites derived from the resultant 1,2-diols. 

In 1988, Sharpless invented his asymmetric dihydroxylation (AD), a catalytic process to convert alkenes to optically active 1,2-diols with known absolute configuration.38 As shown in Figure 3.10, a commercially available reagent AD-mix-a (Aldrich) gives a-l,2-diol from an alkene, while AD-mix-f) affords f>-l,2-diol. This reaction was used by Crispino and Sharpless to synthesize (R)-(+)-JH III (92% ee).39 We also employed this AD reaction to synthesize (+)-JH I (61) and (+)-JH II (62).40 Figure 3.11 summarizes the synthesis of (+)-JH I by means of an AD reaction. 

Accordingly, the synthesis of phthalide 44 began from methyl ketone 27 (Scheme 18). In order to avoid interference of the olefin moiety with haloge-nation of the aromatic ring, asymmetric dihydroxylation was conducted first. Treatment of alkene 27 with AD-mix a in tcrt-butanol/water (1 1) provided diol 27 in a pleasing 87% yield. Inspection of the and NMR spectra did not indicate the presence of a diastereomeric mixture. However, although alkene 27 is structurally well suited to the Sharpless mnemonic, we thought it... 

Abstract The oxidative functionalization of olefins is an important reaction for organic synthesis as well as for the industrial production of bulk chemicals. Various processes have been explored, among them also metal-catalyzed methods using strong oxidants like osmium tetroxide. Especially, the asymmetric dihydroxylation of olefins by osmium(Vlll) complexes has proven to be a valuable reaction for the synthetic chemist. A large number of experimental studies had been conducted, but the mechanisms of the various osmium-catalyzed reactions remained a controversial issue. This changed when density functional theory calculations became available and computational studies helped to unravel the open mechanistic questions. This mini review will focus on recent mechanistic studies on osmium-mediated oxidation reactions of alkenes. 

A highly convergent synthesis of fostriecin (60) via sequential Pd-catalyzed Negishi cross-couplings and regioselective, asymmetric Os-dihydroxylation of the corresponding alkene, has been described by McDonald and Robles. ... 

In connection with studies on the synthesis of complex cell wall glycans, we have developed effective syntheses of the novel branched sugar aceric acid and its C-2 epimer. Control of asymmetry in the installation of the key tertiary centers was effected by either asymmetric dihydroxylation of an appropriate alkene derivative or by thiazole addition to the corresponding ketone. 

Chiral epoxides are extensively employed high-value intermediates in the synthesis of chiral compounds due to their ability to react with a broad variety of nucleophiles. In recent years a lot of research has been devoted to the development of catalytic methods for their production [551, 1141], The Katsuki-Sharpless method for the asymmetric epoxidation of allylic alcohols [1142,1143] and the asynunetric dihydroxylation of alkenes are now widely applied and reliable procedures. Catalysts for the epoxidation of nonfunctionalized olefins have been developed more recently [555, 1144]. Although high selectivities have been achieved for the epoxidation of cA-alkenes, the selectivities achieved with trans- and terminal olefins were less satisfactory using the latter methods. 

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