Dihydroxylation regioselectivity

This strategy can be applied to the synthesis of vinylepoxides, since high enantioselectivity and good regioselectivity can often be obtained in asymmetric dihydroxylation of dienes, resulting in vinylic diols [24, 25], Transformation of the diols into epoxides thus represents an alternative route to vinylepoxides. This strategy was recently employed in the synthesis of (+)-posticlure (Scheme 9.6) [26]. 

With an effective strategy for construction of the diazofluorene established, we set out to prepare the coupling partners required for synthesis of (—)-kinamycin F (6). The synthesis of the enone 117 began with meta-cresol (128, Scheme 3.23). Silylation formed the silyl ether 119 in nearly quantitative yield. Birch reduction of the silyl ether 119 formed the cyclohexadiene derivative 129 in excellent yield. Asymmetric dihydroxylation [52] of 129 occurred regioselectively to afford the... 

Several building blocks were prepared separately (Chart 7). Methyl frans-cinnamate gave by Sharpless enantiocontrolled dihydroxylation a diol from which by a series of stereo- and regioselective transformations (96) and Ru-catalyzed oxidation for transformation of the phenyl into a carboxyl group accompanied by adequate protection (97) and deprotection steps the protected OHAsp derivative 98 was obtained. 

The asymmetric dihydroxylation of dienes has been examined, originally with the use of NMO as the cooxidant for osmium [56a] and, more recently, with potassium ferricyanide as the cooxidant [56b], Tetraols are the main product of the reaction when NMO is used, but with K3Fe(CN)6, ene-diols are produced with excellent regioselectivity. The example of dihydroxylation of trans.trans-1,4-diphenyl-1,3-butadiene is included in Table 6D.3 (entry 21). One double bond of this diene is hydroxylated in 84% yield with 99% ee when the amounts of K3Fe(CN)6 and K2C03 are limited to 1.5 equiv. each. Unsymmetrical dienes are also dihydroxy-lated with excellent regioselectivity. In these dienes, preference is shown for (a) a bans over a cis olefin, (b) the terminal olefin in a,p,y,8-unsaturated esters, and (c) the more highly substituted olefin [56b],... 

A similar cyclisation of an alkene derived from geranyl acetate 24 by dihydroxylation and formation of the epoxide 26 leads to a substituted cyclohexane 28. The Lewis acid ZrCU is used to open the epoxide and the alkene attacks intramolecularly 27 to give eventually the ryn-compound 28 with both substituents equatorial. The alignment of the alkene and the epoxide in a chair conformation 27a is responsible for the diastereoselectivity Note the regioselectivity the less substituted end of the alkene attacks the more substituted end of the epoxide 27. These are just two examples of the very many ordinary ionic reactions that can be used to make six-membered rings. 

Since a,p-unsaturated esters undergo catalytic dihydroxylation in high yield, a reaction of 2 with a number of nucleophiles has been investigated (equation IV). In all reported cases, the nucleophile reacts exclusively at the a-position. In contrast, reaction of epoxides with these nucleophiles shows no such regioselectivity.1... 

The AA reaction is closely related to the asymmetric dihydroxylation (AD). Alkenes are enantioselectively converted to protected 3-aminoalcohols (Scheme 1) by syn-addition of osmium salts under the influence of the chirr 1 bis-Cinchona ligands known from the AD process (see Chap. 20.1). As for the AD reaction, a cooxidant is needed to regenerate the active osmium species. But in the AA process the cooxidant also functions as the nitrogen source. Since two different heteroatoms are transferred to the double bond, regioselectivity becomes an important selectivity issue in addition to enantioselectivity. Moreover, chemoselectivity has to be addressed due to the possible formation of the... 

Overman et al. exercised the CBS reduction strategy during synthesis of the natural opium alkaloid (—)-morphine (50)21 (Scheme 4.3q). Enantioselective reduction of 2-allylcyclohex-2-en-l-one (51) with catecholborane in the presence of the (R)-oxazaborolidinc catalyst (l )-28a provided the corresponding (S)-cyclohexenol 52 in greater than 96% ee. Condensation of this intermediate with phenyl isocyanate, regioselective catalytic dihydroxylation of the terminal double bond, and protection of the resulting diol afforded 53 in 68% overall yield from 51. The ally lie silane 54 for the upcoming iminium ion-ally lsilane cycliza-tion step was obtained in 81% yield by a stereoselective Sn2 displacement of allylic carbamate. 

The first successful osmium-catalyzed asymmetric aminohydroxylation and dihydroxylation of thiophene acrylates have been reported. The aminohydroxylation of 2-thienyl-, 5-bromo-2-thienyl-, and 3-thienylacrylates proceeds with high regio- and enantioselectivity (Equation 75) <1999SL1907. Yields were about 67-68%, with the regioselectivity of 151 over 152 being >15 1. The ee was 99%. 

Aminohydroxylation of unsymmetrically substituted alkenes, in contrast to dihydroxylation, may give two possible regioisomers of aminoalcohol derivatives but asymmetric aminohydroxylation, by using the same catalytic system as that used for Sharpless asymmetric dihydroxylation, can be highly regioselective as well as enantioselective. 

SCHEME 13.49 Sharpless asymmetric dihydroxylation of an allylic silyl ether configuration inversion via regioselective intramolecular displacement of cyclic sulfates. 

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. 

The synthesis of the (+ )-compactin lactone 30, an important component of the statins, illustrates the power of the dihydroxylation methodology when coupled with regioselective sulfite ring opening (Scheme 3.28) [339]. 

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