Ethers epoxidation directed

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The influence of the conformational factors, which play a decisive role in directing oxide fission in the above cases is no longer operative in the case of 3-keto-5a,6a-epoxides and their 3-ethylene ketals. With these substrates the —I effect of the BFs-complexed 3-keto or 3-ketal grouping predominates leading to the fluorohydrins. Thus, treatment of both 5a,6a-oxidopregnane-3,20-dione (35) and its 3,20-bisethylene ketal with BFg-etherate in benzene-ether affords in 45% yield the 6jff-fluoro-5a-hydroxy-derivative (36) and its 3-ethylene ketal, respectively. which are converted into the 6a-fluoro-A -CH3... 

A retroaldol fragmentation subsequent to the addition of p-TsOI I and a small amount of water to epoxide 206, obtained by oxidation of enol ether 205 with DMDO, resulted in the direct formation of dialdehyde hydrate 208, possessing the spirostructure necessary for the construction of the fused-rings core of ( )-ginkoli-de B. Apparently, hydrolysis of the epoxide produces the hemiacetal 207, which undergoes retroaldol fragmentation of the cydobutane to afford the dialdehyde, which forms the stable hydrate 208 (Scheme 8.52) [94]. 

Several reports regarding the directed evolution of enantioselective epoxide hydrolases (EHs) have appeared [23,57-59]. These enzymes constitute important catalysts in synthetic organic chemistry [4,60]. The first two reported studies concern the Aspergillus niger epoxide hydrolase (ANEH) [57,58]. Initial attempts were made to enhance the enantioselectivity of the AN E H -catalyzed hydrolytic kinetic resolution of glycidyl phenyl ether (rac-19). The WT leads to an Evalue of only 4.6 in favor of (S)-20 (see Scheme 2.4) [58]. 

More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Cordova has also shown hydrogen peroxide to be an effective oxidant in the epoxidation of a,P-unsatnrated aldehydes using diarylprolinol ether 30 as the catalyst (Fig. 9) [146, 147], Within these reports it was also shown that the resulting epoxy aldehydes could be used directly in either Wittig or Mannich reactions, providing synthetically useful one-pot protocols to prepare densely functionalised building blocks for further elaboration. 

Z)-awh-4-Hydroxy-l-aIkenyl carbamates 363, when subjected to substrate-directed, vanadyl-catalysed epoxidation , lead to diastereomerically pure epoxides of type 364 (equation 99)247,252,269 qqjggg epoxides are highly reactive in the presence of Lewis or Brpnsted acids to form -hydroxylactol ethers 366 in some cases the intermediate lactol carbamates 365 could be isolated . However, most epoxides 364 survive purification by silica gel chromatography . The asymmetric homoaldol reaction, coupled with directed epoxidation, and solvolysis rapidly leads to high stereochemical complexity. Some examples are collected in equation 99. The furanosides 368 and 370, readily available from (/f)-0-benzyl lactaldehyde via the corresponding enol carbamates 367 and 369, respectively, have been employed in a short synthesis of the key intermediates of the Kinoshita rifamycin S synthesis . 1,5-Dienyl carbamates such as 371, obtained from 2-substituted enals, provide a facile access to branched carbohydrate analogues . 

Numerous studies have been directed toward expanding the chemistry of the donor/ac-ceptor-substituted carbenoids to reactions that form new carbon-heteroatom bonds. It is well established that traditional carbenoids will react with heteroatoms to form ylide intermediates [5]. Similar reactions are possible in the rhodium-catalyzed reactions of methyl phenyldiazoacetate (Scheme 14.20). Several examples of O-H insertions to form ethers 158 [109, 110] and S-H insertions to form thioethers 159 [111] have been reported, while reactions with aldehydes and imines lead to the stereoselective formation of epoxides 160 [112, 113] and aziridines 161 [113]. The use of chiral catalysts and pantolactone as a chiral auxiliary has been explored in many of these reactions but overall the results have been rather moderate. Presumably after ylide formation, the rhodium complex disengages before product formation, causing degradation of any initial asymmetric induction. 

Wu and Brodbelt have studied the gas-phase fragmentation reactions of HOMg(L) complexes of crown ethers and glymes . A common loss involves units of C2H4O, which can either directly occur from the precursor ion, or can be triggered by an initial interligand reaction between HO and L. This latter reaction is illustrated in Scheme 11 for the complex of 12-Crown-4. Thus loss of H2O from the initial adduct 56 yields the ring-opened complex 57, which contains a coordinated alkoxide moiety, which can then lose an epoxide to form the related complex 58. 

Hemminki, K., Falck, K. Vainio. H. (1980) Comparison of alkylation rates and mutagenicity of directly acting industrial and laboratory chemicals. Epoxides, glycidyl ethers, methylating and ethylating agents, halogenated hydrocarbons, hydrazine derivatives, aldehydes, thiuram and dithiocarbamate derivatives. Arch. Toxicol., 46, 277-285... 

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