Protected Epoxy Alcohols

Another protected epoxy-alcohol, rac-2-methylglycidyl benzyl etiier, has been the subject of numerous investigations. Two types of EHs proved to be useful those from various Rhodococcus strains [148-151] and the one from Bacillus subtilis [6,152]. 

Chemoenzymatic access to (S)-3-hydroxytetrahydrofuran. (i) See Yuasa and Tsuruta [146] 79% yield 

8 EPOXIDE HYDROLASES AND THEIR APPLICATION IN ORGANIC SYNTHESIS 

Application of the CIP rule for the determination of the absolute configuration of an epoxide. 

A B ligand detachment at the distal end (C) phantom carbon atom 

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Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

The synthesis of the trisubstituted cyclohexane sector 160 commences with the preparation of optically active (/ )-2-cyclohexen-l-ol (199) (see Scheme 49). To accomplish this objective, the decision was made to utilize the powerful catalytic asymmetric reduction process developed by Corey and his colleagues at Harvard.83 Treatment of 2-bromocyclohexenone (196) with BH3 SMe2 in the presence of 5 mol % of oxazaborolidine 197 provides enantiomeri-cally enriched allylic alcohol 198 (99% yield, 96% ee). Reductive cleavage of the C-Br bond in 198 with lithium metal in terf-butyl alcohol and THF then provides optically active (/ )-2-cyclo-hexen-l-ol (199). When the latter substance is treated with wCPBA, a hydroxyl-directed Henbest epoxidation84 takes place to give an epoxy alcohol which can subsequently be protected in the form of a benzyl ether (see 175) under standard conditions. 

Asymmetric epoxidation of 10a under standard conditions yields the crystalline epoxy alcohol 2a in 95% ee (91% chemical yield). Treatment of 9a with thioanisol in 0.5N NaOH, in rerf-butyl alcohol solution, gives -after protection of the hydroxyl groups as benzyl ethers- the sulfide a (60% overall yield) through an epoxide ringopening process involving a Payne rearrangement. Since the sulfide could not be hydrolysed to the aldehyde 7a without epimerisation at the a-position, it was acetoxylated in 71% yield under the conditions shown in the synthetic sequence (8a... 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

C-3 selectivity has been attained by the use of 2,3-epoxy alcohols having a bulky protective group. Thus, (25) reacts with alkenylmagnesium bromide (26) in the presence of a catalytic amount of Cul to... 

The reaction usually occurs at the less substituted carbon of the oxirane ring (Scheme 62 and Scheme 67) 293,297 However regioisomeric dithianyl alcohols are obtained from 2-lithio-1,3-dithianes and the protected 3, y-epoxy alcohols shown in Scheme 66 (entry b). The observed regioselectivity is very different when methoxymethyl or benzyl protecting groups are used. This has been explained by the different... 

Preparation of the hydroxypentanoic acid fragment was initiated by addition of the protected propargyl alcohol anion 109 to ethylene oxide. After silylation of the resulting alcohol, the ethoxy ethyl group was removed and the alkyne partially reduced to afford the (2)-alcohol 110 in 52% overall yield. Enantiospecific epoxidation of 110 under Sharpless s conditions and subsequent oxidation provided a 69% yield of diastereomerically pure epoxy acid 111. Treatment with trimethylaluminum gave almost exclusively the p-methyl acid, which was acylated to afford 112 (78%). 

Corey prepared the (6E,10Z)-LTB4 (115) from the previously described epoxy alcohol LTB4 synthon 119. Acid-catalyzed rearrangement of the derived phenylcarbonate 120 followed by protection, reductive cleavage of the vicinal carbonate, and cleavage of the resulting diol gave (2E)-r-butyldimethylsilyloxy-... 

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