Epoxides 2-trimethylsilyl, synthesis

Synthesis of 31 by Method I (107,108) and its conversion to the related anti and syn diol epoxide derivatives (32,33) has been reported (108). The isomeric trans-1,lOb-dihydrodiot 37) and the corresponding anti and syn diol epoxide isomers (38,39) have also been prepared (108) (Figure 19). Synthesis of 37 from 2,3-dihydro-fluoranthene (109) could not be accomplished by Prevost oxidation. An alternative route involving conversion of 2,3-dihydrofluoranthene to the i8-tetrahydrodiol (3-J) with OsO followed by dehydration, silylation, and oxidation with peracid gave the Ot-hydroxyketone 35. The trimethylsilyl ether derivative of the latter underwent stereoselective phenylselenylation to yield 36. Reduction of 3 with LiAlH, followed by oxidative elimination of the selenide function afforded 3J. Epoxidation of 37 with t-BuOOH/VO(acac) and de-silylation gave 38, while epoxidation of the acetate of JJ and deacetylation furnished 39. 

Other methods for a-hydroxy ketone synthesis are addition of O2 to an enolate followed by reduction of the a-hydroperoxy ketone using triethyl phosphite 9 the molybdenum peroxide-pyridine-HMPA oxidation of enolates 10 photooxygenation of enol ethers followed by triphenylphosphine reduction 11 the epoxidation of trimethyl silyl enol ethers by peracid 1 - the oxidation of trimethylsilyl enol ethers by osmium tetroxide in N-methylmorpholine N-... 

A similar approach to the hydrolytic methodology uses a chromium-salen complex to open an epoxide with trimethylsilyl azide, as illustrated by the synthesis of the antihypertensive agent, (S)-propranolol (10) (Scheme 9.15).118,119... 

The first issue confronted by Myers was preparation of homochiral epoxide 7, the key intermediate needed for his intended nucleophilic addition reaction to enone 6. Its synthesis began with the addition of lithium trimethylsilylacetylide to (R)-glyceraldehyde acetonide (Scheme 8.6).8 This afforded a mixture of propargylic alcohols that underwent oxidation to alkynone 10 with pyridinium dichromate (PDC). A Wittig reaction next ensued to complete installation of the enediyne unit within 11. A 3 1 level of selectivity was observed in favour of the desired olefin isomer. After selective desilylation of the more labile trimethylsilyl group from the product mixture, deacetalation with IN HC1 in tetrahydrofuran (THF) enabled both alkene components to be separated, and compound 12 isolated pure. 

The selected examples by Cole et al. [120] and Shimizu et al. [121] reported the parallel synthesis of a small library of solid supported dipeptide Schiff bases as ligands for the Ti-catalyzed enantioselective addition of trimethylsilyl cyanide to meso epoxides, and the determination of their catalytic activity on different substrates. The catalyzed addition reaction and the general structure of the dipeptide ligands are shown in Figure 7.15. 

At about the same time, a synthesis of leukotriene-A, also termed SRS-A ( slow reacting substance of anaphylaxis ), which made use of the Wittig olefmation was described77). The ylide of 100 is reacted with ethyl 5-formyl-2,4-pentadienoate 101 to give the ( , , Z, Z)- tetraenoic ester 102. Reduction and mesylation of 102, subsequent conversion into the sulfonium salt, and treatment of the latter with a base yields a sulfonium ylide which is reacted with methyl 4-formylbutanoate 69 to the epoxy-tetraenoic ester 103. After separation of the cis-epoxide by HPLC, 103 was treated with the S-trimethylsilyl derivative of glutathione dimethyl ester N-trifluoroacet-amide. The diastereomeric products thus obtained were separated by means of HPLC and hydrolyzed to 104 77) (Scheme 18). 

Multicomponent linchpin couplings can be carried out with 2-trialkylsilyl substituted 1,3-dithianes 207 and epoxides and was successfully used in the synthesis of natural products182. Tietze and coworkers303 found out that 2-lithio-2-trimethylsilyl-1,3-dithiane 208 reacted with two equivalents of a chiral epoxides in the presence of a crown ether to give first the monoadduct 209, which suffered 1,4-Brook rearrangement304 generating a new dithiane anion 210. Final reaction with an epoxide afforded products 211, which are equivalents of acetone aldol products (Scheme 60). 

Organophosphorus reagents based on triphenylphosphine, or trimethylsilyl iodide, may be used to deoxygenate epoxides to re-form the parent alkene. Reactions based on this, or on a related scheme using the reduction of an iodohydrin, have been used in the synthesis and protection of alkenes as their epoxides (Scheme 2.23). 

These epoxides can be converted to vinyl siloxycyclopropanes m high yield by treatment with base and trimethylsilyl chloride. Transformations of these interesting intermediates (see Section VII) into various products are demonstrated in equation 103. Isolation of oxaspiropentanes is not required in a route to cyclobutanones which are formed by straightforward acid workup (equation 104) . These can either be expanded to y-butyrolactones by oxidation or to an enol ester by a-formylation and acid-induced fragmentation. The latter sequence has been utilized in a synthesis of acorenone... 

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