Stereoselective synthesis asymmetric epoxidation

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

Scheme 7-16 shows that a similar synthetic route leads to the asymmetric synthesis of optically active 62. The synthesis that began from homochiral aldehyde (—)-52 used this newly discovered asymmetric epoxidation three times, 52 —> 58, 58 —> 68, and 68 —> 61, finishing the conversion from 52 to 61 by following a shortened route. The last chiral center to be built is C-27, and the addition of allyltin to the aldehyde derived from 61 proceeds with high stereoselectivity to give the chiral aliphatic segment 62. 

Spino and Frechette reported the synthesis of non-racemic allenic alcohol 168 by a combination of Shi s asymmetric epoxidation of 166 and its organocopper-mediat-ed ring-opening reaction (Scheme 4.43) [74]. Reduction of the ethynyl epoxide 169 with DIBAL-H stereoselectively gave the allenic alcohol 170, which was converted to mimulaxanthin 171 (Scheme 4.44) [75] (cf. Section 18.2.2). The DIBAL-H reduction was also applied in the conversion of 173 to the allene 174, which was a synthetic intermediate for peridinine 175 (Scheme 4.45) [76], The SN2 reduction of ethynyl epoxide 176 with DIBAL-H gave 177 (Scheme 4.46) [77]. 

A Sharpless asymmetric epoxidation features in a synthesis of (S)-chromanethanol (15). In the key cyclisation step, the absolute configuration of the diol is retained by a double inversion (95SL1255). trans-6-Cyano-2,2-dimethylchroman-3,4-diol is obtained from the racemic diol with excellent optical purity by the stereoselective acylation using Candida cylindraceae lipase (95TA123). 

Dialkylamino-aryloxosulfonium alkylides may be employed for enantioselective epoxidation if the ylide with its chiral sulfur center is resolved into its enantiomeric form, " An enantioselective oxirane is obtained by means of a chiral phase-transfer catalyzed procedure with dimethylsulfonium methylide. The utilization of arsonium ylides was reported some time ago. ° A highly stereoselective synthesis of trans-epoxides with triphenylarsonium ethylide has recently been described.Optically active arsonium ylide has been used in the asymmetric synthesis of diaryloxiranes. ... 

The number of catalytic asymmetric transformations involving epoxides has grown considerably, even since this topic was last reviewed in 1996 [1,2]. This chapter will higUight recent progress in asymmetric catalytic ring-opening methods and their increasing importance in the stereoselective synthesis of enantio-enriched compounds. 

In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were recently developed by Shibasaki et al., are highly efficient catalysts in stereoselective synthesis. This new and innovative type of chiral catalyst contains a Lewis acid as well as a Bronsted base moiety and shows a similar mechanistic effect as observed in enzyme chemistry. A broad variety of asymmetric transformations were carried out using this catalysts, including asymmetric C-C bond formations like the nitroaldol reaction, direct aldol reaction, Michael addition and Diels-Alder reaction, as well as C-0 bond formations (epoxidation of enones). Thereupon, asymmetric C-P bond formation can also be realized as has been successfully shown in case of the asymmetric hydrophosphonylation of aldehydes and imines. It is noteworthy that all above-mentioned reactions proceed with high stereoselectivity, resulting in the formation of the desired optically active products in high to excellent optical purity. 

The ether derivatives 0,0,0-trimethylkorupensamine A (248) and B have both been synthesised by a route which commenced with a lengthy sequence to the biaryl 249 from 3,5-dimethylanisole (ref. 95) (Scheme 32). Reduction of 249 with LiAlHa and oxidation gave aldehyde 250 which upon Wadsworth-Emmons-Homer extension, reduction and Sharpless asymmetric epoxidation provided epoxide 251 and the corresponding atropisomer in almost equal amounts which were separated by silica gel chromatography. The derived alcohol 252, obtained by mesylation of 251 and in situ reduction, was then converted into the acetamide 253 by displacement with azide under Mitsunobu conditions followed by reduction and acetylation. Ring closure followed by stereoselective reduction then yielded 0,0,0-trimethylkorupensamine A (248). The synthesis of 0,0,0-triraethylkorupensamine B was accomplished in a similar manner using the atropisomer of 251 obtained in the epoxidation step. 

Take the millions of lives saved by the synthesis of indinavir, for example. This drug would not have been possible had not the Sharpless and Jacobsen asymmetric epoxidations, the catalytic asymmetric reduction, and the stereoselective enolate alkylation, along with many of the methods tried but not used in the final synthesis, been invented and developed by organic chemists in academic and industrial research laboratories. Some of the more famous names involved, like Sharpless, Jacobsen, and Noyori, invented new methods, while others modified and optimized those methods, and still others applied the methods to new types of molecules. Yet all built on the work of other chemists. 

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