Stereoselective Noyori Reduction

An alternative route by the Danishefsky group was developed [142e-g] (Scheme 84). The aldol reaction of ethyl ketone 580, prepared from P-keto ester 579, with aldehyde 581 stereoselectively afforded 582 (dr = 5.4 1). After Troc protection followed by hydrolysis of the enol ether, Suzuki coupling with 583 followed by TBS deprotection gave the desired (12Z)-olefin 584. The Noyori reduction of the P-keto ester 584 gave 3a-alcohol with high stereoselectivity, which was converted into hydroxy carboxylic acid 585. Macrolactonization of 585 was accomplished by the Yamaguchi method, and subsequent deprotection and DMDO oxidation efficiently afforded epothilone B (5b). 

Redox-type reactions show by far the worst performance in meeting the golden atom economical threshold. Three reductions meet this criterion with (AE)min values of 1 hydrogenation of olefins using the Lindlar catalyst (1952), Noyori stereoselective hydrogenation reaction (1985), and Zincke disulphide cleavage reaction (1911) whereas, oxidations... 

Asymmetric reduction of 25-24-oxosteroids. Reduction of the unsaturated 24-oxosteroid 2 with LiAlH, and the (R)-( + )-isomer of Noyori s reagent (1) gives a mixture of the two diols 3 and 4 in the ratio 95 5. The stereoselectivity is reversed by use of (SM )-l. This reaction was used to prepare optically pure (24R)- and (24S)-24-hydroxycholcstcrol and the epimeric pairs of 24,25-dihydroxycholesterol and 25,26-dihydroxycholcsterol.2... 

In a totally different approach, Noyori et al. have used binaphthol-modifled aluminum hydride reagent for enatioselective reduction of alkynyl ketones. Suitably modified boranes can be used for stereoselective reduction of ketones. Along these same lines. Midland" has developed Alpine borane (1, Scheme 21.5), which is excellent for several acetylenic ketones but has been found inefficient for hindered ot,p-acetylenic ketones. To overcome this problem, Brown et al." have introduced P-chlorodiisopinocamphenyl borane 2(-)-DIP-Cl (2, (Scheme 21.5), which reacts well with hindered ketones to provide the corresponding propargyl alcohols in 96 to 99% e.e. 

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. 

The aldehyde 218 possessing 2,6-frans-tetrahydropyran, was synthesized as shown in Scheme 48. /3-Keto ester 220 was reduced by Noyori hydrogenation [97] to give 6-hydroxy ester 221 in 94% ee, which was converted into iodide 222. Asymmetric alkylation using Myers chiral auxiliary [98] with 222, followed by acid treatment, furnished 5-lactone 223 with high stereoselectivity. Reductive acetylation, axial allylation by the Hosomi-Sakurai reaction, and ozonolysis completed the synthesis of 218. 

In 2009, Srihari and group reported on stereoselective total synthesis of synparvolide B and pi-synparvolide A using Noyori s ATH of ketone as a key step. Synparvo-lides (synparvolide A, synparvolide B, and synparvolide C) were isolated from the leaves of Syncolostemon parviflorus, a medicinal plant that is used as an emetic to treat loss of appetite. " Stereoselective reduction of the ketone 141 was accomplished with (5,5)-Noyori s catalyst in i-PrOH to give l,3-fl ti-isomer in 86% yield. 

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