Stereoselectivity reductions, research

Because the Corey synthesis has been extensively used in prostaglandin research, improvements on the various steps in the procedure have been made. These variations include improved procedures for the preparation of norbomenone (24), alternative methods for the resolution of acid (26), stereoselective preparations of (26), improved procedures for the deiodination of iodolactone (27), alternative methods for the synthesis of Corey aldehyde (29) or its equivalent, and improved procedures for the stereoselective reduction of enone (30) (108—168). For example, a catalytic enantioselective Diels-Alder reaction has been used in a highly efficient synthesis of key intermediate (24) in 92% ee (169). 

In addition, stereoselective synthesis of solenopsin A has been reported by four research groups. An approach utilizing the stereoselective reductive de-cyanation (596) starts with aminonitrile 229, prepared from 2-picoline. It was selectively hydrogenated in the presence of Pd-C, followed by alkylation with undecyl bromide, affording 231. Reductive decyanation of 231 with NaBH4 in MeOH led to predominant (8 2) formation of the trans isomer (232) which was then debenzylated to ( )-solenopsin A (Id). The cis product (Ic) was in turn prepared by treatment of 231 with sodium in liquid ammonia followed by de-benzylation (Scheme 10). 

Stereoselective reduction has been a focus of research in synthetic chemistry for many decades. There are numerous examples in the literature which require high... 

Professor Stanislaw Lesniak was born in 1952 in Gorlice (Poland). He obtained his M.Sc. degree in chemistry from the University of Lodz (Poland) in 1976, studying the reactivity of aziridines. He received his Ph.D. in chemistry from the same university in 1983 for study of stereoselective reduction of aziridinyl ketones. He presented his habilitation thesis at the University of Lodz in 1996. Professor Lesniak lectured at the University of Lodz from 1977 and six months at the University Claude-Bernard Lyon 1 in 1987/1988. He was a research fellow in the Department of Chemistry at the University Claude-Bernard Lyon 1 in a group of Prof. Andre Laurent in 1984-85, 1987-1988, and 1991-92. At the same university, he was employed as a CNRS research worker in 2001-02 in the group of Prof. P. Goekjian. The focus of his studies has been synthesis and reactivity of small molecules, radical reactions, and reactions under flash vacuum thermolysis conditions. 

Research activities on heterogeneously-catalyzed stereoselective reductions have generally increased during the past years[l]. Among various functionalities the stereoselective aromatic ring reduction is of importance in the synthesis of fine chemicals such as pharmaceuticals, herbicides, fragrances and liquid crystals. Particularly, substituted phenol derivatives offer the possibility to control the product selectivity via reduction of the prochiral intermediate cyclohexanone [2,3]. 

Direct cleavage of the ally lie methyl ether in 106 with boron tribromide afforded codeine in only minor amounts. Better yields were obtained when 106 was converted to the corresponding carbamate before a selenium dioxide mediated oxidation delivered ketone 107. Stereoselective reduction of the ketone and concomitant generation of the iV-methyl group concluded the synthesis of codeine [60, 68]. This synthesis reported by Stork and co-workers provided a closure to several years of research, some of which has been reported in Ph.D. dissertations [69]. 

The control of chemical selectivity is a classical problem in organic chemistry and an antibody s ability to route reactions via disfavored pathways, as in the asymmetric Diels-Ald reaction, has important practical ramifications. Not surprisingly, extension of this approach to the catalysis of other unselective or energetically demanding reactions has become an important focus of research. Syn eliminations [45], cationic olefin cycliza-tions [46], and enol ether hydrolyses [47] are among the processes that have been investigated. For the purposes of the current discussion, however, the regio- and stereoselective reduction of the diketone 21 [48] illustrates what... 

Most synthetic strategies are aimed toward direct assembly of open-chain systems ( acyclic stereocontrol ). In this manner, individual building blocks containing stereotriads are prepared and then incorporated into the target molecule. This approach mimics polyketide biosynthesis. Many research programs have been dedicated to improve both regio and stereo control, the efficiency of carbon-carbon bonds formation, and then stereoselective reduction of... 

Over the last several years, many powerful protocols for organocatalytic, stereoselective reductions have been developed. After intensive research, these reactions have made a huge leap in terms of reactivity as well as selectivity. Frequently, excellent yields and selectivities (>90%) are obtained for a wide variety of substrates. Recent publications showed that even the often high and therefore problematic catalyst loading could be lowered to competitive levels (1 mol%). Transition metal catalysts still show higher reactivity, allowing lower catalyst loadings, but this gap becomes rapidly smaller. 

Despite the progress made in the stereoselective synthesis of (R)-pantothenic acid since the mid-1980s, the commercial chemical synthesis still involves resolution of racemic pantolactone. Recent (ca 1997) synthetic efforts have been directed toward developing a method for enantioselective synthesis of (R)-pantolactone by either chemical or microbial reduction of ketopantolactone. Microbial reduction of ketopantolactone is a promising area for future research. 

SMP amide enolates have been employed by several research groups. Alkylation of SMP amide enolates gives a-substituted acids (eq 3). Excellent yields and stereoselectivities are observed in the Birch reduction of aromatic SMP amides with subsequent alkylation (eq 4). ... 

Not all organic chemists can be Involved in such exciting projects as the launching of a new anti-AIDS drug. But the chemistry used in this project was invented by chemists in other institutions who had no idea that it would eventually be used to make Crixlvan. The Sharpless asymmetric epoxlda-tion, the catalytic asymmetric reduction, the stereoselective enolate alkylation, and the various methods tried out for the enantiomerically pure amino indanol (resolution, enzymatic kinetic resolution) were developed by organic chemists in research laboratories. Some of these famous chemists like Sharpless invented new methods, some made new compounds, some studied new types of molecules, but all built on the work of other chemists. 

The partial reduction of substrates containing triple bonds is of considerable importance not only in research, but also commercially for stereoselectively introducing (Z)-double bonds into molecular frameworks of perfumes, carotenoids, and many natural products. As with catalytic hydrogenation of alkenes, the two hydrogen atoms add syn from the catalyst to the triple bond. The high selectivity for alkene formation is due to the strong absorption of the alkyne on the surface of the catalyst, which displaces the alkene and blocks its re-adsorption. The two principal metals used as catalysts to accomplish semireduction of alkynes are palladium and nickel. 

Despite the great amount of interest in reductive desulfonylation reactions, very little research has addressed the stereospecific reductive desulfonylation of chiral a-substituted sulfones. Only limited success has been achieved as shown in Eq. 30.50 Lithium naphthalenide is used for the stereoselective SET desulfonylation of anomeric sulfones derived from 2-deoxy-D-glucose derivatives.51-54 The initial homolytic cleavage of the C-SO2 bond generates a cr-radical, which adopts an a-orientation due to stereoelectronic stabilization,55-57 forcing the anomeric substituent to adopt the (3-orientation, an arrangement that is retained through the reduction process (Eq. 31). 

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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