Chiral compound stereoselective synthesis

Uros Groselj was born in Kranj, Slovenia, in 1975. He studied chemistry at the University of Ljubljana and received his B.Sc. in 2000. He continued his studies under the supervision of Professor Dr. Jurij Svete and received his Ph.D. in 2004. Currently, he is working as a researcher in the group of Professor Dr. Branko Stanovnik at the Faculty of Chemistry and Chemical Technology, University of Ljubljana. His research interests encompass synthesis of heterocyclic compounds, stereoselective synthesis, chemistry of terpene enaminones, cycloadditions, and synthesis of chiral ligands. 

M. R. Kula, U. Kragl, Dehydrogenases in the synthesis of chiral compounds" in R. Patel, Stereoselective Biocatalysis, Marcel Dekker, 2000, 839. 

The one chiral centre in (30) is used to set up four other chiral centres stereoselectIvely. Draw out the synthesis, giving the correct stereochemistry for all compounds. 

For stereoselective synthesis of a-aminocarbonyl compounds, a number of protocols have been reported using chiral enolates and A-(alkoxycarbonyl)-0-(arenesulfonyl) hydroxylamines. 

For stereoselective synthesis of a-aminocarbonyl compounds using 0-phosphinyl-hydroxylamines, a few procedures have been developed. Attempted amination of enolates of chiral alkyl 3-hydroxybutanoates with 0-(diphenylphosphinyl)hydroxylamine 4a or with its A,A-diisopropyl derivative 4d were found to be unsuccessful". ... 

The aim of this article is to focus on the diversity of aldonolactones as chiral synthons. The chemistry of aldonolactones was an almost unexplored area when, in 1979, we started our investigations on the reaction of aldonolactones with hydrogen bromide in acetic acid thereby obtaining bromodeoxyaldonolac-tones [1,2]. These compounds have over the years proven to be very versatile compounds for stereoselective synthesis, both in the carbohydrate field, giving access to otherwise less readily obtainable sugars, and as chiral, optically pure synthons in a broader sense within organic chemistry. 

With the increasing demand for chiral nonracemic compounds, stereoselective methods for the synthesis of 1,3-oxazine derivatives and applications of enantiopure 1,3-oxazines in asymmetric transformations have gained in importance in the past decade, as reflected by the increasing trend in the number of publications on this topic, and accordingly by the share of this topic in the present compilation. The limited size of this survey and the scope of this chapter do not allow a discussion here of the applications of 1,3-oxazines in polymer chemistry and the synthesis and properties of 1,3-benzoxazine-containing hetero-calixarenes. 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

M. Tramontini, Synthesis 1982, 605-644 . .Stereoselective Synthesis of Diastereomeric Amino Alcohols from Chiral Aminocarbonyl Compounds by Reduction or by Addition of Organometallic Reagents". 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

Dynamic Resolution of Chirally Labile Racemic Compounds. In ordinary kinetic resolution processes, however, the maximum yield of one enantiomer is 50%, and the ee value is affected by the extent of conversion. On the other hand, racemic compounds with a chirally labile stereogenic center may, under certain conditions, be converted to one major stereoisomer, for which the chemical yield may be 100% and the ee independent of conversion. As shown in Scheme 62, asymmetric hydrogenation of 2-substituted 3-oxo carboxylic esters provides the opportunity to produce one stereoisomer among four possible isomers in a diastereoselective and enantioselective manner. To accomplish this ideal second-order stereoselective synthesis, three conditions must be satisfied (1) racemization of the ketonic substrates must be sufficiently fast with respect to hydrogenation, (2) stereochemical control by chiral metal catalysts must be efficient, and (3) the C(2) stereogenic center must clearly differentiate between the syn and anti transition states. Systematic study has revealed that the efficiency of the dynamic kinetic resolution in the BINAP-Ru(H)-catalyzed hydrogenation is markedly influenced by the structures of the substrates and the reaction conditions, including choice of solvents. 

The reaction was extended to the stereoselective synthesis of compounds bearing three chiral carbons with syn,syn arrangement [497, 498],... 

Using other hypervalent iodine compounds or different reagent combinations, various functional groups can be introduced in the a-position of ketones. a-Tosylations of ketones can be achieved directly using [hydroxy(tosyloxy)-iodo]benzene 6. The major drawback is the low regioselectivity observed in these reactions, although the a-tosylation of silyl enol ethers circumvents this problem. In the last few years some efforts have been done in the synthesis of chiral hypervalent iodine compounds [48, 53-55,113-117], but only a few of them have been used successfully in stereoselective synthesis. With chiral derivatives of type 59 it is possible to a-tosylate propiophenone with about 40% ee [56,118,119]. 

Von Zelewsky has published many examples of the stereoselective synthesis of metal complexes using what he refers to as chiragen ligands. These are enantiopure natural compounds synthesized from the natural product (—)-a-pinene, which is combined with species such as bipyridine units to provide impressive control of metal-centered chirality.159-161 In this section, we will focus on the determination of absolute configurations in terms of stereospecific formation from different points of view in connection with absolute conformations in the ligands. 

---