Chiral template synthesis

Template synthesis and chirality of catenanes, rotaxanes, and pretzelanes including N-macroheterocyclic lactams and related compounds as structure components 99PAC247. 

Stereoselective inverse-demand hetero (4 + 2) cycloadditions. A Chiral Template for C-Aryl Glycoside Synthesis. Chiral allenamides2 4 had been used in highly stereoselective inverse-demand hetero (4 + 2) cycloaddition reactions with heterodienes.5 These reactions lead to stereoselective synthesis of highly functionalized pyranyl heterocycles. Further elaboration of these cycloadducts provides a unique entry to C-aryl-glycosides and pyranyl structures that are common in other natural products (Scheme 1). 

Recently, an essentially unfaulted version of SSZ-33 was synthesized and is referred to as CIT-1. The end member of this family of zeolites was synthesized in a borosilicate composition (22, 23). The CIT-1 corresponds to essentially pure polymorph B. The template used to prepare CIT-1 was the /V, /V, /V- tri m c ill y I - (-) -cis-myrtanylammonium ion (4) shown in Fig. 6. Note that this organocation is chiral but synthesis of CIT-1 does depend on which enantiomer is used. An interesting aspect of the reported CIT-1 syntheses is that the gel was sealed in a silica tube and heated at 175°C for 1 week or at 150°C for 3-5 weeks. It is not clear whether or not CIT-1 has been made any other way, which seems to indicate the silica tube plays a role in the crystallization. 

In some sugar-based lactones, the carbohydrate moiety can serve as a chiral template. For example, the synthesis and characterisation of a novel chiral bicyclic caprolactone 1 was reported in 2003 in six steps from 1,2,5,6-di-O-isopropylidene-a-D-glucofuranose.10 The introduction of... 

Aldonolactones are useful starting materials for the synthesis of modified sugars. They have also been used as chiral templates in synthesis of natural products. Some of them are inexpensive, commercially available products or they may be obtained readily from the respective monosaccharides. The purpose of this chapter is to survey the main reactions of aldonolactones. Previous reviews on the subject include articles on gulono-1,4-lactones (1) and D-ribonolactone (2). Methods of synthesis, conformational analysis, and biological properties are not discussed in this chapter. 

The regio- and stereo-selective functionalization of aldonolactones yields optically active lactones, which are important precursors in natural product synthesis. Concepts such as chiral templates and chirons, derived from carbohydrates, have been ingeniously and widely applied in synthesis (233). Among the commercially available aldonolactones, D-ribono-1,4-lactone is... 

Last year, a short enantioselective total synthesis of herbarumin III (42) in 11% overall yield was published the approach applied uses Keck s asymmetric allylation and Sharpless epoxidation to build the key fragment. Esterification with 5-hexenoic acid and a RCM was used to yield 42. Finally, another asymmetric synthesis of herbarumin III (42) was carried out using (R)-cyclohexylidene glyceraldehyde as the chiral template. The key steps of the synthesis were the enantioselective preparation of the... 

Wullf and Hohn recently described several new stereochemical results (93). They reported the synthesis of a copolymer between a substituted styrene (M ) and methyl methaciylate (M2) having, at least in part, regular. . . M,M M2M MiM2. . . sequences. Polymerization involves the use of a chiral template to which the styrene monomer is loosely bound. After elimination of the template, the polymer shows notable optical activity that must be ascribed to the presence of a chiral stmcture similar to that shown in 53 (here and in other formulas methylene groups are omitted when unnecessaiy for stereochemical information). This constitutes the first stereoregular macromolecular compound having a three monomer unit periodicity. 

In 2005, various groups independently realized the potential of the easily available cinchona alkaloids as chiral templates for the synthesis of the new class... 

Eujii Y, Matsutani K, Kikuchi K. Formation of a specific coordination cavity for a chiral amino-acid by template synthesis of a polymer Schiff-base cobalt(III) complex. Chem Commun 1985 415-417. 

Williams and Fegley (40) utilized his chiral template (Section 3.2.3) as a chiral dipolarophile in the concise synthesis of 5 -( )-cucurbitine, a naturally occurring amino acid isolated from species of pumpkin, that acts as a growth inhibitor to... 

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). 

A detailed study (231-233) reveals that most probably the protonated, adsorbed alcaloid offers the chiral template for the inductive synthesis. It participates as a proton donor in a fast preestablished 2e /2H+ equilibrium followed by a final desorptive step that establishes and stabilizes the acquired molecular configuration. Figure 34 describes the reaction model—albeit somewhat naively and oversimplified. 

Our template synthesis of knots implies that the target molecules are obtained as cationic dicopper(I) complexes. Therefore we considered the possibility of interconverting both enantiomers into a pair of diastereomeric salts [137, 138] by combining them with an optically active anion. Binaphthyl phosphate (BNP") [139] drew our attention because its chirality arises from the binaphthyl core, which is twisted. This helical structure is of the same type as that of die copper double helix, precursor of the knot. Besides, both compounds are aromatic and, thus, we could expect some potentially helpful stacking interactions [87],... 

L. W. Dudycz, Stereoselective synthesis of 6-amino-5,6-ribo-heptafuranouronates with the aid of glycine chiral templates, Nucleosides Nucleotides 10329 (1991). 

K. Kakinuma, Y. Iihama, I. Takagi, K. Ozawa, N. Yamauchi, N. Imamura, Y. Esumi, and M. Uramoto, Diacetone glucose architecture as a chirality template. II. Versatile synthon for the chiral deuterium labelling and synthesis of all diastereomers of chirally monodeuterated glycerol, Tetrahedron 48 3163 (1992). 

For the total synthesis of aminodeoxy sugars from nonsugar precursors, it is logical to turn to amino acids as primary sources of chiral templates. The challenge is to find innovative and stereocontrolled methods of chain extension reactions that lead to higher-carbon aminodeoxy sugars. 

Use of Carbohydrates as Chiral Templates for the Synthesis of the Lipid Portion... 

Since the synthesis of glycolipids involves the synthesis of both the lipid and the oligosaccharide portions, we shall also discuss that part of the recorded lipid synthetic work which has involved the use of carbohydrates. In fact, some of the first-recorded applications of carbohydrate molecules as chiral templates are to be found in the lipid field particularly with the use of 1,2 5,6-di-O-isopropylidene-D-mannitol [33] as a precursor of chiral glycerol derivatives for the synthesis of phospholipids and glycolipids based on glycerol and with the use of glucosamine derivatives for the synthesis of phytosphingosines [34] and since this area has not previously been reviewed, it will be treated with a more historical perspective. 

The sequence of Ugi-4CR + hydrolysis of the amino substituent has been employed in the stereoselective synthesis of chiral a-amino acid derivatives, by using a chiral amine component. Then the chiral template was covalently bound in close proximity to the newly synthesized chiral center. The amine residue of the product must be removable under mild conditions to avoid decomposition of the desired product. Chiral a-ferrocenylamines have been employed with some success [34], but the most useful auxiliaries were carbohydrate amines [35]. 

The number of synthetic routes to the natural 1-hydroxymethyl-pyrrolizidines continues to increase. Robins and Sakdarat have achieved the first synthesis of these necines in optically active form, using natural (-)-4-hydroxy-L-proline as a chiral template.2 The dihydropyrrolizine ester (2) was prepared by regiospecific 1,3-dipolar cycloaddition of ethyl propiolate to the N,0-diformyl derivative (1) of (-)-4-hydroxy-L-proline, followed by deformylation (Scheme 1). Addition... 

Fritz Vogtle Barcelona, Spain Rotaxanes, Catenanes. Pretzelanes- Template Synthesis and Chirality... 

Microwave-assisted Diels-Alder reactions of 9-substituted anthracenes with 2-acetamidoacrylate in DMF generate conformationally constrained bicyclic bisaryl a-amino acid derivatives with high regioselectivity.138 The Sc(OTf)3-catalysed Diels-Alder reaction of anthracenes with methyl vinyl ketone does not proceed via an electron-transfer process from anthracenes to the MVK-Sc(OTf)3 complex.139 (-)-(/ )-9-(l,2-Dimethoxyethyl)anthracene has been used as a chiral template in the Diels-Alder/retro-Diels-Alder sequence for the synthesis of a,j3-unsaturated lactams.140... 

On the basis of this discussion a particularly promising scheme for synthesizing chiral compounds with great isomer purity and high overall yield would be to start with a productive asymmetric synthesis (to assure high yield) and follow by a destructive one (to assure unlimited isomer purity of the desired product). Such a procedure has the essential advantage that under suitable conditions it leads to pure chiral compounds without cumbersome separation of stereoisomers. With proper choice of the reactants the procedure will also permit an effective recovery of the auxiliary chiral materials needed as chiral templates in the asymmetric synthesis. 

This chapter focuses on the importance of cis-1 -amino-2-indanol as a chiral template in the development of new methodologies for the asymmetric synthesis of organic compounds. Other chiral auxiliaries are discussed in Chapter 23. The use of the amino alcohol 1 in resolutions is discussed in Chapter 8, whereas applications of 1 as a ligand are in Chapter 17. 

Fig. 25 Enantioselective non covalent synthesis of double rosettes exploiting the chiral memory effect. Pyridyl residues on the dimelamine units bind chiral dicarboxylic acids leading mainly to one diastereoisomer. Once the chiral templating carboxylic acid is removed by precipitation, the enantioenriched double rosette persists for several hours...

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