Chiral ether

These experiments demonstrate that the surface-catalyzed 2 reaction is far more effident than either the or C pathway for the dehydrative coupling of alcohols over the solid add catalysts tested. High selectivity to configurationally inverted chiral ethers ensues, espedally in the case of the HZSM-5 catalyst, in which the minor C or C paths were further suppressed by "bottling" of 3-ethoxypentane by the narrow zeolite chaimels. 

As the integrity of chiral alcohols are retained in the phase-transfer catalysed O-alkylation, the procedure is valuable for the synthesis of chiral ethers under mild conditions as, for example, in the preparation of alkoxyallenes via the initial formation of chiral propargyl ethers [8]. It has been proposed that a combination of 18-crown-6 and tetra-n-butylammonium iodide provide the best conditions for the O-benzylation of diethyl tartrate with 99% retention of optical purity [9]. 

Cram and co-workers have experimented extensively with chiral recognition in crown ethers derived from various 3-binaphthols (73). In nonpolar solvents, these chiral ethers complex salts of PEA and various chiral a-amino esters (with fast exchange), inducing nonequivalence in their NMR spectra. The senses of proton nonequivalence induced in these solutes have been used to support proposed structures of the diastereomeric solvates (74). 

This type of catalytic strategy has recently been extended to enantio-selective addition of alkyllithiums to certain prochiral imines (Scheme 18) (35). Relevantly, in the presence of a small amount of a chiral ether ligand, 1-naphthyllithium reacts with a sterically hindered imine of l-fluoro-2-naphthaldehyde (conjugate addition/elimination) to afford a binaphthyl compound in greater than 80% ee. 

Methyl-5-hepten-2-one is a valuable precursor for microbial epoxidations and hence the production of chiral ethers with high optical purities. The biotransformation of 6-methyl-5-hepten-2-one (33) by Botryodiplodia malorum CBS 13450 to (/ )-sulcatol (84) was described [61], which is then epoxidised to the (55)-epoxide (85) and opened intramolecularly to cis-(2R,5R)-2-(2 -hydroxyisopropyl)-5-methyltetra-hydrofuran (86) and c/s-(35,67 )-3-hydroxy-2,2,6-trimethyltetrahydropyran (87). Reduction of 6-methyl-5-hepten-2-one (33) with baker s yeast to (5)-sulcatol (88) which was used as substrate for Kloeckera corticis... 

Stoichiometric and catalytic asymmetric reactions of lithium enolate esters with imines have been developed using an external chiral ether ligand that links the components to form a ternary complex.36 The method affords /i-lactams in high enantiomeric excess. 

Asymmetric formation of /i-lactams (38) in high ee has been achieved by reaction of achiral imines (36) with a ternary complex of achiral lithium ester enolate (35), achiral lithium amide, and a chiral ether ligand (37) (in either stoichiometric or catalytic amount) 45 the size and nature of the lithium amide have a considerable effect on the enantioselectivity of the ternary complex. 

Using a similar approach, the first asymmetric synthesis of the benzofu-ran lactone 310 was described, starting from the chiral ether 309 (88JOC860). 

The best known member among the various classes of these iodanes is undoubtedly [hydroxy(tosyloxy)iodo]benzene (HTIB), sometimes called Koser s reagent. It is prepared readily from (diacetoxyiodo)benzene and p-toluenesul-fonic acid monohydrate in acetonitrile. The same method using p-nitroben-zenesulfonic acid or 10-camphorsulfonic acid leads to the corresponding sul-fonyloxy analogs [41,42]. Of special interest are some iodanes of this type coming from a chiral ether. Their preparation was effected by direct oxidation with sodium perborate and the isolated diacetoxy derivatives were separately treated with p-toluenesulfonic acid in acetonitrile (Scheme 8) [43]. 

The conformational minima of a series of chiral ethers have been studied by means of DFT (B3LYP/6-31+G ) and ab initio (MP2/6-311+G ) methods [40]. The protonation of these compounds produces diasteromeric systems depending on the protonated lone pair. The relative energy of the conformers has been analyzed using the QTAIM and NBO methods (Fig. 3.21). 

The most stable conformers of the protonated chiral ether correspond, in all the examples considered in the present article, to a RS chirality (R in the carbon atom and S in the oxygen one). The analysis of the atomic energies within the QTAIM method has been able to attribute the influence of the difference molecular groups to the stability of the RS configuration vs. the corresponding RR one. 

RCM reactions are most frequently employed in the synthesis of 2,5-dihydrofurans as well as dihydropyrrole derivatives . Likewise, RCM provides the most general approach to 3,6-dihydropyrans . In a specific example, dihydropyran 127 bearing a chiral oxacyclic diene can be constructed via enyne metathesis of the chiral ether 126 (Scheme 68) <2002T5627>. The analogous tetrahydropyridine derivatives are prepared by a similar RCM procedure . 

Similarly, chiral bases have found use in the preparation of building blocks for synthesis of alkaloids. A range of A-protected azabicyclic ketones was deprotonated to yield corresponding silylenol ethers (Scheme 30)68-70. The highest ee (93%) was obtained using 42 under internal quench conditions. These chiral ethers found use as key intermediates in the preparation of naturally occurring alkaloids. 

The most promising result was obtained when (S)-tropolone 2-methylbutyl ether (chiral ether) was irradiated within an ephedrine included NaY (Fig. 15) [295,306]. In the absence of ephedrine, diastereomer A is obtained in 53% diaste-reomeric excess. When (— )ephedrine was used as the chiral inductor, the same isomer was enhanced to the extent of 90%. The importance of this result becomes more apparent when one recognizes that irradiation in solution of the same com-... 

Figure 25. Calix(4]arene 1,3-diethers with chiral ether residues possible conformations and their symmetry.

For derivatives of 89 with chiral ether residues, derived from L-amino acids see Okada, Y. Kasai, Y. Nishimura, J. Tetrahedron Lett. 1995, 36, 555-558. 

Table 39. Additions of a y-oxygenated allylic stannane bearing a chiral ether auxiliary to achiral aldehydes. OH OH...

The linked oligopyridine-based foldamers described thus far lack any asymmetric functionalities able to shift the Pand Mhelical equilibrium. The first report attempting to bias the twist sense of a helicate involved chiral ether linkages to a bipy3 strand (Figure 149).825 When these oligomers were com-plexed with 3 equiv of either Cu(I) or Ag(I), only the P helicate was obtained. In this conformation, the... 

Consequently, cyclodehydration of unsymmetrical chiral 1,2-diols should afford predominantly the cyclic chiral ether with retained configuration at the C-2 stereogenic carbon, and (b) as the steric bulk of the attached R group increases, the percent of regioselection or stereospecificity of substitution should also increase. 

Fig. 2.16 Discrimination with non-binding se- selection of protected amino acids by a crown lection sites, (a) Selection principle (b) Chiral ether with remote binaphthyl selection site.

A significant recent development has been the synthesis of PAn s in which chiral substituents have been covalently attached to the aniline rings. Chiral ethers were bound to the aniline monomer before its chemical oxidation by persulfate,139 producing chiral PAn s possessing strong optical activity as evidenced by their CD spectra. Previous routes to chiral PAn s had employed chiral dopant anions to induce chirality into PAn chains. 

The syntheses of the chiral, tridentate P-amino ethers la,b have also been reported [19e]. Amino ether la was prepared from commercially available L-phe-nylalanine via the acyl chloride, and amino ether lb was prepared from commercially available L-2-phenylglycine (Scheme 2). Other ligands (bidentate chiral ethers and amino ethers) were also prepared, and these authors carried out a structure-enantioselectivity relationship study with these various chiral ami-... 

A few examples of stereoselective additions of organomagnesium or -cerium reagents to imines bearing a chiral arenechromium tricarbonyl or dieneiron tricarbonyl residue have been described [539, 1197], Reactions of allylmetals with an oxime bearing a chiral ether functionality can be stereoselective provided that the oxime displays the E configuration [1198],... 

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