Chiral binaphthyl compounds

A large number of chiral crowns have been prepared by numerous groups. The reader is directed to the tables at the end of this chapter to obtain an overview of these structures. It would not be useful to try to recount the synthetic approaches used in the preparation of all of these compounds we have chosen rather to subdivide this mass of compounds into three principal groups. The groups are (1) Cram s chiral binaphthyl systems (2) chiral crowns based on the tartaric acid unit and (3) crowns incorporating sugar subunits. These are discussed in turn, below. 

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

Thus, a slight enantiomeric imbalance in compounds induced by CPL was correlated for the first time to an organic compound with very high ee by asymmetric autocatalysis with amplification of chirality. Moreover, various chiral organic compounds such as 1,1-binaphthyl,[2.2]paracyclophanes, and primary alka-nols due to deuterium substitution have been found to serve as chiral triggers in asymmetric autocatalysis. 

In 2007, Maruoka et al. introduced chiral dicarboxylic acids consisting of two carboxylic acid functionalities and an axially chiral binaphthyl moiety. They applied this new class of chiral Brpnsted acid catalyst to the asymmetric alkylation of diazo compounds withA-Boc imines [91]. The preparation of the dicarboxylic acid catalysts bearing aryl groups at the 3,3 -positions of the binaphthyl scaffold follows a synthetic route, which has been developed earlier in the Maruoka laboratory [92]. 

CL Cooper, JB Davis, MJ Sepaniak. Mechanisms of enantiomeric resolution in cyclodextrin-modified capillary electrophoretic separations of binaphthyl compounds. Chirality 7 401-408, 1995. 

Substituted binaphthyl compounds can be synthesized in high optical yields using nucleophilic aromatic substitution reactions in which the chiral leaving groups are alkoxy moieties derived from naturally occurring alcohols28-29. For example, the condensation of 2-(l-alkoxynaphth-2-yl)-4.5-dihydro-4,4-dimethyl-l,3-oxazole with 1-naphthyllithium or 2-methoxy-l-naphthyl 2-magnesium bromide leads to (ft)- or (.S)-(l,T-binaphthyl-2-yl)-4,5-dihydro-4,4-dimethyl-l,3-oxazole derivatives. 

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. 

The oxidation of alcohols to carbonyl compounds with the stable nitroxyl radical TEMPO (86) as catalyst is a well-known preparative method [134, 135]. Hypochlorite or peracetic acid is usually used as the final oxidizing agent and ca. 1 mol% of catalyst 86 is used. In 1996 Rychnovsky et al. reported the synthesis of the chiral, binaphthyl-derived TEMPO analog 87 [136], Results obtained by use of 0.5-1 mol% of catalyst 87 [136] are listed in Table 10.12. In these oxidation reactions 0.6-0.7 equiv. sodium hypochlorite were used as the final oxidizing agent (plus... 

Among the preparative methods used for obtaining P-chiral phosphorus compounds, there are procedures involving the use of optically pure auxiliaries like (—)-menthol [40], (—)-ephedrin [41,42], or more recently, the kinetic resolution of 1-hydroxymethylalkylphenylphosphine oxides using Pseudomonas or Candida antarctica lipases [43], It has been found that some [(alkyl-substituted)arene] phosphinates and phosphine oxides can also be resolved efficiently by inclusion complexation with optically active 2,2 -dihydroxy-1, 1 -binaphthyl (17) [44],... 

Analytical Properties CSP (chiral stationary phase) 1 — separates some chiral binaphthyl derivatives when mixtures of hexane diethyl ether, dichloromethane, or dioxane are used as the mobile phase CSP 2 — separates compounds with carbamate or amide functions (mixtures of n-hexane and 2-propanol can be used as mobile phase) CSP 3 — separation of compounds separated by CSP 2, as well as separation of compounds with carbonyl or amide functions and some amino alcohols that have pharmaceutical relevance ((3-blockers)... 

The first attempt at enantioselective ring opening of meso-epoxides by using a chiral selenolate was reported in 1988 [90]. Enantiomerically pure seleno-binaphthyl compounds 65-67 were synthesized and applied to the asymmetric ring opening of cyclohexene oxide (Scheme 47). 

The VCD study of the 1,1 -binaphthyl derivatives [110] serves as an example of other structural information that can be obtained by the comparison of experimental and computed VCD. This method allows monitoring not only of absolute chirality of the molecule, but also of the contributions of individual functional groups to the spectra, molecular conformations or some important structural parameter. As an example, we discuss chiral binaphthyls which represent popular building blocks, chiral recognition receptors and catalyst. Controlling the angle between naphthyl planes is important when supramolecular complexes based on these compounds are built. 

The transoid-cisoid equilibrium in crowded binaphthyl compounds generates two enantiomeric cisoid forms which may interconvert. For these compounds, CTI requires heating to proceed (i.e. AG i = 23.5 kcal mol-1 for compound 2, h/2 = 14.5 min at 50 °C). Introduction of substituents increases the barrier to rotation and hence stabilizes the chiral configuration [6]. For example, (S)-1,T-binaphthyl-2,2 -dicarboxylic acid 3 could not be racemized at 175 °C in DMF (Fig. 13.IB). Depending on substituents, racemization may be favored by steric/electro-static repulsions and CTI of dicarboxylate 4 occurs at a lower temperature (AG = 24.4 kcal mol-1 for compound 2, = 51.5 min at 50 °C). 

Methyl-l-phenylisoquinoline (380) is obtained when the oxazoline (379) is heated with phosphorus pentoxide. An efficient synthesis of alkylated and dialkylated acetic acids consists in the alkylation of 4,5-dihydro-oxazoline bound to polystyrene, followed by hydrolysis." The asymmetric synthesis of a series of a-alkylphenylacetic acids C H2 +i CHPhC02H ( = 1-5) from the chiral oxazoline (381) has been described. Another example of the use of oxazolines for asymmetric synthesis is the preparation of the optically active binaphthyl (383) from 1-lithionaphthalene and compound [382 R = (—)-menthyl]. The stereoselective formation of threo-dXdoX products (385 = Et, Pr, n-pentyl, etc from the chiral boron compound... 

Molecules with shapes analogous to screws are also chiral, since they can be right-handed or left-handed. There are several kinds of molecules in which steric factors impose a screwlike shape. A very important case is 1, T-binaphthyl compounds. Steric interactions between the 2 and 8 hydrogens prevent these molecules from being planar, and as a result, there are two nonsuperimposable mirror image forms. 

Scheme 10-130 Methyl 7-deoxycholate provides a chiral template for the enantioselective synthesis of the binaphthyl compound 401.

MBBA AI-(4-methoxybenzylidene)-4-n-butylaniline = —1.8 x lO pm ). These values are close to those obtained with organic compounds of the chiral binaphthyl type. The observations show the formation of chiral nematic phases N under the influence of the doping agent, with values of pitch (p) close to the visible region of the spectrum. The sense of the induced helix is negative (M). In the case of MBBA, the CD spectrum shows a powerful induced negative effect in the region of the imine chromophores of the MBBA receptor. 

Kobayashi obtained enantiopure phthalocyanines by introducing a helical type chiral element, or a chain containing an asymmetric carbon. The use of two or four chiral binaphthyl substituents [(P) or (5)] or [(M) or (/ )], attached to the phthalocyanine via oxo or sulphur bridges, leads to compounds of the type BNpPcM and TNpPcM with M = H2, Zn and Co (Figure 6.32). 

The well known chiral carbon skeleton designated as binaphthyl hinge has been introduced into asymmetric synthesis and resolution of racemates in the form of the derivatives of 2,2 -dihydroxy-l,r-binaphthyl (84, binaphthol). The application of chiral crown compounds containing this binaphthyl tmit for the separation of amino acids and amino acid esters by use of liquid/liquid chromatography has been described particularly by Cram et al. in detail... 

The complete transfer of axial chirality to central chirality during the Stevens rearrangement of binaphthyl compounds is demonstrated (eq 41). Treatment with an excess of BuLi results first into the expected Stevens [l,2]-benzyl shift, which... 

Various oxidations with [bis(acyloxy)iodo]arenes are also effectively catalyzed by transition metal salts and complexes [726]. (Diacetoxyiodo)benzene is occasionally used instead of iodosylbenzene as the terminal oxidant in biomimetic oxygenations catalyzed by metalloporphyrins and other transition metal complexes [727-729]. Primary and secondary alcohols can be selectively oxidized to the corresponding carbonyl compounds by PhI(OAc)2 in the presence of transition metal catalysts, such as RuCls [730-732], Ru(Pybox)(Pydic) complex [733], polymer-micelle incarcerated ruthenium catalysts [734], chiral-Mn(salen)-complexes [735,736], Mn(TPP)CN/Im catalytic system [737] and (salen)Cr(III) complexes [738]. The epox-idation of alkenes, such as stilbenes, indene and 1-methylcyclohexene, using (diacetoxyiodo)benzene in the presence of chiral binaphthyl ruthenium(III) catalysts (5 mol%) has also been reported however, the enantioselectivity of this reaction was low (4% ee) [739]. 

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