Binaphthol, synthesis

When K.yba, Cram and coworkers attempted the synthesis of dibinaphthyl-22-crown-6 from binaphthol and diethylene glycol ditosylate. the reagent ratio was as described either by V or X (Eqs. 3.1 or 3.3). The intent was to make the 22-membered ring. Some of the 11-membered ring was isolated as well (Eq. 3.5). None was apparently observed for the benzo case because the nine-membered ring is less favorable. In short, it is not the intent of the synthesis but the reaction dynamics which determine the product. 

The principal variations on the normal crown synthesis methods were applied in preparing mixed crowns such as those shown in Eq. (3.55) and in forming isomers of the dibinaphthyl-22-crown-6 systems. The latter has been discussed in Sect. 3.5 (see Eq. 3.21) . The binaphthyl unit was prepared to receive a non-naphthyl unit as shown in Eq. (3.57). Binaphthol was allowed to react with the tetrahydropyranyl ether or 2-chloroethoxyethanol. Cleavage of the THP protecting group followed by tosyla-tion of the free hydroxyl afforded a two-armed binaphthyl unit which could serve as an electrophile in the cyclization with catechol. Obviously, the reaction could be accomplished in the opposite direction, beginning with catechol". ... 

Despite the undefined nature of the organometallic species, chirally modified organotita-nium reagents are useful tools in enantioselective synthesis. In particular, the binaphthol-mod-ified phenyltitanium reagent 41 shows excellent enantioselectivity in additions to aromatic aldehydes34-40,41. 

Synthesis of Optically Active Poly(binaphthol) 391Sa... 

In recent years, axially chiral binaphthalene derivatives have emerged as important ligands and chiraUty inducers in organic synthesis. Oxidative coupling of 2-naphthols represents a well estabhshed method for the preparation of binaphthols. The couplings are usually carried out by treating naphthols with more than an equimolar amount of a metal such as Fe(III), Mn(III),... 

The synthesis of a series of chiral organophosphine oxide/sulfide-substituted binaphtholate ligands has recently been reported by Marks and Yu and their corresponding lanthanide complexes characterized. These complexes, generated in situ from Ln[N(TMS)2]3, cleanly catalysed enantioselective intramolecular hydroamination/cyclisation of 1-amino-2,2-dimethyl-4-pentene albeit with a low enantioselectivity of 7% ee (Scheme 10.82). 

Many opportunities conversely are supported by reversible reactions of QM despite the noted complications. One example includes the synthesis and chiral resolution of binaphthol derivatives by two cycles of QM formation and alkylation.77 The reversibility of QM reaction may also be integrated in future design of self-assembling systems to provide covalent strength to the ultimate thermodynamic product. To date, QMs have already demonstrated great success in supporting the opposite process, spontaneous disassembly of dendrimers (Chapter 5). 

Scheme 51 summarizes Mikami s synthesis of (R)-35, employing the car-bonyl-ene reaction of isoprene (A) with glyoxylate (B) to give C as catalyzed by a modified binaphthol-titanium complex [77]. 

Axial Chirality. For a system with four groups arranged out of the plane in pairs about an axis, the system is asymmetric when the groups on each side of the axis are different. Such a system is referred to as an axial chiral system. This structure can be considered a variant of central chirality. Some axial chiral molecules are allenes, alkylidene cyclohexanes, spiranes, and biaryls (along with their respective isomorphs). For example, compound 7a (binaphthol), which belongs to the class of biaryl-type axial chiral compounds, is extensively used in asymmetric synthesis. Examples of axial chiral compounds are given in Figure 1-5. 

Cyanohydrination (addition of a cyano group to an aldehyde or ketone) is another classic reaction in organic synthesis. Enantioselective addition of TMSCN to aldehyde, catalyzed by chiral metal complexes, has also been an active area of research for more than a decade. The first successful synthesis using an (5,)-binaphthol based complex came from Reetz s group142 in 1986. Their best result, involving Ti complex, gave 82% ee. Better results were reported shortly thereafter by Narasaka and co-workers.143 They showed that by... 

Lewis acids of chiral metal aryloxides prepared from metal reagents and optically active binaphthol derivatives have played a significant role in asymmetric synthesis and have been extensively studied.23 However, in Diels-Alder reactions, the asymmetric induction with chiral metal aryloxides is, in most cases, controlled by steric interaction between a dienophile and a chiral ligand. This kind of interaction is sometimes insufficient to provide a high level of enantioselectivity. 

Another method for ketone reduction, BINAL-H asymmetric reduction, can also be used in co-side chain synthesis. An example of applying BINAL-H asymmetric reduction in PG synthesis is illustrated in Scheme 7-27. This has been a general method for generating the alcohol with (15. -configuration. The binaphthol chiral auxiliary can easily be recovered and reused. As shown in Scheme 7-27, when the chiral halo enone 91 is reduced by (S -BINAL-H at — 100°C, product (15S)-92 can be obtained with high enantioselectivity. 

Recently novel methods were reported to make (lR)-trans-chrysanthemic acid including optical resolutions with the (+)-3-caranediol or l,l -binaphthol monoethylether, enzymatic resolution with Arthrobacter globiformis and the asymmetric synthesis with a new Cu catalyst. These methods are reviewed in this section. 

The formation of circular or linear forms seems to depend on balances between kinetic and thermodynamic control iron(II)-poly-2,2 -diimine systems with their substitutionally inert metal centers provide useful systems for disentangling thermodynamic and kinetic contributions. The mechanism of formation of circular helicates is believed to entail a kinetically favored triple helicate intermediate. Self-assembly of chiral dinuclear binaphthol-linked iron(III) porphyrin complexes into extended polynuclear species takes place through the intermediacy of fi-oxo dimers. Predetermined //-oxo-di-iron-dimers may be used in this type of synthesis. 

The incorporation of two nonidentical chiral residues, each supporting C2 symmetry, into a mactocyclic poly ether affords a chiral crown compound with C2 symmetry provided its structure is constitutionally symmetrical. Thus, base-promoted reaction of the half-crown diol prepared from (5)-birraphthol with the half-crown ditosylate d-72 synthesized tom diacetone-manrritol affords (144) the 20-crown-6 derivative (S)-d-113 with C2 symmetry. When d-72 is condensed in like fashion with (/ 5)-binaphthol, then the diastereoisomeric 20-crown-6 derivative (/ )-d-114 can be separated chromatogiaphically tom (S)-d-113. In this matmer, (/ 5)-binaphthol is resolved by the carbohydrate unit during the synthesis. 

The monobenzhydiyl derivative of (S)-binaphthol has played an important role, not only in the synthesis of chiral bisbinaphthyl crown ether derivatives, for example, (55)-124, containing two different bridges between the two binaphthyl units, but also in the provision of an entry into the constimtionally isomeric derivative (5S)-125. Rational stepwise syntheses of macrocyles containing three binaphthyl units have been devised and applied to the synthesis of (SSS)-126 and (RSS)-127. Cleariy, in all these procedures, the C2 symmetry of the chiral building block restricts the number of products (to one ) and defines the symmetries of the macrocycles formed. 

Optically pure l,l -binaphthol and its derivatives have been evaluated as versatile chiral auxiliaries and ligands in asymmetric transformations. Research in this area has provided many efficient and useful methods for the preparation of key chiral building blocks, some of which have been used for the construction of complex natural products. The wide ranging and important applications of such compounds in organic synthesis have stimulated great interest in developing efficient methods... 

Chiral compounds (Continued) epoxy alcohols, 141 formulas, xiii xvii hydroxystannanes, 318 liquid crystals, 350 molecular lattics, 347 natural, 1 NMR spectra, 282 olefins, 173 oxetanones, 326 phenols, 287 see also Binaphthol phenylbutenes, 172 protonating agents, 324 sulfoxides, 159 sulfur ylides, 328 synthesis, I... 

In this context, a chiral hydride reagent, BINAL-H, prepared by modification of lithium aluminum hydride with equimolar amounts of optically pure binaphthol and a simple alcohol, is extremely useful (9b, 18a, 35) Scheme 15 shows the utility of the three-component coupling synthesis. The < > side-chain unit and the hydroxycyclopentenone can be prepared with very high enantioselectivity by reduction of the corresponding enone precursors (35-38). 

The utility of the BINAL-H asymmetric reduction in other PG syntheses is shown in Scheme 16 (35, 39). This asymmetric reduction is a general method for generating the 15S configuration and is highly practical, because the binaphthol ancillary is easily recovered in reusable form from the reaction mixture. In fact, this reduction is undertaken on a multikilogram scale in the Corey synthesis (Ono Pharmaceutical Co.). The observed high diastereoselectivity leading to the desired 155... 

A full account5 describes the enantioselective carbonyl-ene reaction of glyoxylate esters catalyzed by a binaphthol-derived chiral titanium complex that is potentially useful for the asymmetric synthesis of a-hydroxy esters of biological and synthetic importance.6 The present procedure is applicable to a variety of 1,1-disubstituted olefins to provide ene products in extremely high enantiomeric purity by the judicious choice of the dichloro or dibromo chiral catalyst (see Table). In certain glyoxylate-ene reactions involving removal of a methyl hydrogen, the dichloro catalyst... 

The chiral boron complex prepared in situ from chiral binaphthol and B(OPh)3 is utilized for the asymmetric aza-Diels-Alder reaction of Danishefsky s diene and imines [67] (Eq. 8A.43). Although the asymmetric reaction of prochiral imine affords products with up to 90% ee, the double asymmetric induction with chiral imine by using oc-benzylamine as a chiral auxiliary has achieved almost complete diastereoselectivity for both aliphatic and aromatic aldimines. This method has been successfully applied to the efficient asymmetric synthesis of anabasine and coniine of piperidine alkaloides. 

The geometrical isomers and enantiomers of the overcrowded alkenes 15-18 can readily be separated using chiral HPLC. Recently, an asymmetric synthesis of overcrowded alkenes has been developed, involving chirality transfer from an axial single bond to an axial double bond (Scheme 8).32 This methodology is particularly attractive for preparation of larger quantities of enantiomerically pure chiral switches based on overcrowded alkenes. The orientation of the two xanthylidene moieties is dictated by a binaphthol template. After a coupling step and separation of the diastereomers, the bi-xanthylidene is obtained with 96 % e.e. after removal of the template. 

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