Binaphthyl, synthesis

The other primary application of asymmetric Grignard coupling reactions has been in the synthesis of axially chiral binaphthyl and biphenyl derivatives. Hayashi performed a binaphthyl synthesis (equation 6) in 95% ee using a nickel catalyst and ligand (7), a P-O chelating analog to (3). For a similar synthesis of chiral biaryls (equation 7) ligand, (8) was found to yield the most successful results (93% ee). ... 

Two different all-aromatic crowns have been reported ". In 1975, de Jong, Siegel and Cram reported the synthesis of a tri-binaphthyl system in which each oxygen was bound to a naphthalene ring, but aliphatic bridges were used to join the binaphthyl units. Relatives of this compound are discussed further in Sect. 3.13. The synthesis of this molecule (Structure 17, below) was not simple, but was relatively straightforward. An interesting feature of it was the use of ethyl chloroacetate followed by LAH reduction to attach ethyleneoxy units to the naphthol unit. 

In Cram s first synthesis of a chiral bis-binaphthyl system, optically pure binaph-thol and diethylene glycol ditosylate were heated at reflux in tetrahydrofuran solution for 15 h with potassium f-butoxide, two products were obtained. The 1 + 1 product (mp 230—231°) was isolated in 5% and the 2 + 2 product (mp 123—126°) was obtained in 31% yield. The reaction is shown in Eq. (3.51). 

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". ... 

Meyers has also reported the use of chiral oxazolines in asymmetric copper-catalyzed Ullmann coupling reactions. For example, treatment of bromooxazoline 50 with activated copper powder in refluxing DMF afforded binaphthyl oxazoline 51 as a 93 7 mixture of atropisomers diastereomerically pure material was obtained in 57% yield after a single recrystallization. Reductive cleavage of the oxazoline groups as described above afforded diol 52 in 88% yield. This methodology has also been applied to the synthesis of biaryl derivatives. 

A series of chiral binaphthyl ligands in combination with AlMe3 has been used for the cycloaddition reaction of enamide aldehydes with Danishefsky s diene for the enantioselective synthesis of a chiral amino dihydroxy molecule [15]. The cycloaddition reaction, which was found to proceed via a Mukaiyama aldol condensation followed by a cyclization, gives the cycloaddition product in up to 60% yield and 78% ee. 

For the performance of an enantioselective synthesis, it is of advantage when an asymmetric catalyst can be employed instead of a chiral reagent or auxiliary in stoichiometric amounts. The valuable enantiomerically pure substance is then required in small amounts only. For the Fleck reaction, catalytically active asymmetric substances have been developed. An illustrative example is the synthesis of the tricyclic compound 17, which represents a versatile synthetic intermediate for the synthesis of diterpenes. Instead of an aryl halide, a trifluoromethanesul-fonic acid arylester (ArOTf) 16 is used as the starting material. With the use of the / -enantiomer of 2,2 -Z7w-(diphenylphosphino)-l,F-binaphthyl ((R)-BINAP) as catalyst, the Heck reaction becomes regio- and face-selective. The reaction occurs preferentially at the trisubstituted double bond b, leading to the tricyclic product 17 with 95% ee. °... 

The strategy described here explains the different possibilities of enzymatic ammonolysis and aminolysis reaction for resolution of esters or preparation of enantiomerically pure amides, which are important synthons in organic chemistry. This methodology has been also applied for the synthesis of pyrrolidinol derivatives that can be prepared via enzymatic ammonolysis of a polyfunctional ester, such as ethyl ( )-4-chloro-3-hydroxybutanoate [30]. In addition, it is possible in the resolution of chiral axe instead of a stereogenic carbon atom. An interesting enzymatic aminolysis of this class of reaction has been recently reported by Aoyagi et al. [31[. The side chain of binaphthyl moiety plays an important role in the enantiodis-crimination of the process (Scheme 7.14). 

In 2002, Hoveyda et al. reported the synthesis, structure and reactivity of a chiral bidentate Ru-based catalyst 65, bearing a binaphthyl moiety, for olefin metathesis [33]. Preference for a bidentate chiral imidazolinylidene was based on the hypothesis that such a ligand would induce chirality more efficiently. This catalyst was designed by analogy with similar achiral complexes 66 that... 

Other chiral ligands such as BINAP (where BINAP is bis(diarylphosphino)-1,1 binaphthyl) or aminophosphines are also efficient for stereoselective synthesis of chiral-at-metal Ru complexes [39-41]. 

Aromatic and vinylic sulfides take part in cross-coupling reactions with Grignard reagents in the presence of Ni catalysts.336,337 This reaction has been applied to the enantioselective synthesis of binaphthyls using a standard chiral oxazoline ligand (Equation (25)) 338... 

Scheme 6.42 Synthesis of enantiopure 2,2 -diarylated 1,1 -binaphthyls utilizing stereoconservative Negishi cross-coupling reactions.

Borner reported the synthesis of pyrophosphites 149 with chiral binaphthyl substituents [118]. The results showed that the Hg-binaphthyl unit was the best for the Rh-catalyzed hydrogenation of methyl (Z)-2-acetamidocinnamate (48% ee) and dimethyl itaconate (70% ee). 

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. 

The related field involving the hydrocarboxylation of alkenes is also under investigation11481, not least because of its potential importance in the synthesis of NSAI drugs. An indirect way to the latter compounds involves the hydro-vinylation of alkenes. For example catalysis of the reaction of ethylene with 2-methoxy-6-vinylnaphthalene at 70°C using (allylNiBr)2 and binaphthyl (63)... 

In comparison to the N- and S-counterparts, alkoxides possess lower nucleophilicity. Therefore, the reductive elimination process to form the C—O bond is much slower than those to form C— N and C—S bonds [103]. Palucki, Wolfe and Buchwald developed the first intramolecular Pd-catalyzed synthesis of cyclic aryl ethers from o-haloaryl-substituted alcohols [104]. For example, 3-(2-bromophenyl)-2-methyl-2-butanol (91) was converted to 2,2-dimethylchroman (92) under the agency of catalytic Pd(OAc)2 in the presence (S)-(-)-2,2 -bis(di-p-tolylphosphino)-l,r-binaphthyl (Tol-BINAP) as the ligand and K2CO3 as the base. The method worked well for the tertiary alcohols, moderately weE for cychc secondary alcohols, but not for acyclic secondary alcohols. 

K.Y. Musick, Q.-S. Hu, and L. Pu, Synthesis of binaphthyl-oligothiophene copolymers with emissions of different colors systematically tuning the photoluminescence of conjugated polymers, Macromolecules, 31 2933-2942, 1998. 

Somewhat more effective catalysts are obtained by replacing BINAP with TolBINAP, which is 2,2 -bis(di-p-tolylphosphino)-l,l -binaphthyl.4 The presently preferred catalysts are complexes of Ru(OCOCF3)2 with (R)- or (S)-TolBINAP, obtained by treatment of Ru(OAc)2TolBINAP with 2 equiv. of trifluoroacetic acid. Such catalysts promote hydrogenation of typical enamides in 98% ee and 98% yield. This reaction can be used to provide asymmetric synthesis of isoquinoline alkaloids as well as of morphinans used as substitutes for morphine. 

The stannepins which encompass the 2,2 -positions of 1,1 -binaphthyl are interesting because, in their enantiomeric forms, they can bring about stereoselective reactions. Scheme 14 shows the synthesis of the methyltin hydride, which has been used in asymmetric reduction,172 and of the dimethyltin compound, which, via lithiation, can act as the precursor for further derivatives such as the silepins.327... 

A number of hydrides which carry chiral groups have been prepared with the aim of using them in asymmetric synthesis.284 One family of these hydrides carries the (lR,2S,5R)-menthyl (Men ) group,431 as in, for example, Men Me2SnH,432 Men 2MeSnH,433 Men Ph2SnH, and Men 2PhSnH,431 and a second family is based on the chirality of the 1,1 -binaphthyl derivatives.172-174... 

This biocatalytic method is therefore quite promising for the synthesis of complex molecules. Very recently, it was reported 1121] that HRP catalyzes the oxidation of 2-naphthols to l,l -binaphthyl-2,2 -diols with moderate enantiomeric excess (ee 38-64%) (Eq. 5). However, in view of the analytical techniques used, these data have to be questioned [167]. As shown recently, atrop-selective biaryl coupling can only be achieved by means of dirigent protein as chiral auxiliary [122]. 

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