Binaphthyl chiral

A titanium catalyst 20 that incorporates binaphthyl chirality along with imine and phenolic (salen) donors is highly active in addition of silyl ketene acetals to aldehydes.160... 

In contrast to binaphthyls, chiral biphenyl derivatives are challenging systems because their twist ability shows a strong dependence on the molecular structure, which does not conform to the empirical correlation rule described above. In fact, homochiral biphenyls 33-40 are characterized by P helicity along the biphenyl axis. In spite of this common feature, the twisting power spans from a highly positive value for 33-45 to a relatively negative value... 

The enantioselective oxidative coupling of 2-naphthol itself was achieved by the aerobic oxidative reaction catalyzed by the photoactivated chiral ruthenium(II)-salen complex 73. 2 it reported that the (/ ,/ )-chloronitrosyl(salen)ruthenium complex [(/ ,/ )-(NO)Ru(II)salen complex] effectively catalyzed the aerobic oxidation of racemic secondary alcohols in a kinetic resolution manner under visible-light irradiation. The reaction mechanism is not fully understood although the electron transfer process should be involved. The solution of 2-naphthol was stirred in air under irradiation by a halogen lamp at 25°C for 24 h to afford BINOL 66 as the sole product. The screening of various chiral diamines and binaphthyl chirality revealed that the binaphthyl unit influences the enantioselection in this coupling reaction. The combination of (/f,f )-cyclohexanediamine and the (R)-binaphthyl unit was found to construct the most matched hgand to obtain the optically active BINOL 66 in 65% ee. 

Chiral binaphthyls. Chiral binaphthyls can be prepared by reaction of an a-naphthyl Grignard reagent with the chiral 1-methoxy-2-oxazolinyl naphthalene 2. The adduct (3) is converted in two steps to a chiral binaphthyl alcohol (4).2... 

In our synthesis [36] of spiruchostatin A, we followed Simon s procedure for the preparation of 3. We too were unable to achieve the Carreira aldol in good yield. Moreover, the reaction requires the preparation of three noncommercial materials the binaphthyl chiral aminophenol, the t-butyl salicaldehyde, and the silyl ketene acetal. Instead, we opted for a diastereoselective aldol with the Nagao auxiliary. For reasons that are not completely clear, the Nagao thiazolidinethione auxiliary exhibits high diastereoselectivity in acetate aldols unlike the more popular Evans oxazolidinone auxiliary. In this case, aldol adduct 7 was obtained in good yield (Scheme 12-3). Unlike the other syntheses, this was coupled directly to the peptide rather than hydrolyzed to the acid 5. 

Transpositional reduction of allylic carbonates. Pd-catalyzed Sn2 reduction (HCOOH as hydride donor) of allylic carbonates proceeds enantioselectively in the presence of chiral ligands based on binaphthyl. Chiral allylsilanes are readily available in this manner using an MOP-phen ligand. ... 

Scheme 6.16 The Rh/binaphthyl chiral diene-catalyzed addition of arylboronic acids to W,W-dimethylsulfamoyl-protected aldimines, as described Du and coworkers [21].

Triflates of phenols are carbonylated to form aromatic esters by using PhjP[328]. The reaction is 500 times faster if dppp is used[329]. This reaction is a good preparative method for benzoates from phenols and naphthoates (473) from naphthols. Carbonylation of the bis-triflate of axially chiral 1,1 -binaphthyl-2,2 -diol (474) using dppp was claimed to give the monocarboxy-late 475(330]. However, the optically pure dicarboxylate 476 is obtained under similar conditions[331]. The use of 4.4 equiv. of a hindered amine (ethyldiisopropylamine) is crucial for the dicarbonylation. The use of more or less than 4.4 equiv. of the amine gives the monoester 475. 

Chiral separations are concerned with separating molecules that can exist as nonsupetimposable mirror images. Examples of these types of molecules, called enantiomers or optical isomers are illustrated in Figure 1. Although chirahty is often associated with compounds containing a tetrahedral carbon with four different substituents, other atoms, such as phosphoms or sulfur, may also be chiral. In addition, molecules containing a center of asymmetry, such as hexahehcene, tetrasubstituted adamantanes, and substituted aHenes or molecules with hindered rotation, such as some 2,2 disubstituted binaphthyls, may also be chiral. Compounds exhibiting a center of asymmetry are called atropisomers. An extensive review of stereochemistry may be found under Pharmaceuticals, Chiral. 

Catalytic asymmetric hydrogenation was one of the first enantioselective synthetic methods used industrially (82). 2,2 -Bis(diarylphosphino)-l,l -binaphthyl (BINAP) is a chiral ligand which possesses a Cg plane of symmetry (Fig. 9). Steric interactions prevent interconversion of the (R)- and (3)-BINAP. Coordination of BINAP with a transition metal such as mthenium or rhodium produces a chiral hydrogenation catalyst capable of inducing a high degree of enantiofacial selectivity (83). Naproxen (41) is produced in 97% ee by... 

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. 

Cram and his coworkers have pioneered the use of bis-binaphthyl crowns as chiral com-plexing agents for ammonium salts and amino acid salts. In these systems, the chiral binaphthyl unit provides a steric barrier within the macrocycle which allows discrimina-... 

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 structural variations reported by Cram and coworkers relate to an appreciable extent to the various ancillary functions which have been appended to the binaphthyl units or elsewhere in the macrocyclic system. Enhancements of the chiral barrier or functionalization through arms has generally been effected at the 3-or 6-positions. These positions are adjacent to the hydroxyl group or directly across the second ring from it, respectively. 

Lehn and his coworkers have prepared a number of chiral cryptands based upon the 2,2 -binaphthyl unit " . In a typical preparation, the binaphthyl units are treated with bromoacetic acid to form the phenoxyacetic acid derivatives which are then converted into the corresponding diacyl chlorides (75). Reaction of 15 with l,10-diaza-18-... 

If a bridged bis-crown is used instead of diaza-18-crown-6, the cryptand contains two macrorings facing each other (see Table 8.5). Note also that the 2,2 -binaphthyl unit has been used extensively by Cram and his coworkers to provide chirality to mono-cyclic systems as well (see Sect. 3.13). 

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. 

In 1994 Yamamoto et al. developed a novel catalyst which they termed a "Brmsted acid-assisted chiral Lewis acid" (BLA) [10] (Scheme 1.14, Table 1.3). The catalyst 7 was prepared from (R)-3,3 -dihydroxyphenyl)-2,2 -dihydroxy-l,l -binaphthyl by reaction with B(OMe)3 and removal of methanol [10a, dj. The Brmsted acid is essential for both the high reactivity of the Lewis acid and the high enantioselectivity - the... 

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. °... 

Armstrong and Jin [15] reported the separation of several hydrophobic isomers (including (l-ferrocenylethyl)thiophenol, 1 -benzylnornicotine, mephenytoin and disopyramide) by cyclodextrins as chiral selectors. A wide variety of crown ethers have been synthesized for application in enantioselective liquid membrane separation, such as binaphthyl-, biphenanthryl-, helicene-, tetrahydrofuran and cyclohex-anediol-based crown ethers [16-20]. Brice and Pirkle [7] give a comprehensive overview of the characteristics and performance of the various crown ethers used as chiral selectors in liquid membrane separation. 

The disclosure, in 1982, that cationic, enantiopure BINAP-Rh(i) complexes can induce highly enantioselective isomerizations of allylic amines in THF or acetone, at or below room temperature, to afford optically active enamines in >95 % yield and >95 % ee, thus constituted a major breakthrough.67-68 This important discovery emerged from an impressive collaborative effort between chemists representing Osaka University, the Takasago Corporation, the Institute for Molecular Science at Okazaki, Japan, and Nagoya University. BINAP, 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (Scheme 7), is a fully arylated, chiral diphosphine which was introduced in... 

Optically active 1,1 -binaphthyl-based polymers incorporate chiral 1,17-binaphthyl units into the polymer backbone and possess stable main-chain... 

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