Dicarboxylic axially chiral

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. 

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]. 

Finally, the recognition of axially chiral l,12-dimethylbenzo[c]phenan-threne-5,8-dicarboxylate (1) enantiomers by cyclodextrins was found to be much more efficient [19]. The preliminary H NMR binding studies in D20 showed no changes in spectra of the substrate after addition of a-cyclodextrin. However, in the spectra of the (P) and (M) enantiomers of the tetrahelicene 1, significant chemical shift changes occurred after the addition of (3-cyclodextrin and y-cyclodextrin. Detailed measurements were performed to determine complexation constants and using the ROESY 2D NMR spectra the structures... 

Scheme 24.21 Asymmetric addition to imines catalysed by axially chiral dicarboxylic acids.

Finally, a direct Mannich-type approach has been developed for the enantioselective synthesis of hydrazines and amines (Scheme 16.40). Thus, by trapping with alkyl diazoacetates some in s/iw-generated acyclic azomethine imines, in the presence of axially chiral dicarboxylic acids, a series of a-diazo-(3-hydrazino esters were obtained with excellent enantioselectivities [86]. 

Asymmetric inverse-electron-demand 1,3-dipolar cycloaddition of C,A-cyclic azomethine imines with c-rich dipolarophiles was accomplished with a high stereo-selectivity by using an axially chiral dicarboxylic catalyst (40)." The metal-free silicon Lewis-acid-catalysed 3-1-2-cycloadditions of A-acylhydrazones with cyclopentadiene provides a mild access to pyrazolidine derivatives in excellent... 

It has been shown that chirality does not necessarily need to be located on a tetrahedral carbon atom, as in the case of the fran -epoxy dicarboxylates (Scheme 2.33) [238]. For example, the axial chirality of the racemic iron-tricarbonyl complex [239] and of the allenic carboxylic ester shown below [240], was well recognized by PLE. 

The apphcation of the rhodinm(l)-catalyzed double [2+2+2] cycloaddition approach to the synthesis of symmetric biaryl diphosphoms compounds was first accomplished in the reactions of l,4-bis(diphenylphosphinoyl)bnta-l,3-diyne with terminal diynes to give achiral biaryl bisphosphine oxides [23a]. Cj-Symmetric axially chiral biaryl diphosphonates were obtained with perfect enantioselectivity by using a phosphonate-substituted 1,3-bntadiyne and internal 1,6-diynes (Scheme 21.19) [23b]. Axially chiral biaryl dicarboxylates were also obtained by this method [23b]. 

In 2012, Maruoka and coworkers developed a new catalytic asymmetric Ugi-3CR through the use of an axially chiral dicarboxylic acid 27 [28], In the approach, a variety of aldehydes, 2-benzoyloxyphenyl isocyanide (26), and an acyclic azomethine imine 25 were initially reacted, yielding heterocyclic compounds 28 in excellent yields and good enantiomeric excesses (Scheme 7.11). Upon acid hydrolysis of the heterocyclic compound 28a, the corresponding a-hydrazino amide 29 was obtained without loss of enantioselectivity (bottom-left. Scheme 7.11). 

Two orientations of the allyl amine, with the E- (trans) configuration around the C=C bond in the Rh(I)-(S)-(— )BINAP complex, are presented. The detailed topology of (—)-BlNAP, however, is of the outmost importance for the understanding of the enantioselectivity or sterochemical bias of allylic migration. Therefore, structural formulae of BINAP enantiomers and the X-ray structure of the Ru(II) dicarboxylate complex of (5)-( )-BlNAP are presented in Figure 9.1 [14]. The structure of the complex is characterized by the axial chirality of the dinaphthyl unit and the butterfly Uke disposition of the aromatic rings in the diphenylphosphine unit. 

Maruoka and co-workers reported the first catalytic asymmetric three-component 1,3-dipolar cycloaddition of terminal alkynes with acyclic azomethine imines generated in situ from the corresponding aldehydes and hydrazides, which was realized using CuOAc/Ph-pybox and axially chiral dicarboxylic acid cocatalysts (Scheme 27) [48]. This transformation has abroad tolerance with regard to the substrates, affording diverse chiral 3,4-disubstituted pyrazolines with high enantioselectivities. The role of the axially chiral dicarboxylic acid is to generate the protonated acyclic azomethine imine, which then reacts with chiral Cu-acetylide. 

Figure 7.5 Axially chiral C2-symmetric dicarboxylic acids.

The axially chiral dicarboxylic acid 27b was also uniquely reactive in achieving the highly enantioselective addition of aldehyde N,N-diaIkylhydrazones, a readily... 

Recently, Maruoka and coworkers have also developed an asymmetric inverse electron demand 1,3-dipolar cycloaddition of C,A -cyclic azomethine imines with fort-butyl vinyl ether catalyzed by a newly developed axially chiral dicarboxylic acid having diarylmethyl groups at the 3,3 -positions (Scheme 7.7) [18]. Based on this finding, the concept of the inverse electron demand umpolung 1,3-dipolar cycloaddition was introduced as a strategy for switching the regioselectivity of the cycloaddition from that of the titanium BINOLate-catalyzed normal electron demand 1,3-dipolar cycloaddition with enals (Table 7.3) by... 

A three-component Ugi-type reaction using A/ -alkylbenzohydrazide (instead of amine) has been catalysed by an axially chiral binaphthyl dicarboxylic acid and found to proceed with up to 93% ee with an acyclic azomethine imine. Stereoselectivity of a Ugi reaction starting from an oxanorbornenone / -amino acid, R CHO, and RNC has been improved through solvent selection. ... 

Axially chiral dicarboxylic acids were introduced by Maruoka and coworkers as a new class of Bronsted acid catalysts in 2007 [176]. The enantioselective Mannich... 

A. Compound 72 is drawn in 73 in its most stable chair conformation, with the bulkier C02H groups equatorial and the smaller F axial. The name is wj.v-5-fUiorocyclohexane-r-l,c7j-3-dicar-boxylic acid or 5[3-fluorocyclohexane-lot,3a-dicarboxylic acid. A plane of symmetry through C 2) and C 5) of 72 rules out chirality. 

Enantiomer-differentiating hydrolysis with pig liver esterase has, as with other hydrolases, become an important method for resolution (Table 11.1-5). Kinetic resolution of oxirane mono- and dicarboxylic acid esters with pig liver esterase proceeds effeciently with good selectivities, as demonstrated in the cases 14 and 15. Resolution is of course not restricted to enantiomers with central chirality. Axial and planar chiral racemic ester have been resolved with moderate to good results with pig liver esterase (33-36). 

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