Aromatic chirality method

A successful application of the aromatic chirality method (6) has led to the determination of the absolute configuration of (-)-amurensine (24), thus establishing the absolute configuration of the isopavine bases as shown in expression 24a 161). This result was later verified by the correlation of optical rotations and ORD curves of (—)-argemonine (5) and (—)-amurensinine (25) 67,70,160) as well as of their first-step Hofmann degradation products 160). 

The absolute configuration of amurensine (56b) was determined by Shamma and Nakanishi, who applied the so-called aromatic chirality method of CD analysis (584). 

The absolute configuration of the isopavine alkaloids has been established by means of the useful aromatic chirality method, and (—)-amurensine possesses the absolute configuration depicted in structure (36). The fact that the pa vines and isopavines have the identical absolute configuration points to the possibility of a common biogenetic precursor, such as a 4-hydroxytetrahydrobenzyliso-quinoline, for these alkaloids. 

The absolute configurations of ochotensine, ochotensimine, ochrobirine, and lumaritine have been established using the aromatic chirality method. In each case, the methylenedioxy-group in ring D is below the mean plane of the molecule... 

The absolute configurations of all the rhoeadine and papaverrubine alkaloids have now been elucidated using the aromatic chirality method. For instance, ( + )-glaudine is represented by structure (191), (+ )-epiglaudine by (192), and ( + )-oreodine by (193). ... 

The full details of the X-ray crystallographic analysis of the synthetic / -isomer of cryptostyline II have been published along with an added proof of its stereochemistry by the aromatic chirality method. ... 

The Cotton effects may be classified into three types168 those arising from chirally perturbed local achiral chromophores (ketones, /i.y-unsaturated ketones, double bonds, benzoates, aromatic compounds) those arising from inherently achiral chromophores, such as conjugated dienes or a,/3-unsaturated ketones those arising from interaction of the various electric transition moments when two or more chromophores which are chirally disposed are positioned nearby in space, intra- or intermolecularly (exciton chirality method)169. 

The power of the exciton chirality method lies in its applicability to molecules having functional groups which are not chromophores in the usual sense (such as hydroxy, amino or thiol groups), but can be converted to a chromophoric derivative, such as an unsaturated or aromatic acyl derivative. This procedure is extremely useful for the determination of the absolute configuration of products of stereoselective synthesis having a hydroxy, amino or thiol group at the stereogenic center. 

The configuration at C-3 was demonstrated to be S by exhaustive ozonolysis of 1 to the known p-amino acid 3 (72). The relative configuration at C-1 compared with C-3 was shown to be trans by NMR methods, and the absolute configuration at the biphenyl linkage was elucidated by application of the exciton chirality method (13) on the fully aromatized chiral naphthyl isoquinoline 4 (72). The structure 1 thus deduced for ancistrocladine was later confirmed by X-ray analysis (72). 

The one-pot synthesis of helical aromatics, 13,14-dialkyldibenzo[fc,/] [4,7]-phenanthrolines (78) together with their stability against racemiza-tion and the assignment of absolute configuration assisted by experimental and theoretical circular dichroism were reported by Tanaka et al. (04JOC7794). For R = CH3, AH = 87.5kJ moC and AS = -24.1J mol (and not kJ moC as reported). The absolute configuration of these molecules was established on the basis of the CD exciton chirality method (exciton-coupled CD) together with theoretically calculated spectra. 

A knowledge-based chiral method development strategy can be very effective on chiral column selection. For example, a chiral screening method was used to monitor the enantiomeric purity of an atropisomeric dmg candidate. It returned the Chiralcel OD-RH column in reversed phase with a baseline enantioseparation of both atropi-somers (Fig. 12a). There was a need to redevelop the chiral method as the compound moved into development stages. Based on possible interaction sites around the chiral asymmetric axis of the compound (a primary amine for ionic and H-bonding interactions and an aromatic ring for k-k interaction), Chirobiotic V2 was tested since... 

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. 

A large amount of fuel and environmentally based analysis is focused on the determination of aliphatic and aromatic content. These types of species are often notoriously difficult to deconvolute by mass spectrometric means, and resolution at the isomeric level is almost only possible by using chromatographic methods. Similarly, the areas of organohalogen and flavours/fragrance analysis are dominated by a need to often quantify chiral compounds, which in the same way as aliphatic... 

More recently, the same type of hgand was used to form chiral iridium complexes, which were used as catalysts in the hydrogenation of ketones. The inclusion of hydrophihc substituents in the aromatic rings of the diphenylethylenediamine (Fig. 23) allowed the use of the corresponding complexes in water or water/alcohol solutions [72]. This method was optimized in order to recover and reuse the aqueous solution of the catalyst after product extraction with pentane. The combination of chiral 1,2-bis(p-methoxyphenyl)-N,M -dimethylethylenediamine and triethyleneglycol monomethyl ether in methanol/water was shown to be the best method, with up to six runs with total acetophenone conversion and 65-68% ee. Only in the seventh run did the yield and the enantioselectivity decrease slightly. 

The reaction of the stable and readily available N-protected (a-aminoacyl)benzotriazoles 215 (Equation 36) with amidoximes 206 in ethanol gave the N-protected 5-amino-substituted 1,2,4-oxadiazoles 216 in high yield, under mild conditions and with good (>97%) retention of chirality <2005ARK36>. The method is also applicable to aromatic (V-acylbenzotriazoles, giving access to 5-aryl-l,2,4-oxadiazoles in 73-82% yield. 

Kwakman et al. [65] described the synthesis of a new dansyl derivative for carboxylic acids. The label, N- (bromoacetyl)-A -[5-(dimethylamino)naphthalene-l-sulfonyl]-piperazine, reacted with both aliphatic and aromatic carboxylic acids in less than 30 min. Excess reagent was converted to a relatively polar compound and subsequently separated from the derivatives on a silica cartridge. A separation of carboxylic acid enantiomers was performed after labeling with either of three chiral labels and the applicability of the method was demonstrated by determinations of racemic ibuprofen in rat plasma and human urine [66], Other examples of labels used to derivatize carboxylic acids are 3-aminoperylene [67], various coumarin compounds [68], 9-anthracenemethanol [69], 6,7-dimethoxy-l-methyl-2(lH)-quinoxalinone-3-propionylcarboxylic acid hydrazide (quinoxalinone) [70], and a quinolizinocoumarin derivative termed Lumarin 4 [71],... 

Chiral catalysts remain primary targets for immobilization by using similar methods. Since the steric arrangement of bulky aromatic groups of chiral ligands is the primary source of optical induction, most approaches use the chelate backbone of ligands for functionalization in order to minimize interference with the chelate (aryl) conformation. 

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