Carboxylic acids chiral, oxidation

The reaction with Af-Boc protected allyl amine was carried out in a 10 mmol scale with a ratio of substrate/Rh = 10 000 1 for 24 h without affecting the regio-and stereochemistry found in the prehminary screening (Scheme 4.79). The iV-mono-protected P -amino aldehyde was converted into the corresponding P -amino carboxylic acid by oxidation or into the corresponding 1,3-hydroxy amine by reduction. Both are valuable chiral building blocks. 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Cleavage of the addition product 5 can be easily performed by treatment with dilute ( 1 %) aqueous alcoholic hydrochloric acid which liberates the chiral amino alcohol 3 and an a-hydroxy aldehyde. The latter can be further oxidized to the oc-hydroxy carboxylic acid 6 with sodium chlorite33. 

Desilylation of the major jjw-isomer, followed by oxidative cleavage with sodium metaperiodate, liberates the 3-hydroxy-2-methyl carboxylic acids. The immolative character of this method, i.e., the destruction of the chiral auxiliary reagent in the final glycol cleavage, is a drawback. 

Adam, W., Lazarus, M., Boss, B. et al. (1997) Enzymic resolution of chiral 2-hydroxy carboxylic acids by enantioselective oxidation with molecular oxygen catalyzed by the glycolate oxidase from spinach (Spinacia oleracea). The Journal of Organic Chemistry, 62 (22), 7841-7843. 

Trost et al.59 were the first to report enantioselectivity in the transition metal-catalyzed Alder-ene reaction. Several different acids were surveyed for the degree of efficacy in oxidizing the Pd(0) precursor to the active Pd(n) species and for compatibility with the catalyst, substrate, and product. Among acids surveyed were several chiral carboxylic acids products of reactions using these optically active acids were formed with modest enantioselectivity. (A)-binaphthoic acid gave the most promising result, with the cyclized product 83 obtained with 33% ee (Equation (52)). 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Applications. In the last decade a lot of research has been devoted to the development of catalytic routes to a series of asymmetric carboxylic acids that lack the acetamido ligand as additional functionality. In Figure 4.17 four are listed, which are important as anaesthetics for rheumatic diseases. Their sales in beat many bulk chemicals the turnover of Naproxen (retail) in 1990 was 700 million for 1000 tons. S-Naproxen is now being produced by Syntcx via resolution with a chiral auxiliary. The main patents from Syntex expired in the U.S. in 1993, the reason for a lot of activity to study alternative synthetic routes. Routes leading to an asymmetric centre are o asymmetric hydrogenation of an unsaturated acid, o asymmetric carbohydroxylation of a styrene precursor, o asymmetric hydroformylation of a styrene precursor and oxidation. 

Spent 2,2,6,6-tetramethyl-l-oxopiperidinium can be regenerated directly at a platinum anode in aqueous acetonitrile and aldehyde products do not undergo further oxidation to the carboxylic acid [37]. Either of the two racemic quinolyl-l-oxyls 4 functions better as catalyst for the oxidation of primaiy and secondary al-kanols, but the chiral forms do not achieve selective oxidation of one enantiomer of... 

The methyl and benzyl esters of proline were also used as chiral auxiliaries in respective acrylamides, but the isoxazoline cycloadducts were obtained with only poor to modest stereoselectivity (189,190). The related indoline-2-carboxylic acid derivative 33, however, showed excellent ability to direct nitrile oxide attack, favoring one rotamer (Scheme 6.37), and thereby leading to 3-phenylisoxazoline-5-carboxamide... 

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