Tartaric acid stereochemistry

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

For the tetraric acids, the trivial name tartaric acid remains in use, with the stereochemistry given using the R,S system. Esters are referred to as tartrates (the second a is elided). 

The configuration of (-)-glyceraldehyde was related through reactions of known stereochemistry to (+)-tartaric acid. 

In 1815 Biot12) recognized that certain liquid organic compounds and also the solutions of some solid substances like saccharose, camphor, and tartaric acid are capable of rotating the plane of linearly polarized light. He ascribed this to some inherent property of the compound molecules. This initiated a development which led to the concept of stereochemistry. 

By using either one of these photosystems, one-electron (3-activation of a,(3-unsaturated carbonyl compounds produced carbon-centered radical precursors which cyclize efficiently and stereoselectively to tethered activated olefins or carbonyl groups. The 1,2-anti-stereochemistry observed contrasts with the general trend of syn-stereochemistry expected in 5-hexenyl radical cyclizations. Application of this methodology was successfully demonstrated by the stereoselective synthesis of optically pure C-furanoside, starting from L-tartaric acid (Scheme 38) [57,58]. 

Later, Pasteur 15) had arrived at the general stereochemical criterion for a chiral or dissymmetric molecular structure. Thus, the specific rotations of the two sets of sodium ammonium tartrate crystals in solution, isolated from the racemic mixture by hand-picking, were equal in magnitude and opposite in sign, from which Pasteur inferred that enantiomorphism of the dextro- and laevorotatory crystals is reproduced in the microscopic stereochemistry of the (+)- and (—)-tartaric acid molecules. The term dissymmetry or chirality is used when there is no superimposability between the two enantiomers, as seen in Sect. 2.1. 

Probably the best known early crown ether example is the chundle reported by Jullien and Lehn (Jullien and Lehn, 1988). Their strategy used a central crown ether unit with sidearms radiating from it. The stereochemistry of the sidearms was fixed by incorporation of tartaric acid units within the macrocycle. The name was given because the compound was a channel formed from a bundle of fibers. In this first report, no information about insertion or transport appeared, and the assertion that the compound was a channel apparently rested on the intent of the design. Later work from this group showed that related compounds, called bouquet molecules, did conduct cations, albeit rather slowly (Canceill etal., 1992). 

An understanding of the three-dimensional structures of molecules has played an important part in the development of organic chemistry. The first experiments of importance to this area were reported in 1815 by the French physicist J. B. Biot, who discovered that certain organic compounds, such as turpentine, sugar, camphor, and tartaric acid, were optically active that is, solutions of these compounds rotated the plane of polarisation of plane-polarized light. Of course, the chemists of this period had no idea of what caused a compound to be optically active because atomic theory was just being developed and the concepts of valence and stereochemistry would not be discovered until far in the future. 

The stereochemistry of a solute is also important, as is shown by the differences between the partial molar volumes and compressibilities of stereoisomers of tartaric acid and its potassium salts in water (Mathieson and Conway, 1975). 

The relative stereochemistry of the major adducts is assigned to be syn, and the predominant re face-attack of enol ethers at the aldehyde carbonyl carbon has been confirmed when a natural tartaric acid derivative is used as a Lewis acid ligand. The use of an unnatural form of tartaric acid as a chiral source gives the other enantiomer, as expected. Almost perfect asymmetric induction are achieved with the syn adducts. 

Tartaric acid, HOOCCHOHCHOHCOOH, has played a key role in the development of stereochemistry, and particularly the stereochemistry of the carbohydrates. In 1848 Louis Pasteur, using a hand lens and a pair of tweezers, laboriously separated a quantity of the sodium ammonium salt of racemic tartaric acid into two piles of mirror-image crystals and, in thus carrying out the first resolution of a racemic modification, was led to the discovery of enantiomerism. Almost exactly 100 years later, in 1949, Bijvoet, using x-ray diffraction—and also laboriously—determined the actual arrangement m space of the atoms oY the sodium rubidium salt of (-f )-tartaric acid, and thus made the first determination of the absolute configuration of an optically active substance. 

To determine the absolute configuration of optically active organic compounds, there are two nonempirical methods. One is the Bijvoet method in the X-ray crystallographic structure analysis, which is based on the anomalous dispersion effect of heavy atoms. - The X-ray Bijvoet method has been extensively applied to various chiral organic compounds since Bijvoet first succeeded in determination of the absolute stereochemistry of tartaric acid in 1951. The second method is a newer one based on the circular dichroism (CD) spectroscopy. Harada and Nakanishi have developed the CD dibenzoate chirality rule, a powerful method for determination of the absolute configuration of glycols, which was later generalized as the CD exciton chirality method. 8 The absolute stereochemistry of various natural products has been determined by application of this nonempirical method. 

Compounds 7 and 8 (cyclobutanes are usually drawn in this style) are termed cis and trans, respectively. Further, 7 and 8 are diastereoisomers, though neither is chiral this is significant in that diastereoisomers encountered previously, e.g. (R, R) and meso tartaric acids, have at least one chiral member. Indeed, this observation is general for disubstituted saturated cyclic hydrocarbons provided that the number of carbon atoms in the ring, n, is even and that the substituents are located at carbon atoms 1 and 1 + nil). For cyclobutanes this corresponds to C(l) and C(3), and for cyclohexanes C(l) and C(4). The stereochemistry of 1,2-disubstituted cyclobutanes is analogous to that of cyclopropanes. 

A stereocontrolled synthesis of the side-chain acid 186 of isoharringtonine from (R,R)-(-l-)-tartaric acid was reported by Zhang etal. (63) (Scheme 30). Dimethyl (2R, 3i )-tartrate acetonide (182) was allylated in the presence of lithium diisopropylamide to give 183, which underwent base-catalyzed epimerization to 184. Catalytic hydrogenation, followed by hydrolysis and by treatment with methanol in the presence of sulfuric acid, yielded the half ester 185, which was treated with aqueous trifluoroacetic acid to provide the side-chain acid of isoharringtonine (186) with the appropriate stereochemistry. 

The amine 2 is made by a chemical reaction - the reductive amination of ketone 1. The starting material 1 and the reagents are all achiral so the product 2, though chiral, must be racemic. Reaction with one enantiomer of tartaric acid 3 forms the amine salt 4, or rather the amine salts 4a and 4b. Examine these structures carefully. The stereochemistry of tartaric acid 3 is the same for both salts but the stereochemistry of the amine 2 is different so these salts 4a and 4b are diastereoisomers. They have different physical properties the useful distinction, discovered by trial and error, is that 4b crystallises preferentially from a solution in methanol leaving 4a behind in solution. Neutralisation of 4b with NaOH gives the free amine (S) -2, insoluble in water and essentially optically pure. 

Glyceraldehyde, of which 107 and 109 arc protected forms, is the only three-carbon sugar. There are two four-carbon sugars erythrose 111 and threose 113. Both exist in hemiacetal (furanose) and open chain forms and both are chiral but their symmetry properties differ. The tetrols formed by reduction of the aldehydes are me so erythritol 112 and C2 symmetric threitol 114 having the same stereochemistry as tartaric acid 35. Threose or threitol can be oxidised to tartaric acid. These sugars are the origin of the terms erythro and three sometimes used to describe such diastereomeric relationships. 

The imide 189 is easily made from protected tartaric acid 190 and the vinyl silane 188 coupled in a Mitsunobu reaction. Reduction of one of the carbonyl groups of the imide 191 may seem tricky but the molecule is C2 symmetric so the two carbonyl groups are the same and once one is reduced the molecule is a much less reactive amide. The stereochemistry of the acetate in 192 does not matter as it disappears in the cyclisation to 186. Notice that the alkene geometry is retained. 

D-Tartaric acid dehydratase (E.C. 4.2.1.81) and the stereochemical counterpart l-tartaric acid dehydratase (E.C. 4.2.1.32) are able to catalyze the conversion of oxaloacetic acid to d- and L-tartaric acid respectively. The actual addition of water to the C-C double bond is most likely to occur at the enol tautomer, and the resulting tartaric acid has the 2S,3S (D-stereo isomer made by E.C. 4.2.1.81) or 2R,3R (l-tartaric acid dehydratase) configuration. Despite the stereochemistry of the reactions catalyzed, the lack of available enzyme and the instability of the enzymes in presence of oxygen131 have hampered their application in organic synthesis thus far. 

The 3D space dimension was introduced—again simultaneously—by two chemists, Van t Hoff and Le Bel, in order to distinguish between pairs or even larger numbers of isomers depicted by the same connectivity table or classical structural formula but lowering each other s melting point and therefore not identical. The two optically active tartaric acids and their inactive meso isomer are examples. The new organic subfield of stereochemistry specified the direction in space of the four bonds radiating from carbon. 

It is interesting that tartrate was the first resolved compound [1] as well as the first compound whose absolute configuration was established it is fitting that this seminal work was done at the van t Laboratories of the University of Utrecht. Given the role tartaric acid played in the establishment of the field of stereochemistry, it was perhaps inevitable that it would also play a major role in asymmetric synthesis, as will be seen in a number of examples throughout this book. 

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