Stereochemistry and Racemization

For a carbanion derived from a tetrahedral carbon (i.e., sp hybridized) to exhibit chirality, it must either remain pyramidal or if inversion occurs, one face must 

Nuclear magnetic resonance (NMR) has proven to be a very powerful technique for probing the structures of carbanions in the condensed phase. In particular, much work has been completed on the ion-pairing behavior of carbanions with lithium cations as well as the formation of aggregates of these lithium salts. A full discussion of this topic, particularly the methodology, is beyond the scope of this chapter, but a brief overview is appropriate. 

The situation becomes even more complex when other lithium salts are present in the solution. For example, when a lithium halide such as LiBr is added to solutions of alkyllithiums, mixed aggregates are formed where a bromide anion takes the 

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Neutral Complexes. Interaction of acetylacetone and hydrous Rh2G3 gives the trisacetylacetonate, which has been resolved into enantiomeric forms. It undergoes a variety of electrophilic substitution reactions of the coordinated ligand, such as chlorination. The stereochemistry and racem-ization of the cis- and trans-isomers of the unsymmetrical trifluoroacetyl-acetonate have been studied by nmr spectroscopy the compound is extremely stable to isomerization. 

The relative stereostructure of 9-acetyl-7-hydroxy-l,2-dimethyl-7-meth-oxycarbonyl-4-phenyl-6-oxo-l, 4,7,8-tetrahydro-6/7-pyrido[l, 2-u]pyri-midine-3-carboxylate 122 was justified by an X-ray diffraction analysis (97JOC3109). The stereochemistry and solid state structure of racemic trans-6,9-//-l, 6-dimethyl-9 z-ethoxy-9-hydroxy-4-oxo-l,6,7,8,9,9 z-hexahydro-4//-pyrido[l,2- z]pyrimidine-3-carboxylate (123), adopting a cw-fused conformation, were determined by X-ray investigations (97H(45)2175). 

It should be stressed that this treatment of polymer stereochemistry only deals with relative configurations whether a substituent is "up or down" with respect to that on a neighboring unit. Therefore, the smallest structural unit which contains stereochemical information is the dyad. There are two types of dyad meso (m), where the two chiral centers have like configuration, and racemic /-), where the centers have opposite configuration (Figure 4.1). 

The study of optical isomers has shown a similar development. First it was shown that the reduction potentials of several meso and racemic isomers were different (Elving et al., 1965 Feokstistov, 1968 Zavada et al., 1963) and later, studies have been made of the ratio of dljmeso compound isolated from electrolyses which form products capable of showing optical activity. Thus the conformation of the products from the pinacolization of ketones, the reduction of double bonds, the reduction of onium ions and the oxidation of carboxylic acids have been reported by several workers (reviewed by Feokstistov, 1968). Unfortunately, in many of these studies the electrolysis conditions were not controlled and it is therefore too early to draw definite conclusions about the stereochemistry of electrode processes and the possibilities for asymmetric syntheses. 

In this scheme, RS and SR represent enantiomers, and so on, and 5 represents some fraction. The following are the possibilities (1) Direct attack by SH on RX gives SR (complete inversion) in a straight Sn2 process. (2) If the intimate ion pair R X is formed, the solvent can attack at this stage. This can lead to total inversion if Reaction A does not take place or to a combination of inversion and racemization if there is competition between A and B. (3) If the solvent-separated ion pair is formed, SH can attack here. The stereochemistry is not maintained as tightly and more racemization (perhaps total) is expected. (4) Finally, if free R" " is formed, it is planar, and attack by SH gives complete racemization. 

The Yl/A isotherms of the racemic and enantiomeric forms of DPPC are identical within experimental error under every condition of temperature, humidity, and rate of compression that we have tested. For example, the temperature dependence of the compression/expansion curves for DPPC monolayers spread on pure water are identical for both the racemic mixture and the d- and L-isomers (Fig. 13). Furthermore, the equilibrium spreading pressures of this surfactant are independent of stereochemistry in the same broad temperature range, indicating that both enantiomeric and racemic films of DPPC are at the same energetic state when in equilibrium with their bulk crystals. 

Optically active selenoxides are known to be unstable toward racemization. An optically active selenoxide having a steroidal frame was obtained for the first time by Jones and co-workers in 1970.7 Enantiomeric selenoxides were prepared by Davis et al. in 1983,8 and an enantiomerically pure selenoxide was isolated for the first time by us in 1989.9 Many optically active selenoxides, which are kinetically stabilized by bulky substituents, were synthesized over the last two decades, and their stereochemistry and stability toward racemization were studied.3,5,10 Recently, some optically active selenoxides, which were thermodynamically stabilized by the intramolecular coordination of a Lewis base to the selenium atom, have been isolated. Optically active selenoxides 1 and 2 were obtained by optical resolution on chiral columns, and their stereochemistry and stability toward racemization under various conditions were clarified (Scheme 1).11,12... 

When it is necessary to specify the internal stereochemistry of the group, a prefix is required. In vinyl polymers there are meso (m) and racemic (r) diads and mm, mr, rr triads. The latter may be called isotactic, heterotactic and syndiotactic triads, respectively. Stereoregular vinyl polymers can be defined in terms of the regular sequences of diads thus an isotactic vinyl polymer consists entirely of m diads, i.e., it corresponds to the following succession of relative configuration -mmmmmm-, whereas a syndiotactic vinyl polymer consists entirely of r diads, corresponding to the sequence -rrrrrrr-. Similarly, a vinyl polymer consisting entirely of mr (= rm) triads is called a heterotactic polymer. 

The synthesis of chiral, non-racemic a-amino acids remains an interesting field of investigation and the synthesis of fully protected a,a-disubstituted a-amino acids 331 via the Beckmann rearrangement of tosylated oximes was achieved (equation 123). As expected, the migrating group was able to retain the original stereochemistry and good yields and excellent enantioselectivities were observed ... 

The bis-carbazole alkaloids contain previously known monomeric carbazoles as structural subunits. All bis-carbazole alkaloids were isolated only from plants of the genus Murray a, until 1996, when clausenamine-A (203) (see Scheme 2.48) was isolated from the stem bark of C. excavata. The plant M. euchrestifolia is one of the richest sources of carbazole alkaloids. The bis-carbazoles often co-occur with monomeric carbazoles in the root bark, stem bark, and leaves of this plant (3,5-7,158,159). The aspect of atropisomerism for axially chiral, bis-carbazoles was considered only recently. Thus, in many cases it is not clear whether the isolated natural products are racemic or enantiomerically pure. Moreover, little attention has been paid to the relationship between their stereochemistry and biological activity. 

The first-order markov model describes a polymerization where the penultimate unit is important in determining subsequent stereochemistry. Meso and racemic dyads can each react in two ways ... 

Although the treatment described above has been limited to polymerizations proceeding by meso and racemic placements, the various models can also be adopted to describe the stereochemistry of 1,4-propagation in 1,3-dienes. 

Other differences between singlet (concerted) insertion and triplet (abstraction-recombination) carbene insertion are seen in selectivity, stereochemistry, and the kinetic deuterium isotope effect. The triplet states are more selective in C—H insertion than the singlets. For example, the triplet shows higher tertiary to primary selectivity than the singlet in the insertion reaction with 2,3-dimethylbutane. Singlet carbene is shown to insert into C—H bond with retention of configuration, while racemization is expected for triplet insertion reaction from the abstraction-recombination mechanism. For example, the ratios of diastereomeric insertion product in the reaction of phenylcarbene with roc- and mcTO-2,3-dimethylbutanes are 98.5 1.5 and 3.5 96.5, respectively. ... 

Stereochemistry Inversion and racemization Inversion (backside attack)... 

Wynberg studied stereochemistry of the McMurry reductive dimerization of camphor in detail (64). In Scheme 37, A and B are homochiral dimerization products derived by the low-valence Ti-promoted reduction, while C and D are achiral heterochiral dimers. The reaction of racemic camphor prefers homochiral dimerization (total 64.9%) over the diastereomeric heterochiral coupling (total 35.1 %). Similarly, as illustrated in Scheme 38, oxidative dimerization of the chiral phenol A can afford the chiral dimers B and C (and the enantiomers) or the meso dimer D. In fact, a significant difference is seen in diastereoselectivity between the enaritiomerically pure and racemic phenol as starting materials. The enantiomerically pure S substrate produces (S,S)-B exclusively, while the dimerization of the racemic substrate is not stereoselective. In the latter case, some indirect enantiomer effect assists the production of C, which is absent in the former reaction. Thus, it appears that, even though the reagents and reaction conditions are identical, the chirality of the substrate profoundly affects the stability of the transition state. 

Oxidative Addition of Alkyl Halides to Palladium(0). The stereochemistry of the oxidative addition (31) of alkyl halides to the transition metals of group VIII can provide information as to which of the many possible mechanisms are operative. The addition of alkyl halides to d8-iridium complexes has been reported to proceed with retention (32), inversion (33), and racemization (34, 35) via a free radical mechanism at the asymmetric carbon center. The kinetics of this reaction are consistent with nucleophilic displacement by iridium on carbon (36). Oxi-... 

Sulfoxidation of the (+)-Noe-lactol (ROH) ester 21 of racemic 6,11 -dihydrodibenzo[, < ]thicpin-l 1 -ol 20 gave a separable mixture of four diastereomers 22a-d <2001TA975>. X-Ray structural analysis of one of these, 22a, established its relative stereochemistry, and its absolute configuration was established by the known configuration of the Noe-lactol fragment. Subsequent manipulation provided resolved 6,ll-dihydrodibenzo[, < ]thiepin-ll-ol 20 and assigned the configurations of all four sulfoxides 22a-d. 

Stereoselectivity in the reaction of acyclic ketone 270 is different from that of the cyclic ketone 256. The acetate in 271, prepared by reduction of the ketone 270 to alcohol with LiAlH and acetylation, was displaced with Me A1 from the exo side to give 272 with retention of the stereochemistry. No racemization of benzyl cation was observed. However, reaction of 270 with MeLi gave 274. The OH group of 274 was removed with hydride from the less hindered side as shown by 275 to give 276 with... 

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