Carbon chirality

If a tetrahedral center in a molecule has two identical substituents, it is referred to as prochiral since, if either of the like substituents is converted to a different group, the tetrahedral center then becomes chiral. Consider glycerol the central carbon of glycerol is prochiral since replacing either of the —CH9OH groups would make the central carbon chiral. Nomenclature for prochiral centers is based on the (R,S) system (in Chapter 3). To name the otherwise identical substituents of a prochiral center, imagine... 

Carbon-Chiral Allylsilanes by Asymmetric Grignard Cross-Coupling... 

Glucose may form a chain type structure such as the one pictured below. All of the carbon atoms except the one at the top and the one at the bottom are chiral. The four different groups making the fourth carbon chiral are outlined. 

A review article reports information regarding the preparation, handling, and storage of this important 3-carbon chiral source.9 Our experience with the compound demonstrates that it tends to polymerize and readily adds water to form hydrate 1 in aqueous solution, from which it is extracted with only difficultly. Both hydrated and polymerized aldehyde can contaminate samples and result in lowered optical rotation values, even though no racemization has occurred. The present procedure provides... 

The most common feature in chiral molecules is a tetrahedral (i.e. sp -hybridized) carbon atom with four different atoms or groups attached. Such a carbon atom is called a chiral carbon or an asymmetric carbon. Chiral molecules do not have a plane of symmetry. 

The principal question addressed, is there any kind of chiral recognition in electron transfer reactions involving GO or HRP and enantiomerically pure metal complexes. The chirality of optically active metal complexes may be different. Examples include central carbon chirality, when a complex has a side chain with an asymmetric sp3 carbon (Chart 2A), planar chirality as in the case of asymmetrically 1,2-substituted ferrocenes (Chart 2B,C), and central metal chirality when an octahedral central metal itself generates and enantiomers (Chart 2D) (202). These three types are discussed in this section. 

The very first two reports dealing with the central carbon chirality set up a fog of scientific intrigue. Electrochemical studies of Marx-Tibbon et al, have suggested that (S)-7V,7V-dimethyl-l-ferrocenylethyla-mine (Chart 2A) reacts with reduced GO twice as fast as the corresponding R enantiomer (203). Less than a year later, Alzari and co-workers could not reproduce the results and the enantioselec-tivity has not been observed for this pair of enantiomers (204). Careful reading of the both publications raises some questions. The study of the effect of ALV-dimethyl-1 -ferrocenylethylamine... 

For the synthesis of atorvastatin we developed an efficient process that allows for direct cyanation of lactone 2 [21] to cyanomethyl lactone 3 to finally afford the well known atorvastatin precursor 5 (Scheme 6.3) [22]. It is worth pointing out that the two synthetic routes to the advanced statin intermediates 5 and 6 described here avoid ultra-low temperature chemistry, heavy metal catalysts, metal-organic species, and chromatographic purification steps. The DERA-catalyzed chemistry to form the six-carbon chiral unit is cost competitive and operated on a commercial scale. 

S. Hanessian, P. C. Tyler, and Y. Chapleur, Reaction of lithium dimethylcuprate with confor-mationally biased acyloxy enol esters. Regio and stereocontrolled access to functionalized six-carbon chiral synthons. Tetrahedron Lett. 22 4583 (1981). 

To address limitations in the use of glyceraldehyde acetonide (43) as a three-carbon chiral building block, butane-2,3-diacetal-protected glyceraldehyde (44, R1 = R2 = H) has been prepared. It undergoes diastereoselective aldol reactions with a range of carbonyl compounds esters, thioesters, and ketones. The work has been extended (g) to other derivatives such as the a-substituted aldehyde (44, R1 = Me, allyl) and the methyl ketone (44, R2 = Me).122a,b... 

General Three Carbon Chiral Synthons from Carbohydrates Chiral Pool and Chiral Auxiliary Approaches... 

The familiar carbon chiral center has four different substituents as shown in 3-hydroxybutanoic acid (compound e in Figure 3.43). This chiral center is designated R in accordance with the well-known priority-sequence rules in the enantiomeric compound, the chiral center is designated 5. Both enantiomers give the same NMR spectrum in an achiral solvent, as does the racemate. Because of the chiral center, there is no symmetry element, and the methylene protons are diastereotopes. 

The C=N bond of simple imines possesses modest reactivity toward intermolecular radical additions, so such acceptors have rarely been exploited. To enhance their reactivity toward nucleophilic radicals, electron-withdrawing groups at the imine carbon have been effective, as demonstrated by Bertrand in radical additions to a-iminoesters prepared from chiral amines [25]. Also, more reactive oxime ethers have been exploited extensively for radical addition, mainly through the longstanding efforts of Naito [26]. In most cases, stereocontrol has been imparted through the substituents on the imino carbon chiral O-substituents on oximes for stereocontrol were ineffective, presumably due to poor rotamer control [27, 28]. 

Chapter 8 discussed the stereochemistry of substitution reactions—that is, what happened to the stereochemistry when the reaction occurred at a carbon chirality center. This section discusses the regiochemistry of the elimination reaction—that is, what happens when a reaction can produce two or more structural isomers. The structural isomers that can often be produced in elimination reactions have the double bond in different positions. As shown in Figure 9.5, elimination of hydrogen chloride from neomenthyl chloride produces two structural isomers but in unequal amounts. 

Another type of irregularity results if the vinyl monomer that is used to make an addition polymer has two different substituents on one end of the double bond. Propylene (propene), with a hydrogen and a methyl group on one of the vinyl carbons, provides an example. When such a monomer polymerizes, a new stereocenter (an asymmetric carbon chirality center) is created each time a new monomer is added ... 

The term stereocenter (stereogenic atom) is not consistently defined. The original (Mislow) definition is given here. Some sources simply define it as a synonym for an asymmetric carbon (chiral carbon) or for a chirality center. 

Figure 14. Alternative syntheses of the 5-carbon chiral unit, (R)-2-methylbutyric...

The potassium alkoxide acts as a nucleophile in the Sn2 displacement on CH3CH2Br in step 2. It is the C-Br bond of bromoethane, however, not the C-O bond of the alkoxide, that is broken. No inversion at the carbon chirality center occurs in step 2. 

Bromooctane is a secondary bromoalkane, which undergoes Sn2 substitution. Since SN2 reactions proceed with inversion of configuration, the configuration at the carbon chirality center is inverted. (This does not necessarily mean that all R isomers become S isomers after an Sn2 reaction. The R,S designation refers to the priorities of groups, which may change when the nucleophile is varied.)... 

Scheme 16 Sulfur to carbon chirality transfer with enantioenriched allylic sulfinates...

Scheme 94 First example of sulfur to carbon chirality transfer in a Type M rearrangement...

Scheme 95 Transition-state models for sulfur to carbon chirality transfer in Type M rearrangements...

Figure 1 Molecular structures of verapamil and its N-demethyiated metabolite, norverapamil, The carbon chiral center is designated by the asterisk.

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