Chiral derivatives carbons

There are a number of important kinds of stereogenic centers besides asymmetric carbon atoms. One example is furnished by sulfoxides with nonidentical substituents on sulfur. Sulfoxides are pyramidal and maintain dieir configuration at room temperature. Unsymmetrical sulfoxides are therefore chiral and exist as enantiomers. Sulfonium salts with three nonidentical ligands are also chiral as a result of their pyramidal shape. Some examples of chiral derivatives of sulfur are given in Scheme 2.1. 

Hayashi et al. [18] have synthesized two diastereoisomers of 2,2 -bis[4-(alkyl)oxazol-2-yI]-l,T-binaphthyl,bis(oxazoline) derivatives possessing both binaphthyl axial chirality and carbon centered chirality (structures 9 and 10, Scheme 5). 

Remarkable success has been achieved by Fryzuk and Bosnich (247) using the complex [Rh(5,5-chiraphos)(COD)]+, where the chiral ligand 25,55-bis(diphenylphosphino)butane, a diphosphine chiral at carbons (25), is readily synthesized from 2R,3R-butane diol. TheZ-isomers of the prochiral a-N-acylaminoacrylic acid substrates were hydrogenated at ambient conditions to / -products with very high enantiomeric excess indeed, leucine and phenylalanine derivatives were obtained in complete optical purity. Catalytic deuteration was shown to lead to pure chiral f3-carbon centers as well as a-carbon centers in the leucine and phenylal-... 

This is an equilibrium reaction, and it raises a couple of points. First, there are two a-positions in the ketone, so what about the COCH3-derived enolate anion The answer is that it is formed, but since the CH3 group is not chiral, proton removal and reprotonation have no consequence. Racemization only occurs where we have a chiral a-carbon carrying a hydrogen substituent. Second, the enolate anion resonance structure with charge on carbon is not planar, but roughly tetrahedral. If we reprotonate this, it must occur from just one side. Yes, but both enantiomeric forms of the carbanion will be produced, so we shall still get the racemic mixture. 

We reported a catalytic enantioselective cyanosUylation of ketones that produces chiral tetrasubstituted carbons from a wide range of substrate ketones [Eq. (13.31)]. The catalyst is a titanium complex of a D-glucose-derived ligand 47. It was proposed that the reaction proceeds through a dual activation of substrate ketone by the titanium and TMSCN by the phosphine oxide (51), thus producing (l )-ketone cyanohydrins ... 

Chiral bicyclic lactams such as those described here are useful in reaching a variety of chiral quaternary carbon derivatives. Thus, 1 can be doubly alkylated to the... 

The asymmetric cyclopropanation of a-bromocyclohexenone with cyanoacetate 31 has been achieved under phase-transfer conditions by the use of cinchona alkaloid-derived catalyst, which constructs chiral quaternary carbons on the cyclopropane... 

There are several methods for the preparation of optically pure 3-carbon compounds from carbohydrates. These fall into 3 major categories namely the cleavage of carbohydrate chains to form the desired compounds directly, the transformation of a (larger) carbohydrate-derived fragment to a 3-carbon one and the use of carbohydrates as a chiral auxiliaiy to induce chirality into a pro-chiral 3-carbon fragment. We will review the first approach and discuss our efforts in the other two areas more fully. 

The palladium-catalyzed arylation and alkenylation of olefins, which were first discovered in the 1970 s by Heck (7,2) and Mizoroki (3) and have been often called the "Heck reaction", are versatile synthetic means for making a carbon-carbon bond. These reactions have been extensively used for organic synthesis during the past two decades (4-7). However, no reports on the "asymmetric Heck reaction" have been appeared until very recently. Shibasaki reported an asymmetric intramolecular cyclization of alkenyl iodides to give c/j-decalin derivatives of 80-91% ee (8-10). Overman reported an intramolecular cyclization of alkenyl triflate, giving a chiral quaternary carbon center of 45% ee (77). We report herein the first example of intermolecular asymmetric Heck-type arylation of cyclic olefins catalyzed by (7 )-BINAP-coordinated palladium complexes (Scheme 1) (12,13). 

Besides stereoselective alkylations of glycine-derived enolates, enantioselective construction of chiral quaternary carbon centers from a-amino acids is one of the most challenging topics in current organic synthesis , since nonproteinogenic a,a-disubstituted amino acids often show a remarkable influence on the conformation of peptides. Moreover, they can act as enzyme inhibitors or as building blocks for the synthesis of a wide range of natural products . 

Formation of Chiral Quaternary Carbon. Birch reduction-alkylation of benzoic acids and esters establishes quaternary carbon centers. Neighboring stereocenters will influence the stereochemical outcome of the tandem reaction sequence. The following example illustrates how a chiral auxiliary (derived from prolinol) controls the stereoselection in the Birch reduction-alkylation step. ... 

Asymmetric alkylation of P-keto carbonyl derivatives under phase-transfer conditions is a very convenient and useful way to construct a chiral quaternary carbon center. In 2002, Dehmlow and coworkers reported the asymmetric benzylation of the cyclic (3-ketoester, 2-(tert-butoxycarbonyl)cyclopentanone (70) in the presence of the cinchoninium PTC 72 in excellent chemical yield with 46% ee (Scheme 6.21) [46]. 

Diastereoselective allylzincations of achiral cyclopropenone acetals, addressing the control of the relative configuration at the newly formed C-C bond (centers C3 and C4) and of chiral derivatives such as 20 (R = H), addressing chirality transmission through a spiro carbon center, have been investigated. In the presence of bis(oxazoline) ligands, enantioselective reactions of this kind can also be performed. ... 

As mentioned earlier, all but one of the syntheses of LTB4 reported to date have employed aldehyde esters 21a (methyl ester) or 21b (ethyl ester), derived from 2-deoxy-D-ribose, as the source of chirality at carbon 5. Two syntheses of LTB4 have been reported from the Merck Frosst laboratories, two from the laboratory of Professor Corey, and one by Nicolau. 

Chiral bis(l, 2-dioximato)cobalt(II) complexes synthesized from ( + )-camphor (A-C overleaf)67 68 are useful catalysts in the additions of diazo esters to phenylethene derivatives. Interestingly, the two catalysts (A and B) which induce remarkably high optical yields produce opposite chirality at carbon-1 of the resulting cyclopropanes, Apparently it is the geometry around the metal center which is crucial for optical induction and which might be quasi-enan-tiomeric for complexes A and B68. The alternative complex C. which incorporates ( , -configurated bisoxime ligands, is a much less effective cobalt catalyst. 

Unlike carbon chemistry where a similar type of reaction invariably takes place by an inversion process for chiral derivatives, both inversion and retention processes compete with one another for chiral derivatives of silicon. The factors influencing the dominance of one process over the other generally are known from studies2 conducted under a variety of experimental conditions. 

The gradated reactivities of allylic acetates and carbonates have been exploited in synthesis. Thus chiral c/s-4-acetoxycyclohex-2-enol is converted into either one of the enantiomers of 2,4-cyclohexadien-l-ylacetic acid by direct displacement with sodiomalonate followed by acetylation, elimination, and saponification, or by displacement of the derived carbonate followed by elimination of the unreacted acetate. 

A more general approach concentrates on the chiral modification of the carbene ligand. Some examples based on a chiral carbene carbon side chain are depicted in Figure 4. [68] The reaction of alkoxy- and amino(cyclohexenyl)carbene complexes with 1 -pentyne afforded diastereomeric tetralin complexes in moderate yields. [69] The sense of stereoselection was found to depend on the substitution pattern of the cyclohexenyl substituent. Whereas 5-methyltetralin derivatives were obtained in low preference for the syn complex, a higher preference for the anti diastereomer was observed synthesizing the 8-methyltetralin complexes 50 (Scheme 27). [69]... 

Much attention has been paid to molecular design of effective guest molecules to induce the photochemical flip of polarization in ferroelectric LC systems. An azobenzene derivative with a chiral cyclic carbonate group (13) was designed to induce a large value of polarization and examined as a chiral dopant to induce a... 

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