Quaternary asymmetric carbon atom

Optically active barbiturates important in pharmacy, are obtained by classical synthesis and resolution procedures [14]. A new approach to the synthesis of optically active barbiturates is enantioselective catalysis with Pd complexes. An example is shown in Scheme 10 on the right side. The synthesis of the enantiomers of a N-methyl barbiturate containing a quaternary asymmetric carbon atom is achieved by allylation of the corresponding precursor with allyl acetate. Pd/triphenylphosphine complexes are efficient catalysts for this reaction which give a racemic mixture of the product. The reaction proceeds via a jt-allyl complex of Pd as an intermediate (Scheme 10, left side). This 7t-allyl complex is attacked by the nucleophile, the anion of N-... 

An example of a compound whose chiral discrimination poses the utmost difficulty is a saturated quaternary hydrocarbon bearing similar substituents on the asymmetric carbon atom, with a representative example being 5-ethyl-5-propylundecane,i.e., (n-butyl)ethyl(n-hexyl)(n-propyl)methane (Fig. 8) [ 106]. The enantiomer of this hydrocarbon exhibits practically no optical rotation ( of < 0.001) between 280 and 580 nm. The compound is a chiral, but to all intents an optically inactive, compound. To the best of our knowledge, the chirality of this compound has not been discriminated using any current method. Mislow called such hidden chirality cryptochirality [ 14,107]. 

FIGURE 7-2 Muscarinic Antagonists belladonna alkaloids and quaternary analogs. The blue C identifies an asymmetric carbon atom. 

For an adamantane-type compound, it is possible to substitute the four tertiary hydrogen atoms and make four quaternary carbon atoms. These carbon atoms can be asymmetric if the four substituents are chosen properly. It is possible to specify these chiral centers separately, but their chiralities can also be so interlinked that they collectively produce one pair of enantiomers with only one chiral center. Usually it is more convenient to collectively specify the chirality with reference to a center of chirality taken as the unoccupied centroid of the adamantane frame. 

The study of Fuji et al. shows that the addition of lithium enolate 75 to ni-troamine 74 is readily reversible quenching conditions are thus essential for getting a good yield of product 76. An equilibrium mixture of the adducts exists in the reaction mixture, and the elimination of either the prolinol or lactone moiety can take place depending on the workup condition (Scheme 2-34). A feature of this asymmetric synthesis is the direct one pot formation of the enantiomer with a high ee value. One application of this reaction is the asymmetric synthesis of a key intermediate for indole type Aspidosperma and Hun-teria alkaloids.68 Fuji69 has reviewed the asymmetric creation of quaternary carbon atoms. 

The first asymmetric total synthesis of (+)-lycorine is outlined in Scheme 15. While our earlier applications of the Birch reduction-alkylation of chiral benzamide 5 were focused on target structures with a quaternary stereocenter derived from C(l) of the starting benzoic acid derivative, the synthesis of 64 demonstrates that the method also is applicable to the construction of chiral six-membered rings containing only tertiary and trigonal carbon atoms. s... 

The bisferrocenylbisphosphine 15 has been reported to be an enantioselective chiral ligand for the rhodium-catalyzed asymmetric Michael addition of a-cyano carboxy-lates [85] to vinyl ketones (Scheme 2-60). The tranj-chelation of 15 generates efficient chiral surroundings around the rhodium atom to produce a quaternary chiral carbon center with up to 89% ee. 

The tetrahedral geometry is found most commonly at a normal sp carbon centre. However, it may be found in other situations. For example, there is no need for the chiral centre to be a carbon atom, i.e. other tetravalent asymmetrical centres such as a quaternary ammonium salt would suffice. In passing, it ought to be noted that there needs only to be a very small difference in the four groups in order for optical activity to arise. This may be illustrated by the isotopically labelled sulphone, R1R2S180160, which is optically active. 

Strecker reaction to establish a new stereocenter is subject to asymmetric induction, capable of creating either a tertiary" or quaternary carbon atom in the presence of 59. The peptido-imine 60 proves to be an excellent ligand for the Ti(IV)-mediated cyanation of aldimines. On catalysis of the bicyclic guanidine 61 the addition of HCN to A-benzhydrylaldimines affords a-amino nitrile derivatives with moderate to good ee. ... 

Cyclopropanone acetals with a quaternary carbon atom in chiral form can be established by addition of bisoxazoline-ligated allylzinc reagents to the cyclopropenes.The t-BuLi/(-)-sparteine combination favors Br-Li exchange and also promotes enantioselection in the intramolecular addition of aryllithium to an o-alkenyl side chain (e.g., indoline synthe-j.ijj) I28.I29 Moderate asymmetric induction is shown in the hydroarylation of norbomene in the presence of 63. 

The scope of the methodology was expanded by the same gronp involving Mannich reactions of cyclic 1,3-dicarbonyl compounds 49a-d with different types of A -acylimines such as 50a-b to afford the corresponding addncts 51a-g, containing an asymmetric quaternary carbon atom. These products were obtained in generally excellent yields, good de s and ee s of up to 99% (Scheme 5.26) [36]. 

The progress in NMR hardware to support the structure elucidation of limited quantity samples allowed to exploit the ADEQUATE experiment to a greater extent [2,93,94]. The advantage of the ADEQUATE pulse sequence originates from C-C magnetization step transfers that allow to specifically differentiate between Jch and Jch bonds which is not possible from HMBC-based experiments. It also includes connectivity information to non-protonated carbon atoms. Thus, multiplicity-edited H-C HSQC and 1,1-ADEQUATE experiments were co-processed to yield a C—C correlation plot [28]. The map was diagonally symmetric in case of adjacent Jcc-coupled protonated carbons and asymmetric in case of Jcc between protonated and quaternary carbons. It was emphasized that the latter responses were observed at the C shift of the protonated carbon in the FI direction and the correlation at the C shift of the quaternary carbon in the F2 dimension, cf. exemplarily for the methylene Cl 1 and the carbonyl CIO in Fig. 5.12. The well-known compound strychnine served as proof-of-principle for the HSQC-1,1-ADEQUATE. 

HPLC is one of the most universal methods for determining the enantiomeric composition of substances and mixtures in a short time frame. Its application is not restricted to molecules in which chirality is based on a quaternary carbon atom with four different substituents it can also be employed for compounds containing a chiral silicon, nitrogen, sulfur, or phosphorus atom. Likewise, asymmetric sulfoxides or aziridines, the chirality of which is based on a lone electron pair, can be separated. Chirality can also be traced back to helical structures, as in the case of polymers and proteins to the existence of atropiso-merism, the hindered rotation about a single bond, as observed, for example, in the case of binaphthol, or to spiro compounds. 

The p -hybridized carbon atom of the carbonyl group has frequently been reduced by asymmetric reagents to yield the 5p -hybridized carbon atom of an optically active alcohol. For example, Horner and Brich have studied electrochemical reduction of acetophenone in the presence of optically active quaternary ammonium salts or crown ethers. The optical purity achieved was low. In contrast, the conversion of the sp -hybridized carbon atom of a carbonyl compound into the sp -hybridized carbon atom of an optically active amine, a process common in Nature, has been exemplified using an artificial pyridoxamine analogue by Kuzuhara et aC Optical yields were moderate. 

Acrylates 2.184 are also good components in the coupling reaction with diyne 2.183, and asymmetric quaternary stereo sites are created on a ring carbon atom of the adduct 2.185 (Scheme 2.64) [61, 115]. 

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