Resolution protonated ketone

In the case of the ketone (12), a racemic mixture was converted to an optically active mixture (optical yield 46%) by treatment with the chiral base (13). This happened beeause 13 reacted with one enantiomer of 12 faster than with the other (an example of kinetic resolution). The enolate (14) must remain coordinated with the chiral amine, and it is the amine that reprotonates 14, not an added proton donor. 

Chiral amines can also be produced using aminotransferases, either by kinetic resolution of the racemic amine or by asymmetric synthesis from the corresponding prochiral ketone. The reaction involves the transfer of an amino group, a proton and two electrons from a primary amine to a ketone, and proceeds via an intermediate imine adduct. A variety of chiral amines can be obtained with high to very high ee-values. Several transformations have been developed and can be carried out on a 100-kg scale [94]. 

As a final example of the use of proton NMR invoking spin diffusion to study miscibility of polymer blends, the use of CRAMPS to remove proton dipolar coupling in a blend of an aromatic poly(ether-imid) (PEI), and a poly(aryl-ether-ketone) (PEEK), with detection of the magnetization of the C in the blend under high resolution conditions is cited [51]. Here, detailed information on the chemical composition of the phases present, as inferred from high resolution NMR of C, is linked to typical sizes of domains as reflected in spin diffusion of proton magnetization. 

The intermediate enolate formed in a Michael reaction normally undergoes protonation to give the ketone product. However, in the presence of an aldehyde, a Michael/Aldol cascade can occur. Using the racemic Michael acceptor (11.41), Shibasaki has demonstrated an enantioselective and diastereoselective Michael/Aldol cascade involving the malonate nucleophile (11.42) and the aldehyde (11.43). The process also involves a kinetic resolution of the starting material. Not only is this a remarkable example of several aspects of stereoselectivity, the product (11.44) is a useful prostaglandin precursor. 

Only one proton (consequence of severe twisting at C(l)-C(2) bond). ) Assignment based on corresponding radicals deuterated at C(2) and C(3) (flD = 0.175 mT). Assignment by [71Rusl]. By reduction of the ketone with Na K alloy in DMOE a similar spectrum without resolution of t-butyl splittings was obtained. Carbon atoms of t-butyl groups at C(3). ... 

In the NMR investigation of solutions, the effects of paramagnetic substances in solution on the proton resonance peaks of the solvent may be of particular significance. Certain europium(III) and praseodymium(III) chelates, for example, behave as Lewis acids towards donor solvents such as alcohols, ethers, esters and ketones. As a result of this acid-base interaction the proton resonance peaks undergo shifts which favour, among others, the resolution of the PMR spectrum. 

A number of other asymmetric enolate protonation reactions have been described using chiral proton sources in the synthesis of a-aryl cyclohexanones. These include the stoichiometric use of chiral diols [68] and a-sulfinyl alcohols [69]. Other catalytic approaches involve the use of a BlNAP-AgF complex with MeOH as the achiral proton source, [70] a chiral sulfonamide/achiral sulfonic acid system [71,72] and a cationic BINAP-Au complex which also was extended to acyclic tertiary a-aryl ketones [73]. Enantioenriched 2-aryl-cyclohexanones have also been accessed by oxidative kinetic resolution of secondary alcohols, kinetic resolution of racemic 2-arylcyclohexanones via an asymmetric Bayer-Villiger oxidation [74] and by arylation with diaryhodonium salts and desymmetrisation with a chiral Li-base [75]. 

In 1997, chemists from the Process Exploration Labs at Bristol-Myers Squibb Company reported their development of a simple asymmetric synthesis of d-sotalol 105, a Class III antiarrythmia compound, utilising a CBS reduction as the key step (Scheme 14.34). ° Previous efforts towards synthesis of d-sotalol had utilised techniques such as mandelic acid resolution, chiral chromatography and use of chiral homogeneous hydrogenation. The synthesis of d-sotalol via a CBS reduction is of interest as the molecule contains a methanesulfonamide NH proton, which clearly does not interfere with the yield or enantioselectivity of the process despite the acidic nature of this substituent. The authors discuss the various elements of the reduction process that they investigated and conclude that the optimal procedure involves addition of 1 M BH3 THE over a few minutes to a mixture of the (5 )-2-MeCBS catalyst and substrate ketone 102 in MTBE held at room temperature. Under these reaction conditions (on a 1.8 mmol scale), alcohol 103 was obtained in 92% yield with 96% ee. In this instance, the enantiomeric excess was calculated by conversion of the alcohol product to... 

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