Achiral ketones

I.5.3.5.2. Addition to a-SuIfiny l-a,/MJnsaturated Ketones Achiral Organometallic Reagents... 

If the a carbon atom of an aldehyde or a ketone is a chnality center its stereo chemical integrity is lost on enolization Enolization of optically active sec butyl phenyl ketone leads to its racemization by way of the achiral enol form... 

Enol form [achiral may be converted to either (R) or (S) sec butyl phenyl ketone]... 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achiral enol or enolate ion. The 5/) -hybridized carbon that is the chirality center in the starting ketone becomes 5/) -hybridized in the enol or enolate. Careful kinetic studies have established that the rate of loss of optical activity of 5cc-butyl phenyl ketone is equal to its rate of hydrogen-deuterium exchange, its rate of bromination, and its rate of iodina-tion. In each case, the rate-detennining step is conversion of the starting ketone to the enol or enolate anion. 

By treatment of a racemic mixture of an aldehyde or ketone that contains a chiral center—e.g. 2-phenylpropanal 9—with an achiral Grignard reagent, four stereoisomeric products can be obtained the diastereomers 10 and 11 and the respective enantiomer of each. 

The importance of chemical syntheses of a-amino acids on industrial scale is limited by the fact that the standard procedure always yields the racemic mixture (except for the achiral glycine H2N-CH2-COOH and the corresponding amino acid from symmetrical ketones R-CO-R). A subsequent separation of the enantiomers then is a major cost factor. Various methods for the asymmetric synthesis of a-amino acids on laboratory scale have been developed, and among these are asymmetric Strecker syntheses as well. ... 

Closely related to the concept of chirality, and particularly important in biological chemistry, is the notion of prochirality. A molecule is said to be prochiral if can be converted from achiral to chiral in a single chemical step. For instance, an unsymmetrical ketone like 2-butanone is prochiral because it can be converted to the chiral alcohol 2-butanol by addition of hydrogen, as we ll see in Section 17.4. 

No information is available as to whether raceniization of the carbonyl compound takes place under the reaction conditions, since the investigation was performed with the racemates. An extensive study of the addition of these reagents to achiral ketones was published in 1980110. 

I.3.3.3.3.I.2. Simple Diastereosclectivity Reactions with Achiral Aldehydes and Ketones... 

Addition of Chiral Etiolates to Achiral Carbonyl Compounds 1.3.4.2.1. Chiral Ketone Enolates 1.3.4.2.L1. yi H-Sclectivc Ketone Enolates... 

Furthermore, both (E)- and (Z)-enolborinates add to aldehydes in a stereoconvergcnt manner, giving predominantly, syn-/J-hydroxycarbonyl compounds49. In contrast, only moderate induced diastereoselectivity is obtained in the reaction of achiral aldehydes with C2-symmetric enolborates, whereby the chiral information is located in the ligand at the metal atom50. The ee of the product /1-hydroxy ketones ranges from 4 to 72%. 

Achiral ketones, for example, 3-pentanone, can be converted predominantly into (Z)-boron enolates [(Z)/( )>97 3] by treatment with (- )-diisopinocampheylboron triflate. Subsequent addition to aldehydes, followed by an oxidative workup procedure, delivers /i-hydroxy ketones with a diastcrcomeric ratio of 95 5 to 98 2 (synjanli) and the xpn-products with 66 to 93% ee33. 

On the other hand, when induction relics exclusively on the auxiliary, as is the case for isopinocampheylborinatcs derived from achiral ketones, only moderate enantioselectivity is achieved. Thus, /1-hydroxy ketones are obtained with 53-78% ee53. 

The achiral enolate 1 reacts with symmetrical ketones to provide aldol-type products1. 

Racemic 5-methyl-5 -(sodiomethyl)-A-(4-methylphenylsulfonyl)sulfoximine reacts with ketones to give an initial methylene transfer which produces an intermediate epoxide that is ring expanded to the oxctanc56. Application to 4-rerf-butylcyclohexanonc affords a single oxetane in 69% yield. While only achiral alkylidcne transfer reagents were utilized, in principle this reaction is amenable to the asymmetric synthesis of oxetanes. 

In the above cases, an optically active reducing agent or catalyst interacts with a prochiral substrate. Asymmetric reduction of ketones has also been achieved with an achiral reducing agent, if the ketone is complexed to an optically active transition metal Lewis acid. ... 

There are other stereochemical aspects to the reduction of aldehydes and ketones. If there is a chiral center to the carbonyl group, even an achiral reducing agent can give more of one diastereomer than of the other. Such diastereoselective reductions have been carried out with considerable success. In most such cases Cram s rule (p. 147) is followed, but exceptions are known. ... 

In 2008, these authors reported a new strategy to attach chiral trans-l-arenesulfonylamino-2-isoborneolsulfonylaminocyclohexane to an achiral Frechet dendron (polyether having a repeated 3,5-dioxybenzyl structure) by a radical approach.The dendrimers obtained were successfully used in the enantioselective nucleophilic alkylation and arylation of ketones, providing... 

Condensation of /V-benzylhydroxylamine with various aldehydes and ketones in CH2CI2 in the presence of anhydrous magnesium sulfate has made it possible to carry out successful syntheses of a great number of chiral and achiral sugar-containing N-benzylnitrones (partly presented in Table 2.3) (191-208). 

Addition of ketene silyl acetals to aldehydes and ketones is also mediated by achiral palladium(ll) acetate-diphosphine complexes (Equation (109)).46S,46Sa Although the precise mechanism is still unclear, high catalytic activity may be ascribed to the intermediacy of palladium enolates. 

Besides the above-mentioned catalytic asymmetric hydrogenation method for preparing fluorine-containing compounds, other reactions such as asymmetric reduction of achiral fluorine-containing ketones are also feasible methods for preparing chiral fluorinated compounds. For example, the oxazabor-olidine system, which has been discussed in Chapter 6, can also be employed in the catalytic reduction of trifluoromethyl ketones. Scheme 8 40 depicts some examples.85... 

The enantioselective addition of a nucleophile to a carbonyl group is one of the most versatile methods for C C bond formation, and this reaction is discussed in Chapter 2. Trifluoromethylation of aldehyde or achiral ketone via addition of fluorinated reagents is another means of access to fluorinated compounds. Trifluoromethyl trimethylsilane [(CF SiCFs] has been used by Pra-kash et al.87 as an efficient reagent for the trifluoromethylation of carbonyl compounds. Reaction of aldehydes or ketones with trifluoromethyltrime-thylsilane can be facilitated by tetrabutyl ammonium fluoride (TBAF). In 1994, Iseki et al.88 found that chiral quaternary ammonium fluoride 117a or 117b facilitated the above reaction in an asymmetric manner (Scheme 8-42). 

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