Stereochemistry carbonyl groups

A very important relationship between stereochemistry and reactivity arises in the case of reaction at an 5 carbon adjacent to a chiral center. Using nucleophilic addition to the carbonyl group as an example, it can be seen that two diastereomeric products are possible. The stereoselectivity and predictability of such reactions are important in controlling stereochemistry in synthesis. 

A number of groups have criticized the ideas of Dauben and Noyce, especially the concept of PDC. Kamernitzsky and Akhrem, " in a thorough survey of the stereochemistry of addition reactions to carbonyl groups, accepted the existence of SAC but not of PDC. They point out that the reactions involve low energies of activation (10-13 kcal/mole) and suggest that differences in stereochemistry involve differences in entropies of activation. The effect favoring the equatorial alcohols is attributed to an electrostatic or polar factor (see also ref. 189) which may be determined by a difference in the electrostatic fields on the upper and lower sides of the carbonyl double bond, connected, for example, with the uncompensated dipole moments of the C—H bonds. The way this polar effect is supposed to influence the attack of the hydride is not made clear. 

Peroxyacids transfer an oxygen atom to the alkene with syn stereochemistry—both C-0 bonds form on the same face of the double bond-through a one-step mechanism without intermediates. The oxygen atom farthest from the carbonyl group is the one transferred. 

Steps 6-8 of Figure 29.5 Reduction and Dehydration The ketone carbonyl group in acetoacetyl ACP is next reduced to the alcohol /S-hydroxybutyry] ACP by yS-keto thioester reductase and NADPH, a reducing coenzyme closely related to NADH. R Stereochemistry results at the newly formed chirality center in the /3-hydroxy thioester product. (Note that the systematic name of a butyryl group is biitanoyl.)... 

It is worth pointing out that the stereochemistry of intermediate 147 at C-9 and C-10 is inconsequential since both positions will eventually bear trigonal carbonyl groups in the final product. The synthetic problem is thus significantly simplified by virtue of the fact that any or all C9-C10 diol stereoisomers could be utilized. A particularly attractive means for the construction of the C9-C10 bond and the requisite C8-C10 functionality in 147 is revealed by the disconnection shown in Scheme 41. It was anticipated that the venerable intermolecular aldol reaction could be relied upon to accomplish the union of aldehyde 150 and methyl glycolate (151) through a bond between carbons 9 and 10. 

On the other hand, in the presence of Lewis acids such as titanium(lV) chloride or eerium(TIT) chloride, the (S)-e s-conformer predominates via chelation of the two carbonyl groups and a reversed stereochemistry of the addition reaction is observed1 °. 

If there is a carbonyl group in the branch (or a terminal COOH or its equivalent), its position (assigned lowest number when stereochemistry is being considered) is used to define the configurational prefix (see examples 1 and 3 in Chart V). Use of the R,S system is generally preferred, as less open to misinterpretation. 

The product did indeed have the same structure as (34) but the stereochemistry was still unknown. If a carbonyl group is added (FGA) to give ketone (39), disconnection via standard Grignard routes to available optically active (40) is possible. 

In the discussion of the stereochemistry of aldol and Mukaiyama reactions, the most important factors in determining the syn or anti diastereoselectivity were identified as the nature of the TS (cyclic, open, or chelated) and the configuration (E or Z) of the enolate. If either the aldehyde or enolate is chiral, an additional factor enters the picture. The aldehyde or enolate then has two nonidentical faces and the stereochemical outcome will depend on facial selectivity. In principle, this applies to any stereocenter in the molecule, but the strongest and most studied effects are those of a- and (3-substituents. If the aldehyde is chiral, particularly when the stereogenic center is adjacent to the carbonyl group, the competition between the two diastereotopic faces of the carbonyl group determines the stereochemical outcome of the reaction. 

The stereochemistry of the reaction depends on the Lewis acid. Protic acids favor retention of configuration, as does TMSOTf. Most metal halides give mixtures of inversion and retention, but A1(CH3)3 gives dominant inversion.142 Inversion is suggestive of direct carbonyl group participation. 

Most workers try to explain the final stereochemistry of the OH group on the basis of adsorption. That is, the mode of adsorption determines the resulting stereochemistry, assuming that the addition of hydrogen occurs cis from the surface up to the bottom of the adsorbed carbonyl group. Most investigators seem to assume that the carbonyl is protonated in acidic media and the mode of adsorption of this species is different from the unprotonated species (in neutral and basic media). 

Figures 40-43 compare the position of the bridging carbonyl group in each diastereomeric pair and the effects of stereochemistry on their force-area curves at 25°C. It is clear that there is a large effect of stereochemistry on the energetics of compression and expansion for a wide variety of ketodiacid surfactants all of the ketodiadds in this study showed a dependence of the shapes of their IT/A isotherms on their stereochemistry. Several facts are striking. In every case there is a sharp differentiation between the behavior of films cast from meso- and ( )-isomers. The isotherms for the...

Synthesis of the common intermediate C (4), and its further conversion to 2 and 3 is illustrated in Scheme 7-3. Two racemic compounds, ( )-7 and ( + )-10, are prepared from readily available starting materials 5 and 8, respectively (Scheme 7-2). Coupling of 7 and 10 gives a mixture of diastereomers 11. An intramolecular aldol reaction of 11 catalyzed by D-proline yields diastereomers 12 and 13 in equal molar ratios (about 36% ee for each diastereomer). Compound 12, the desired ketone, is converted to 14, which is further purified by crystallization to give the compound in the desired stereochemistry in sterically pure form. Reduction of the ketone carbonyl group and subsequent methoxy... 

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