Conformation of carbonyl compounds

The preferred conformations of carbonyl compounds, like 1-alkenes, are eclipsed rather than bisected, as shown below for ethanal and propanal. The barrier for methyl group rotation in ethanal is 1.17kcal/mol. Detailed analysis has indicated that small adjustments in molecular geometry, including a-bond lengthening, must be taken into account to quantitatively analyze the barrier. The total barrier can be dissected into nuclear-nuclear, electron-electron, nuclear-electron, and kinetic energy (At), as described in Topic 1.3 for ethane. MP2/6-311+G (Mf,2p) calculations lead to the contributions tabulated below. The total barrier found by this computational approach is very close to the experimental value. Contributions to the ethanal energy barrier in kcal/mol are shown below. 

The preferred conformations of carbonyl compounds, like 1-alkenes, are eclipsed rather than bisected. Interestingly, it is the alkyl group, rather than the hydrogen, that is eclipsed with the carbonyl group. For propionaldehyde, conformation E has been determined by microwave spectroscopy to be 0.9 kcal/mol more stable than F... 

Simple allyl alkali metal compounds have only a small capability for discriminating between diastereotopic faces of carbonyl compounds. Although a matter of simple diastereoselectivity, this can be concluded from the reaction of conformationally locked 4-/erf-butylcyclohexanone... 

Deprotonation of carbonyl compounds by chiral amide bases followed by trapping with silylating agents or aldehydes has become a common method for de-symmetrizing prochiral and conformationally locked 4-substituted cyclohexanones and bicyclic ketones. The literature through 1997 has been reviewed [45]. 

Oxidation of carbonyl compounds was interpreted by Malaprade as conforming to the a-glycol type by the assumption that the reaction proceeds through the hydrated form of the carbonyl group, >C(OH)2. This hypothesis is useful in interpreting the results of the oxidation of some complex compounds, intermediates of the type RCHOHCHO being oxidized like the a-glycols. 

We have seen that LDA forms enolates of carbonyl compounds, carboxylic esters, and carboxylic amides via cychc and six-membered transition states with the chair conformation. This geometry of the transition state for enoiate formation has consequences if a stereogenic C=C double bond is generated. 

Here, in particular, the Cotton effect (CE) of the (n, n ) band of carbonyl compounds (around 280 nm) was of central importance For the establishment of the relationship between molecular structure (conformation) and the (n, n ) CE several rules with various theoretical backgrounds (and various levels of sophistication) are available ... 

While this approach has been applied primarily to nucleophilic reactions of carbonyl compounds, it can also be used to determine the primary direction of hydrogenation since adsorption on a catalyst surface is preferred from the less hindered side of the carbonyl group. The synthesis of dl ephedrine (20) was accomplished by the hydrogenation of the amino ketone, 19, one enantiomer of which is depicted in Eqn. 14.17.5 xhe hydrogen bond to the carbonyl oxygen helps fix the conformation with hydrogenation taking place from the side of the... 

The chiral phosphonates 31a,e, possessing optically active BINOL as an auxiliary, also demonstrated their ability as asymmetric inducers in the dissymmetrization of carbonyl compounds. In order to achieve both high enantioselectivity and good chemical yield, addition of zinc chloride was quite effective in these transformations [8]. It is known that bicydo[3.3.0]octane derivatives usually adopt either W-, S-, or V-shaped conformations, and the observed stereochemistry of the alkene 92a was best explained by considering an initial approach of the nucleophile to the W-shaped bicyclo[3.3.0]octanone in the direction in which steric interaction between the reagent and the substrate is minimized. 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

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