Carbonyl compounds unsaturated, conformation

There are some cases where both types of photocycloaddition take place. For example, cinnamaldehyde and crotonaldehyde yield, upon irradiation with 2-methyl-2-butene, both the oxetane and the cyclobutane products.26 In marked contrast, mesityl oxide, as similar as it would appear to be to crotonaldehyde (Table I), is stable to irradiation in the presence of both isobutylene and isopropanol.37,74 These differences in reactivity of a,/9-unsaturated carbonyl compounds have been attributed to conformational (that is, s-cis or s-trans) differences.74... 

An empirical increment system permits prediction of charge distribution in a,/ -unsaturated carbonyl compounds, assuming additivity of electronic effects and neglecting the conformational dependence of carbon-13 chemical shifts [290]. Moreover, carbonyl and alkenyl carbon shifts of a, /3-unsaturatcd ketones may be used to differentiate between planar and twisted conjugated systems, as shown in Table 4.29 [291] and outlined for phenones in Section 3.1.3.8. 

Lithium cuprates react with a, p-unsaturated carbonyl compounds by 1,4-addition. The diastereomers A and B will be the expected products whose relative proportions will depend upon the precise reaction conditions. On the assumption that stabilisation of the starting material in the conformation shown occurs through complexation with metal ions a preferential attack of the silyl group will take place from the side nearest the reader, i.e. from the least hindered side, and hence a preponderance of A in the product mixture will be expected. It was actually observed that not only the yield but also the diastereomeric ratio was strongly dependent upon the amount of dimethylsulfane in the reaction mixture (or complexed to the cuprate). In the presence of 0.75 mol% dimethylsulfane with respect to the added cuprate, the ratio of A to B is dramatically increased (diastereomeric ratio 97 3), whilst in the absence of dimethylsulfane it is approximately 1 1 [7]. 

The structure of the organometallic and of the a. -unsaturated carbonyl compound, as well as the experimental conditions, play a crucial role in controlling the regiochemistry of the reaction. In general, enals possess a higher tendency to react at their C-1 site than enones and ene esters and increasing the substitution around the C-1 (or the C-3) site favors the reaction at the C-3 (or at the C-1) site of the enones. Furthermore, the compounds which possess either a privileged cisoid conformation, or the lowest half-wave potential of electrolytic reduction, or the lower level of their LUMO orbitals, react predominantly at the C-3 site (PhCH=CHC(=0)Ph PhCH—iCHC(=0)Me =< MeCH—CHC(—0)Ph MeCH—CHC(==0)Me). 

Common error alert a,fi-Unsaturated carbonyl compounds are not particularly acidic at the a-carbon atoms. The C=0 tt bond prefers to be in conjugation and coplanar with the C=C tt bond, so the C-H cr orbital does not overlap with the C=0 tt orbital. An unfavorable conformational change is required before deprotonation of the a-carbon can even begin. Note that the low acidity of a,(3-unsatu-rated carbonyl compounds as compared with their saturated congeners contradicts the general rule that C(sp2) is more acidic than C(sp3), all else being equal. 

For the general aspects of the conformation (s-cis vs. s-trans) of unsaturated carbonyl compounds, see Stereochemistry of Organic Compounds, Eliel, E.L., Wilen,... 

The predominant conformation of a,P-unsaturated carbonyl compounds (aldehydes, ketones, esters) can vary when Lewis adds are coordinated to the carbonyl group, ft has been experimentally shown that the s-trans conformer of acrolein is more stable than the s-ds conformer, in the absence of any Lewis add. The two conformers are of almost equal stability in the case of acrylic acid or methyl acrylate 83] (Figure L21). The barriers between these conformers are low (4-9 kcal mol ). Interconversion is rapid, and the Curtin-Hammett principle ( 1.3) can be applied. 

Enones. Simple a,/3-unsaturated carbonyl compounds also show thermodynamically a preference for the s-trans conformation. Acrolein has a smaller difference in energy than butadiene between the s-trans 2.134a and s-cis 2.134b conformations of 7 kJ mol-1 (1.7 kcal mol ), but a similar barrier to rotation of... 

The case of a,6-unsaturated carbonyl compounds is analogous to that of 1,3-dienes, in that conjugation favors coplanarity of the C=C—C=0 system. The rotamers that are important are the s-trans and s-cis conformations. Microwave data indicate that the s-trans form is the only conformation present in detectable amounts in 2-propenal (acrolein). ... 

The 1,4-adducts are readily obtained when a S-unsaturated carbonyl compounds are treated with methylthio(trimethyl)silane (52). The reaction conforms to Saville s rule as the product formation involves [s s] S C and [h hl O Si interactions. 

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