Stereochemistry ketones, solvent effect

None of these mechanistic proposals is sufficiently general to use to rationalize all of the stereochemical data observed on the hydrogenation of a,[3-unsaturated ketones. By a judicious combination of segments of each of these proposals along with the Horiuti-Polanyi mechanism (2), it is possible, however, to develop a uniform mechanistic rationale that can be useful in determining the effect of solvent on product stereochemistry. In addition, the influence of hydrogen availability, the type and quantity of catalyst, and the nature of other substituents on the reacting molecule on the product isomer distribution can also be more readily understood. 

Rules 1 and 2 may be accepted as a generalization based primarily on the results obtained over platinum catalysts. However, there have been known many examples of the exception to this rule,153 since the stereochemistry of hydrogenation may be influenced by many factors, such as the solvent, the temperature, the hydrogen pressure, and the basic or acidic impurity associated with catalyst preparation, as well as the activity of the catalyst, and since the effects of these factors may differ sensitively with the catalyst employed and by the structure of the ketone hydrogenated. 

The ease and the stereochemical course of hydrogenation of a,p-unsaturated ketones are particularly influenced by the nature of the solvent and the acidity or basicity of the reaction mixture. Some efforts have been made to rationalize the effect of the various parameters on the relative proportions of 1,2- to 1,4-addition, as well as on the stereochemistry of reduction. For example, the product distribution in -octalone hydrogenation in neutral media is related to the polarity of the solvent if the solvents are divided into aprotic and protic groups. The relative amount of cis- -decalone decreases steadily with decreasing dielectric constant in aprotic solvents, and increases with dielectric constant in protic solvents, as exemplified in Scheme 21 (dielectric constants of the solvents are indicated in parentheses). Similar results were observed in the hydrogenation of cholestenone and of testosterone. In polar aprotic solvents 1,4-addition predominates, whereas in a nonpolar aprotic solvent hydrogenation occurs mainly in the 1,2-addition mode. 

Similarly, for alkenes derived from saturated methyl ketones the regioselectivity is determined by starting hydrazone ( ) (Z) ratios in some solvents but not in others. Thus 2-octanone trisylhydrazone, which is an inseparable 85 15 mixture of ( )- and (Z)-isomers, gives an 85 15 ratio of l-octene 2-octene if vinyllithium formation is carried out in THF, but a 98 2 ratio of the same products when 10% TMEDA-hexane is the solvent. The implication of this observation is that in THF the regioselectivity is determined by azomethine stereochemistry but that in TMEDA-hexane it is not. Note, however, that in this case a iyn-directing effect does not occur in TMEDA, whereas in the previous example it does. Thus more than 10 years after it was asserted that a detailed explanation of the observed solvent dependencies...await further studies owing to the complexities of the reaction system. , little headway has been made. 

Bromohydration, Bromolactonization, and Other Additions to C=C. The preferred conditions for the bromohydration of afkenes involves the portionwise addition of solid or predissolved NBS (recrystallized) to a solution of the alkene in 50-75% aqueous DME, THF, or f-butanol at 0 °C. The formation of dibromide and a-bromo ketone byproducts can be minimized by using recrystallized NBS. High selectivity for Markovrukov addition and anti stereochemistry results from attack of the bromonium ion intermediate by water. Aqueous DMSO can also be used as the solvent however, since DMSO is readily oxidized under the reaction conditions, significant amounts of the dibromide byproduct may be produced. In the bromohydration of polyalkenic compounds, high selectivity is regularly achieved for attack of the most electron-rich double bond (eq 20). With famesol acetate, squalene, and other polyisoprenes, choice of the optimum proportion of water is used to effect the selective bromohydration at the terminal double bond (eq 21), and the two-step sequence shown is often the method of choice for the preparation of the corresponding epoxides. ... 

Factor (c) appears to depend on complex interacting effects and deserves detailed discussion. When the proton nmr spectrum of a polar substance, typically but not always a ketone (83), dissolved in an aromatic hydrocarbon is compared with that obtained in a saturated hydrocarbon, large shifts of up to 1.5 ppm are frequently observed. These shifts are either upfield or downfield, depending on the stereochemistry of each proton-bearing group (84). This general behavior, known as ASIS (aromatic solvent-induced shifts), has been reviewed by Foster and Lazio (85). 

Since the products with acyclic olefins are aldehydes and ketones, the reaction conditions must be altered to form saturated products whose stereochemistry can be determined. The basic assumption is that the change in reaction conditions does not change the mode of addition. The first study with a monoolefin, which is outlined in Scheme 7, used 1,2-dideuteroethene as substrate and CO to trap the intermediate to form a lactone whose stereochemistry could be determined. This lactone could only have arisen from anti addition to the initial rr-complex, 1. Several facts concerning this study need to be emphasized. First, the solvent is CH3CN rather than water, which could have a profound effect on mechanism. Second, in this system the Pd(ll) almost certainly exists as dimers and it had been shown previously that dimeric species in wet acetic acid underwent anti hydroxypalladation. Third, the system is chloride starved so PdCl/, which is reactive in water, cannot be formed. Finally, the reactive species is almost certainly not 1 but rather Pd(ll)-carbonyls since CO bonds very strongly to Pd(ll). The CO coordination... 

Studies of solvent and multiplicity effects on the efficiency and stereochemistry of cyclobutanol formation from 1-adamantylacetone are reported. Quantum-yield measurements indicate that efficiency is about three times greater in methanol than in benzene. The cyclobutanol product ratio (339) (340) is 1,0—1.8 1 from Ty of the ketone and ca. 5 1 for the excited singlet state reaction. The stereoselectivity of the excited singlet state reaction accords with the picture in which the short-lived 1,4-biradical undergoes rehybridization with preferential rotation and closure, for steric reasons, to yield (339) rather than (340). 

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