1,4-Addition reaction thermodynamic control

The 1,4-addition is thermodynamically controlled. This reaction forms the thermodynamic product. At higher temperatures, more molecules have sufficient energy to cross the second barrier in the reverse direction and establish an equilibrium. The equilibrium allows the less stable 1,2-addition product to convert to the more stable 1,4-addition product. 

Addition of hydrogen halide (1 mol) to a diene (1 mol) is a method of greater preparative value. This reaction is illustrated by the addition of hydrogen bromide to isoprene (Expt 5.64) the overall 1,4-addition process (thermodynamically controlled), as opposed to the 1,2-addition (kinetically controlled), predominates under the conditions specified. 

The 1,4-addition (or conjugate addition) of resonance-stabilized carbanions. The Michael Addition is thermodynamically controlled the reaction donors are active methylenes such as malonates and nitroalkanes, and the acceptors are activated olefins such as a,P-unsaturated carbonyl compounds. 

As the OH addition reactions are controlled by kinetics rather than by thermodynamics, the primary OH adduct radicals are not necessarily the thermodynamically most stable radicals. Thus, a number of rearrangement and water elimination reactions take place. For example, Thy60H is more stable than ThySOH by 42 kj mol but Thy60H is formed preferentially. As has been shown in the case of 1,3-dimethyluracil in a detailed product study, acid catalysis converts the kinetically favored C6 OH adduct into the... 

Heats of reaction Heats of reaction can be obtained as differences between the beats of formation of the products and those of the starting materials of a reaction. In EROS, heats of reaction arc calculated on the basis of an additivity scheme as presented in Section 7.1. With such an evaluation, reactions under thermodynamic control can be selected preferentially (Figure 10.3-10). 

The composition of the products of reactions involving intermediates formed by metaHation depends on whether the measured composition results from kinetic control or from thermodynamic control. Thus the addition of diborane to 2-butene initially yields tri-j iAbutylboraneTri-j -butylborane. If heated and allowed to react further, this product isomerizes about 93% to the tributylborane, the product initially obtained from 1-butene (15). Similar effects are observed during hydroformylation reactions however, interpretation is more compHcated because the relative rates of isomerization and of carbonylation of the reaction intermediate depend on temperature and on hydrogen and carbon monoxide pressures (16). 

Dimethylborane+propene C2 and 2-propyldimethyl borane depict the regioisomeric transition state and addition product. Calculate the energies of these species relative to those of the alternative transition state and product. Given these energy differences, and the experimental observation that this addition is almost completely selective for the anti-Markovnikov product, does it appear that this reaction is under kinetic or thermodynamic control Explain. 

Obtain the energies of the possible products that might result from HCl addition to isoprene (isoprene+HCt), and rank them from most to least stable. Which product(s) would form if the reaction were controlled by thermodynamics, i.e., product energy ... 

Specific alterations of the relative reactivity due to hydrogen bonding in the transition state or to a cyclic transition state or to electrostatic attraction in quaternary compounds or protonated azines are included below (cf. also Sections II, B, 3 II, B, 5 II, C and II, F). A-Protonation is often reflected in an increase in JS and therefore the relative reactivity can vary with the significance of JS in controlling the reaction rate. Variation can also result from rate determination by the second stage of the SjjAr2 mechanism or from the intervention of thermodynamic control of product formation. Variation in the rate and in the reactivity pattern of polyazanaph-thalenes will result when nucleophilic substitution [Eq. (10)] occurs only on a covalent adduct (408) of the substrate rather than on its aromatic form (400). This covalent addition is prevented by any 4-... 

Entries 7, 8, and 10 describe so-called Idnetically controlled syntheses starting from activated substrates such as ethyl esters or lactose. In two reaction systems it was possible to demonstrate that ionic liquids can also be useful in a thermodynamically controlled synthesis starting with the single components (Entry 11) [39]. In both cases, as with the results presented in entry 6, the ionic liquids were used with addition of less than 1 % water, necessary to maintain the enzyme activity. The yields observed were similar or better than those obtained with conventional organic solvents. 

The electrophilic addition of HBr to 1,3-butadiene is a good example of how a change in experimental conditions can change the product of a reaction. The concept of thermodynamic control versus kinetic control is a useful one that we can sometimes take advantage of in the laboratory. 

Conjugated dienes undergo several reactions not observed for nonconjugated dienes. One is the 1,4-addition of electrophiles. When a conjugated diene is treated with an electrophile such as HCl, 1,2- and 1,4-addition products are formed. Both are formed from the same resonance-stabilized allylic carbocation intermediate and are produced in varying amounts depending on the reaction conditions. The L,2 adduct is usually formed faster and is said to be the product of kinetic control. The 1,4 adduct is usually more stable and is said to be the product of thermodynamic control. 

Both primary and secondary amines add to a /S-unsaturated aldehydes and ketones to yield /3-amino aldehydes and ketones rather than the alternative imines. Under typical reaction conditions, both modes of addition occur rapidly. But because the reactions are reversible, they generally proceed with thermodynamic control rather than kinetic control (Section 14.3), so the more stable conjugate addition product is often obtained to the complete exclusion of the less stable direct addition product. 

The basc-eatalyzcd addition of nilroalkancs to carbonyl compounds is a reversible reaction and proceeds under thermodynamic control. Thus low (R, R )/(R, S ) selectivities arc observed in the classical Henry reaction which leads to the silylated x-nitro alcohols 2. 

Lithiated areneacetonitriles react with a,/i-unsaturated ketones at low temperatures using short reaction times to give both 1,2- and 1,4-adducts. The 1,2-addition is reversible and under thermodynamic control (higher temperatures and longer reaction times) only the 1,4-adducts, i.e., <5-oxonitriles, arc obtained. When lithiated arylacetonitrile is added to 2-substituted 2-cy-cloalkenones in THF or in THF/HMPA mixtures at — 70-0°C, followed by protonation or alkylation under kinetically controlled conditions, predominantly cis- or fnms-2,3-disubstitut-ed cycloalkanones respectively, are obtained. 

An interesting approach to zr n.v-2,3-disubstituted cyeloalkanones is offered by auxiliary controlled intramolecular Michael additions. The diastereoselectivity depends on the chiral alcohol used193> l94. When the borneol derivative 7 was used as substrate, a single diastereomer of 8 resulted when the reaction was performed at 25 "C under thermodynamic control with a catalytic amount of sodium hydride in benzene. 

In most cases, more 1,4- than 1,2-addition product is obtained. This may be a consequence of thermodynamic control of products, as against kinetic. In most cases, under the reaction conditions, 15 is converted to a mixture of 15 and 16, which is richer in 16. That is, either isomer gives the same mixture of both, which contains more 16. It was found that at low temperatures, butadiene and HCl gave only 20-25% 1,4 adduct, while at high temperatures, where attainment of equilibrium is more likely, the mixture contained 75% 1,4 product. 1,2 Addition predominated over 1,4 in the reaction between DCl and 1,3-pentadiene, where the intermediate was the symmetrical (except for the D label) HjCHC—CH—CHCH2D. Ion pairs were invoked to explain this result, since a free ion would be expected to be attacked by Cl equally well at both positions, except for the very small isotope effect. 

Evans Jr. and coworkers reported a similar olefination reaction employing spirooxyphosphoranes of type 66. Upon treatment with a strong base (LiHMDS) and subsequent addition of benzaldehyde, the reaction proceeded to form anionic P(VI) intermediates (67,6 -106 to -116 ppm) that decomposed at room temperature to form the corresponding olefins and spiropentaoxyphosphoranes [ 105]. The stereoselectivity (E Z ratio) of the double bond-forming reaction depended upon the conditions evidence indicated the possibility of kinetic or thermodynamic control (Scheme 21). 

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