q A conjugated system refers to a system of pi electrons which consists of three or more 2pz AO’s on directly connected atoms. The resulting pi MO’s are then delocalized over three or more atoms.
q A conjugated diene is a molecule which contains two alkene linkages which are in conjugation, giving a four atom (also 4 AO) delocalized system.
q Simple example of a conjugated system is 1,3-butadiene, in which the two pi bonds are directly connected so as to allow continuous overlap over the entire system of four carbon atoms.
q Dienes which are not conjugated dienes are exemplified by 1,2-propadiene (allene) and 1,5-pentadiene. In the latter, the two alkene linkages are separated by a saturated carbon atom, so that the pi overlap is not continuous. In the former, the two pi bonds are perpendicular and do not interact or delocalize. But 1,3-pentadiene is a conjugate diene.
Nomenclature. The suffix “diene” is used to describe a molecule having two “ene” linkages. A single number is used to designate the starting position of each double bond, e.g. as shown below. Note that when naming a substance as a diene, the numbering system of the parent chain begins at the end of the chain closes to one of the double bonds.
Conformations of Conjugated Dienes.
q In order to have a conjugated system of AO’s, in which all of the 2p AO’s are parallel (e.g., all 2pz), all 4 of the carbons of the diene system must be coplanar, as we will see further in a moment.
q This means that there are only two ground state conformations of such a conjugated diene. One is called s-trans and the other s-cis.
q The cis or trans designation is based upon the relationship around the central, formally single C-C bond.
q The s-trans conformation is more thermodynamically stable because the s-cis conformation has a steric repulsion between the two inside hydrogens.
q However, both conformations are found at least to some extent. We will see that although the s-trans conformation is preponderant, the s-cis conformation is extremely important in some reactions.
q It should also be noted that in some cyclic systems, this inside repulsion is not present, and the molecule is rigidly compelled to have the s-cis conformation (no other stable conformation exists). In other cyclic cases, the s-trans conformation may be the only one available; i.e., there is 0% s-cis.
3. [2 pts] Using the above drawings, explain why these planar conformations are strongly favored over other, nonplanar, conformations. Show any relevant overlaps by means of orbital depictions.
Only in the planar conformations are the 2p AO’s at C2 and C3 parallel, so as to give maximum overlap and resonance stabilization. (See drawing above for orbital overlaps)
4. [1 pts]Name one type of effect would normally tend to disfavor the planar forms. Torsional effects.
5. [1 pts] Which one of the two planar forms is the more stable? Explain, using a structural illustration. The s-trans-conformation is the more stable one because of the inside H/H steric repulsion in the s-cis conformation.
q Note that one or both of the ene linkages may have the capability of existing as either the cis or trans isomer. In such a case, the locant must be preceded by a cis or trans or E/Z specification.
q When a terminal carbon of the conjugated system has a cis or Z substituent (anything other than H), the s-cis conformation is essentially unpopulated, because it is too high in energy.
q In both cases shown above, the s-trans conformation is predominant, but in the first case it is the exclusive conformer.
q Since the four electrons of the two double bonds are delocalized over a four atom conjugated system, we would expect that this pi system is more stable than the sum of two alkene double bonds. This is the case, although the stabilization is relatively small (perhaps less than 8 kcal/mol) because the second resonance structure is relatively higher in energy than the first one (one less bond; charge separation).
q Nevertheless, this resonance makes it relatively difficult to rotate around the central (C2-C3) double bond, because at the 90o dihedral angle shown below, all traces of resonance stabilization are lost, and the diene linkages are independent (not conjugated). Rotation occurs, but requires about 8 kcal/mol, a larger energy than required for rotation around typical C-C single bonds.
q Interestingly, two products are formed, in one of which HBr has in effect added to the 1 and 4 positions (the terminal positions) of the diene, with both of the original double bonds being broken and replaced by one which has shifted to the central carbons of the original diene. This is the first product shown above: trans-4-bromo-2-butene (also the cis isomer is formed in small amounts).
q In effect the proton has added to C1 and the bromide ion to the C4 position. This kind of product is said to derive from conjugate addition to the diene.
q In the other product (3-bromo-1-butene), a proton has added to C1 and a bromide ion to C2. This is a more or less normal 1,2 addition to an alkene double bond. The other double bond remains unaffected.
q The formation of two products is the result of the circumstance that the intermediate carbocation (generically, an allylic type carbocation) is a conjugated system in which the electrons are delocalized over 3 atoms, and the positive charge over the two terminal atoms of the allylic conjugated system.
q The nucleophile can react at either site of positive charge, giving one or the other of the two products.
Allylic Resonance Stabilization. Allylic resonance stabilization is large, because in the parent allyl cation there are two equivalent resonance structures. In other derivatives of the allyl carbocation, the structures may not be exactly equal in energy but are close enough to give similarly large resonance stabilizations. In the parent allyl cation, there is a half unit of positive charge on C1 and also the same amount on C3, but none on C2. We can say that there is extensive carbocation character at both of these terminal carbons, so a nucleophile can react equally readily at either position (but not at C2).
q In the case of an unsymmetrical allylic carbocation, the two resonance structures are not equal in energy, and the real structure, while intermediate, will more closely resemble the structure of lower energy.
q In the addition to 1,3-butadiene, such an unsymmetrical allylic cation is formed.
q The first structure drawn above is of lower energy than the second canonical structure, because the first is a secondary carbocation canonical structure, while the second is a primary carbocation canonical structure.
q The real structure (resonance hybride) more closely resembles the lower energy structure, which has a secondary carbocation center.
q Therefore, the resonance hybrid has more carbocation character at the secondary than at the primary carbon.
q The bromide ion therefore reacts preferentially (more rapidly) at the site of higher positive charge density. That is, at the secondary carbon, to give:
q However, the rates of reaction at the two sites are not too different, so that the second product is also formed in competition with the above product, by reaction at the primary carbon. This product is the conjugate addition product.
q This is kinetic control (or, rate control). The two products are formed in 80% and #0% amounts when the reaction is carried out at low temperature. Under these conditions, the products, once formed, do not equilibrate with each other, so that the observed product mixture represents the ratio in which they were originally formed.
q When the very same reaction is carried out at room temperature, the same products are formed, but the product ratio is significantly changed. Under these conditions, the conjugate addition product (shown below) is the major product (about 80%) and the 1,2-addition product is the minor product (about 20%).
q It is not because the reaction of bromide ion with the allylic carbocation has suddenly changed its preference for reacting at the secondary site, but because at room temperature these two products are equilibrating to give the thermodynamically more stable product in excess.
q The reason the conjugate (1,4) addition product is thermodynamically more stable is that it has a disubstituted alkene moiety, while the 1,2 addition product is only monosubstituted.
q The mechanism by which the two bromides equilibrate is given below and simply involves the reformation of the allylic carbocation/bromide ion pair.
Suppose two products, A and B, are formed in a certain reaction and product A is the major product. You want to know whether this product mixture is kinetically controlled or thermodynamically controlled. How could you test whether the product mixture is kinetically controlled (therefore requiring an analysis in terms of Competing Transition States to explain the preference for one product or the other) or thermodynamically controlled (thereby requiring an analysis of the relative stabilities of the two products).
q We could, e.g., obtain pure samples of A and B.
q Subject each individually pure isomer to the exact reaction conditions, including temperature, solvent, reaction time, etc.
q If A remains pure A, without isomerizing, and B remains pure B, after this reaction time, the product mixture was kinetically controlled. Essentially, this experiment shows that both products are stable under the reaction conditions, once formed, and do not rearrange into the other.
q On the ther hand, if pure A and pure B both rearrange to the same mixture of A and B as obtained in the original reaction, the product mixture is thermodynamically controlled.
One of the most useful reactions in synthetic organic chemistry is the Diels-Alder reaction, which consists of the reaction of a conjugated diene (specifically in its s-cis conformation) with an alkene (preferably an electron deficient alkene).
q The Diels-Alder reaction is especially important in organic synthesis for two main reasons. First, it accomplishes the formation of two carbon carbon bonds. Secondly, it enables one to construct a cyclic, six-membered ring system. Both of these aspects allow one to accomplish a dramatic increase in molecular complexity for the purpose of synthesizing complex molecules.
q Consider the prototype (simplest) Diels-Alder cycloaddition reaction between 1,3-butadiene and ethane, shown below.
q This reaction involves breaking three pi bonds and forming one new pi bond plus two new sigma C-C bonds. There is a net conversion of 2 pi bonds to two sigma bonds, so this is highly favorable.
q Recall that converting two molecules into one is entropically unfavorable, but the large enthalpic preference for sigma bonds is dominant.
q In the context of a Diels-Alder reaction, the alkene is referred to as the dienophile.
q The reaction mechanism is a concerted one, with all bonds being made and broken in a concerted way.
q The TS model for this reaction is developed below, using resonance theory, and R and P-like structures.
q Characterization: The TS has a cyclic 6e conjugated system. Four pi electrons come from the conjugated diene system and two from the alkene pi bond.
q Since 6e cyclic conjugated systems are especially favorable (Huckel Rule), this is a relatively favorable TS. [Not that is is an energy minimum, but the energy maximum is lowered considerably by the stability of the pi electron system.
q Such transition states can be called “aromatic TS’s”.
q Note that, since ethene must bond simultaneously to Carbons 1 and 4 of the diene, the s-cis conformation of the diene is absolutely required. The terminal atoms of the s-trans conformer are much two far apart to be bridged by a single ethene unit. Although the equilibrium mixture contains only abut 2% of the cis conformer, the equilibrium is re-established rapidly, so that the supply of the needed conformer is continuously and rapidly being restored.
q Any diene which cannot adopt the s-cis conformation for some reason (as we have previously noted), cannot undergo the Diels-Alder reaction. Dienes which exist only in the cis conformation are especially apt at undergoing the Diels-Alder reaction.
q A more representative AO model of the cyclic TS is given below:
Hypothetical Reactions Which Would Have to Occur via an Antiaromatic TS.
q The reaction between two ethene units to give a cyclobutane is thermodynamically more difficult than the Diels-Alder reaction because of the ring strain present in the four-membered ring.
q However, it is also much, much less favorable kinetically because the TS is a cyclic system of 4 electrons, which is especially unfavorable. Such TS’s can be called antiaromatic TS’s.
q Although examples of such reactions are known, they typically require powerfully forcing conditions and, importantly, when they are forced to occur they do not occur via a concerted pathway, so that they avoid the unstable 4e system. [One bond is formed at a time, in a radical mechanism]
Diels-Alder Reactions with Electron Deficient Dienophiles.
For reasons which we will not delve into, ethene itself and other simple alkenes are not the best dienophiles for Diels-Alder reactions. However, alkenes which have electron withdrawing substituents are much better. They react under much milder conditions ( sometimes at RT) and in better yield. Ester functions are among those which strongly accelerate the Diels-Alder reaction.
q The equation below illustrates the reactions of a pair cis/trans isomers containing two ester functions in the dienophile with an especially reactive cyclic diene, which exists exclusively in the s-cis conformation. The trans isomer of the dienophile is called dimethyl fumarate; the cis isomer is dimethyl maleate.
q We especially want to note the reaction stereochemistry. The cis dienophile reacts to give two products, both of which have the ester functions cis to one another, i.e., the stereochemistry present in the original dienophile (cis) is completely retained in the products. In the same way, the trans dienophile isomer gives a single product, which has the ester functions trans to one another. In both instances, the stereochemical relationships of the esters to one another in the reactant are 100% retained in the product.
q This signifies that the addition to the dienophile (an alkene) has occurred with syn stereospecificity. Recall that syn stereospecific reactions are typically associated with concerted mechanisms. The observed reaction stereochemistry is fully consistent with the postulated concerted mechanism. Similar results have been observed for a wide variety of Diels-Alder reactions, which are virtually always syn stereospecific.
q If the reaction had been stepwise, forming an intermediate diradical or other intermediate, it would be expected that both dienophile isomers would have formed a mixture of all of the three products.
q In the reaction of dimethyl maleate with 1,3-cyclopentadiene, the first isomer is strongly predominant. The ester functions in this predominant isomer are described as having the endo configuration, which the ester functions in the minor isomer are described as having the exo configuration. These two isomers are more specifically diastereoisomers.
q Typically, Diels-Alder reactions have a preference for placing substituents in the endo configuration. [We will not pursue the subject of why this is, at present]