The Carbonyl Ene Reactions

DAMIETTA UNIVERSITY

CHEM-405: PERICYCLIC REACTIONS

LECTURE 10

Dr Ali El-Agamey 1 LEARNING OUTCOMES LECTURE 10

 (1) Sigmatropic rearrangements -Acid catalysis - [2,3] sigmatropic rearrangements

 (2) Ene Reactions

 (3) The Carbonyl Ene Reactions

 (4) Retro-Ene Reactions

2 Sigmatropic Rearrangements Acid catalysis

 Some types of sigmatropic shifts were reported to occur solely as acid-catalyzed processes. The best known example is benzidine rearrangements.1

 Homework: Write the mechanism of the previous reaction? 3 Sigmatropic Rearrangements Acid catalysis

 Other examples : The addition of Lewis acid catalysts, e.g. BCl3, lowers the temperatures necessary for Claisen rearrangements of allyl phenyl ethers from about 200 oC to below RT.

4 Sigmatropic Rearrangements Acid catalysis

 [1,5] shifts of benzyl groups in cyclohexadienones, which requires temperatures above 150 oC in the absence of catalysis, proceed at RT when catalyzed by solutions of sulfuric acid in acetic acid.

 Homework: Write the mechanism of the previous reaction? 5 [m,n] Sigmatropic Rearrangements

[2,3] sigmatropic rearrangements:  The [2,3]-sigmatropic rearrangement is a thermal isomerization reaction involving six electrons and a five-membered cyclic TS.1

 The [2,3] sigmatropic rearrangement of alloxycarbanions is known as the Wittig rearrangement.2

6 [m,n] Sigmatropic Rearrangements

[2,3] sigmatropic rearrangements:

 The starting material is a benzyl allyl ether and undergoes [2,3]-sigmatropic rearrangement to make a new C–C sigma bond at the expense of a C–O sigma bond—a bad bargain this as the C–O bond is stronger.1  The balance is tilted by the greater stability of the oxyanion in the product than of the carbanion in the starting material. The new bond has a 2,3 relationship to the old and the TS is a ﬁve-membered ring.1

7 [m,n] Sigmatropic Rearrangements

[2,3] sigmatropic rearrangements:

 The dominant FMO interaction in the TS of the [2,3] sigmatropic rearrangement is between Ψ2 of both components. The reaction proceeds suprafacially with respect to both components.1,2

Ψ3 Ψ2 Ψ2 Ψ1 Ψ1

8 [m,n] Sigmatropic Rearrangements

[2,3] sigmatropic rearrangements:

 Reaction of an allylic alcohol with PhSCl gives an unstable sulfenate ester that rearranges on heating to an allylic sulfoxide by a [2,3]-sigmatropic rearrangement involving both O and S.1

9 [m,n] Sigmatropic Rearrangements

[2,3] sigmatropic rearrangements:

 The key to identifying a [2,3] sigmatropic rearrangement is that an allylic group migrates from a heteroatom to an adjacent atom (which may be C or another heteroatom).1

10 Questions

 Homework: Write the structure of A and the mechanism of the following reaction?

11 Pericyclic Rearrangements Ene Reactions1

 The ene reaction shares some characteristics with both the Diels–Alder reaction and the [1,5] sigmatropic rearrangement.

 Like the Diels–Alder reaction: -The ene reaction is always a six-electron reaction -It has one four-electron component, the ene, and one two-electron component, the enophile. The two-electron component is a pi bond. The four-electron component consists of a pi bond and an allylic 12 sigma bond. Pericyclic Rearrangements Ene Reactions1

 The ene reaction shares some characteristics with both the Diels–Alder reaction and the [1,5] sigmatropic rearrangement.

 The atom at the terminus of the sigma bond is usually H; the other five atoms involved in the ene reaction may be C or heteroatoms.  Because the ene reaction involves six electrons, it is suprafacial with respect to all components.

14 Ene Reactions1

 The suprafacial reactivity of the enophile means that the two new bonds to the enophile form to the same face. When the enophile is an alkyne, the two new sigma bonds in the product are cis to one another.

15 Pericyclic Rearrangements Ene Reactions1

16 Ene Reactions1

 Ene reactions involving five C atoms and one H usually require very high temperatures (>200 °C) to proceed. The reaction occurs at much lower temperature if the H atom is replaced with a metal atom in the metalla-ene reaction. The metal may be Mg, Pd, or another metal.

17 Ene Reactions1

 As with Diels-Alder reactions, electron-withdrawing groups on the enophile and electron-donating groups on the ene speed up the reaction.  The regiochemistry with an unsymmetrical enophile 6.5 is such that the major product 6.6 has the alkene carbon attacking the β–position of the enone system and the hydrogen atom going to the α–position.

18 Ene Reactions1

 Lewis acid catalysis 6.7 → 6.8 has made the reaction much more amenable.1

 For most ordinary alkenes and enophiles, Lewis acid catalysis to make the enophile more electrophilic, or an intramolecular reaction (or both!), is necessary for an efﬁcient ene reaction.2

19 Pericyclic Rearrangements The Carbonyl Ene Reactions1  Carbonyl groups, particularly in aldehydes, can act as “enophiles” in ene reactions. In these reactions, allylic hydrogens of alkenes are transferred to carbonyl oxygens, and the carbon atoms of the carbonyls react with the double bonds, converting the carbonyl groups to alcohols.1

20 The Carbonyl Ene Reactions1

 The important interaction is between the HOMO of the ene system and the LUMO of the carbonyl group—and a Lewis-acid catalyst can lower the energy of the LUMO still further.

 If there is a choice, the more electrophilic carbonyl group (the one with the lower LUMO) reacts.

i The Carbonyl Ene Reactions1

22 The Carbonyl Ene Reactions1  Ene reactions with carbonyl groups can be catalyzed by dimethylaluminum chloride as in Eq. 29a.

23 Retro-Ene Reactions1

 A number of synthetically useful elimination reactions proceed thermally, with no base or acid required. These elimination reactions proceed through a concerted retro-ene mechanism. (The mechanism is sometimes called Ei.) The thermal elimination of acetic acid from alkyl acetates and the elimination of RSCOSH from alkyl xanthates (the Chugaev reaction) are retro-ene reactions.

 Retro-ene reactions are partly driven by the gain in entropy. (Entropic contributions to ∆G° are much more important at the high temperatures required for ene reactions.) 24 Ene Reactions1  Conclusions:

 Ene reactions make one new sigma bond at the expense of one pi bond, like electrocyclic reactions, but they are fairly easy to distinguish from electrocyclic reactions otherwise. Look for allylic transposition of a double bond and transfer of an allylic H atom.  In a retro-ene reaction, a nonallylic H is transferred to an allylic position and one new pi bond at the expense of one sigma bond.

25 Retro-Ene Reactions1

 Homework: Write the mechanism of the previous reaction and the structure of any other by-products? 26 The Carbonyl Ene Reactions1

 One carbonyl ene reaction is of commercial importance as it is part of a process for the production of menthol used to give a peppermint smell and taste to many products. This is an intramolecular ene reaction.

 Homework: Write the mechanism of the first step reaction? 27 The Carbonyl Ene Reactions1

 Homework: Write the mechanism of the previous reaction?