For the last few tutorials, we have been discussing olefination reactions.
A rather unique and intriguing approach to olefins is the Ramberg-Bäcklund reaction, described
for the first time by Swedish chemist Ludwig Ramberg and his student Birger Bäcklund in 1940.
The reaction starts with alpha-halo sulfones, where X is most commonly chlorine or bromine,
and it induces extrusion of SO2 using a strong base. The product is an olefin, usually a mixture
of E and Z isomers, unless the sulfone is cyclic. Although this reaction may appear rather bizarre
in comparison to other, more linear olefin syntheses, it has been used rather frequently.
Its advantages are that alpha-halo sulfones are available through a variety of methods,
as well as the fact that highly substituted olefins can be made, and especially strained
ones, which would be more problematic to synthesize through an intermolecular process.
The mechanism of the reaction is rather straightforward. The first step is the formation
of a carbanion through the agency of the base. Keep in mind that the sulfone group is highly
electron-withdrawing and capable of stabilizing a negative charge on the adjacent carbon,
a little bit like a carbonyl. Thus, common bases like hydroxide or tert-butoxide ions
can form the carbanion. Once formed, the carbanion finds a leaving group in the same molecule in the
form of the halogen just two atoms away. Thus, an SN2-like intramolecular reaction follows,
with formation of a strained three-membered ring. A three-membered ring with two carbons and a
sulfur is called a thiirane. Since the sulfur is completely oxidized,
we called this intermediate thiirane dioxide. These rings have a tendency to fragment.
The reaction of extrusion of SO2 is an example of a cheletropic reaction. We have introduced
pericyclic reactions in previous tutorials, and a cheletropic reaction is a subset within pericyclic
reactions. In the most classical example that we have discussed at great length, the Diels-Alder
reaction, two new bonds are made simultaneously between two different sets of carbon pairs, so
four carbons are involved in the formation of new sigma bonds. Of course, in the retro-Diels-Alder,
two bonds are being broken between two different pairs of carbons, which is the precise opposite.
In a cheletropic reaction, on the other hand, two bonds are being formed or broken to the same atom.
In this case the sulfur loses two S-C bonds in one step. This reaction is concerted,
and therefore whatever the stereochemistry we had in the thiirane dioxide,
that will be retained through to the olefin. Of course, it is not trivial to make pure
E or Z 1,2-disubstituted thiirane dioxides. Simple alpha-halo sulfones yield a mixture
in which the Z isomer predominates, for reasons which are not fully understood.
E-olefins are accessible usually if excess base is used, because the thiirane dioxide
can equilibrate to the more stable E isomer, and fragments stereospecifically to the E-olefin.
In terms of the starting material, there are many methods for making the required
alpha-halo sulfone. The most common one is alpha-halogenation of a sulfide
with N-chlorosuccinimide, followed by oxidation of the alpha-chloro sulfide with a peracid.
Another involves the alpha-chlorination of an alpha-lithiosulfone, but there are many others.
Given the lack of complete stereoselectivity of the reaction, it is often used in cyclic systems,
where the Z-geometry of the double bond is ensured by the excessive strain of
the hypothetical E-olefin. Two examples are shown here. The yields are sometimes modest to fair, but
some of the targets are challenging. For example, the synthesis of cyclobutenes is very difficult,
and few olefin syntheses can match the success of the Ramberg-Bäcklund approach in this case.
There are many modifications of the Ramberg-Bäcklund reaction, in which a wide
variety of leaving groups are used. An example is the epoxy-Ramberg-Bäcklund reaction, in which the
leaving group is an epoxide. This leads to allylic alcohols, often in very good E selectivity.
Due to its versatility, the Ramberg-Bäcklund olefin synthesis continues to find widespread
use in synthesis, and 80 years after its discovery it is still receiving new creative applications.