Regioselectivity of E1 Reactions

E1 reactions are regioselective and just like in the E2 mechanism,

the Zaitsev product predominates due to the higher stability of the
more substituted alkene:

Notice that in the reaction above, water was used as a weak base and
the E1 elimination was favored by heating the reaction. If heat is not
applied, weak base/nucleophile favors the SN1 reaction:
On the other hand, using a strong base favors the E2 mechanism. One
advantage of the E2 mechanism is that the regiochemical outcome of
reaction can be controlled by choosing a strong unhindered or a
sterically hindered base:
Contrary to this, the E1 mechanism favors Zaitsev’s product and we
cannot change this regioselectivity even if a sterically hindered alcohol is
used as a weak base.

One possibility of forming the Hoffman product in an E1 and E2

reactions is the resonance-stabilization of the less-substituted alkene:
Rearrangements in E1 Reactions
Even though Zaitsev’s product is the major regioisomer in E1 reaction,
you need to always keep in mind the possibility of rearrangements for
any unimolecular mechanism going through a carbocation intermediate:
The carbocation formed in the first step undergoes a 1,2-hydride shift to
form a more stable tertiary carbocation which is then attacked by the
base.
In general, remember, E2 and SN2 reactions are more useful because of a
better control on the regio- and stereochemistry of the reaction since
they do not form carbocations which may undergo rearrangements.

Elimination Reactions
Zaitsev’s Rule – Regioselectivity of E2
Elimination Reactions
Zaitsev’s Rule
Suppose you have this alkyl halide and need to determine all the
products of an E2 reaction when it is treated with a strong base such as
sodium ethoxide.

Remember in E2 reactions, we’re first going to identify all the β

hydrogens and draw the products of elimination based on each set of
these β hydrogens. In this case, we have β hydrogens on the right side
of the leaving group (Br) and on the two methyl groups.

So, one product is going to be the alkene where the double bond is in
the middle:
On the other hand, the hydrogens on each methyl group give the same
alkene since they are equivalent as confirmed by the symmetry plane
and the structure of the alkenes:

What is interesting is it turns out that only one of these two alkenes is
the major product. The ratio is about 80:20 in favor of the more
substituted alkene:

The reason for this is the stability of the alkenes. Remember the more
substituted alkenes are more stable. Adding groups on the double bond
increases the stability of the alkene:
Now, checking our products, we can see that it is a mixture of a
trisubstituted alkene with a disubstituted alkene and the trisubstituted
alkene is the major product of this elimination reaction:

So, the more substituted alkene is the major product of E2

elimination because of its higher stability.
Russian chemist Alexander Zaitsev was the first who observed this
pattern and the reaction is named after him. The Zaitsev’s rule states
that in an elimination reaction, the more substituted alkene is the major
product.

Hoffman Product
The Zaitsev’s rule is not always followed in E2 reactions.
For example, if we treat the same alkyl halide with a sterically
hindered base (large/bulky) such as for example the potassium tert-
butoxide, we see the opposite trend. The less substituted alkene is
the major product despite the fact that it is less stable.

This is known as the Hoffman’s rule which states that if we treat the
alkyl halide (or other suitable substrates) with a strong sterically
hindered base, the major product is going to be the less substituted
alkene.
The reason for this is that it is easier for the bulky base to access the
protons that are not hindered by other carbons.

And because the protons of the methyl groups are more accessible than
the protons of the CH2 group, the less substituted alkene forms faster
and is the major product in this case.
So, to summarize, if you need the more substituted alkene, use a
sterically non-hindered base.
If the lees substituted alkene is the target, then use a sterically
hindered base.
The most common sterically hindered and non-hindered bases are
shown above.

These two rules are very applicable in organic synthesis because they
allow controlling what alkene we want to synthesize. And these alkenes
can further be used for preparing other products.

Regioselectivity of E2 Reaction
The Zaitsev’s and Hoffman’s rules demonstrate the principle
of regioselectivity in elimination reactions.
Regioselective means that the reaction selectively produces one
regioisomer as the major product. The two alkenes are regioisomers
since the double bonds are in different regions. That’s one way to
remember this but also notice that the alkenes are constitutional
isomers. So regioselectivity is the preferred formation of one
constitutional isomer.