The document provides an in-depth overview of group transfer reactions, outlining their classification, mechanisms, and key examples such as ene reactions, diimide reductions, and various eliminations. It discusses the concerted nature of these reactions, the role of frontier orbitals, and factors influencing reactivity and selectivity. Important concepts include the Woodward-Hoffmann rules and the thermal versus Lewis acid-catalyzed pathways for these pericyclic processes.

1. Dr. Harish Chopra
Professor
Department of Chemistry
SLIET, LONGOWAL

2. The group transfer reactions are pericyclic processes where
one or more groups of atoms are transferred from
one molecule to another in a concerted process. Unlike other
pericylic reaction classes, group transfer reactions do not have
a specific conversion of pi bonds into sigma bonds or vice
versa. Like all pericyclic reactions, they must obey
the Woodward–Hoffmann rules. The most common group
transfer reactions are:
 ene Reactions and its variants like Conia-ene and metallo-
ene reactions
 Reduction of alkenes and alkynes with diimides
 syn β-elimination of xanthate esters, amine oxides,
selenoxides, and sulphoxides.

3. The ene reaction (also known as the Alder-ene reaction) was
discovered by Kurt Alder in 1943 is a chemical reaction
between an alkene with an allylic hydrogen (the ene) and
a compound containing a multiple bond (the enophile), in
order to form a new σ-bond with migration of the ene double
bond and 1,5 hydrogen shift. The product is a substituted alkene
with the double bond shifted to the allylic position.
H
Y
X Y
X H
ENE
Alkene
Alkyne
Arene
Allene
C-Heteroatom
ENOPHILE
C=C
C=O
C=N
C=S
O=O
N=N
C C

4. ENES are π-bonded molecules that contain at least one
active hydrogen atom at the allylic, propargylic, or α-
position.
The common ene components include:
olefinic, acetylenic, allenic, aromatic, cyclopropyl, and
carbon-hetero bonds.
Strained enes and fused small ring systems undergo ene
reactions at much lower temperatures.
In addition, ene components containing C=O, C=N and
C=S bonds have been reported, but such cases are rare.

5. ENOPHILES are π-bonded molecules which have electron-
withdrawing substituents that lower significantly
the LUMO of the π-bond.
The common enophiles contain:
 Carbon-carbon multiple bonds (olefins, acetylenes,
benzynes),
 Carbon-hetero multiple bonds (C=O in the case of
carbonyl-ene reactions, C=N, C=S, C≡P),
 Hetero-hetero multiple bonds (N=N, O=O, Si=Si,
N=O, S=O),
 Cumulene systems (N=S=O, N=S=N, C=C=O, C=C=S,
SO2)
 Charged π systems (C=N+, C=S+, C≡O+, C≡N+).

6. CONCERTED PATHWAY
The reaction can be designated as [σ2s + π2s + π2s] in the
Woodward-Hoffmann notation. The main frontier-orbital
interaction occurring in an ene reaction is between
the HOMO of the ene and the LUMO of the
enophile. Concerted, all-carbon-ene reactions have, in
general, a high activation barrier. However, the activation
barrier DECREASES along the enophiles in the order
H2C=CH2 > H2C=NH > H2C=CH(COOCH3) > H2C=O >
H2C=PH > H2C=S, as the reaction becomes more and more
asynchronous and/or the activation strain decreases.

7. RADICAL MECHANISM
When a concerted mechanism is geometrically unfavorable, a
thermal ene reaction can occur through a stepwise biradical
pathway. Another possibility is a free-radical process,
if radical initiators are present in the reaction mixture. E.g.,
the ene reaction of cyclopentene with diethyl azo-
dicarboxylate can be catalyzed by free-radical initiators.

8. The success of an ene reaction is largely determined by the
steric accessibility of the ene allylic hydrogen. In general,
methyl and methylene H atoms are abstracted much more
easily than methine hydrogens.
THERMAL ENE REACTIONS: The order of reactivity for the
abstracted H atom is primary> secondary> tertiary,
irrespective of the thermodynamic stability of the internal
olefin product.
LEWIS-ACID PROMOTED ENE REACTIONS: The pair
enophile/Lewis acid employed determines largely the relative
ease of abstraction of methyl vs. methylene hydrogens.
The major regioisomeric product will come from the
transition state in which transient charges are best stabilized
by the orientation of the ene and enophile.

9. The DIASTEREOSELECTIVITY with respect to the
newly created chiral centres leads to the preferential
formation of an ENDO PRODUCT, but steric effects can
easily modify this preference .

10. Intramolecular ene reactions
are usually more facile and show
high regio- and stereoselectivities
than intermolecular ene
reactions. Based on the position of
attachment of the tether
connecting the ene and enophile,
the intramolecular ene reactions
have been classified as types I, II,
III, and IV reaction. In these type
of reactions, the orbital overlap
between the ene and enophile is
largely controlled by the geometry
of the approach of components. .
R
1
CH2
R
2
H
R
1
R
2
H
R1
= CH2
, O ; R2
= H, COOEt
TYPE - IV
HX
Y
X
YH
X
Y
H
YH
X
X
Y
H
X
YH
X=Y : RC=R1
R2
, HC=O , HC=NR
TYPE - I
TYPE - II
TYPE - III

11. Thermal ene reactions showed several DRAWBACKS,
such as very high temperatures and the formation of side
reactions in some cases like proton-catalyzed olefin
polymerization or isomerization reactions. Since
enophiles are electron-deficient, it was reasoned that
their complexation with Lewis acids accelerates the ene
reaction.

12. In the case of directed carbonyl-ene reactions, high
levels of regio- and stereo-selectivity have been observed
upon addition of a Lewis acid, which can be explained
through chair-like transition states. Some of these
reactions can run at very low temperatures and still
afford very good yields of a single regioisomer.

13. The Conia-Ene reaction is an intra-molecular, thermal
or Lewis acid-catalysed reaction of unsaturated
carbonyl compounds to yield cyclised products.
MECHANISM: The mechanism involves enolization of
unsaturated carbonyl compound followed by a concerted
1,5-hydrogen shift to give the cyclic product.

14. Reactions that generate
cyclopentane and cyclohexane
derivatives in good yields
normally proceed at 350°C, but
medium-sized rings need
higher temperatures and the
yield is considerably lower.
Conia Ene Reaction
Retro-ene Reaction
For acetylenic substrates, double bond migration often occurs
to favour a higher degree of substitution. No such migration is
observed when a terminal methyl group stabilizes the exo-
double bond, or if the reaction is conducted at lower
temperatures – (E.g., β-diketone as substrate).

15. The metallo-ene reaction involves a six-member
cyclic transition state that brings an allylic species and an
alkene species together to undergo a rearrangement. For
metallo-ene reaction, a metal ion (Mg, Zn, Pd, Ni etc.) acts
as the migrating group instead of a hydrogen atom in the
classic ene reaction.
CLASSIFICATION:
Intramolecular: These are of
TWO types [ Type I ; Type II]
Intermolecular.
Carbon linkage connects the
alkene fragment to the terminal
carbon of the allyl fragment
The alkene fragment is connected to the
internal carbon of the allyl fragment

16. REGIO-SELECTIVITY:
For Type II reaction, two
possible products can be
expected if the two termini of
the allyl piece are
unsymmetrically substituted,
depending on which carbon
engages in the formation of a
new sigma bond. It has been
found that the more
substituted terminus of the
allyl part will participate in
new sigma bond formation
regardless of the length of the
internal carbon linkage.

17. STEREO-SELECTIVITY:
Since a six-member cyclic
transition state is involved in
metallo-ene reaction, high level of
stereoselectivity can be expected
due to the conservation of orbital
symmetry. Indeed, it has been
found that the cis product is
formed as the predominant
product kinetically, while the
trans product could also be
obtained selectively under
thermodynamic conditions.

18. DIIMIDE is converted into dinitrogen with reduction (net
addition of dihydrogen) of the unsaturated functionality in the
presence of unpolarized alkenes, alkynes or allenes.
Diimide formation is the rate-limiting step of the process, and
a concerted mechanism involving cis-diimide has been
proposed. This reduction represents a metal-free alternative
to catalytic hydrogenation reductions, and does not lead
to the cleavage of sensitive O–O and N–O bonds.

19. MECHANISM:
Diimide reductions result in the syn addition of
dihydrogen to alkenes and alkynes. This observation has
led to the proposal that the mechanism involves
concerted hydrogen transfer from cis-diimide to the
substrate. The cis isomer is the less stable of the two;
however, acid catalysis may speed up equilibration of
the trans and cis isomers.
+

20. The peroxides, are not affected by the
conditions of diimide reductions
Selective reduction of less
substituted double bonds
Allenes are reduced to the more highly
substituted alkenes in low yields
Iodoalkynes are an exception to the rule
that alkenes cannot be synthesized
from alkynes. Diimide reduction of
iodoalkynes gives cis-iodoalkenes

21. The Ei mechanism (Elimination Internal/Intra-
molecular), also known as a thermal syn
elimination or a pericyclic syn elimination, is a
special type of elimination reaction in which
two vicinal substituents on an alkane framework
leave simultaneously via a cyclic transition state to
form an alkene in a syn elimination. This type of
elimination is unique because it is thermally activated
and does not require additional reagents unlike regular
eliminations which require an acid or base, or would in
many cases involve charged intermediates. This reaction
mechanism is often found in pyrolysis.

22. Depending on the compound, elimination may take
place through a four, five, or six-membered
transition state.
Four Membered
Transition State
Five Membered
Transition State
Six Membered
Transition State

23. There are many factors that affect the product
composition of Ei reactions, but typically they follow
HOFMANN’S RULE and lose a β-hydrogen from the least
substituted position, giving the alkene that is less
substituted (the opposite of Zaitsev's rule). Some factors
affecting product composition include steric
effects, conjugation, and stability of the forming alkene.
For acyclic substrates, the Z-isomer is typically the minor
product due to the destabilizing gauche interaction in the
transition state, but the selectivity is not usually high.

24. The pyrolysis of N,N-dimethyl-2-phenylcyclohexylamine-
N-oxide shows how conformational effects and the
stability of the transition state affect product
composition for cyclic substrates. In the trans isomer,
there are two cis-β-hydrogens that can eliminate. The
major product is the alkene that is in conjugation with
the phenyl ring, presumably due to the stabilizing effect
on the transition state. In the cis isomer, there is only
one cis-B-hydrogen that can eliminate, giving the non-
conjugated regioisomer as the major product.

25. ESTER PYROLYSIS: The pyrolytic decomposition
of esters is an example of a thermal syn elimination. At
temperatures above 400°C, esters containing β-hydrogens
can eliminate a carboxylic acid through a 6-membered
transition state, to give an alkene.

26. SULFOXIDE ELIMINATION: β-hydroxy phenyl-
sulfoxides were found to undergo thermal elimination
through a 5-membered cyclic transition state, yielding β-
keto esters and methyl ketones after tautomerization.

27. CHUGAEV ELIMINATION: The Chugaev elimination is
the pyrolysis of a xanthate ester, resulting in
an olefin. To form the xanthate ester, an alcohol reacts
with carbon disulfide in the presence of a base, resulting
in a metal xanthate which is trapped with an alkylating
agent (typically methyl iodide). The olefin is formed
through the thermal syn elimination of the β-hydrogen
and xanthate ester. The reaction is irreversible because
the resulting by-products, CS2 and CH3SH, are very
stable.

28. BURGESS DEHYDRATION REACTION: is synthesis of
alkenes from the dehydration of secondary and tertiary
alcohols through a sulfamate ester intermediate. The
reaction conditions used are typically very mild, giving it
some advantage over other dehydration methods for
sensitive substrates. The reaction was applied during the
first total synthesis of taxol to generate an exo-methylene
group on the C ring.

29. SELENOXIDE ELIMINATION: The selenoxide
elimination has been used in converting aldehydes,
ketones and esters to their α,β-unsaturated derivatives.
The mechanism involved is a thermal syn elimination
through a 5-membered cyclic transition state. Selenoxides
are preferred for this type of transformation over
sulfoxides due to their increased reactivity toward β-
elimination, in some cases allowing the elimination to
take place at room temperature .

30. COPE ELIMINATION: The Cope elimination (Cope
reaction) is the elimination of a tertiary amine oxide to yield
an alkene and a hydroxylamine through an Ei mechanism.
Cyclic amine oxides (5, 7-10-membered nitrogen containing
rings) can also undergo internal syn elimination to yield
acyclic hydroxylamines containing terminal alkenes .

31. Resources /Further Reading
1. Modern Methods of Organic Synthesis, W.
Carruthers; Cambridge Press UK
2. Pericyclic Reactions, Ian Fleming, Oxford University
Press, UK
3. NPTEL Lectures and Videos
4. https://en.wikipedia.org/wiki/Ene_reaction
5. https://www.organic-chemistry.org/namedreactions/
alder-ene-reaction.shtm
6. Other internet sources

32. Thank You