Rearrangements:

In a rearrangement reaction a group moves from one atom to another in the same molecule.1 Most
are migrations from an atom to an adjacent one (called 1,2-shifts), but some are over longer
distances. The migrating group (W)

may move with its electron pair (these can be called nucleophilic or anionotropic rearrangements;
the migrating group can be regarded as a nucleophile), without its electron pair (electrophilic or
cationotropic rearrangements; in the case of migrating hydrogen, prototropic rearrangements), or
with just one electron (free-radical rearrangements). The atom A is called the migration origin and B
is the migration terminus. However, there are some rearrangements that do not lend themselves to
neat categorization in this manner. Among these are those with cyclic transition states (18-27–18-
36).
As we will see, nucleophilic 1,2-shifts are much more common than electrophilic or free-radical 1,2-
shifts. The reason for this can be seen by a consideration of the transition states (or in some cases
intermediates) involved. We represent the transition state or intermediate for all three cases by 1, in
which the two-electron
 A–W bond overlaps with the orbital on atom B, which contains zero, one, and two electrons, in the case of
nucleophilic, free-radical, and electrophilic migration, respectively. The overlap of these orbitals gives rise to
three new orbitals, which have an energy relationship similar to those on p. 72 (one bonding and two degenerate
antibonding orbitals). In a nucleophilic migration, where only two electrons are involved, both can go into the
bonding orbital and 1 is a low-energy transition state; but in a free-radical or electrophilic migration, there are,
respectively, three or four electrons that must be accommodated, and antibonding orbitals must be occupied. It
is not surprising therefore that, when 1,2-electrophilic or free-radical shifts are found, the migrating group W is
usually aryl or some other group that can accommodate the extra one or two electrons and thus effectively
remove them from the three-membered transition state or intermediate

MECHANISMS
Nucleophilic Rearrangements2:

Broadly speaking, such rearrangements consist of three steps, of which the actual migration is the second:
This process has been called the Whitmore 1,2-shift.3 Since the migrating group carries the electron pair with it, the
migration terminus B must be an atom with only six electrons in its outer shell (an open sextet). The first step therefore is
creation of a system with an open sextet. Such a system can arise in various ways, but two of these are the most
important:
1. Formation of a Carbocation. These can be formed in a number of ways (see p. 247), but one of the most common
methods when a rearrangement is desired is the acid treatment of an alcohol to give 2 from an intermediate
oxonium ion. These two steps are of course the same as the first two steps of the SN1cA or the E1 reactions of alcohols.

2. Formation of a Nitrene. The decomposition of acyl azides is one of several ways in which acyl nitrenes 3 are formed
(see p. 293). After the migration has taken place, the atom at the migration origin (A) must necessarily have an open
sextet. In the third step, this atom acquires an octet. In the case of carbocations, the most common third steps are
combinations with a nucleophile (rearrangement with substitution) and loss of Hþ (rearrangement with elimination).
Although we have presented this mechanism as taking place in three steps, and some reactions do take place in
this way, in many cases two or all three steps are simultaneous. For example, in the nitrene example above, as the
R migrates, an electron pair from the nitrogen moves into the C–N bond to give a stable isocyanate, 4.

In this example, the second and third steps are simultaneous. It is also possible for the second and third steps to be
simultaneous even when the ‘‘third’’ step involves more than just a simplemotion of a pair of electrons. Similarly,
there are many reactions in which the first two steps are simultaneous; that is, there is no actual formation of a
species, such as 2 or 3. In these instances, it may be said that
R assists in the removal of the leaving group, with migration of R and the removal of the leaving group taking place
simultaneously.Many investigations have been carried out in attempts to determine, in various reactions, whether
such intermediates as 2 or 3 actually form, or whether the steps are simultaneous (see, e.g., the discussions on pp.
1381, 1563), but the difference between the two possibilities is often subtle, and the question is not always easily
answered.4
In many reactions, there is no question about which group migrates. For example, in the Hofmann, Curtius, and similar
reactions there is only one possible migrating group in each molecule, and one can measure migratory aptitudes only by
comparing
the relative rearrangement rates of different compounds. In other instances, there are two or more potential migrating
groups, but which migrates is settled by the geometry of the molecule. The Beckmann rearrangement (18-17) provides
an example. As we have seen, only the group trans to the OH migrates. In compounds whose geometry is not restricted in this
manner, there still may be eclipsing effects (see p. 1502), so that the choice of migrating group is largely determined by
which group is in the right place in the most stable conformation of the molecule.31 However, in some reactions, especially
the Wagner–Meerwein (18-1) and the pinacol (18-2) rearrangements, the molecule may contain several groups that,
geometrically
at least, have approximately equal chances of migrating, and these reactions have often been used for the direct study of
relative migratory aptitudes. In the pinacol rearrangement, there is the additional question of which OH group leaves
and which does not, since a group can migrate only if the OH group on the other carbon is lost.
We deal with the second question first. To study this question, the best type of
substrate to use is one of the form

R2C CR′2
OH OH

since the only thing that determines migratory aptitude is which OH group comes off. Once the OH group is gone, the
migrating group is determined.
As might be expected, the OH that leaves is the onewhose loss gives rise to the more stable carbocation. Thus 1,1-
diphenylethanediol (19) gives diphenylacetaldehyde (20), not phenylacetophenone (21). Obviously, it
does not matter in this case whether phenyl has a greater
inherent migratory aptitude than hydrogen or not. Only the hydrogen can migrate because 22 is not formed. As we
know, carbocation stability is enhanced by
30 For

groups in the order aryl > alkyl > hydrogen, and this normally determines which side loses the OH group. However,
exceptions are known, and which group is lost may depend on the reaction conditions (e.g., see the reaction of
53, p. 1586).In order to answer the question about inherent migratory aptitudes, the obvious type of substrate to use (in
the pinacol rearrangement) is
RRC CRR
OH OH
, since the
same carbocation is formed no matter which OH leaves, and it would seem that
a direct comparison of the migratory tendencies of R and R0 is possible. On closer inspection, however,
Longer Nucleophilic Rearrangements:
The question as to whether a group can migrate with its electron pair from A to C in W–A–B–C or over longer distances has
been much debated. Although claims have been made that alkyl groups can migrate in this way, the evidence is that
such migration is extremely rare, if it occurs at all. One experiment that demonstrated this was the generation of the 3,3-
dimethyl-1-butyl cation Me3CCH2CH2
If 1,3-methyl migrations are possible, this cation would appear to be a favourable substrate, since such a migration would
convert a primary cation into the tertiary 2-methyl-2-pentyl cation Me2CCH2CH2CH3, while the only possible 1,2 migration
(of hydride) would give only a secondary cation. However, no products arising from the 2-methyl-2-pentyl cation were
found, the only rearranged products being those formed by the 1,2 hydride migration.43 1,3 Migration of bromine
has been reported.However, most of the debate over the possibility of 1,3 migrations has concerned
not methyl or bromine, but 1,3 hydride shifts.45 There is no doubt that apparent 1,3 hydride shifts take place (many
instances have been found), but the question is whether they are truly direct hydride shifts or whether they occur by
another

mechanism. There are at least two ways in which indirect 1,3-hydride shifts can take place: (1) by successive 1,2-shifts or (2)
through the intervention of protonated cyclopropanes (see p. 1565). A direct 1,3-shift would have the transition
state A, while the transition state for a 1,3-shift involving a protonated cyclopropane intermediate would resemble B. The
evidence is that most reported 1,3 hydride shifts are actually the result of successive 1,2 migrations,46 but that in some cases
small amounts of products cannot be accounted for in this way. For example, the reaction of 2-methyl-1-butanol with KOH and
bromoformgave a mixture of alkenes, nearly all of which could have arisen from simple
elimination or 1,2-shifts of hydride or alkyl. However, 1.2% of the product was 33
However, the same reaction applied to 2-methyl-2-butanol gave no 33, which demonstrated that 36 was not formed from 35.
The conclusion made was that 36 was formed directly from 34. This experiment does not answer the question
as to whether 36 was formed by a direct shift or through a protonated cyclopropane, but from other evidence48 it appears
that 1,3 hydride shifts that do not result from successive 1,2 migrations usually take place through protonated
cyclopropane intermediates (which, as we saw on p. 1565, account for only a small percentage of the product in any case).
However, there is evidence thatdirect 1,3 hydride shifts by way of A may take place in super acid solutions.49

However, there is evidence that direct 1,3 hydride shifts by way of A may take place in super acid solutions.49
Although direct nucleophilic rearrangements over distances >1,2 are rare (or perhaps nonexistent) when the migrating
atom or group must move along a chain, this is not so for a shift across a ring of 8–11 members. Many such transannular
rearrangements are known.50 Several examples are given on p. 223. This is the mechanism of one of these:51

It is noteworthy that the methyl group does not migrate in this system. It is generally true that alkyl groups do not undergo
transannular migration.52 In most cases, it is hydride that undergoes this type of migration, though a small amount of phenyl
migration has also been shown.53
Rearrangement is usually predominant in neopentyl and neophyl types of substrates, and with these types normal
nucleophilic substitution is difficult (normal elimination is of course impossible). Under SN2 conditions, substitution is
extremely slow;98 and under SN1 conditions, carbocations are formed that rapidly rearrange. However, free-radical
substitution, unaccompanied by rearrangement, can be carried out on neopentyl systems, though, as we have seen (p.
1574), neophyl systems undergo rearrangement as well as substitution.

An interesting application of this reaction is the conversion of tricyclic molecules to adamantane and its derivatives.
.It has been found that all tricyclic alkanes containing 10 carbons are converted to adamantane by treatment with a Lewis
acid, such as AlCl3. If the substrate contains >10 carbons, alkyl-substituted adamantanes are
produced. The IUPAC name for these reactions is Schleyer adamantization.Two examples are
The Pinacol Rearrangement
1/O-Hydro,3/hydroxy-(2/ ! 3/alkyl)-migro-elimination

When vic-diols (glycols) are treated with acids,123 they can be rearranged to give aldehydes or ketones, although elimination
without rearrangement can also be accomplished. This reaction is called the pinacol rearrangement; the reaction
gets its name from a prototype compound pinacol (Me2COHCOHMe2), which is rearranged to pinacolone (Me3CCOCH3).124 In
this type of reaction, reductioncan compete with rearrangement.125 The reaction has been accomplished many times, with
alkyl, aryl, hydrogen, and even ethoxycarbonyl (COOEt)126 as migrating
groups. In most cases, each carbon has at least one alkyl or aryl group, and the reaction is most often carried out with tri- and
tetrasubstituted glycols. As mentioned earlier, glycols in which the four R groups are not identical can give rise to more than
one product, depending on which group migrates (see p. 1568 for adiscussion of migratory aptitudes). A noncatalytic reaction
is possible in supercritical water.127
Stereodifferentiation is possible in this reaction.128 When TMSOTf was used to initiate the reaction, it was shown to be highly
regioselective.129 Mixtures are often produced, and which group preferentially migrates may depend on the reaction
conditions, as well as on the nature of the substrate. Thus the
action of cold, concentrated sulfuric acid on 53 produces mainly the ketone 54 (methyl migration), while treatment of 53
with acetic acid containing a trace of sulfuric acid gives mostly 55 (phenyl migration).130 If at least one R is hydrogen,
aldehydes can be produced as well as ketones. Generally, aldehyde formation is favored
by the use of mild conditions (lower temperatures, weaker acids), because under more drastic conditions the aldehydes
may be converted to ketones (18-4). Thereaction has been carried out in the solid state, by treating solid substrates with
HCl gas or with an organic solid acid.131

The mechanism involves a simple 1,2-shift. The ion 56 (where all four R groups are Me) has been trapped by the addition of
tetrahydrothiophene.132 It may seem odd that a migration takes place when the positive charge is already at a tertiary
position, but carbocations stabilized by an oxygen atom are even more stable than tertiary alkyl cations (p. 242). There is also
the driving force supplied by the fact that the new carbocation can immediately stabilize itself by losing a proton.
The Favorskii Rearrangement
2/Alkoxy-de-chloro(2/ ! 1/alkyl)-migro-substitution:

The reaction of a-halo ketones (chloro, bromo, or iodo) with alkoxide ions193
to give rearranged esters is called the Favorskii rearrangement.194 The use of
hydroxide ions or amines as bases leads to the free carboxylic acid (salt) or amide, respectively, instead of the ester. Cyclic a-
halo ketones give ring contraction, as in the conversion of 65–66

The reaction has also been carried out on a-hydroxy ketones195 and on a,b-epoxy ketones, which give b-hydroxy acids.196 The
fact that an epoxide gives a reaction analogous to a halide indicates that the oxygen and halogen are leaving groups in a
nucleophilic substitution step.

Through the years, the mechanism197 of the Favorskii rearrangement has been the subject of much investigation; at least
five different mechanisms have been proposed. However, the finding198 that 67 and 68 both give 69 (this behavior is
typical) shows that any mechanism where the halogen leaves and R1 takes its place is invalid, since in such a case 67
would be expected to give 69 (with PhCH2 migrating), but 68 should give PhCHMeCOOH (with CH3 migrating).
That is, in the case of 68, it was PhCH that migrated and not methyl. Another important result was determined by
radioactive labeling. 65, in which C-1 and C-2 were equally labeled with 14C, was converted to 66. The product was found
to contain 50% of the label on the carbonyl carbon, 25% on C-1, and 25% on C-2.1
The type of intermediate that best fits the circumstances is a cyclopropanone,201 and the mechanism (for the general case)
is formulated (replacing R1 of our former symbolism with CHR5R6, since it is obvious that for this mechanism an a hydrogen is
required on the non-halogenated side of the carbonyl):

The intermediate corresponding to 71 in the case of 65 is a symmetrical compound, and the three-membered ring can be
opened with equal probability on either side of the carbonyl, accounting for the results with 14C. In the general
case, 71 is not symmetrical and should open on the side that gives the more stable carbanion.202 This accounts for the fact
that 67 and 68 give the same product. The intermediate in both cases is 70, which always opens to give the
carbanion stabilized by resonance. The cyclopropanone intermediate (71) hasbeen isolated in the case where R2 ¼ R5 ¼ t-Bu
and R3 ¼ R6 ¼ H,203 and it

has also been trapped.204 Also, cyclopropanones synthesized by other methods have been shown to give Favorskii products on
treatment with NaOMe or other bases.205
 The mechanism discussed is in accord with all the facts when the halo ketone contains an a hydrogen on the
other side of the carbonyl group. However, ketones that do not have a hydrogen there also rearrange to give the
same type of product.
This is usually called the quasi-Favorskii rearrangement. An example is found inthe preparation of Demerol:

The quasi-Favorskii rearrangement obviously cannot take place by the cyclopropenone mechanism. The mechanism that is
generally accepted (called the semibenzilic mechanism207) is a base-catalyzed pinacol:

rearrangement-type mechanism similar to that of 18-6. This mechanism requires inversion at the migration terminus and
this has been found.208 It has been shown that even where there is an appropriately situated a hydrogen, the semibenzilic
mechanism may still operate.
The Hofmann Rearrangement:
Bis(hydrogen)-(2/ 1/N-alkyl)-migro-detachment (formation of isocyanate)

In the Hofmann rearrangement, an unsubstituted amide is treated with sodium hypobromite (or sodium hydroxide and
bromine, which is essentially the same thing) to give a primary amine that has one carbon fewer than the starting
amide.266 The actual product is the isocyanate, but this compound is seldom isolated 267 since it is usually hydrolyzed under the
reaction conditions. The R group may be alkyl or aryl, but if it is an alkyl group of more than about six or seven
carbons, low yields are obtained unless Br2 and NaOMe are used instead of Br2 and NaOH.268 Another modification uses
NBS/NaOMe.269 Under these conditions the product of addition to the isocyanate is the carbamate RNHCOOMe (16-8),
which is easily isolated or can be hydrolyzed to the amine. Side reactions when NaOH is the base are formation of ureas
RNHCONHR and acylureas RCONHCONHR by addition, respectively, of RNH2 and RCONH2 to RNCO (16-20). If
acylureas are desired, they can be made the main products by using only one-half of the usual quantities of Br2 and NaOH.
Another side product, but only from primary R, is the nitrile derived from oxidation of RNH2 (19-5). Imides react to give
amino acids, for example, phthalimide gives o-aminobenzoic acid. a-Hydroxy and a-halo amides give aldehydes and ketones
by way of the unstable a-hydroxy- ora-haloamines. However, a side product with an a-halo amide is a gem-dihalide.
Ureas analogously give hydrazines.
The mechanism follows the pattern outlined on p. 1606.
The first step is an example of 12-52 and intermediate N-halo amides (80) have been isolated. In the second step, 80
lose a proton to the base. Compound 80 is acidic because of the presence of two electron-withdrawing groups (acyl
and halo) on the nitrogen. It is possible that the third step is actually two steps: loss of bromide to form a nitrene,
followed by the actual migration, but most of theavailable evidence favors the concerted reaction.270
The Curtius Rearrangement:
Dinitrogen-(2/ ! 1/N-alkyl)-migro-detachment

The Curtius rearrangement involves the pyrolysis of acyl azides to yield isocyanates.279 The reaction gives good yields of
isocyanates, since no water is present to hydrolyze them to the amine. Of course, they can be subsequently
hydrolyzed, and indeed the reaction can be carried out in water or alcohol, in which case the products are amines, carbamates,
or acylureas, as in 18-13.280 This is a very general reaction and can be applied to almost any carboxylic acid:
aliphatic, aromatic, alicyclic, heterocyclic, unsaturated, and containing many functional groups. Acyl azides can be prepared as
in 10-43 or by treatment of acylhydrazines (hydrazides) with nitrous acid (analogous to 12-49). The Curtius
rearrangement is catalyzed by Lewis or protic acids, but these are usually not necessary for good results.

The mechanism is similar to that in 18-13 to give an isocyanate. Also note the exact analogy between this reaction and 18-8.
However, in this case, there is noevidence for a free nitrene and it is probable that the steps are concerted.281
The R groups may be alkyl, aryl, or hydrogen, though if hydrogen migrates, the product is the unstable R2CNH. The
mechanism is essentially the same as that of the Curtius rearrangement. However, in pyrolysis of tertiary alkyl
azides, there is evidence that free alkyl nitrenes are intermediates.283 The reactioncan also be carried out with acid catalysis,
in which case lower temperatures canbe used, though the acid may hydrolyze the imine (16-2). Cycloalkyl azides give
ring expansion:

Aryl azides also give ring expansion on heating, for example:

The O-acyl derivatives of hydroxamic acids286 give isocyanates when treated with bases or sometimes even just on heating,
in a reaction known as the Lossen rearrangement.287 The mechanism is similar to that of 18-13 and 18-14

In a similar reaction, aromatic acyl halides are converted to amines in one laboratory
step by treatment with hydroxylamine-O-sulfonic acid

A chiral Lossen rearrangement is known.

There are actually three reactions called by the name Schmidt reaction, involving the addition of hydrazoic acid to carboxylic
acids, aldehydes and ketones, and alcohols and alkenes.290 The most common is the reaction with carboxylic acids,
illustrated above.291 Sulfuric acid is the most common catalyst, but Lewis acids have also been used. Good results are
obtained for aliphatic R, especially for long chains. When R is aryl, the yields are variable, being best for sterically
hindered compounds like mesitoic acid. This method has the advantage over 18-13 and 18-14 in that there is just one
laboratory step from the acid to the amine, but conditions are more drastic.292 Under the acid conditions employed, the
isocyanate is virtually never isolated.

The reaction between a ketone and hydrazoic acid is a method for ‘‘insertion’’ of NH between the carbonyl group and one R
group, converting a ketone into an amide.

Either or both of the R groups may be aryl. In general, dialkyl ketones and cyclic ketones react more rapidly than alkyl aryl
ketones, and these more rapidly than diaryl ketones. The latter require sulfuric acid and do not react in concentrated
HCl, which is strong enough for dialkyl ketones. Dialkyl and cyclic ketones react sufficiently faster than diaryl or aryl alkyl
ketones or carboxylic acids or alcohols so that these functions may be present in the same molecule without interference.
Cyclic ketones give lactams:
With alkyl aryl ketones, it is the aryl group that generally migrates to the nitrogen, except when the alkyl group is bulky.295
The reaction has been applied to a few aldehydes, but rarely. With aldehydes the product is usually the nitrile (16-16).
Even with ketones, conversion to the nitrile is often a side reaction, especially with the type of ketone that gives 17-30. A
useful variation of the Schmidt reaction treats a cyclic ketone with an alkyl azide (RN3)296 in the presence of
TiCl4, generating a lactam.297 An intramolecular Schmidt reaction gives bicyclic amines by treatment of a cyclic alkene having
a pendant azidoalkyl group with Hg(ClO4)2, and then NaBH4.298 Another variation treats a silyl enol ether of a
cyclic ketone with TMSN3 and photolyzes the product with UV light to give a lactam.299 aAzido cyclic ketones rearrangement
to lactams under radical conditions (Bu3SnH/AIBN).300
Alcohols and alkenes react with HN3 to give alkyl azides,301 which in the course of reaction rearrange in the same way as
discussed in reaction 18-14.282
The Mitsunobu reaction (10-17) can be used to convert alcohols to alkyl azides, and an alternative reagent for azides,
(PhO)2PON3, for use in the Mitsunobu is now available.302
There is evidence that the mechanism with carboxylic acids293 is similar to that of 18-14, except that it is the protonated
azide that undergoes the rearrangement:
The first step is the same as that of the AAC1 mechanism (16-59 which explains why good results are obtained with
hindered substrates. The mechanism with ketones involves formation of a nitrilium ion 82, which reacts with water.

The intermediates 81 have been independently generated in aqueous solution.304 Note the similarity of this mechanism to
those of ‘‘insertion’’ of CH2 (18-9) and of O (18-19). The three reactions are essentially analogous, both in products and
in mechanism.293,305 Also note the similarity of the latter part of this mechanism to that of the Beckmann rearrangement (18-
17).
Beckmann oxime-amide rearrangement:

When oximes are treated with PCl5 or a number of other reagents, they rearrange to substituted amides in a reaction called
the Beckmann rearrangement.306 Among other reagents used have been concentrated H2SO4, formic acid, liquid
SO2, SOCl2 , silica gel,308 MoO3 on silica gel,309 RuCl3,310 Y(OTf)3. .
HCl–HOAc-Ac2O, POCl3,312 BiCl3,313 neat with FeCl3,314 and polyphosphoric acid.315 The reaction has been done in supercritical
water316 and in ionic liquids.317 A polymer-bound Beckman rearrangement has been reported.318 Simply heating the oxime of
benzophenone neat leads to N-phenyl benzamide.319 The oximes of cyclic ketones give ring enlargement and form the lactam,320
as in the formation of caprolactam (83) from the oxime of cyclohexanone. Heating an oxime of a cyclic ketone, neat, with AlCl3
also leads to the lactam,321 as does microwave irradiation of an oxime on Montmorillonite K10 clay.322 Other solvent-
free reactions are known.323 Treatment of a cyclic ketone with NH2OSO3H on silica gel followed by microwave irradiation also
gives the lactam.324 Cyclic ketones can be converted directly to lactams in one laboratory step by treatment with NH2OSO2OH
and formic acid (16-14 takes place first, then the Beckmann rearrangement).325 Heating a ketone with hydroxylamine HCl and
oxalic acid also gives the amide.326 Note that the reaction of an imine with BF3.OEt2 and m-chloroperoxybenzoic acid leads to a
formamide.327

Of the groups attached to the carbon of the CN unit, the one that migrates in the Beckman rearrangement is generally
the one anti to the hydroxyl,
In the first step of the mechanism, the OH group is converted by the reagent to a better leaving group, for example, proton
acids convert it to OH2. After that, the mechanism334 follows a course analogous to that for the Schmidt reaction of
ketones (18-16) from the formation of nitrilium ion 82 on:335 Alternatively, the attack on 82 can be by the leaving group, if
different from H2O. For example, when PCl5 is used to induce the reaction, a N–O–PCl4 species is formed, which
generates 82. Intermediates of the form 82 have been detected by nmr and uv spectroscopy.336 The rearrangement has also
been found to take place by a differentmechanism, involving formation of a nitrile by fragmentation, and then addition by
a Ritter reaction (16-91).337 Beckmann rearrangements have also been carried out
photochemically.338

If the rearrangement of oxime sulfonates is induced by organoaluminum reagents,339 the nitrilium ion intermediate 82 is
captured by the nucleophile originally attached to the Al. By this means an oxime can be converted to an imine,
an imino thioether (R–NC–SR), or an imino nitrile (R–NC–CN).340 In the last case, the nucleophile comes from added
trimethylsilyl cyanide. The imineproducing reaction can also be accomplished with a Grignard reagent in benzene
or toluene.341 In a related reaction, treatment of spirocyclic oxaziridines with MnCl(TPP)342 or
photolysis343 leads to a lactam.
It goes to the oxygen rather than to the nitrogen . Many examples of transannular
reaction are known as . A few are: