Research: Science and Education
Polar Addition to C=C Group: Why Is Anti-Markovnikov
Hydroboration–Oxidation of Alkenes Not “Anti-“?
Predrag-Peter Ilich,* Lucas S. Rickertsen, and Erienne Becker
Division of Molecular and Life Sciences, Loras College, Dubuque, Iowa 52001; *peter.ilich@loras.edu
Naming organic reactions, reagents, or even
mechanisms after their purported discoverers has been a
time-honored practice in organic chemistry education and
research. There is a good reason for this in education as
the names often pro- vide a mnemonic for not one but a
number of different re- actions, substrates, and reagents.
For example, an alcohol can lose the equivalent of a water
molecule in the Zaytsev fash- ion, or the elimination of
the same group of atoms can fol- low the Hofmann
regioselectivity, to yield a different isomer of the alkene
product. The Markovnikov rule seems to present another
such case: instructors introduce it to explain why, for
example, propene and hydrogen chloride will give 2-
chloropropane and not 1-chloropropane:
The usefulness of this name becomes apparent when students
realize that the same “rule” applies to reactions as seemingly
different as oxymercuration–demercuration of 1-methyl-
cyclohexene and deuterobromination of cholesterol. However,
teaching (and learning) the numerous electrophilic addition
reactions to doubly and triply bonded carbon atoms becomes
a rather daunting task when compounded with the concepts
of carbocation rearrangement, reaction stereoselectivity, and
product chirality. At the stage when most students begin to
grasp the meaning of two concepts, Markovnikov regiose-
lectivity and anti-stereochemistry, the instructor “breaks”
the rule by introducing hydroboration–oxidative
hydroxylation, a reaction that proceeds with syn-
stereochemistry to give an anti-Markovnikov product.
Eventually, however, these reac- tions, the rules, and the
exceptions to the rules have been learned and memorized but
the term Markovnikov will be never again mentioned in the
course. One may wonder
Figure 1. Addition of HCl to propene, the G3MP3 energies and
the reactant charges.
www.JCE.DivCHED.org • Vol. 83 No. 11 November 2006 • Journal of Chemical Education
whether assigning 2-propanol as “Markovnikov” and 1-pro-
panol as “anti-Markovnikov” is the best way to introduce
and explain the nature of an electrophilic addition to
multiply- bonded carbon atoms.
Some three decades ago Jones hailed the Markovnikov
rule as “an excellent pedagogic example” suitable for
correla- tion with “general theory” (1). Subsequently,
Isenberg and Grdinic, in the analysis of the “peroxide
effect” (2), cite the “gradually modified” rule, in the form
reprinted in contem- porary sophomore organic chemistry
textbooks: “In [the] addition of the molecule X–Y … the
more positive part of the attacking molecule goes to that
carbon of the double bond that is less substituted,…” (3).
Recently, Hessley, on the ba- sis of the AM1 (4) enthalpies
of selected reactants and prod- ucts, suggested a “logical
extension” of the rule for the case of hydroboration–
oxidation reactions (5). Gooch, on the other hand, citing
qualitative chemical and pedagogic argu- ments, calls for an
outright abandonment of the Markovnikov term (6).
So we decided to take another look at the thermody-
namics of electrophilic addition reactions to alkenes. We
have used an electronic structure method, G3MP3 (7), to
calcu- late Gibbs energies (energy) and electron density
distribu- tions (8) (charge) of selected alkenes and their
intermediates and products. In particular, we have focused
our analysis on two parameters: (i) the charge distribution in
alkene and (ii) the energy difference between reactants and
intermediates. The intermediates in some of the reactions we
have studied are positively charged, and often very unstable,
species; in the case of hydroboration–oxidative
hydroxylation of alkenes the intermediates are neutral, stable
molecules. However, as we show in our analysis, it is the way
an intermediate forms, not its chemical nature, that
determines the overall reaction.
Results and Discussion
Hydrogenchlorination of Propene
This reaction begins with a proton transfer from H—
Cl to the vinyl group to form a carbocation intermediate,
fol- lowed by the addition of chloride anion to yield the
prod- uct. If a proton with a positive charge of 0.24 ends
up on
=CH2, the negatively charged vinyl carbon (  –0.39), 2-
propenium cation will form; this intermediate will yield 2-
chloropropane as the final product. If in the first reaction
step the proton “chooses” the less negatively
charged vinylidine carbon,   –0.15, the more
“expensive” (by 84 kJ/mol) 1-propenium cation will form.
In the absence of re- arrangement, the 1-propenium cation
will lead to the less stable 1-chloropropane product,
(Figure 1). The observed product is the more stable 2-
chloropropane. It appears that the best charge match in the
first reaction step results in a more stable intermediate;
this intermediate subsequently de- termines the form of
the final product. This reaction course
1
Research: Science and Education
Figure 2. Addition of BH3 to propene and conversion to propanol,
the G3MP3 energies and the reactant charges.
is not peculiar to the addition of a proton: the same charge–
energy pattern obtains for the electrophilic addition of, for
example, sulfonium cation, a species considerably larger and
more complex than a proton (see Table 1).
Hydroboration–Oxidation of Propene
This reaction is presented as a simple sequence of the
re- actants propene and BH3, the intermediates 1-
propaneborane and 2-propaneborane, and the products 1-
propanol and 2- propanol (Figure 2). As in the previous
case, the first reaction step occurs between the doubly
bonded carbon atoms of the alkene substrate and the
positively charged center of the re- agent. But in BH3 the
hydrogen role is “reversed”, and it is the boron atom that is
the positive center in the molecule. In the first reaction
step, if boron binds to the more negative vinyl carbon a
more stable 1-boranepropane will form, if bo- ron binds to
the less negative vinylidene carbon the (slightly) less
stable 2-boranepropane will form. Unlike the propene
carbocations, the boranealkanes are stable molecules. In a
sub- sequent reaction of a boranealkane, initially reported
by Jonhson and Van Campen (9) and subsequently
developed
Figure 3. Addition of IN 3 to 1,1-dimethoxy-2-
dimethylpropene, the G3MP3 energies and the
reactant charges.
tions1,2 suggest the formation of only one intermediate, best
described as 2-iodo-1,1-dimethoxy-2-methylpropenium cat-
ion (we estimate that 1-iodo-1,1-dimethoxy-2-methylpropene
cation would be 3–8 kJ/mol less stable).
If the more stable intermediate should determine the
form of the final product then the expected product, 1-
azido- 2-iodo-1,1-dimethoxy-2-methylpropane, will be 12
kJ/mol less stable than the most stable product, 2-azido-1-
iodo-1,1- dimethoxy-2-methylpro-pane, another example
of energy level crossing. But the first reaction step closely
follows the pattern observed in the previous reactions: the
binding of the electrophilic positive center to a more
negative alkene car- bon atom yields a more stable
intermediate.
The experimental reports on a similar compound, 1-
2 Journal of Chemical Education • Vol. 83 No. 11 November 2006 • www.JCE.DivCHED.org
by Brown and Rao (10), the BH2 group will be “washed off
“ through a nucleophilic attack by a peroxide anion (basic
me- dium) and replaced by OH. The more stable 1-
boranepropane will thus yield 1-propanol, which, though less
stable than the 2-isomer, is the major reaction product. In a
situation when a more stable intermediate yields a less
stable final product we say that the energy levels cross in the
course of the reac- tion. The energy level crossing in Figure 2
also tells us that in this reaction the major product is
determined—or we may say “locked”—by the form of
the most stable intermediate, not by the stability of the
product isomers. Level crossing is not a necessary feature of
hydroboration–oxidative hydroxy- lation reaction of
alkenes. For example, 1-methyl-1- cyclopentene will react
with BH3 to form the 6 kJ/mol more stable 1-methy-2-
boranecyclopentane, which upon oxidative hydroxylation
yields the 17 kJ/mol more stable 2-methyl-1- cyclopentanol,
the major product (see Table 1). In both hydroboration–
oxidative hydroxylation reactions presented here, the one
involving level crossing and the one without level crossing,
the form of the final product is determined by the structure of
the reaction intermediate created through a best charge
matching between the electron-rich substrate and the
electrophilic reagent.
Addition of Iodoazide
to 1,1-Dimethoxy-2-methyl-1-propene
Perhaps as a complement to Markovnikov’s initial
ob- servation (11) a rule of thumb has been developed
stating that, in the initial reaction step, the hydrogen (proton)
in the electrophile will “join” the more hydrogenated
alkene car- bon. This seemingly intuitive rule goes a long
way to explain the regioselectivity of the addition of H—X
(X  Cl, Br, I, OH2) to unequally substituted alkenes. More
importantly, this rule works well in cases where hydrogen is
replaced by I, HO3S, H2B, and other positive centers.
Unfortunately, this rule is of no use in cases where no
hydrogen atom is present on either alkene carbon center, as
in the case of the addition of iodoazide to 1,1-dimethoxy-2-
methyl-1-propene (dimethylketene dimethyl acetal) (Figure
3). Our calcula-
chloro-2-nitrosyl-1,1-dimethyoxy-2-methylpropane (12), and
the reactions of iodoazide with some cyclic alkenes (13)
sup- port our regioselectivity but the overall evidence is
hardly unequivocal.
The problem with applying the “hydrogen goes with
hydrogens” rule to the previous reaction is expected; however,
the fact that the same rule fails to predict the
regioselectivity of an electrophilic addition to an unequally
hydrogenated alkene is not expected. We demonstrate the
latter case with the addition of one equivalent of DCl to 1-
methylene-3- methyl-2,4-cyclopentadiene (Scheme I, 1).
A textbook application of the Markovnikov rule would
suggest 1-chloro- 1-deuteromethyl-3-methyl-2,4-
cyclopentadiene (Scheme I, 2), as the major kinetically
controlled product and 1-chloro-3- deutero-methyl-1-methyl-
 Research: Science and Education

2,4-cyclopentadiene (Scheme I, 3), as the major

thermodynamically controlled product of the re- action.
Our analysis of the six possible carbocation
intermedi-
ates and thirty-one possible reaction products of this reac-
tion suggests a very different picture (see Table 1).
Summary
We summarize the results of our calculations in Table 1
and as follows:
(i)
In the first reaction, the addition of hydrogen chloride to
propene is predicted and observed to give the more stable
2-chloropropane and not the less stable 1-isomer.
(ii) A 2-chloropropane isomer (2-chloro-1-sulfonylpropane) is
predicted and observed to be the major product in the sec-
ond reaction as well.
(iii) In the third example, the major product of the addition of
one equivalent of deuterium chloride to 1-methylene-3-
me- thyl-2,4-cyclopentadiene is predicted to be neither
the ex- pected major kinetically controlled product
1-chloro-1-deuteromethyl-3-methyl-2,4-cyclopentadiene nor
the expected major thermodynamically controlled product
1-chloro-3-deuteromethyl-1-methyl-2,4-cyclopentadiene
(Scheme I,) but 1-chloro-2-deutero-1-methyl-3-
methylene- 4-cyclopropene.
(iv) The fourth reaction, hydroboration–oxidative
hydroxylation of propene, is predicted, and observed, to
yield the less stable 1-propanol and not the more stable
2-propanol.
(v) Contrary to it, hydroboration–oxidative hydroxylation
of 1-methyl-1-cyclopentene is predicted, and observed, to
give the more stable 2-methyl-1-cyclopentanol but not
the less stable 1-methyl-1-cyclopentanol.
(vi) Finally, the addition of iodoazide (or another mixed halo-
gen–pseudohalogenide, nitrosylchloride) to the
hydrogenless 1,1-dimethoxy-2-methyl-1-propene is
predicted, and in some cases observed, to give the less
stable 1-iodo-2-azido (or 2-chloro-1- nitrosyl) but not the
more stable 2-iodo-1- azide (or more stable 1-chloro-2-
nitrosyl) product.

Table 1. Summary of Six Polar Additions to Alkenes

Reactants Intermediatea Productb

(i)

(ii)

(iii)

(iv)

(v)

Scheme I. Expected addition of one equivalent of DCl to 1-methyl-
ene-3-methyl- 2,4-cyclopentadiene
(vi)
a
Best charge match and minimum energy. bAll products, except for
product vi, were determined by the intermediate. Product vi had no
unique path; different products were formed.

The major product in the first, second, and fifth reac- sible products. The popular form of the Markovnikov rule
tions is the most stable final product. In the fourth and sixth stating that “hydrogen goes with hydrogens” is satisfied in the
reactions the major product has been predicted, and observed, first reaction, and if extended beyond Markovnikov’s
to be the less stable final product. In the third reaction the original statement (11), to equate the binding proton with “a
major product is ranked fourth on the energy scale of pos-
www.JCE.DivCHED.org • Vol. 83 No. 11 November 2006 • Journal of Chemical Education 3
Research: Science and Education
positively charged electrophilic center”, the rule applies to
the second, fourth, and fifth reactions. The rule, either in
the standard or the extended form, is useless in the case of
addition reactions to fully substituted alkenes, given by the
sixth example. Finally, the rule, applied either in the original
or extended form, fails to predict the form of the cation in-
termediate and the final product in the third reaction. So what
is common to these six addition reactions? Clearly, it is not
the size or structure of the electrophilic agent or the number
of hydrogen atoms on the alkene carbon centers, nor is it
the structure or the lowest energy of the final product of the
reaction. There is, however, a clear common thread in these
reactions and we state it in the following way:
An electrophilic addition reaction to an alkene is
de- termined by the charge distribution in the
alkene and the most stable reaction intermediate.
In each reaction presented in Table 1 the most stable
in- termediate forms when an electrophile binds to the
most nega- tively charged alkene carbon atom in the
substrate molecule. The form of this intermediate will
determine the major final product of the addition reaction.
We call the confluence of these two events the charge–
energy, or C–E, match.
It may seem that our C–E argument reaffirms the spirit
of the Markovnikov rule; in fact we completely redefine this
reaction type by using the tools and knowledge not available
137 years ago. First, we shift the focus of the analysis from
the final reaction product to the reaction intermediate. Sec-
ond, we characterize the alkene substrate in terms of elec-
tron density distribution rather than describe it by the number
and distribution of hydrogen atoms. Third, we pos- tulate that
the type of electrophilic agent is largely irrelevant in the first
reaction step. If the C–E match in the first reac- tion step is
indeed interpreted as the essence of the Markovnikov
regioselectivity then the rule should be restated in the
following way:
Every true electrophilic addition to an alkene is a
Markovnikov-type reaction.
We should also remind ourselves that a number of ad-
dition reactions to alkenes do not meet these conditions. For
example, the additions of amines, amides, and alkoxides to
alkenes proceed with difficulty, lack of regioselectivity, or do
not occur at all. Typically, these reactions have to be assisted
either through strong and specific “neighboring group” or
solvent participation, catalysis by a transition element, or ca-
talysis by an enzyme. Although products of many such reac-
tions are labeled as Markovnikov (or, more often, anti-
Markovnikov) a simple analysis, as presented above, sug-
gests that these reactions may not be determined by a first-
step intermediate, characteristic to electrophilic addition
reactions. In this sense they should not even be considered
Markovnikov-type addition reactions; we may choose to call
tions were carried out using the GAUSSIAN-03 program, see:
Frisch, Æ.; Frisch, M. Gaussian 03 User’s Reference; Gaussian,
Inc.; Pittsburgh, PA, 2003.
2. Natural Bond Order, NBO, electron densities (e.g., Foster,
J. P.; Weinhold, F. J. Am. Chem. Soc. 1980, 102, 7211–7218)
were calculated using the B3LYP hybrid functionals (e.g., Frisch,
Æ.; Frisch, M. Gaussian 03 User’s Reference; Gaussian, Inc.;
4 Journal of Chemical Education • Vol. 83 No. 11 November 2006 • www.JCE.DivCHED.org
them “non-Markovnikov” or, alternatively, we may drop
the name altogether.
Our conclusions are based on first-principles, thermo-
dynamic calculations known to be comparable to or better
than experimental thermochemical data (8). Though the
method we have used is computationally fairly intensive we
have obtained all the results reported here in a relatively
short time, running relatively inexpensive software on a
desktop PC. Computer programs of comparable quality and
capabili- ties are also available free of charge. 3 The molecular
energies and atomic charges that have been reported on the
pages of this Journal exhibit similar trends to our results and
were ob- tained using simpler software and in a fraction of
time (5). While the use of computational tools will benefit
the study of organic chemistry, we are not suggesting that an
analysis of the type presented above, even in a simpler form,
would be suitable for the majority of sophomore organic
chemistry students. We do think, however, that the nature of
electro- philic addition reactions to alkenes should be
explained cor- rectly, using the qualitative arguments
summarized in Table
1. The concepts we have used, energy difference and elec-
tron density, are not new to students. Organic chemistry in-
structors use them to explain much of the course material,
from dipole moments to cis–trans isomers, to carbocation
rearrangements, to heats of combustion, to zwitterionic forms
of amino acids.
Most of the electrophilic addition reactions to alkenes
given in sophomore organic chemistry textbooks can be ex-
plained correctly using only qualitative arguments, for ex-
ample, the higher stability of branched carbocations, or the
position of boron on the electronegativity scale. For the more
complicated cases the instructor should supply the actual
atomic charges, easily obtained using one of the “molecular
modeling” programs. Students will benefit from this
approach in two ways: first, by learning the essence of
electrophilic ad- dition reactions to alkenes using simple,
robust and highly portable concepts and, second, by not
having to memorize names and terms of limited use. Finally,
an instructor of or- ganic chemistry resorting more often to
modern, easily ac- cessible and very powerful computational
methods, is likely to acquire new insight into old, seemingly
familiar things.
Acknowledgments
PPI would like to thank Una Ilich, The Ohio State
Uni- versity, Columbus, Ohio, for editorial help; William
Kirk, Mayo Foundation, Rochester, Minnesota, for help
with bib- liography; the Department of Chemistry and
Biochemistry, Loras College, Dubuque, Iowa, for a
desktop microcomputer; and the Iowa Science Foundation
(Grant # ISF 04-13) for a quantum chemistry software
package.
Notes
1. Effective-core-potential, ECP, methods were used to cal-
culate Gibbs energies and atomic charges for compounds with ele-
ments beyond third-row, where the G3MP3 method is not
applicable (reaction given in Figure 3, for example). The ECP cal-
culations were carried out using the Los Alamos National Labora-
tory Double Zeta, or LANL2DZ, basis set and the hybrid Becke’s
3-parameter, Lee, Yang, and Parr’s functional (B3LYP). All
calcula-
Pittsburgh, PA, 2003, and references therein) with the LANL2DZ
(reaction iii) basis sets. The electron densities, the charges
throughout the text, (natural or Mullikan) are given as electron
charge fraction per cubic
 Research: Science and Education

5. Hessley, R. K. J. Chem. Educ. 2000, 77, 794–797. Initio Molecular Orbital Theory; Wiley-Intersicence: New York,
6. Gooch, E. E. J. Chem. Educ. 2001, 78, 1358–1359. 1986; Chapter 2.8.
7. Curtiss, L. A.; Redfern, P. C.; Raghavachari, K.; Rassolov, V.; 9. Johnson, J. R.; van Campen, M. G., Jr. J. Am. Chem. Soc.
Pople, J. A. J. Chem. Phys. 1999, 110, 4703–4709. 1938, 60, 121–124.
8. Hehre, W. J.; Radom, L.; Schleyer, P. von R.; Pople, J. A. Ab 10. Brown, H. C.; Rao, B. C. S. J. Am. Chem. Soc. 1956, 78, 5694–
5695.
Bohr radius [qe /a 03]; 1 q 
e 1.6  10
–19
C and 1 a  52.9 pm. 11. Markovnikoff, W. Ann. Chem. Pharm. 1870, 153, 228–259,
3. General Atomic and Molecular Electronic Structure Sys- to cite: “…wenn ein unsymmetrisch constituirter Kohlenwasserstoff
tem (GAMESS). http://www.msg.ameslab.gov/GAMESS/ sich mit einer Haloïdwasserstofsäure verbindet, so addirt sich
GAMESS.html (accessed Jul 2006). das Haloid an das weniger hydrogenisirte
Kohlenwasserstoffatom,
Literature Cited …” — “… when an asymmetric hydrocarbon reacts with
(binds to) a hydrogen halide (acid) the halogen adds to the
1. Jones, G. J. Chem. Educ. 1961, 38, 296–300. less hy- drogenated carbon atom, … .”
2. Kharasch, M. S.; Mayo, F. R. J. Am. Chem. Soc. 1933, 55, 12. Oglobin, K. A.; Kunovskaya, D. M. Zh. Obsch. Khim. 1965,
2468–2496. 1, 1713–1715.
3. Isenberg, N.; Grdinic, M. J. Chem. Educ. 1969, 46, 601–605. 13. (a) Crotti, P.; Chini, M.; Uccello-Baretta, G.; Macchia, F. J.
4. Dewar, J. J. S.; Zoebisch, E. G.; Healy, E. F. J. Am. Chem. Org. Chem. 1989, 54, 4525–4529. (b) Cambie, R. C.;
Soc. 1985, 107, 3902–3909. Jurlina,
J. L.; Rutledge, P. S.; Woodgate, P. D. J. C. S. Perkin 1, 1982,
315–325.

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