When hydrogen bromide adds across propene, two products could theoretically form: 1-bromopropane or 2-bromopropane. Yet experimentally, 2-bromopropane dominates overwhelmingly. This selectivity isn't random—it emerges from fundamental principles governing how electrons distribute themselves in reactive intermediates.

Vladimir Markovnikov articulated his famous rule in 1870, observing that hydrogen adds to the carbon bearing more hydrogens while the halogen attaches to the more substituted carbon. But the rule itself is merely descriptive. The explanatory power lies in understanding why carbocation stability dictates this outcome—and why certain conditions flip the selectivity entirely.

Mastering regiochemistry in electrophilic additions requires moving beyond memorizing rules to understanding the electronic logic beneath them. Once you internalize how charge stabilization governs intermediate formation, you can predict outcomes across diverse substrates and deliberately engineer selectivity in synthetic applications.

Electrophilic addition to alkenes proceeds through a two-step mechanism. First, the π-electron cloud attacks an electrophile—typically a proton from HX—generating a carbocation intermediate. This carbocation then captures a nucleophile to complete the addition. The critical selectivity-determining step is carbocation formation, because whichever carbon bears the positive charge dictates where the nucleophile ultimately attaches.

Carbocation stability follows a clear hierarchy: tertiary > secondary > primary > methyl. This ordering reflects hyperconjugation—the stabilizing interaction between the empty p-orbital of the carbocation and adjacent C-H σ-bonds. More alkyl substituents mean more hyperconjugative donors, spreading positive charge across a larger molecular framework and lowering the intermediate's energy.

Consider propene reacting with HBr. Protonation at C1 generates a secondary carbocation at C2, while protonation at C2 would create a primary carbocation at C1. The energy difference between secondary and primary carbocations typically spans 12-15 kcal/mol—a substantial thermodynamic preference that translates into kinetic selectivity through the Hammond postulate. The transition state leading to the more stable carbocation lies lower in energy.

This carbocation-stability framework extends beyond simple alkenes. Allylic and benzylic systems show enhanced stability through resonance delocalization. Substrates with electron-donating groups adjacent to potential cationic centers exhibit predictable biases. The mechanistic principle remains constant: identify which protonation pathway generates the more stabilized positive charge, and that pathway dominates product formation.

Takeaway

In electrophilic additions, always identify which protonation generates the more stable carbocation—the reaction pathway leading to that intermediate determines the major product.

Markovnikov selectivity assumes an ionic mechanism proceeding through carbocation intermediates. Switch to a radical mechanism, and the selectivity inverts. When HBr adds to alkenes in the presence of peroxides or under UV irradiation, 1-bromopropane becomes the major product from propene—the exact opposite of ionic addition.

The peroxide effect initiates a radical chain process. ROOR undergoes homolytic cleavage, generating alkoxy radicals that abstract hydrogen from HBr to produce bromine radicals. These bromine radicals add to the alkene's π-bond, but now stability considerations favor different intermediates. A bromine radical adding to C2 of propene generates a primary carbon radical at C1, while addition to C1 creates a secondary radical at C2.

Carbon radical stability follows the same ordering as carbocations—tertiary > secondary > primary—due to analogous hyperconjugative stabilization. Therefore, the bromine adds to generate the more substituted radical, placing bromine on the less substituted carbon. Subsequent hydrogen atom transfer from HBr completes the anti-Markovnikov product.

This mechanistic divergence provides synthetic chemists with a powerful selectivity switch. The same reagents yield opposite products depending on conditions. Ionic addition of HBr gives Markovnikov products; radical addition with peroxide initiators gives anti-Markovnikov products. Note that this peroxide effect operates specifically with HBr—HCl and HI don't exhibit analogous reversals due to unfavorable bond dissociation energetics in the radical chain.

Takeaway

Peroxides or UV light switch HBr additions from ionic to radical mechanisms, inverting selectivity—use this deliberately to access either regioisomer from the same starting materials.

A systematic approach to predicting regiochemistry begins with identifying the reaction type. For standard electrophilic additions (HX, H₂O/H⁺, alcohol/H⁺), apply Markovnikov logic: determine which protonation generates the more stable carbocation. For hydroboration-oxidation, expect anti-Markovnikov hydration through the concerted, non-carbocation pathway. For HBr with peroxides, predict anti-Markovnikov bromination via radical intermediates.

Substrate analysis requires evaluating all factors affecting carbocation stability. Beyond simple alkyl substitution, consider resonance contributors and inductive effects. Vinyl ethers protonate to give carbocations stabilized by oxygen lone-pair donation—the positive charge develops α to oxygen despite that carbon being less substituted. Styrene derivatives generate benzylic cations with resonance stabilization into the aromatic ring.

Electronic effects from substituents modulate baseline preferences. Electron-donating groups (alkoxy, amino) adjacent to one carbon enhance cation stability at that position. Electron-withdrawing groups (carbonyl, cyano, nitro) destabilize adjacent positive charges, often overriding simple substitution patterns. A methyl vinyl ketone doesn't follow naive Markovnikov predictions because the carbonyl group dramatically destabilizes positive charge at the β-carbon.

Steric considerations occasionally influence product distributions, particularly in crowded systems or with bulky reagents. However, electronic effects generally dominate regiochemical outcomes in electrophilic additions. When evaluating unfamiliar substrates, map out the possible carbocation intermediates, assess their relative stabilities considering all electronic factors, and predict the major product as arising from the more stable intermediate.

Takeaway

For any electrophilic addition, systematically evaluate carbocation stability considering substitution, resonance, and inductive effects—electronic factors almost always trump steric considerations in determining regiochemistry.

Markovnikov's rule encodes a deeper truth about chemical reactivity: reactions proceed through the lowest-energy accessible pathway, and intermediate stability governs that selection. Understanding the electronic basis for carbocation stabilization transforms a memorized rule into a predictive framework.

The anti-Markovnikov exceptions reinforce rather than contradict this logic. Radical mechanisms operate by the same stability principles applied to different intermediates. Recognizing when ionic versus radical pathways dominate allows deliberate control over product distribution.

This mechanistic thinking extends far beyond textbook alkene additions. The same electronic principles governing carbocation stability inform reaction design across organic synthesis, from industrial polymer production to pharmaceutical manufacturing. Master the logic, and the predictions follow naturally.