Orgo 1 strategies: finding and comparing alkene hydration products

academics chemistry organic chemistry

We all know Orgo 1 professors love stereoisomers. Consider the equation A + B = C. Most professors expect you to fill in the question mark with all possible products and then indicate the major product(s), while other professors may provide you a potential C and then ask you if the statement is True or False.

Whatever the case, you've likely learned alkene addition reactions first, and you’re likely trying to memorize the three hallmark hydration reactions:

acid-catalyzed hydration: H2SO4 (aq)

oxymercuration-reduction: Hg(OAc)2 (aq) followed by NaBH4

and hydroboration-oxidation: BH3-THF followed by H2O2, NaOH (aq)

Yes, it’s important to memorize that:

acid-catalyzed hydration results in syn + anti addition

 oxymercuration-reduction results in anti addition

 and hydroboration-oxidation results in syn addition

However, it’s about here where the memorization should stop. It’s tempting to memorize that acid-catalyzed hydration results in racemic mixtures, but this simply isn’t always the case. Think about it. If you’re powering through this mechanism and there’s already a chiral center present elsewhere, you’re going to be left with two diastereomers, not two enantiomers, and therefore not a racemic mixture. For example:

Andrew 1-2.png

The latter two hydration reactions have a different issue. Namely, it’s impossible to mentally envision their products without showing any work.

What am I suggesting? Mechanism. Only by learning to power through mechanisms quickly and with confidence will you be able to determine and compare alkene hydration products. The following methods are how I teach my students to systematize the process.

Acid-Catalyzed Hydration (syn + anti addition)

Since this mechanism is carbocation-based, we expect our H2O nucleophile to attack the planar sp2 carbocation from the top and bottom face with equal probability, which results in equal syn + anti addition – right?

But wait! We already forgot something. The mechanism is carbocation-based . . . meaning rearrangements like hydride and alkyl shifts are possible, and things can get messy.

With this in mind, the system for determining all products of this hydration method is as follows:

  1. Create carbocation — listen to Markovnikov’s rule
  2. Look for a potential better carbocation (i.e. hydride/alkyl shifts)
  3. Account for equal syn + anti addition at all carbocations
    1. Addition at original carbocation gives you minor products
    2.  Addition at better carbocation gives you major products

Example:

Andrew 2-2.png

I put the original carbocation in a place Markovnikov would respect. Just note that your professor may want you to show anti-Mark. products to technically satisfy the all products condition. Moving on . . .

Andrew 3-2.png

I performed a hydride shift to get to a benzylic carbocation–the best carbocation we got! As you can see, we technically get two new carbocations since the hydride can shift to either face of the original carbocation. To finish up . . .

Andrew 4-1.png

There’s no way we could’ve done that in our heads!

Oxymercuration-Reduction (anti addition) 

Ah . . . Three-membered intermediates. Tackling these is best shown with an example.

Example:

Following Hg(OAc)2 dissociation, the nucleophilic pi-bond of the below alkene can attack the resultant Hg(OAc)+ from either the top or bottom face. I always show attack from the top face to stay consistent when solving different problems, and I recommend you do the same. Check it out . . .

Andrew 5-2.png

I labeled the above substituents in orange and blue to emphasize that, during ring creation, you must preserve the original stereochemistry. I rotated the middle molecule to better show this stereochem.

Next, you should recognize that three-membered ring opening is an anti process. We now draw an “anti-skeleton” based on where the nucleophile is going–in this case, Markovnikov placement.

Andrew 6-1.png

Again, which anti-skeleton you choose—top or bottom—depends on where the nucleophile attacks.

We next fill in and populate the anti-skeleton. Keep substituents previously on wedges on wedges, and keep substituents previously on dashes on dashes. In other words, don’t touch anything!

Andrew 7-1.png

Using our beginning example and skipping the mechanistic details, the process looks like this:

Andrew 8-1.png

In summary: 

  1. Form a three-membered ring on one face only, and place alkene substituents on appropriate wedges/dashes
  2. Draw an anti-skeleton based on point of Nu: attack
  3. Populate the anti-skeleton; don’t touch the wedges/dashes 

Hydroboration-Oxidation (syn addition)

Shortcutting a hydroboration-oxidation mechanism is similar to powering through an oxymercuration-reduction mechanism. The main difference is we use two “syn-skeletons.” Using the same example with the new conditions:

Andrew 9-1.png

As you can see, we once again took note of what substituents are on what side of the double-bond. Since hydroboration-oxidation follows a syn-mechanism, we must now draw two syn-skeletons to account for both top and bottom face addition.

Andrew 10.png

Finally, we populate both skeletons and keep in mind that the hydroxyl goes to the less substituted (anti-Mark.) side. Wrap up by filling in the substituents. Don’t touch the wedges or dashes.

Andrew 11-1.png

In summary:

  1. Take note of substituents’ stereochem; rotate alkene to show wedges/dashes
  2. Draw two syn-skeletons
  3. Populate both syn-skeletons; don’t touch the wedges/dashes

Conclusion

Phew! You can now systematically power through the three main alkene hydration mechanisms. My strong advice is to get comfortable determining the resultant stereochemistry. On exams, professors love to provide you with potential products and ask if they are, in fact, possible products. The only way to safely solve this problem with confidence is to compare the configurations (R/S) of your own products with the configurations of those given by the professor. Have fun!  

Comments

topicTopics
academics study skills medical school admissions MCAT SAT college admissions expository writing strategy English writing MD/PhD admissions LSAT physics GMAT GRE chemistry academic advice graduate admissions biology math interview prep law school admissions ACT language learning test anxiety personal statements premed career advice MBA admissions test prep AP exams homework help creative writing MD study schedules mathematics computer science Common Application history research summer activities secondary applications philosophy organic chemistry economics supplements admissions coaching dental admissions 1L grammar statistics & probability PSAT psychology law legal studies ESL reading comprehension CARS PhD admissions SSAT calculus covid-19 logic games engineering USMLE admissions advice medical school mentorship Latin Spanish biochemistry parents AMCAS English literature case coaching verbal reasoning DAT STEM adjusting to college dental school excel genetics political science skills French Linguistics MBA coursework Tutoring Approaches academic integrity astrophysics chinese classics freewriting gap year letters of recommendation mechanical engineering technical interviews units Anki DO Social Advocacy algebra amino acids art history artificial intelligence business careers cell biology cold emails data science diversity statement finance first generation student geometry graphing kinematics linear algebra mental health pre-dental presentations quantitative reasoning revising software engineering study abroad tech industry time management work and activities writer's block 2L AAMC DMD IB exams ISEE Japanese MD/PhD programs MMI Sentence Correction algorithms analysis essay argumentative writing athletics business skills executive function fellowships functions genomics infinite information sessions international students internships logic networking office hours outlining poetry proofs reading recommendations research fit resume scholarships science social sciences statement of purpose trigonometry 3L ADHD Academic Interest ChatGPT EMT FlexMed Fourier Series Greek Health Professional Shortage Area Italian JD/MBA admissions Lagrange multipliers London MD vs PhD Montessori National Health Service Corps Pythagorean Theorem Python Shakespeare Step 2 TMDSAS Taylor Series Truss Analysis Zoom acids and bases active learning architecture art art and design schools art portfolios bacteriology bibliographies biomedicine boarding school brain teaser burnout campus visits cantonese capacitors capital markets central limit theorem centrifugal force chem/phys chemical engineering chess chromatography class participation climate change clinical experience community service competitions constitutional law consulting cover letters creative nonfiction curriculum dementia demonstrated interest dimensional analysis distance learning econometrics electric engineering electricity and magnetism embryology entropy escape velocity evolution extracurriculars fundraising harmonics health policy history of medicine history of science hybrid vehicles hydrophobic effect ideal gas law immunology induction infinite series