Alkyne Hydroboration With “R2BH”

Hydroboration-Oxidation of Alkynes

• As seen in the previous chapter, hydroboration of alkenes with borane (BH₃) followed by oxidation (NaOH, H₂O₂) gives alcohols with anti-Markovnikov regioselectivity (See article: Hydroboration-Oxidation of Alkenes)
• Hydroboration of alkynes is also selective for the anti-Markovnikov product. However, after oxidation with NaOH/H₂O₂ , we generally do not get the simple addition product (enol). Instead we get aldehydes (with terminal alkynes) or ketones (with internal alkynes). These are constitutional isomers of the expected enol.
• Enols are in equilibrium with their constitutional isomers (aldehydes or ketones), a phenomenon known as keto-enol tautomerism (See article: Keto-Enol Tautomerism). Since C-O pi bonds are stronger than C-C pi bonds, equilibrium generally favors the keto form.
• Although BH₃ can be used for the hydroboration of alkynes (and many textbooks / courses teach this) dialkylboranes such as di-siamylborane (“Sia₂BH”) or 9-BBN (9-Borabicyclo[3.3.1]nonaneare) are better choices. Dialkylboranes (usually abbreviated R₂BH, since they can be considered equivalent for our purposes) generally give higher yields than BH₃ in the hydroboration of alkynes.

Table of Contents

1. 1. Hydroboration of Alkynes: Not The Products You Expected
   2. Dialkylboranes (R₂BH) Such As Disiamylborane and 9-BBN Are Often Used Instead of BH₃ For Hydroboration of Alkynes
   3. Hydroboration of Alkynes: The Mechanism
   4. Summary
   5. Notes
   6. Quiz Yourself!
   7. (Advanced) References and Further Reading

1. Hydroboration of Alkynes: Not The Products You Expected!

Back in the chapter on alkenes, we learned that alkenes can undergo hydroboration with reagents like borane (BH₃) or diborane (B₂H₆). (See article: Hydroboration-Oxidation of Alkenes).  In hydroboration, a C-C pi bond is broken, and a C-H and C-B bond are formed. A notable aspect of the reaction is that the C-B bond tends to form on the least substituted carbon of the alkene.   After oxidation of the borane (usually with NaOH/H₂O₂) we then get an alcohol.

In contrast to acid-catalyzed hydration of alkenes, which forms alcohols on the more substituted carbon of the alkene (“Markovnikov” regioselectivity)  [See article – Hydration of Alkenes With Aqueous Acid], hydroboration gives us an alcohol on the least substituted carbon of the alkene (“anti-Markovnikov” regioselectivity). [See article – Hydroboration of Alkenes]

If a reaction works on alkenes, it makes sense to try to apply it to alkynes. After all, there’s only one extra pi bond. What difference could just one extra pi bond make?  [Narrator: This is organic chemistry. Of course one extra pi-bond can make a huge difference, mwa-ah-ah (evil laugh)].

If hydroboration follows the same pattern of bonds formed/ broken as that for alkenes, along with anti-Markovnikov selectivity, we should expect to end up with the “alkene-alcohol” (usually referred to as an “enol”) below after oxidation.

When terminal alkynes undergo hydroboration, we don’t get this product. Instead, we get… an aldehyde!

What the…?  You might (rightly) be shaking your head or insisting that this is a misprint.  Who ordered this?

How did we end up with a C–O pi bond instead of a C–C pi bond?

The only thing that seems consistent here is that the C-O bond forms on the least substituted end of the alkyne (anti-Markovnikov regioselectivity).

Likewise, when internal alkenes undergo hydroboration, the products aren’t enols either. They’re ketones.

(When internal alkynes are attached to groups of similar size, there is no “least substituted” side of the alkyne and therefore no “anti-Markovnikov” selectivity.  So we get mixtures of ketones). 

So what’s going on here? We expected enols, and end up with aldehydes (or ketones) instead. How?

If you look closely and squint, you may notice that the observed products (aldehydes and ketones)  are constitutional isomers of our expected (“enol”) products. (Same molecular formula, different connectivity).

And it turns out that the enols do form, at least as the initial product. But alkenes attached to OH groups (enols) can readily undergo conversion to a constitutional isomer containing a C-O pi bond  instead of a C-C pi bond. These constitutional isomers are in equilibrium with each other, and equilibrium tends to favor the form with the C-O (pi) bond. This is known as “keto-enol tautomerism“. [See article: Keto-enol Tautomerism]

It’s not magic. It’s just that hydroboration-oxidation of alkynes is a gateway to enols, and a fundamental property of enols is that they are in equilibrium with their keto form. We’ll cover this in more detail in Org 2.

(In my opinion, it’s these kinds of unexpected diversions that make organic chemistry is fun! Note: your definition of “fun” may vary).

2. Dialkylboranes (R₂BH) Such As Disiamylborane and 9-BBN Are Often Used Instead of BH₃ For Hydroboration of Alkynes

Although BH₃ can be used for the hydroboration of alkynes, and it often appears in class notes and exams, in practice it’s more common to use dialkylboranes (R₂BH) for hydroboration of alkynes. In a dialkylborane, two of the B-H bonds have been replaced by bonds to an alkyl group (R).  The remaining B-H is perfectly capable of performing hydroboration reactions.  [Note 1]

One of the main advantages of using R₂BH is that it has better anti-Markovnikov selectivity. The better selectivity arises since the bulky R groups prefer to be close to the alkyne C–H for steric reasons. (If you make a model of what a “Markovnikov-selective” hydroboration would look like with a dialkylborane, you’d find that the alkyl groups on the borane can bump into the alkyl group adjacent to the triple bond). 

Three reagents commonly used for hydroboration of alkynes include disiamylborane, 9-BBN (9-Borabicyclo[3.3.1]nonane), and catecholborane.

While these reagents do have their subtle differences, for our purposes these reagents can all considered to be equivalent, and we often just abbreviate them as “R₂BH” instead of drawing them out.

Here are some examples of hydroboration of alkynes with disiamylborane and 9-BBN , which we will just abbreviate as “R₂BH”):

See if you can draw the product in this case:

Click to Flip

3. Hydroboration of Alkynes: The Mechanism

Let’s take a closer look into the mechanism of the hydroboration of alkynes with R₂BH. How does this reaction work?

The mechanism is essentially the same as that in the hydroboration of alkenes, except that we have to draw a mechanism for keto-enol tautomerism of the resulting enol.

In the first step, a concerted hydroboration reaction happens such that the new C-B bond is formed on the carbon bearing the most hydrogens (i.e. the terminal carbon of the alkyne) and a new C-H bond is formed on the more substituted carbon of the alkyne (Step 1). Both the C-H and C-B bonds are formed on the same side of the alkyne, an example of syn addition.

As discussed in the article on hydroboration of alkenes [link], the main reason for anti-Markovnikov selectivity in hydroboration is that the carbon best able to support partial positive charge (the “more substituted” carbon) will be most stabilized when it lines up with the atom bearing a partial negative charge. Since H is more electronegative (2.2) than B (2.0), it’s actually the H that forms a bond to the more substituted carbon, while the partially positive boron forms a bond with the terminal carbon of the alkyne.

Steric effects can also be important, particularly with alkynes. anti-Markovnikov selectivity can be increased by using R₂BH instead of BH₃. The idea is that the large, bulky alkyl groups will have fewer steric interactions when they are adjacent to the terminal C-H bond on the alkyne.  

After hydroboration, the resulting alkenylborane (sometimes, “vinylborane”) is then treated with an oxidant – commonly, hydrogen peroxide (H₂O₂) in the presence of aqueous base (NaOH/H₂O). Base deprotonates hydrogen peroxide, which attacks the boron (Step 2, form B–O).

The oxygen-oxygen bond in peroxides is quite weak (about 40 kcal/mol) . What happens next is that the pair of electrons in the C–B bond act as a nucleophile, attacking oxygen (Step 3, form C–O, break C–B) and breaking the O–O bond. The curved arrow we draw to show electron flow might remind you of the mechanism we see in hydride shifts and alkyl shifts. (See article – Rearrangement Reactions – Hydride Shifts)

Throughout this process, configuration on the alkene is conserved. That is, the C-O bond that is formed here remains on the same side of the alkene as the C–H bond.

This gives us a molecule where the oxygen remains bonded to boron (a boronic ester). In the presence of aqueous base (NaOH/H2O), the O-B bond is cleaved (Step 4), resulting in a species with a carbon-carbon pi bond attached to a negatively charged oxygen. This is the conjugate base of an enol, and is known as an enolate.

In the presence of water, the enolate undergoes protonation at carbon, (Step 5) resulting in formation of the C-O pi bond and the final aldehyde product. (We’ll have a lot more to say about enols and enolates in Org 2).

4. Summary

Hydroboration of alkynes gives us a new method for the synthesis of aldehydes (with terminal alkynes) and ketones (with internal alkynes).

Previously, we’ve only been able to access aldehydes and ketones through oxidative cleavage of alkenes with ozone (O₃) (See article: Ozonolysis of Alkenes)

The reaction to form ketones is generally only useful if we’re starting with a symmetrical ketone. Otherwise, we will often end up with mixtures!

Notes

Note 1. The first attempt to get terminal alkynes to undergo hydroboration resulted in an intractable mess. Details here. It was later found that the main problem is that BH₃ does a second hydroboration, and we end up with the diborane, below.

To make a long story short, yields for converting this into aldehydes are not very high. The major product from hydroboration of 1-hexyne was 1-hexanol, which formed when mild acid (water!) was added to the di-borylated product. [see Ref]

A significant amount (10%)  of 1,2-hexanediol was also formed, indicating that regioselectivity for the terminal alkyne was not very good (about 9:1 for each hydroboration = about 80% overall).

This was much improved with disiamylborane, which gives good yields of aldehydes and only performs a single hydroboration on the terminal alkyne. [Ref]

Another useful reagent for hydroboration of alkynes is catecholborane. This cleanly gives the vinyl boronic esters, below. [Ref]

These boronic esters undergo an important reaction with alkenyl halides in the presence of a palladium catalyst known as cross-coupling. The variant with boron has become known as the Suzuki reaction, which has become one of the most commonly used reactions in modern organic chemistry.

So hydroboration of alkynes is important not just for the production of aldehydes from alkynes, also for the formation of alkenyl boronic esters.

Quiz Yourself!

Click to Flip

(Advanced) References and Further Reading

Some online books (some available through Archive.org, some not)

• Boranes in Organic Chemistry
• Organic Syntheses via Boranes

1. Nobel Lecture. H.C. Brown (1979). [Link] H.C. Brown won the 1979 Nobel Prize (with George Wittig) for the development of boron reagents in organic chemistry.
2. Hydroboration. XI. The Hydroboration of Acetylenes—A Convenient Conversion of Internal Acetylenes into cis-Olefins and of Terminal Acetylenes into Aldehydes
   Herbert C. Brown and George Zweifel
   Journal of the American Chemical Society 1961 83 (18), 3834-3840
   DOI: 10.1021/ja01479a024 
   From the abstract: “The treatment of internal acetylenes, such as 3-hexyne, with the theoretical quantity of hydroborating reagent results in the formation of the corresponding trivinylborane. However, under the same conditions, terminal acetylenes such as 1-hexyne undergo dihydroboration predominantly.”
3. Germinal Organometallic Compounds. I. The Synthesis and Structure of 1,1-Diborohexane
   G. Zweifel and H. Arzoumanian
   Journal of the American Chemical Society 1967 89 (2), 291-295
   DOI: 10.1021/ja00978a022
   From the abstract: “The hydroboration of 1-hexyne with diborane in a 3:1 ratio results in the formation of a polymeric dihydroborated product. Oxidation of this material with alkaline hydrogen peroxide produces 80% 1-hexanol and only 10-12% 1,2-hexanediol. This points to an initial rapid hydrolysis of the dihydroboration intermediate….The use of either [disiamylborane] or dicyclohexylborane as the hydroborating reagents gives the 1,1-diboro- derivatives in 90-96% yield.”
4. Hydroboration. XXXIX. 1,3,2-Benzodioxaborole (catecholborane) as a new hydroboration reagent for alkenes and alkynes. General synthesis of alkane- and alkeneboronic acids and esters via hydroboration. Directive effects in the hydroboration of alkenes and alkynes with catecholborane
   Herbert C. Brown and S. K. Gupta
   Journal of the American Chemical Society 1975 97 (18), 5249-5255
   DOI: 10.1021/ja00851a038
5. A convenient stereoselective synthesis of substituted alkenes via hydroboration-iodination of alkynes
   George. Zweifel, Henri. Arzoumanian, and Charles C. Whitney
   Journal of the American Chemical Society 1967 89 (14), 3652-3653
   DOI: 10.1021/ja00990a061
6. Hydroboration. 50. Hydroboration of representative alkynes with 9-borabicyclo[3.3.1]nonane – a simple synthesis of versatile vinyl bora and gem-dibora intermediates
   Herbert C. Brown, Charles G. Scouten, and Ronald Liotta
   Journal of the American Chemical Society 1979 101 (1), 96-99
   DOI: 10.1021/ja00495a016 
7. PALLADIUM-CATALYZED REACTION OF 1-ALKENYLBORONATES WITH VINYLIC HALIDES: (1Z,3E)-1-PHENYL-1,3-OCTADIENE
   Miayura, N.; Suzuki, A.
   Org. Synth. 1990, 68, 130
   DOI:15227/orgsyn.068.0130
   A procedure by Nobel Laureate Akira Suzuki for the hydroboration of an alkyne with catecholborane. The resulting product can then be subsequently used in a Pd-catalyzed Suzuki coupling reaction.