[Donaldson Tan]

Is carbonyl addition in acidc condition also subjected to the same regioselectivity of carbonyl addition in basic condition?

In basic addition, the OH^- attacks the alpha carbon at 109^o to the C=O. This is a purely nucleophilic addition. In constrast to acidic condition, whereby the C=O bond is first protonated. The positive charge is then transferred to the alpha carbon, followed by nucleophilic addition at the alpha carbon. I think the absence of the C=O bond in the acidic condition intermediate results in the loss of the regioselectivity. Can someone confirm this for me?

Are all carbonyl additions at equilibrium?

[Yggdrasil]

What do you mean by regioselectivity?  Are you saying that the nucleophile will attack the oxygen instead of the carbon?

The nucleophile attacks the carbonyl carbon at a 109^o angle because the HOMO of the nucleophile is interacting with the pi* orbital of the C-O bond.  Since carbon is the less electronegative of the two, the Pi* orbital resides primarily on the carbon and since its an antibonding orbital, most of the electron density is away from the internuclear space (hence the angle greater than 90).  The relative energy of the Pi* orbital will change in acidic and basic conditions, but I don't think the geometry of the Pi* orbital will change much.

[Donaldson Tan]

I describe the addition of a nucleophile to the C=O in basic conditions as regioselective because the nucleophile must attack the C=O at 109^o to the C=O bond. This angle is the result of balance between steric hindrance and electronic repulsion between the electron rich C=O bond and the electron cloud of the nucleophile. Since the protonation of the C=O results in the conversion of C=O to C-O, the electronic repulsion that was present in the basic condition scenario is absent. This should mean the nucleophile should be free to attack the alpha carbon in any direction in acidic condition.

[Yggdrasil]

The main reason for attacking at a 109^o angle is not steric or electric repulsion.  It has its basis in the interactions of the molecular orbitals of the two compounds.  Introductory ochem courses will present the steric/electric explanations as crude explanations but the real explanation lies in molecular orbital theory.  The protonated carbonyl still retains the Pi bond linking the carbon and oxygen (although it is weakened), and I think that the geometry of the Pi* orbital still requires nucleophilic attack to occur at a 109^o angle.

[lemonoman]

The main reason for attacking at a 109^o angle is not steric or electric repulsion.  It has its basis in the interactions of the molecular orbitals of the two compounds.  Introductory ochem courses will present the steric/electric explanations as crude explanations but the real explanation lies in molecular orbital theory.  The protonated carbonyl still retains the Pi bond linking the carbon and oxygen (although it is weakened), and I think that the geometry of the Pi* orbital still requires nucleophilic attack to occur at a 109^o angle.

I agree.  The orbitals you speak of point away from each other because of the electronic interactions between them (if I remember correctly).

I will also add that after a couple years of the steric- and electronic- repulsion ideas...I still can't quite get my head around the molecular orbitals, and as a result, I've struggled more than I probably should have in upper-year organic courses in particular.

[Will]

I was told that the angle the HOMO on the nucleophile attacks the LUMO on the carbon in the carbonyl group is 107^o (from the C=O bond), and it was known as the Bürgi-[someone else!] trajectory. I only remember the Bürgi bit- I tried searching Bürgi in google and couldn't find anything .

Are all carbonyl additions at equilibrium?

I don't think all nucleophilic additions to the carbonyl group are at equilibrium, for example the addition of LiAlH₄ (or AlH₄^-).

[lemonoman]

I was told that the angle the HOMO on the nucleophile attacks the LUMO on the carbon in the carbonyl group is 107^o (from the C=O bond), and it was known as the Bürgi-[someone else!] trajectory. I only remember the Bürgi bit- I tried searching Bürgi in google and couldn't find anything .

Oh yeahhh, I forgot about that...

"The nucleophile approaches the carbonyl carbon in the p-plane at an angle of 109º (the Bürgi-Dunitz angle) above or below the plane formed by the substituents on the carbonyl group." (from users.ox.ac.uk/~mwalter/web_05/year1/year1_notes/carbonyl_chemistry/carbonyl_reactions.shtml)

Suprisingly, "Dunitz" only gets a single hit from the entire forum.  But 109° is indeed the angle and Burgi-Dunitz is indeed its name.

[barcrphd]

I describe the addition of a nucleophile to the C=O in basic conditions as regioselective because the nucleophile must attack the C=O at 109^o to the C=O bond. This angle is the result of balance between steric hindrance and electronic repulsion between the electron rich C=O bond and the electron cloud of the nucleophile. Since the protonation of the C=O results in the conversion of C=O to C-O, the electronic repulsion that was present in the basic condition scenario is absent. This should mean the nucleophile should be free to attack the alpha carbon in any direction in acidic condition.

i think the defnition of regioselectivity has to be checked. i think it is the preference of an attacking group to a certain region/site in the molecule under a given situation than the angle of attack.
also i feel, the angle 109, is it the angle at which the nucliophile attack? can we say so? i think the nucliophile attacks the reaction site from all directions but only those attacks which are at angles somewhere near 109 degree are fruitful or are having  high probability of reaction. the answer as somebody suggested lies with MO orientation.

[Will]

I only remember the Bürgi bit- I tried searching Bürgi in google and couldn't find anything .

Stupid me... If I had searched Bürgi trajectory I would've found Dunitz- or looked it up in my organic chem book in the index (I really should have looked in there!).

Anyways having found it in my organic chem book it made the same mistake as my teacher- it says the angle is 107^o . I'm really fed up of chemistry books (and teachers!) making mistakes. Below are a couple of pics of the errors.

As lemonoman found, all the websites shown by google about Bürgi-Dunitz trajectory (apart from some wierd french website) say that the angle is 109^o.
Someone outa correct this error in the book- I don't know how it got past the editors... honestly .

[movies]

To address geodomes original question, the carbonyl will be activated toward addition in both cases.  In acid, the carbonyl gets activated by H⁺ and in base it would be activated by whatever cation is around (for example, if you use NaOH, then the oxygen will complex to Na⁺ before the nucleophile attacks).

[Donaldson Tan]

if you use NaOH, then the oxygen will complex to Na⁺ before the nucleophile attacks).

If that is the case, I can use any NaX solution, where X^- is a weak nucleophile, isn't it?

[movies]

Sure.  The thing is that the reverse reaction is usually pretty favorable because you make a strong C=O double bond, so even with reasonably good nucleophiles (e.g., cyanide) the addition is reversible.