[azmanam]

While over reduction of unsat'd aldehydes may occur under reduction conditions, 1,4-reduction under LAH conditions is not one I'm familiar with.  A cursory search through SciFinder and Beilstein confirms.  I found an example with DIBAL-H, CuMe/HMPA, but that's usually good for 1,4-reduction instead of 1,2-reduction (I've done the selective 1,4-reduction with these conditions before). 

At any rate, the authors of the  methodology paper tested that theory by independently preparing the unsaturated aldehyde and subjecting it to the reaction conditions.  The ratio of desired(unsat'd alcohol) to undesired(sat'd alcohol) was 98:2.  For reference, under the original reaction conditions (using the malonic ester), the ratio was closer to 75:25 unsat'd:sat'd.

That would be the most logical answer, but the mechanism is not intercepted at the neutral, unsaturated aldehyde.  It is intercepted before that point.  In the undesired mechanistic pathway, the neutral, unsaturated aldehyde is not formed.

[Squirmy]

I didn't realize that over-reduction was more of a problem with NaBH4 than LAH... http://pubs.acs.org/doi/pdf/10.1021/jo00829a039

I happened upon Marshall's paper looking for examples, and one of their very first hypotheses was similar to my suggestion. They dug deeper with experiments as good scientists do, but I think you could've given some further experimental details in the original question, particularly the bit about the a,b-unsaturated aldehyde giving very little saturated alcohol. 

[azmanam]

Good, I'm actually kinda glad someone else knows the answer now.  Maybe you can help give hints that I wouldn't think of.  Sorry if my question was unclear.  What might you have added to the question for part 2 that might be of help to others?

[Squirmy]

I was just whining...it wasn't an unclear question, but with as many possible routes as they explored, I  thought a little guidance would've been useful (keeping track of the letters and numbers in Scheme 2 was loads of fun!!).

What I will add...While the a,b-unsaturated aldehyde gave almost entirely allylic alcohol under the rxn conditions, the analogous ester gave significant amounts of saturated alcohol. They also prepared the corresponding carboxylic acid which provided more saturated alcohol than the aldehyde, but less than the ester.

[azmanam]

keeping track of the letters and numbers in Scheme 2 was loads of fun!!

ugh. tell me about it.  judicious use of highlighter and redrawing/renumbering cpds from pg 2 was necessary.

Thanks for the tips.  Who wants to take a crack at pt 2?

[orgopete]

I don't know that I agree entirely with your mechanism, but that is only a small quibble. I argue that the aldehyde will reduce faster than the ester, but that is just me.

The question is where is the enolate picking up a proton under those conditions? Workup, I guess.

This is the more difficult question. Indeed, where is the proton coming from? If conjugate addition is made to the unsaturated ester, I don't see the ester enolate reducing further. If the a trivalent aluminum complexes with the ester oxygen first, then perhaps an aluminum hydride can add similarly to borane. The ester can be reduced normally and the product will be an alkyl aluminum product. Protonation on carbon will give the saturated alcohol plus the aluminum. I don't know though.

[azmanam]

I don't know that I agree entirely with your mechanism, but that is only a small quibble. I argue that the aldehyde will reduce faster than the ester

I would think it would, too.  The authors note that you can get to the desired product going that route... but if you start with independently prepared unsaturated ester (a necessary intermediate if hydride reduces aldehyde before ester), you end up with more saturated alcohol than the reduction of the malonic ester should call for.  They propose that because of the significant formation of saturated alcohol through the unsaturated ester pathway, the main reaction mechanism does not involve preferential reduction of the aldehyde over the ester to give the unsaturated ester intermediate.

If conjugate addition is made to the unsaturated ester

Eh, aluminum hydride is too hard of a base to do 1,4-reduction.  The authors do not propose formation of the saturated alcohol through a 1,4-reduction of the unsaturated ester... but they do invoke the unsaturated ester as part of the mechanism for the formation of the undesired saturated alcohol.

then perhaps an aluminum hydride can add similarly to borane

Another intriguing possibility, and one I hadn't considered. It would make sense, considering boron and aluminum are part of the same family.  But the authors also do not propose a mechanism similar to the borane mechanism.

the product will be an alkyl aluminum product.  Protonation on carbon will give the saturated alcohol plus the aluminum

Interestingly, carbon-aluminum bonds are invoked (and deemed very important) to the mechanism in the undesired pathway... but again not through a mechanism analogous to borane reduction.

[orgopete]

I don't know that I agree entirely with your mechanism, but that is only a small quibble. I argue that the aldehyde will reduce faster than the ester

I would think it would, too.  The authors note that you can get to the desired product going that route... but if you start with independently prepared unsaturated ester (a necessary intermediate if hydride reduces aldehyde before ester), you end up with more saturated alcohol than the reduction of the malonic ester should call for.  They propose that because of the significant formation of saturated alcohol through the unsaturated ester pathway, the main reaction mechanism does not involve preferential reduction of the aldehyde over the ester to give the unsaturated ester intermediate.

Maybe, maybe not. I could argue that technically, they are not using the same reductants in each case. The malonate immediately consumes one hydride making the aluminate an oxyaluminate. Will that reductant give the same ratio? However, I'd rather concede this point.

If conjugate addition is made to the unsaturated ester

Eh, aluminum hydride is too hard of a base to do 1,4-reduction.  The authors do not propose formation of the saturated alcohol through a 1,4-reduction of the unsaturated ester... but they do invoke the unsaturated ester as part of the mechanism for the formation of the undesired saturated alcohol.

Well, there is no point in my arguing this one as it seemed mechanistically implausible to pick up a proton during the reduction.

then perhaps an aluminum hydride can add similarly to borane

Another intriguing possibility, and one I hadn't considered. It would make sense, considering boron and aluminum are part of the same family.  But the authors also do not propose a mechanism similar to the borane mechanism.

the product will be an alkyl aluminum product.  Protonation on carbon will give the saturated alcohol plus the aluminum

Interestingly, carbon-aluminum bonds are invoked (and deemed very important) to the mechanism in the undesired pathway... but again not through a mechanism analogous to borane reduction.

Okay, I found that LAH can reduce a propargyl alcohol to an allyl alcohol through a cyclic oxyaluminum intermediate in which the hydride and aluminum have added on opposite sides. I presume a similar intermediate forms. Mechanistically, I could imagine its formation via complexation of the aluminum with the pi electrons and addition of hydride to that complex. Protonation should replace the aluminum with a proton from the solvent to form a saturated alcohol.

[azmanam]

Hmmm... I can't definitively say that doesn't happen, only that the authors do not propose that kind of cyclic species.  The net result would be something akin to the borane addition, with aluminum at the distal carbon.

We've discussed how the unsaturated ester is a key intermediate in this pathway.  The authors propose arriving at the unsaturated ester in the same way they get to the unsaturated aldehyde.  Here is that pathway drawn out.

We just need to figure out how to get from the unsaturated ester to the satuated alcohol.  Net reaction is addition of 3 equivalents of hydride and loss of EtO-, then protic workup.

[orgopete]

Below is my suggested route. I would expect this to be an intermolecular reduction. I think the orientation of the cyclic complex would prevent an intramolecular transfer like a hydroboration reaction. In the next step, aluminum, with four pairs of electrons, will not hold its electrons tightly and thus, they would be easily protonated. That would cleave a carbon-aluminum bond and replace it with a proton (or deuterium as shown).

I don't know whether my suggested route is correct or not. It is impossible for me to be critical of this old paper (this is from the 1960s right?). As I recall, in the original paper, they heat the heck out of it to get it to go to completion. I really don't know what the results are for the control experiments nor the propargyl alcohol example I cited earlier. I could imagine that acrolein is readily reduced to allyl alcohol without formation of the saturated alcohol. If I remember correctly, cinnamyl alcohol can also be reduced to a saturated alcohol with LAH, but I didn't look that up. Because the intermediates would be more likely to contain hydrogen (hydride) rather than an oxygen, that may make the aluminum a better Lewis acid (or not?). A similar mechanism may take place from the acetal intermediate. This may be more facile than from acrolein itself. I don't know. I am just guessing. However, I think the mechanism I have proposed should agree with the electron demand of the reagents involved.

[azmanam]

I think intramolecular is probably fine.  The paper doesn't mention evidence either way.  Your deuterium quench provides me with a source for a hint.  The deuterium is not proposed to be incorporated at the distal carbon.  The deuterium is incorporated at the tertiary carbon (what would have been the middle malonic carbon atom in the starting material).  And possibly also on oxygen.

Below is a scheme and some tables from the paper for your perusing pleasure.  The optimized conditions are in table 1, entry 7.  Note in table 2, starting with independently prepared unsaturated aldehyde gives mainly allylic aclohol.  But starting with independently prepared ester, the amount of saturated alcohol jumps, and stays relatively high even under optimized conditions.

[azmanam]

Both of your last two images show the reduction of the alkene after complete reduction of the carbonyl functionality.  If that were the case, the independently prepared aldehyde and ester should react the same, yes?  So the mechanisms must diverge before complete reduction of the carbonyl functionality to the alkoxide.

[orgopete]

Both of your last two images show the reduction of the alkene after complete reduction of the carbonyl functionality.  If that were the case, the independently prepared aldehyde and ester should react the same, yes?  So the mechanisms must diverge before complete reduction of the carbonyl functionality to the alkoxide.

I agree that my suggestion maybe or is completely wrong. Now that you have posted some data and even Marshall's (partial) suggestion, it is clear that I don't have a clue.

First:

Eh, aluminum hydride is too hard of a base to do 1,4-reduction.  The authors do not propose formation of the saturated alcohol through a 1,4-reduction of the unsaturated ester... but they do invoke the unsaturated ester as part of the mechanism for the formation of the undesired saturated alcohol.

In Table II (ex 2), Marshall suggests that up to 91% of the product comes from 1,4-addition. Isolation of the saturated aldehyde convinces me the enolate is a likely intermediate.

If 1,4-addition is occurring as indicated by Marshall, then saturated alcohol from the aldehyde does not make sense, Table II. Why shouldn't it also result in the saturated aldehyde?

I believe that Marshall was skeptical of these results also. It appeared that post reduction reactions were taking place. The aldehyde was best isolated by inactivating the LAH or limiting LAH available during work up, Table I (ex 5 & 6). That is, looking at the work up conditions, I argue that different product ratios indicate that further reaction takes place between the initial reflux and isolation of the product.

I agree the ester may not have been the primary intermediate. However, a simple 1,4-addition, and work up should release the ester. A 1,4-addition to the unsaturated aldehyde gives the enolate, the enolate goes to aldehyde. If reduction continues during work up, the aldehyde is reduced to the alcohol. While that doesn't completely explain ex 2 & 3 of Table II, but does go in the right direction. If reductant is depleted, then less saturated alcohol and more aldehyde is isolated. When it isn't the opposite. However, since the work up is depleting the hydrides available, a mixed result is found.

I didn't look this up, but will tri-t-butoxyaluminum hydride do a conjugate addition to an aldehyde? It doesn't reduce aldehydes. That was the reason I was hesitant to decisively say what would or wouldn't happen. A big excess of LAH is used and a number of alkoxides are generated to give new reductants. While LAH may not give saturated aldehyde to a great extent, the allyl alcohols can generate alkoxyaluminum hydrides that could be responsible for the small amount of conjugate addition that may have been responsible for the saturated alcohol from the aldehyde. Marshall did not add an equivalent amount of ethanol to the reaction to see what effect the intermediate hydrides may have had on the reduction. However, it seems safe to say that LAH will react faster with an aldehyde than mono-, di- or trialkoxyaluminum hydrides would. Hey, its only a guess.

[azmanam]

In Table II (ex 2), Marshall suggests that up to 91% of the product comes from 1,4-addition

I think he's saying that, after analyzing the product mixture, 91% comes from net 1,4-reduction, and 9% from net 1,2-reduction.  I think this is plausible comparing table II, entries 2 and 3.  Beginning with the independently prepared ester, and keeping everything the same except the workup conditions, the amount of sat'd alcohol and allylic alcohol change.

I argue that different product ratios indicate that further reaction takes place between the initial reflux and isolation of the product.

Yes.  In fact, I have a part 3 (!) waiting in the wings once we wade through the formation of the saturated alcohol.

If reduction continues during work up

While we'll see that more interesting things happen depending on workup conditions, it won't end up being further reduction.  All the reductions happen pre-workup.

We're weeding out just about all other possible options.  We'll get to this mechanism by process of elimination if we have to!  This is a great discussion, imho, because it mimics real world mechanistic elucidation.  Consider a hypothesis, test it, see if the mechanism holds up.  Here's where we are so far, based on our discussion.  We've tried intercepting just about every intermediate along the way.  There aren't too many more intermediates to intercept.

[azmanam]

Alright.  Let's get this jump started again.

I've posted what the authors propose as the mechanism for the formation of the saturated, undesired byproduct.  The key step is highlighted in red.  The mechanism diverges at the point of the aldehyde/ester anion.  Hydride addition to the ester is invoked in the formation of the unsaturated, desired product.  Hydride addition to the aldehyde is proposed in the formation of the saturated, undesired byproduct.   

To illustrate: beginning with independently prepared unsaturated aldehyde (what would be formed from hydride addition to the ester in the major pathway) gives 98% desired product, and 2% undesired product.  beginning with independently prepared unsaturated ester (what would be formed from hydride addition to the aldehyde in the minor pathway) gives 9% desired product, 40% undesired product, and 48% saturated aldehyde (see image, blue).

Note the large total amount of saturated product (aldehyde and alcohol).  This seems to indicate S_N2' displacement of EtO^- by H^- is faster than carbonyl anion collapse to the unsaturated aldehyde.  Collapse to unsaturated aldehyde would put the mechanism back on the path to the desired product.

Now, anyone interested in a part three!

QUESTION:  We've talked at length about reduction of the independently prepared unsaturated ester gives primarily saturated alcohol as the predominant product (9:40 selectivity).  I just posted the proposed mechanism for the formation of the saturated alcohol.  Interestingly, introduction of ethyl formate into the the reaction mixture reverses the selectivity to give more unsaturated, desired alcohol than saturated, undesired alcohol (24:12 selectivity).  Provide a mechanism for this conversion of the minor pathway into the major product.