Today I realized that I had mistakenly made the ratio of DIBAL to Weinreb amide to be 1:1, not the intended 1.5:1, in my first attempt to perform this reduction. I also realized that the paper that I have been following did two closely related reductions, one at roughly 50% higher concentration of Weinreb amide than the other one (0.15 moles per liter of solvent versus 0.10 moles per liter of THF), and I had used the lower concentration reaction as my model. Today I set up a second reaction, and I used the starting material that I had re-purified. I used the correct ratio of DIBAL, and I dissolved the amide into enough THF to mimic the higher concentration reaction. If the reaction follows second-order kinetics, then using the reduced volume of THF should increase the rate by a factor of approximately 2.25. The increased amount of DIBAL should also increase the rate. The DIBAL reagent is 1.0 M in THF.
I am monitoring by TLC. I tried simply spotting the reaction mixture without a micro-extraction. There is a strong spot at the baseline but there are other spots as well. The first time point, which was about 2.5 hours into the reaction, suggested to me that there was roughly a 25/75 ratio of aldehyde to starting material (the aldehyde has a higher Rf. Therefore, I decided to continue running the reaction, but I let it warm to about 2 °C, versus using an ice/salt bath at < 0 °C, which is what I had used for the first reaction and the first part of the second reaction. For the time being, I am tempted to avoid letting the reaction come to room temperature. Any further thoughts?