Previously on this blog: modelling the reduction of cinnamaldehyde using one molecule of lithal shows easy reduction of the carbonyl but a high barrier at the next stage, the reduction of the double bond. Here is a quantum energetic exploration of what might happen when a second LAH is added to the brew (the usual ωB97XD/6-311+G(d,p)/SCRF=diethyl ether).
In a comment at the end of the first post on this theme, I had noted some crystal structures containing in effect HxAl.Li(OR)y units (x=3,4; y=0-3), noting the variety of structural motifs. The current exploration does not even attempt to cover this range of possibilities, but it is informed by the types of weak interaction that these structures reveal. I will nevertheless accept that whatever pathway is revealed here is likely to represent an energetic upper bound and recognise that lower energy pathways may well exist but are yet to be explored.
Species | Relative ΔG298, kcal/mol | FAIR Data-DOI |
---|---|---|
I12 | 0.0 | [2] |
TS34-1 | 24.1 | [3] |
I34-1 | 25.5‡ | [1] |
I34-2 | 25.0‡ | [4] |
P34 | -8.8 | [5] |
In summary, the first step in the reduction of cinnamaldehyde to cinnamyl alcohol requires just one molecule of “LiAlH4” as reductant and has a very low barrier to reaction. To construct a reasonable model to account for the slower further reduction of the C=C bond requires adding a further LiAlH4, the key feature being the availability of a lithium centre to stabilise out the forming benzylic carbanion. No doubt even better models might include the effects of adding e.g. a third molecule of LAH, and a much more extensive exploration of the various conformational options. But I think the present model might be good enough to augment the apparently relatively limited mechanistic speculations found in text books on the topic.
†You sometimes see this phrase in articles reporting transition state location. What is means it that I tried a half-dozen what I thought were reasonable possibilities, and none of them satisfactorily converged. This semi-random exploration of the potential energy surface revealed a very flat energy potential, with lots of conformational possibilities. At this point, you have to decide whether it is worth the time to continue hunting.
This post has been cross-posted in PDF format at Authorea.
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