Hexacyclinol as a test case: ab initio C13 chemical shift prediction
Anybody heard of this natural product called hexacyclinol and how doubts were raised about its synthesis and structure? Kidding obviously. I am going to assume that any organic or related chemist who has not heard of hexacyclinol has not heard of Robert Burns Woodward by default.
Well, in any case, recall that the high point of that deb(acle)ate was Scott Rychnovsky's demonstration by using quantum chemical prediction of C13 chemical shifts that a structure quite different from hexacyclinol fit the C13 NMR data much better compared to JJLC's structure. To do this Rychnovsky used DFT methods and the mpw1pw91 functional which was tried, tested and proven to be a reliable tool for C13 chemical shift prediction by Bifulco and others. (excellent general review here which deals with calculation of both shifts and 2 and 3 bond homo and heteronuclear coupling constants)
The point of value for the organic chemist from the whole exercise was the fact that C13 chemical shift prediction could not just be used to distinguish regioisomers whose identity might be ambiguous but, based on Rychnovsky's analysis, also can be used to correctly assign misassigned C13 peaks. To me this is the greatest benefit of the analysis for the practicing organic chemist.
Henry Rzepa and Christopher Braddock at Imperial College in London have now demonstrated the application of this increasingly valuable method to the correct assignment of some interesting halogenated natural products called obtusallenes. In this case there was ambiguity about the positions of a chlorine and a bromine. The proton chemical shifts were very similar and could not be used to assign the positions. Rzepa and Braddock used the mpw1pw91 functional not just for the chemical shift calculation but also for the optimization. Fast computational power has made this possible now. The bottom line is that average C13 shift deviations are much more for the incorrect regioisomer. Using the method, the authors also re-assigned two ambiguous peaks. In addition, they determine that the 6-31G (d,p) basis set gives some errors for certain functional groups while using the aug-cc-pVDZ basis set (all that's left to say is "warp speed" now) basis set eliminates these errors.
A short, neat demonstration of the increasing value of quantum chemical NMR prediction methods for the practical organic chemist.
Braddock, D.C., Rzepa, H.S. (2008). Structural Reassignment of Obtusallenes V, VI, and VII by GIAO-Based Density Functional Prediction. Journal of Natural Products, 71(4), 728-730. DOI: 10.1021/np0705918