Determination of relative stereochemistry

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The review article [1] discusses use of ^2,3J_CH, ³J_HH scalar couplings and ¹³C chemical shifts for assignment of relative stereochemistry of centers (marked in bold) in -CHX-CHY- and -CHX-CH₂-CHY- hydrocarbon fragments, where X and Y are polar substituents.

²J_CH couplings are useful when C atom is bonded to an electronegative atom, whereas and ³J_CH and ³J_HH couplings work for all aliphatic systems [1].

Matsumori et al.[2] showed that ^2,3J_CH and ³J_HH coupling constants can be used to determine relative stereochemistry of two adjacent stereocenters in acyclic hydrocarbons. The analysis is based on the assumption (supported by molecular mechanics calculations) that most acyclic hydrocarbons substituted with -OH, -OCH₃, -CH₃ and other non-bulky substituents favor gauche or anti conformations within 10^o accuracy. Also authors state that this J-based method to determine relative stereochemistry works for the cases where one rotamer is at least 85% populated.

Rychnovski et al. [3] showed that relative stereochemistry of 1,3-diols may be determined as syn- or anti- by analyzing the carbon shifts after functionalizing the 1,3-diols to acetonides. If the 1,3-diols have a syn- orientation to one another, the acetonide will have a chair conformation and the methyl carbons of the acetonide will have different shifts due to one being axial, the other being equitorial. If the diols are anti-, then the acetonide will exist as a twist boat conformation and the methyl carbons will have similar carbon shifts.

References

1. Bifulco, G and Dambruoso, P and Gomez-Paloma, L and Riccio, R. Determination of Relative Configuration in Organic Compounds by NMR Spectroscopy and Computational Methods. Chem Rev 107(9):3744--79, 2007. BibTeX [bifulco07]

2. Matsumori, N and Kaneno, D and Murata, M and Nakamura, H and Tachibana, K. Stereochemical determination of acyclic structures based on carbon-proton spin-coupling constants. A method of configuration analysis for natural products. J Org Chem 64(3):866--876, 1999. BibTeX [matsumori99]

3. Rychnovsky, SD and Rogers, B and Yang, G. Analysis of two carbon-13 NMR correlations for determining the stereochemistry of 1, 3-diol acetonides. The Journal of Organic Chemistry 58(13):3511--3515, 1993. BibTeX [rychnovski93]

4. Riccio, R and Bifulco, G and Cimino, P and Bassarello, C and Gomez-Paloma, L. Stereochemical analysis of natural products. Approaches relying on the combination of NMR spectroscopy and computational methods. Pure and Applied Chemistry 75(2-3):295--308, 2003. BibTeX [riccio03]

5. Marquez, BL and Gerwick, WH and Williamson, RT. Survey of NMR experiments for the determination of n J (C, H) heteronuclear coupling constants in small molecules. Magn Reson Chem 39:499--530, 2001. BibTeX [marquez]

6. Ciminiello, P and Dell'Aversano, C and Fattorusso, E and Forino, M and Magno, S and Di Rosa, M and Ianaro, A and Poletti, R. Structure and Stereochemistry of a New Cytotoxic Polychlorinated Sulfolipid from Adriatic Shellfish. Journal of the American Chemical Society 124(44):13114--13120, 2002. BibTeX [ciminello02]

7. Murata, M and Matsuoka, S and Matsumori, N and Paul, GK and Tachibana, K. Absolute configuration of amphidinol 3, the first complete structure determination from amphidinol homologues: application of a new configuration analysis based on carbon-hydrogen spin-coupling constants. J Am Chem Soc 121:870--871, 1999. BibTeX [murata99]