Vicinal 1H鈥?sup>1H NMR Coupling Constants from Density Functional Theory as Reliable Tools for Stereochemical Analysis of Highly Flexible Multichiral Center Molecules

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• 作者：Fabian Lo虂pez-Vallejo ; Mabel Fragoso-Serrano ; Gloria Alejandra Sua虂rez-Ortiz ; Adriana C. Herna虂ndez-Rojas ; Carlos M. Cerda-Garci虂a-Rojas ; Rogelio Pereda-Miranda
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：August 5, 2011
• 年：2011
• 卷：76
• 期：15
• 页码：6057-6066
• 全文大小：979K
• 年卷期：v.76,no.15(August 5, 2011)
• ISSN：1520-6904

文摘

A protocol for stereochemical analysis, based on the systematic comparison between theoretical and experimental vicinal ¹H鈥?sup>1H NMR coupling constants, was developed and applied to a series of flexible compounds (1鈥?b>8) derived from the 6-heptenyl-5,6-dihydro-2H-pyran-2-one framework. The method included a broad conformational search, followed by geometry optimization at the DFT B3LYP/DGDZVP level, calculation of the vibrational frequencies, thermochemical parameters, magnetic shielding tensors, and the total NMR spin鈥搒pin coupling constants. Three scaling factors, depending on the carbon atom hybridizations, were found for the ¹H鈥揅鈥揅鈥?sup>1H vicinal coupling constants: f_{(sp3)鈥?sp3)} = 0.910, f_{(sp3)鈥?sp2)} = 0.929, and f_{(sp2)鈥?sp2)}= 0.977. A remarkable correlation between the theoretical (J^pre) and experimental ¹H鈥?sup>1H NMR (J^exp) coupling constants for spicigerolide (1), a cytotoxic natural product, and some of its synthetic stereoisomers (2鈥?b>4) demonstrated the predictive value of this approach for the stereochemical assignment of highly flexible compounds containing multiple chiral centers. The stereochemistry of two natural 6-heptenyl-5,6-dihydro-2H-pyran-2-ones (14 and 15) containing diverse functional groups in the heptenyl side chain was also analyzed by application of this combined theoretical and experimental approach, confirming its reliability. Additionally, a geometrical analysis for the conformations of 1鈥?b>8 revealed that weak hydrogen bonds substantially guide the conformational behavior of the tetraacyloxy-6-heptenyl-2H-pyran-2-ones.