Diastereoisomeric Assignment in a Pacifenol Derivative Using Vibrational Circular Dichroism
Diastereoisomeric Assignment in a Pacifenol Derivative Using Vibrational Circular Dichroism
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DOI：
10.1002/chir.20801
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发表时间：
2009-01-01
期刊：
影响因子：
2
通讯作者：
Joseph-Nathan, Pedro
中科院分区：
文献类型：
--
作者：
Munoz, Marcelo A.;Chamy, Cristina;Joseph-Nathan, Pedro
半合成（-）-（2 R，5 R，5aR，8 zeta，9aS）-2，8-二溴-2，5，9，9a-四氢-5-羟基-5，8，10，10-四甲基-6H-2，5a-亚甲基-1-苯并氧杂环庚三烯-7（8H）-酮（3或4），由（-）-（2 R，5 R，5aR，7S，8 S，9aS）-2，7-二溴-8-氯-2，5，7，8，9，9a-六氢-5，8，10，10-四甲基-6H-2，5a-亚甲基-1-苯并氧杂环庚烯-5-醇（pacifenol 1）的振动圆二色性（VCD）测定方法研究。非对映异构体3和4的振动光谱（IR和VCD）使用密度泛函理论（DFT）在B3 LYP/DGDZVP理论水平上计算两种构象，在每种情况下，这两种构象占在前10 kcal/mol范围内发现的总能量分布。8 R非对映异构体3的DFT构象优化表明环己酮几乎仅以船形构象存在，其中β-赤道溴原子和α-轴向甲基位于羰基的手性中心α，而对于8 S非对映异构体4，5：1构象分布有利于椅子构象与a轴溴原子和β-赤道甲基计算，由于公知的椅式相对于船式的相对稳定性，这表明合理的非对映异构体将是8 S分子。反应产物的IR光谱与3和4的计算光谱的比较没有提供非对映异构体归属的方法，而从VCD光谱的比较中，立即明显的是，重排的分子具有如3所示的8 R绝对构型，这与单晶X射线衍射研究一致，
The configuration of a chiral center in semisynthetic (-)-(2R,5R,5aR,8 zeta,9aS)-2,8-dibromo-2,5,9,9a-tetrahydro-5-hydroxy-5,8,10,10-tetramethyl-6H-2,5a-methano-1-benzoxepin-7(8H)-one (3 or 4), prepared in two steps from (-)-(2R,5R,5aR,7S,8S,9aS)-2, 7-dibromo-8-chloro-2,5,7,8,9,9a-hexahydro-5,8,10,10-tetramethyl-6H-2,5a-methano-1-benzoxepin-5-ol, known as pacifenol 1, has been determined using vibrational circular dichroism (VCD) measurements. The vibrational spectra (IR and VCD) of diastereoisomers 3 and 4 were calculated using density functional theory (DFT) at the B3LYP/DGDZVP level of theory for the two conformers that in each case account for the total energetic distribution found in the first 10 kcal/mol range. The DFT conformational optimization of the 8R diastereoisomer 3 indicates the cyclohexanone exists almost exclusively in a boat conformation with a beta-equatorial bromine atom and an a-axial methyl group at the chiral center alpha to the carbonyl group, while for the 8S diastereoisomer 4 a 5: 1 conformational distribution in favor of a chair conformation with an a-axial bromine atom and a beta-equatorial methyl group is calculated, suggesting due to well-known chair versus boat relative stabilities that the plausible diastereoisomer would be the 8S molecule. A comparison of the IR spectrum of the reaction product with the calculated spectra of 3 and 4 provided no means for the diastereoisomeric assignment, while from comparison of the VCD spectra it became immediately evident that the rearranged molecule possesses the 8R absolute configuration as shown in 3, in concordance with a single crystal X-ray diffraction study that could