Absolute Configurational Assignments of Secondary Amines by CD-Sensitive Dimeric Zinc Porphyrin Host

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• 作者：Xuefei Huang ; Naoko Fujioka ; Gennaro Pescitelli ; Frank E. Koehn ; R. Thomas Williamson ; Koji Nakanishi ; and Nina Berova
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：September 4, 2002
• 年：2002
• 卷：124
• 期：35
• 页码：10320 - 10335
• 全文大小：771K
• 年卷期：v.124,no.35(September 4, 2002)
• ISSN：1520-5126

文摘

A general chiroptical protocol for determination of absolute configuration of secondary aminesincluding acyclic and cyclic aliphatic amines, aromatic amines, amino acids, and amino alcohols is described.The chiral substrate is linked to the achiral carrier moiety (3-N-Boc-amino-propyl-N-Boc-amino)acetic acid1 (BocHNCH₂CH₂CH₂BocNCH₂COOH), which after deprotection, yields a bidentate conjugate, capable offorming a 1:1 host/guest complex with dimeric zinc porphyrin host 2. As in the cases of primary aminesand secondary alcohols reported earlier, the complexation of secondary amine conjugates to porphyrintweezer host 2 represents a stereodifferentiating process, where the large (L) group at the stereogeniccenter (assigned on the basis of conformational energies A value) protrudes from the porphyrin bindingpocket. This leads to formation of host/guest complexes with a preferred porphyrin helicity that exhibitintense exciton split CD spectra. It was found that the chiral sense of porphyrin twist is clearly controlledby the stereogenic center despite the Z/E conformational complexity around the tertiary amide bond ofsecondary amine conjugates that has greatly hampered previous configurational assignments. Thus, incases where there is no ambiguity regarding the relative steric size of substituents, the observed CD coupletcan be applied for straightforward assignment of absolute configurations. In addition, to extend the applicationto more difficult cases a molecular mechanics calculation approach using the Merck Molecular Force Field(MMFFs) was developed; this provides conformational information of host/guest complexes and leads toprediction of preferred porphyrin helicity independent of conformational A values. This chiroptical protocolin combination with molecular modeling represents a general method for configurational assignments ofsecondary amines.