College of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People's Republic of China.
Chirality. 2010 Aug;22(8):744-53. doi: 10.1002/chir.20828.
Axially chiral biphenyls such as (M,S)-3k have been conveniently obtained by crystallization of their diastereomeric mixtures, which were synthesized from racemic 4,4'-dimethoxy-5,6,5',6'-bis(methylenedioxy)-2-carboxylester-2'-carboxyl-biphenyls 4 and chiral amino alcohols (R)-alaninol, (S)-alaninol, (S)-valinol, and (S)-phenylalaninol. A crystallization-induced configuration transformation of the biphenyls was thus achieved. It was found that amide formation of an (S)-valinol or (S)-phenylalaninol at the 2'-position of the biphenyl usually induced the deposition of crystals with the (M)-configuration from ethanol in yields higher than 50%. The absolute configurations (ACs) of two crystalline biphenyls have been determined by X-ray crystallographic analysis. The ACs of nine biphenyls have been assigned based on their CD spectra. Further, stability investigation of these axially chiral biphenyls revealed that the ACs could revert upon redissolution. The energy barrier to epimerization between (P,R)-3b and (M,R)-3b was measured as DeltaG(#) = 21.45 kcal/mol and the half-life in ethanol at 301 K was 17.1 h.
手性轴联联苯如（M，S）-3k 可以通过其非对映异构体混合物的结晶方便地获得，这些混合物是由外消旋 4,4'-二甲氧基-5,6,5',6'-双（亚甲基二氧基）-2-羧酸酯-2'-羧酸联苯 4 和手性氨基醇（R）-丙氨酸、（S）-丙氨酸、（S）-缬氨酸和（S）-苯丙氨酸合成的。因此，实现了对联苯的结晶诱导构型转化。发现联苯 2'-位的酰胺形成（S）-缬氨酸或（S）-苯丙氨酸通常会导致（M）-构型的晶体从乙醇中以高于 50%的产率沉积。通过 X 射线晶体学分析确定了两个结晶联苯的绝对构型（ACs）。根据它们的 CD 光谱，确定了九个联苯的 ACs。此外，这些手性轴联联苯的稳定性研究表明，ACs 可以在重新溶解时反转。（P，R）-3b 和（M，R）-3b 之间的外消旋化的能垒被测量为 DeltaG（#）=21.45 kcal/mol，在 301 K 的乙醇中的半衰期为 17.1 h。
