当前位置: X-MOL 学术J. Phys. Org. Chem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effects of protecting group and counter‐anion on fluorination, bromination, and intramolecular cyclization of phenethylamine diaryliodonium salts: Quantum chemical analysis
Journal of Physical Organic Chemistry ( IF 1.9 ) Pub Date : 2020-12-30 , DOI: 10.1002/poc.4177
Hyoju Choi 1 , Young‐Ho Oh 1
Affiliation  

We analyze the effects of protecting group(s) and counter‐anion on the relative efficiency of fluorination, bromination and intramolecular cyclization of phenethylamine diaryliodonium salts (1) for nucleophilic fluorination using CsF as a model system for the synthesis of radiopharmaceuticals such as 18F‐dopa and 18F‐dopamine. We demonstrate by quantum chemical analysis that protection of –NH2 by –Boc groups strongly influences the relative yields of nucleophilic fluorination versus side reactions (bromination and intramolecular cyclization) through intricate interactions with iodonium, counter‐anion (Br, F, or OMs) to iodonium, and counter‐cation Cs+ to the nucleophile F. Protection of the amino by one or two –Boc group(s) render fluorination to be strongly favored over bromination/cyclization. Possibility of direct attack by counter‐anion is assessed. We propose that mesylate (–OMs) would be much better counter‐anion than Br because of its much weaker nucleophilicity. F is also preferred as a counter‐anion, because using it would exclusively give fluorinated product. We also estimate the capability of crown ether (18‐crown‐6) as a Lewis base promoter for enhancing the rates of fluorination.

中文翻译:

保护基和抗衡阴离子对苯乙胺二芳基碘鎓盐的氟化,溴化和分子内环化的影响:量子化学分析

我们使用CsF作为合成18 F等放射性药物的模型系统,分析了保护基团和抗衡阴离子对苯乙胺二芳基碘鎓盐(1)进行亲核氟化的氟化,溴化和分子内环化的相对效率的影响-多巴和18 F-多巴胺。我们证明通过量子化学分析,保护的-NH 2由-Boc基团强烈地影响通过与碘鎓,反阴离子复杂的相互作用(BR亲核氟化相对于副反应(溴化和分子内环化)的相对产量-,F - ,或OMs的- ),以碘和抗衡阳离子铯+的亲核试剂˚F - 。一个或两个–Boc基团对氨基的保护使得氟化作用远胜于溴化/环化作用。评估了抗阴离子直接攻击的可能性。我们建议甲磺酸盐(–OMs )比Br 更好的抗衡阴离子因为它的亲核性很弱。˚F -也优选作为反阴离子,因为使用它会完全放弃氟化产物。我们还估计了冠醚(18-crown-6)作为路易斯碱促进剂增强氟化速率的能力。
更新日期:2020-12-30
down
wechat
bug