Eckert Philip, Organ Michael G
Centre for Catalysis Research and Innovation (CCRI), Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, K1N6N5, Canada.
Chemistry. 2022 Jun 21;28(35):e202200665. doi: 10.1002/chem.202200665. Epub 2022 May 12.
Bulky Pd-N-heterocyclic carbene (NHC) catalysts (e. g., N-(di-2,6-(3-pentyl)phenyl), IPent) have been shown to have significantly higher reactivity in a wide variety of cross-coupling applications (i. e., C-C, C-S, C-N) than less hindered variants (e. g., N-(di-2,6-(isopropyl)phenyl), IPr). Further, chlorinating the backbone of the NHC ring sees an even greater increase in reactivity. In the cross-coupling of (hetero)aryl electrophiles to secondary alkyl nucleophiles, making the N-aryl groups larger reduces the amount of β-hydride elimination leading to alkene byproducts and chlorinating the NHC core had an even greater effect, all but eliminating alkene formation. In the present study involving the cross-coupling of primary alkyl electrophiles and nucleophiles, a sharp and surprising reversal of all of the above trends was observed. Bulkier catalysts had generally slower rate of reaction and β-hydride elimination worsened leading to extensive amounts of alkene byproducts.
大位阻的钯-N-杂环卡宾（NHC）催化剂（例如，N-（二-2,6-（3-戊基）苯基），IPent）已被证明在多种交叉偶联应用（即C-C、C-S、C-N）中比位阻较小的变体（例如，N-（二-2,6-（异丙基）苯基），IPr）具有显著更高的反应活性。此外，对NHC环的主链进行氯化会使反应活性进一步大幅提高。在（杂）芳基亲电试剂与仲烷基亲核试剂的交叉偶联中，增大N-芳基基团的尺寸会减少导致烯烃副产物的β-氢消除量，而对NHC核心进行氯化的效果更显著，几乎消除了烯烃的生成。在本研究涉及的伯烷基亲电试剂和亲核试剂的交叉偶联中，观察到上述所有趋势出现了急剧且惊人的逆转。位阻更大的催化剂通常反应速率较慢，并且β-氢消除加剧，导致大量烯烃副产物的生成。
