Impact of N‐Aryl‐ and NHC Core‐Substituents on the Coupling of Alkylzinc Nucleophiles: Is Bigger always Better?

Eckert, Philip; Organ, Michael G.

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.

NUCLEOPHILES; ELIMINATION reactions; ALKENES; ELECTROPHILES; CATALYSTS

Chemistry - A European Journal, 2022, Vol 28, Issue 35, p1

0947-6539

Academic Journal

10.1002/chem.202200665