Cobalt-catalyzed synthesis of amides from alkenes and amines promoted by light

Abstract

Catalytic methods to couple alkene and amine feedstocks are valuable in synthetic chemistry. The direct carbonylative coupling of alkenes and amines holds promise as a perfectly atom-economical approach to amide synthesis, but general methods remain underdeveloped. Herein, we report an alkene hydroaminocarbonylation catalyzed by unmodified, inexpensive cobalt carbonyl under mild conditions and low pressure promoted by light. Silane addition after the reaction enables sequential cobalt-catalyzed amide reduction, constituting a formal alkene hydroaminomethylation. These methods exhibit exceptional scope across both alkene and amine components with high chemo- and regioselectivity and proceed efficiently even in the absence of solvent. The formation of a hydridocobalt through photodissociation of a carbonyl ligand is proposed to enable catalytic activity under mild conditions, which addresses a long-standing challenge in catalysis.

Fig. 1.. Carbonylative transformations and catalysts.

(A) Fundamental carbonylative couplings of alkylamines and alkenes. (B) Light-promoted dissociation of CO generates the active metal hydride catalyst in the presence of Lewis basic alkylamines. (C) Cobalt-catalyzed synthesis of amides or amines by hydroaminocarbonylation and hydroaminomethylation under mild conditions promoted by light.

Fig. 2.. Hydroaminocarbonylations catalyzed by cobalt carbonyl.

All yields are of isolated product. Percent selectivity is provided in examples involving minor regioisomers. See Supplementary Material for reaction details. *2 equiv alkene. †5 equiv amine. ‡5 mol % Co₂(CO)₈.

Fig. 3.. Hydroaminomethylations catalyzed by cobalt carbonyl.

All yields are of isolated product. See Fig. 2 for l/b ratios and Supplementary Material for reaction details. *2 equiv alkene. Rt, room temperature.

Fig. 4.. Highlighting the practicality of the amide synthesis.

(A) Hydroaminocarbonylation of a mixture of octenes converges to the linear product with high regioselectivity. (B) The hydroaminocarbonylation is efficient with low catalyst loading on decagram scale in the absence of reaction solvent.

Fig. 5.. Proposed catalytic cycle for the hydroaminocarbonylation.

This unique catalytic mode of unmodified cobalt carbonyl enables a general hydroaminocarbonylation of alkenes which constitutes a remarkably efficient, 100% atom-economical approach to amides from fundamental chemical building blocks under mild reaction conditions. The successful transformations of alkenes ranging from propylene to complex alkaloid natural products, and amines from ammonia to drug compounds highlight the versatility of this method, which we anticipate will prove broadly useful in contexts ranging from the preparation of medicinally relevant, functionalized small molecules to industrial scale chemical production.