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. 2020 Feb 26;26(12):2586-2591.
doi: 10.1002/chem.201904994. Epub 2020 Feb 21.

Stoichiometric Photochemical Carbene Transfer by Bamford-Stevens Reaction

Sripati Jana  1 , Fang Li  1 , Claire Empel  1 , Dennis Verspeek  1 , Polina Aseeva  1 , Rene M Koenigs  1
Affiliations

Stoichiometric Photochemical Carbene Transfer by Bamford-Stevens Reaction

Sripati Jana et al. Chemistry. .

Abstract

The photolysis of diazoalkanes is a timely strategy to conduct carbene-transfer reactions under mild and metal-free reaction conditions, and has developed as an important alternative to conventional metal-catalyzed carbene-transfer reactions. One of the major limitations lies within the rapidly occurring side reaction of the carbene intermediate with remaining diazoalkane molecules that result in the use of an excess of the reaction partner and thus impacts on the reaction efficiency. Herein, we describe a protocol that takes advantage of the in situ generation of donor-acceptor diazoalkanes by Bamford-Stevens reaction. Following this strategy, the concentration of the diazoalkane reaction partner can be minimized to reduce unwanted side reactions and to now conduct photochemical carbene transfer reactions under stoichiometric reaction conditions. We have explored this approach in the C-H and N-H functionalization and cyclopropanation reaction of N-heterocycles and could demonstrate the applicability of this method in 51 examples.

Keywords: C−H functionalization; N−H functionalization; carbenes; cyclopropanation; photochemistry.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Photochemical carbene‐transfer reactions: conventional vs. in situ approach.
Scheme 2
Scheme 2
a) Reaction of tosyl hydrazone 4 a and Cs2CO3 (1.5 equiv) in the dark; b) Reaction of tosyl hydrazone 4 a and Cs2CO3 (1.5 equiv) under irradiation with 470 nm LEDs (3 W); c) Reaction of tosyl hydrazone 4 a and Cs2CO3 (1.5 equiv) in the presence of N‐methyl indole (5, 1.0 equiv) under irradiation with 470 nm LEDs (3 W); Color coding: orange tosyl hydrazone 4 a, blue methyl phenyldiazoacetate 1, grey diazine 3, brown N‐methyl indole 5, green C−H functionalization product 6 a.
Scheme 3
Scheme 3
Investigation of the substrate scope with N‐protected indole heterocycles.
Scheme 4
Scheme 4
C−H functionalization of different N‐heterocycles under stoichiometric conditions.
Scheme 5
Scheme 5
N−H functionalization under stoichiometric conditions.
Scheme 6
Scheme 6
Cyclopropanation of heterocycles under stoichiometric conditions.
See this image and copyright information in PMC

References

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