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. 2020 Oct 16;22(20):8106-8110.
doi: 10.1021/acs.orglett.0c03061. Epub 2020 Oct 2.

Copper-Catalyzed Propargylation of Nitroalkanes

Raphael S Kim  1 , Linh V Dinh-Nguyen  1 , Kirk W Shimkin  1 , Donald A Watson  1
Affiliations

Copper-Catalyzed Propargylation of Nitroalkanes

Raphael S Kim et al. Org Lett. .

Abstract

Using a commercially available, inexpensive, and abundant copper catalyst system, an efficient α-functionalization of nitroalkanes with propargyl bromides is now established. This mild and robust method is highly functional group tolerant and provides straightforward access to complex secondary and tertiary homopropargylic nitroalkanes. Moreover, the utility of these α-propargylated nitroalkanes is demonstrated through downstream functionalization to biologically relevant, five-membered N-heterocycles such as pyrroles and 2-pyrrolines.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Propargylation of Nitroalkanes
Scheme 1.
Scheme 1.
Synthesis of Secondary and Tertiary Homopropargylic Nitroalkanes a20 h. b 20 mol % CuBr. c 20 mol % CuBr, 20 h.
Scheme 2.
Scheme 2.
Pyrroles Synthesis Using Modification of Dixon’s Protocol. a4Å MS, DMSO. b10 mol % PPh3AuCl/AgPF6, PhMe, 110 °C.
Scheme 3.
Scheme 3.
Preparation of 2-Pyrrolines from Homopropargylic Nitroalkanes aZn dust, AcOH. bBzCl, Et3N, DCM. c10 mol % PPh3AuCl/AgOTf, PhMe, 110 °C. d Yield over 2-steps.
See this image and copyright information in PMC

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