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. 2021 Jun 18;23(12):4538-4542.
doi: 10.1021/acs.orglett.1c01180. Epub 2021 Jun 7.

Copper-Catalyzed Three-Component Alkene Carbofunctionalization: C-N, C-O, and C-C Bond Formation from a Single Reaction Platform

Travis L Buchanan  1 , Samuel N Gockel  1 , Alexander M Veatch  1 , Ya-Nong Wang  1 , Kami L Hull  1
Affiliations

Copper-Catalyzed Three-Component Alkene Carbofunctionalization: C-N, C-O, and C-C Bond Formation from a Single Reaction Platform

Travis L Buchanan et al. Org Lett. .

Abstract

A general system achieving three-component intermolecular carbofunctionalization of alkenes is presented, including carboetherification, carboesterification, carboarylation, and carboamination. The scope of the reaction is presented with respect to the carbon electrophile, the olefin, and the nucleophile. Furthermore, the synthesis of γ-lactams via a carboamination reaction is demonstrated in a telescoped three-step protocol.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
A. Access to diverse γ-aminocarbonyl compounds through alkene carboamination. B. Prevalence of γ-aminocarbonyl compounds among biologically active molecules. C. Mechanistic hypothesis for three-component alkene carbofunctionalization.
Scheme 1.
Scheme 1.
Scope of three-component alkene carboetherification with phenolsa aAlkene (0.75-1.5 mmol), α-haloester (1.0 mmol), aryl alcohol (0.50 mmol), and DCE (1.0 mL) combined under N2. See SI for additional details. bTriethylamine (2.0 equiv) used instead of KF. cPMDTA (N,N,N’,N’’,N’’-pentamethyldiethylenetriamine, 10 mol %) used instead of bpy.
Scheme 2.
Scheme 2.
Additional nucleophiles in three-component alkene carbofunctionalizationa a3 (0.20-0.40 mmol), 4 (0.40 mmol), nucleophile (0.20-0.40 mmol), and DCE (0.40 mL) combined under N2. bConducted with Cu(MeCN)4PF6. cConducted with K3PO4 (2.0 equiv). dConducted with Cu(OTf)2. See SI for additional details.
Scheme 3.
Scheme 3.
Access to γ-lactams via three-component alkene carboimination reactiona Reaction conditions: 1) Cu(OTf)2 (5.0 mol %), bpy (5.0 mol %), K3PO4 (0.22 mmol) Alkene (0.40 mmol), 4 (0.40 mmol), 10 (0.20 mmol), and DCE (0.40 mL) combined under N2; 2) 1:1 2.5 M HCl:MeOH (2.0 mL), 60 °C, 1 h. 3) Na2CO3 (0.60 mmol), MeOH (1.0 mL), 60 °C, 2 h. aSee SI for additional details.
See this image and copyright information in PMC

References

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