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. 2023 Jun 30;25(25):4638-4643.
doi: 10.1021/acs.orglett.3c01396. Epub 2023 Jun 15.

[3 + 2] Cycloadditions of Tertiary Amine N-Oxides and Silyl Imines as an Innovative Route to 1,2-Diamines

Sarah L Hejnosz  1 , Danielle R Beres  1 , Alexander H Cocolas  1 , Martin J Neal  1 , Benjamin S Musiak  1 , Marianne M B Hanna  1 , Aaron J Bloomfield  1 , Thomas D Montgomery  1
Affiliations

[3 + 2] Cycloadditions of Tertiary Amine N-Oxides and Silyl Imines as an Innovative Route to 1,2-Diamines

Sarah L Hejnosz et al. Org Lett. .

Abstract

We have developed a one-pot synthetic method for producing 1,2-diamines from easily prepared and commercially available precursors through a formal umpolung process. Our method utilizes an efficient [3 + 2] cycloaddition as the key step in forming substituted 1,2-diamines in moderate to high yields. These resulting compounds can undergo subsequent transformations, demonstrating their utility as synthetic building blocks for more complex scaffolds. Finally, we propose a reasonable mechanism for this transformation using density functional theory modeling, justifying the experimental observations.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Synthetic Methods Forming 1,2-Diamines Highlighting Common Disconnections
Scheme 2
Scheme 2. Three-Step One-Pot Synthesis Generating 1,2-Diamines
Scheme 3
Scheme 3. Substrate Scope of Silyl Imines and N-Oxides
Reactions carried on a 0.4–2.4 mmol scale. Conditions: N-oxide (1.0 equiv), LDA (3.0 equiv), THF (0.10 M), silyl imine (1.0 equiv), and from −78 °C to room temperature (RT); hydroxylamine hydrochloride (5.0 equiv), 1.2 M HCl (0.01 M), and 65 °C. The reaction was carried out on a 2.4 mmol scale. Hydroxylamine was not used.
Scheme 4
Scheme 4. Transformations of 1,2-Diamine 4a
Figure 1
Figure 1
Proposed mechanism for [3 + 2] cycloaddition of TMAO and a silyl imine.
See this image and copyright information in PMC

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